WORLD HEALTH ORGANIZATION
ORGANISATION MONDIALE DE LA SANT~
REGIONAL OFFICE FOR
THE WESTERN PACIFIC
BUREAU REGIONAL DU PACIFIQUE OCCIDENTAL
REGIONAL COMMITTEE
Eighteenth Session Taipei 13-19 September 1967 Provisional agenda item 9
11 September 1967 ORIGINAL: ENGLISH
BRIEF REPORTS RECEIVED FROM GOVERNMENTS ON THE PROGRESS OF THEIR HEALTH ACTIVITIES
Attached are brief reports received from the following governments in the Region on the progress of their health activities:
*
Australia Guam Hong Kong
(English only) (English only)
Japan MUaysia New Zealand Philippines Republic of Korea (English only) Singapore Taiwan
*
We ste rn 5 amoa
Trust Territo!7 of
~he
(English only)
Pacific Islands
*
Distributed to Chief Representatives only.
e
Commonwealth Department of Health
Annual Report 1966·67
COMMONWEALTH DEPARTMENT OF HEALTH
y
Annual report .r.,
Director-General of Health
1966-67
CANBERRA, 1967
Contents
5 12 23 24 27 29 87 41 49 54 56 57 62 64 67 71 74 76 77 81
Introduction Xational Health Benefits Tuberculosis Public Health Therapeutic Substances Quarantine Management Services Xorthern Territory Health Australian Capital Territory Health ~ational
Fitness
Commonwealth Health Laboratories School of Public Health and Tropical Medicine Institute of Child Health ~ational
Biological Standards Laboratory
Commonwealth Acoustic Laboratories Commonwealth X-Ray and Radium Laboratory Commonwealth Bureau of Dental Standards Institute of Anatomy National Health and Medical Research Council World Health Organisation Commonwealth Grants Appendix I-Statistics Appendix 2-Publications Directory of Senior Officers
84 91
117 122
3
The Honourable A. J. Forbes, M.C., M.P., Minister for Health, Commonwealth of Australia. I present herewith my report of the activities of the Commonwealth Department of Health for the year ended 30th June, 1967.
w. D. Refshauge, Director-General of Health, 31st August, 1967, Canberra, A.C.T.
Introduction
The scientific advances in the post-war era and the application of modern managerial techniques have benefitted mankind to an immeasurable extent. It would, at first sight, seem logical to assume that these developments would reduce the effort, facilities and finance necessary to further raise the level of health in the community. Instead the reverse is true. Health expenditure is not a self-eliminating expense, because the more success it achieves the more possibilities for further improvement are opened up. The advanced stage reached by medical science means that we are now able to tackle in a positive way many disease factors which were previously beyond remedial scope. While many more lives are saved there are, because of increasing longevity, comparatively more conditions associated with old age which require continued and long-term treatment in hospitals and by other health agencies. At the same time research is revealing or confirming health factors among the population which must cause some re-thinking of traditionally accepted priorities. As more of the older health problems, such as communicable diseases, are brought under control our attention can be directed to the more recently identified problems. It is becoming more and more apparent that many of these recently understood, or acknowledged, health problems-such as drug dependence, traffic accidents, alcoholism and cigarette smoking-cannot be solved solely through public health techniques applied by the traditional public health machinery. The causes of many of these health problems are related to behaviour rather than to accidents of biology and their remedies involve changes in well established social practices as well as medical aspects. It is interesting to reflect that hygiene, perhaps the greatest of the health lessons learnt and accepted by mankind, involved major changes in social attitudes. Health administration and legislation in Australia is, of course, already inextricably interwoven with social and welfare services and protection. But, because the solution to many contemporary health problems will involve changing social attitudes, there does seem a need to promote even closer working relationships between the health, social and educational The days when medicine and nursing were agencies of our society. almost the only professions engaged directly in health programmes have gone. Today administrators, social scientists, educationalists and technologists of all kinds play an increasingly important part. The skills of all these people are necessary if we are to ensure that the knowledge so hardly won by research is employed to the best advantage. We have a situation in Australia in which the controls over diseases that have been mastered must be maintained, in which the social benefits that have themselves done so much to improve health and happiness are being maintained and improved and in which newly identified problems challenge our resources of skill and money. In all countries of the world 5
more and more resources are being devoted to the improvement of health. In the purely financial sense, an indicator of the increased commitment to health services in Australia may be seen in the expenditure by the Commonwealth Department of Health. In the past ten years the Department's expenditure has increased by 200 per cent from $92.7 million in 1956-57 to $278.1 million in 1966-67. As the funds devoted to health services have increased and the methods of administration have become more complex, the number of people directly involved in providing the services has also expanded. Thiil trend has been accentuated in the Australian Capital Territory and the Northern Territory, the health services for which are adminstered by the Commonwealth Department of Health, by significant population increases.
()yganisatio n In July 1966 a new division was established within the Department to formulate and implement policy on all matters relating to health services in the Australian Capital Territory. The staff of this division is being built up to the required strength to cope with the many problems posed by the rapid growth of the A.C.T. population. The population growth in the Northern Territory and the development of the Territory as a wholeparticularly in mining-has also caused administrative problems and these have been further complicated by the distances and other physical factors involved in providing services to the more remote areas. To overcome these administrative difficulties, a Southern Regional OtJice of the Department has been established at Alice Springs. The complexities of administration of health services in Australia are not, of course, confined to the activities of the Commonwealth alone. Health services are largely provided by State and local government authorities, religious and charitable organisations and by private enterprise. Much of the progress made in the public health field in the past two or three decades has been due to the close working partnership achieved between Commonwealth and State agencies and the uniformity of approach to problems which has grown out of the work of the Nation;1 Health and Medical Research Council. SUTvey.~
As health activities are extended and as the inter-relationship of professional disciplines and agencies becomes more complex, it becomes more necessary than ever to obtain accurate, empirical information on which to base judgments. To assist in making such decisions the National Health and Medical Research Council has sponsored a number of surveys and others have been sponsored directly by the Commonwealth Government. During the past year, for instance, the first part of the report on the National Morbidity Survey was published, a survey to test the degree of immu~ity to poliomyelitis among children in the A.C.T. was begun and a maJ?r rese.arch project to investigate the problem of atypical mycobacterIa-whICh cause a tuberculosis type disease-was arranged. 6
Tuberculosis The earlier diagnosis of tuberculosis resulting from the mass X-ray campaigns conducted over recent years and modern methods of treatment have had the gratifying effect of almost halving the incidence of tuberculosis in Australia over the last ten years. The incidence ratio has fallen from 46.4 per 100,000 in 1956 to 21.8 per 100,000 in 1966. Information compiled in the Department's Tuberculosis Division revealed that since 1949, when the joint campaign against tuberculosis by the Commonwealth and the States was begun, 2,539 hospital beds previously reserved for tuberculosis patients had been handed over to the State hospital authorities for other uses. A further 406 beds had been closed. The survey also revealed, however, that there were still 2,558 beds reserved for use by tuberculosis patients and this, together with the number of notifications of the disease still being received, emphasises that there is no room for complacency.
Quarantine Not only does the Department of Health have to cope with the complexities of advanced medical technology but advances in other fields, particularly in transportation, have created problems which make the administration of quarantine legislation much more difficult. The introduction in Australia of container handling of overseas cargoes is going to create many problems for the Quarantine Service. By way of illustration, it is estimated that by 1972 about 80 per cent of the freight between the United Kingdom and Australia and 60 per cent of that between Europe and Australia will be in containers. The operation of all three branches of the Quarantine Service will be affected by container handling of cargo. For the General Quarantine Branch the main problem will be to determine whether the containers hold goods which are prohibited or restricted under quarantine legislation and whether containers, when landed, harbour vermin such as rats. The main problem for the Animal Quarantine Branch will concern documentation of the container contents, particularly those containers which are not opened at the terminal or bulk breaking depot in the port of arrival. For Plant Quarantine, the main concern will be the timbers used in the construction of the containers, particularly as the life cycle of the timber pests they could harbour may include a stage of aerial flight allowing rapid and wide dissemination of its species. The cleaning and disinfection of the containers and the question of soil adhering to them will be common problems in both animal and plant quarantine. The success of container handling will depend largely on the speed of operation and it will be necessary to streamline quarantine procedur~s so that the flow of goods will not be interfered with any more than IS essential. At the same time it must be ensured that no loop-hole is left by which any diseases of man, animal or plant that are at present excl~?ed by the quarantine barrier may enter Australia. Transport authontI~s, importers and exporters will have great responsibilities to comply wIth Government requirements designed to ensure that the health and economic security of Australia are not jeopardised. 7
National Health Act The National Health Act was amended twice during the year. These amendments altered the definition of 'pensioner' to permit more people to receive benefits under the National Health Act, made provision for the Commonwealth benefit payable to public hospitals for the free treatment of pensioners to be increased and also for the standard rate hospital fund benefit to be increased. Further details of these legislative changes are given in the section of this report headed National Health Benefits.
I nternational Health As a member of the World Health Organisation, Australia, and as a consequence the Commonwealth Department of Health, is involved in the world-wide battle being waged against disease. As the Department's involvement has increased there has naturally been a constant increase in the volume of work to be dealt with. To cope with this a new International Health Section was established this year. In my last report I mentioned that Australia had become a contributor to the International Agency for Research on Cancer, which was established to plan, promote and develop research into the causes, treatment and prevention of cancer, principally by sponsoring and co-ordinating research in established national laboratories. It has been most encouraging to watch the development of the Agency over the last year. It is also pleasing to report that at the 20th World Health Assembly I, as the Australian Delegate, was appointed to the Executive Board of the World Health Organisation.
Australia now maintains three medical teams in South Vietnam. The medical teams are staffed by highly qualified personnel and include surgeons, physicians, anaesthetists, medical and surgical registrars and general practitioners, together with nurses, pathology technicians and radiographers. The Australian medical teams have found their services in great demand as they have become known to the local population. They have won a high reputation both among the Vietnamese people in the localities where they have been stationed and with the Vietnamese Ministry of Health. The long range purpose of this medical aid effort is to help the Vietnamese to develop their own medical services and, consequently, one of the main duties of Australian medical personnel who work in Vietnam is to assist in the training of Vietnamese medical workers. One area in which there has been a particularly close association between the World Health Organisation and the Department has been in adverse drug reaction reporting. It is now almost three years since the Australian adverse drug reaction reporting scheme was begun and in this time 870 reports of adverse reactions have been received by the Department's Registry from the medical profession. Of these 454 have been regarded as being of a serious nature. This internal programme has complemented that of overseas countries and the World Health Organisation. It is I feel, indicative of the high regard felt overseas for the work being d~ne 8
in this country by the Department and the Australian Drug Evaluation Committee that Dr B. W. Royall, Assistant Director-General of the Therapeutic Substances Branch and Secretary of the Australian Drug Evaluation Committee, should have been given the task of developing and maintaining a world-wide system of monitoring adverse drug reactions for the World Health Organisation. Since the initial proposal of the World Health Organisation to conduct a pilot research project for an international drug monitoring scheme, scientific conferences were held in November 1965 and June 1966 to determine technical details such as the selection of information to be exchanged and the exact form of presentation, including dictionaries and codes and communication procedures. As a result of these discussions, a new adverse drug reaction report form has been designed for use within Australia which will facilitate reporting by doctors and enable Australia to participate in the WHO scheme. In May 1967, at the 20th World Health Assembly, the Director-General of WHO reported that, following negotiations with the Government of the United States of America, funds to support the drug monitoring scheme were now available together with suitable office space and equipment and data processing facilities. This accumulation of data on the adverse effects of drugs on a world-wide scale by a central body will result in more efficient drug surveillance and will lessen the probability of serious adverse reactions occurring in any of the participating countries.
L
Drug Surveillance in Australia Several significant developments took place in the Australian drug surveillance scheme during 1966-67. The first report of the Australian Drug Evaluation Committee, covering the years 1963-66, was published in April 1967, and made available to all interested bodies. This report highlights the valuable contribution by the Committee in the evaluation of new drugs and in the adverse reaction reporting scheme. A major development in the reporting programme has been the feedback of information contained in the Registry of Adverse Drug Reactions. A cumulative list of suspected adverse reactions was sent to the various professional colleges, teaching hospitals, universities and medical institutions in September 1966 and again in March 1967 on a trial basis. The response was most encouraging and consideration is now being given to distributing these lists to all members of the medical profession. This step would fulfil the wider functions envisaged in the establishment of the Registry in 1964 and also help stimulate the level of reporting. The drug surveillance system depends almost entirely on the information fed to it by a variety of sources including the medical profession, the drug manufacturers and health authorities both within Australia and overseas. I would like to record my appreciation, and that of my Department, for the excellent co-operation received from all parties since the inception of our Registry of Adverse Reactions in 1964. I am confident that this high level of co-operation will continue to ensure the success of the drug surveillance system. 9
Pharmaceutical Benefits The administration of the Pharmaceutical Benefits Scheme involves three problems which are important and are continuing in their nature. These are the safety and efficacy of drugs, the methods of limiting availability of pharmaceutical benefits and the increasing cost of the Scheme. I have already indicated the measures taken concerning the safety of drugs and these are more fully reported later in this report. Related to this problem, however, is the listing of drugs as pharmaceutical benefits, Le., as drugs available at the taxpayer's expense. Because of the inherently complex structure of the human being no person is absolutely the same as his fellow and a drug which may be safe for the great majority may cause adverse reactions in a small minority. It follows that the more widespread the use of a particular drug, the more chances there are of side effects occurring. From time to time instances occur where doctors or patients feel that restrictions imposed on the availability of drugs as pharmaceutical benefits are too severe. However, any restrictions or limitations on the quantities of drugs which may be provided as pharmaceutical benefits are made only on the recommendations of the Pharmaceutical Benefits Advisory Committee. This Committee is an expert, independent and statutory body and its existence is a safeguard against any possible arbitrary, bureaucratic actions on the listing of drugs. In relation to the problem of the rising cost of the scheme, I have to agaiu report an upward trend in costs. The cost to the Commonwealth of the Pharmaceutical Benefits Scheme in the year under review was $101.3 million, an increase of $9.5 million over the previous year. The volume of prescribing in the past year increased by 7.4 per cent and the average price of prescriptions by 2.6 per cent. The increase in average price does not represent general price increases but reflects the influence of drugs recently added to the list of benefits and which are more expensive than other drugs used for similar purposes. Instances of this are shown in the Table on page 19. The second Table on page 19 illustrates the increase in prescribing after the listing of new products within certain therapeutic groups-for example, anti-rheumatics, non-mercurial diuretics and drugs acting on blood vessels. These figures illustrate the extent to which the new drugs have come to be widely prescribed. In each of the cases quoted the new drug represented an addition or an improvement to a range of effective drugs already in wide use for the same conditions as those for which the new drug was indicated. However, the levels of prescribing for the new drugs were not compensated for by corresponding declines in the use of the older drugs in the particular groups. Prescribing at the Government's expense is, as I have said before, One of the major simply prescribing at the community's expense. problems in administration of the Scheme is the assessment of whether the cost to the community of pharmacological treatment is being inflated by the use of high priced drugs in cases where less expensive drugs would be equally effective. This complex problem is the subject of a continuous ~
/'
10
study in my Department and it is our objective, in co-operation with the medical profession, to reduce it as far as it is reasonable and practicable to do so.
Dependence-PJ'oducing Drugs It seems to me to be anomalous, but at the same time it appears to be true, that to cope with modern day life, where there are so many aids to easy living, many people apparently need sedatives, tranquillisers, stimulants and the like. Throughout the world there is a general recognition that dependence-producing drugs are a significant problem and one cannot ignore the small but growing problem here in Australia. At the 20th World Health Assembly two resolutions regarding dependence-producing drugs were passed. The first of these restricts the use of L.S.D. to scientific and special medical purposes, provides for supervision by health authorities of production, distribution and use and advocates educational programmes. The second provides for supervision of transactions of psychotropic drugs from production to retail sale, licensing of producers and traders and prohibition of possession without authority. Adequate national control of psychotropic drugs is a prerequisite to effective international control, but the difficulty in framing legislation to control these drugs is that central nervous system stimulants and depressants include many useful substances. The problem, in essence, is to provide controls which do not interfere with the legitimate use of such drugs, but which deny them to irresponsible users. In Australia it is recognised that there is a problem of illegal supply of dependence-producing drugs and that there is a possibility of illegal manufacture of L.S.D. With other hallucinogenic drugs, L.S.D. has been placed on the Fourth Schedule of the Customs (Prohibited Imports) Regulations, which means that these substances may be imported only by licensed importers with the permission of the Comptroller-General of Customs. In all cases he refers applications to my Department for advice before granting or refusing permission. Within each of the States and the Territories L.S.D. is made available only to approved psychiatrists.
11
National Health Benefits
Expenditure on national health benefits, which comprise hospital, medical and pharmaceutical benefits and payments under the Pensioner Medical Service, increased by $19.7 million in 1966-67 to reach the highest figure yet recorded of $226.9 million. There was a general rise in all areas, the greatest being for pharmaceutical benefits, which increased by $9.5 million to account for expenditure of $101.3 million. At the same time hospital benefits increased by $6.7 million, medical benefits by $2.6 million and Pensioner Medical Service payments by $1.0 million. The rise in hospital benefits is attributable, to a certain extent, to the increase from 1 January 1967 in the payments made to public hospitals for the free treatment of pensioners from $3.60 to $5.00 and, to a lesser extent, to the increase in the ' standard rate' benefit for Special Account contributors. The full effect of these changes will, of course, not be felt until 1967-68. The graph illustrates the upward trend in national health benefits over the last five years. Expenditure on National Health Benefits 1962-63 to 1966-67
$ Million Pharmaceutical Benefits Hospital Benefits I Medical Benefits Pe
I
I
Medical Service
I 963'{'4
o 12
50
100
150
200
250
Hospital Benefits Commonwealth benefits paid towards meeting the cost of hospital and nursing home treatment in 1966-67 totalled $67,398,000, an increase of 11.0 per cent over the previous year. In addition, amounts paid by registered organisations by way of hospital fund benefits increased from $57,562,000 in 1965-66 to $69,011,000 in 1966-67. Statistics relating to hospital benefits are set out in Tables 2 to 7 on pages 91 to 93.
Insured Patients in Approved Hospitals Membership of registered hospital benefits organisations increased to 3,657,000, an increase of 168,000 over the previous year. The number of contributors and dependants covered by voluntary hospital benefit insurance continued to increase with 9,342,000 persons, or 80.0 per cent of the population, covered at 30 June 1967. During the year public hospital charges were increased in all States and the Northern Territory. Most organisations introduced new tables to assist their members to meet the increased hospital charges. In some cases, however, the basic unit of benefit paid by the organisations did not enable the introduction of tables with benefits coinciding with the increased charges. The rise in hospital charges appears to have made contributors more aware of the need for increased hospital coverage and was responsible for a substantial movement into higher benefit tables. This movement, together with the continued growth and expansion of the health insurance organisation membership, resulted in fund benefit payments reaching a record level.
Special Accounts The operation of Special Accounts enables registered organisations to provide certain minimum fund benefits to contributors in respect of claims which would otherwise be disallowed under pre-existing ailment, chronic illness or maximum fund benefit rules. These minimum benefits are referred to as ' standard rate' benefits. However, where a contributor is insured in a table paying a fund benefit which is less than the standard rate, he receives benefit at the insured rate instead of the standard rate. These benefits are made possible because the Commonwealth guarantees the payments from Special Accounts and reimburses organisations for any deficits which may be incurred. The National Health Act was amended by Act No. 44 of 1966, which was assented to on 18 October 1966. The Special Account provisions were amended by increasing the standard rate benefit in relation to hospital fund benefit from $1.60 to $3.00 per day. The amendment came into force on 1 January 1967, and applied to hospital treatment on and after that date. Special Account membership increased from 32,143 at 30 June 1966 to 33,491 at 30 June 1967. It would appear that funds are continuing to make more use of their Special Accounts as a means of reducing their Ordinary Account liability. 13
Pensioners ill Public Hospitals Under Section 54 of the National Health Act, the Commonwealth pays a benefit for each day that a pensioner or dependant receives free public ward treatment in a public hospital. Prior to 1 January 1967 this benefit was at the rate of $3.60 per day. But, from this date, the rate was increased to $5.00 per day as a result of an amendment to the National Health Act.
Uninsw'ecl Patients in Approved Hospitals Expenditure on Commonwealth hospital benefits for uninsured patients increased from $2,371,000 in 1965-66 to $2,376,000 in 1966-67. It would appear that this slight increase, which occurred in spite of a rise in the membership of health insurance organisations and in the number of people who became eligible for free public ward treatment in public hospitals as a result of the relaxation of the pensions means test and inereases in the rates of pensions, may be attributed to the increased utilisation of hospital facilities by uninsured patients.
Nursing Home Patients The steady growth in the number of approved nursing homes and beds available for nursing home patients continued during 1966-67. As a result of this increase in the availability of beds, Commonwealth nursing horne benefits paid during the year totalled $22,767,000, an increase of $1,544,000 over the previous year.
Approval oj Hospitals and Nursing Homes The following are details of new premises approved in 1966·67 as hospitals or nursing homes for the purposes of the payment of Commonwealth benefits under the National Health Act:No.
Beds
No.
Beds
HospitalsPublie Private. Totals
10 8 18
519 277 796
Nursing HomesPublic 6 Private. 61 Totals 67
242 1,325 1,567
After allowing for variations arising from revocation of approvals and adjustment of bed capacities, the number of approved premises and beds as at 30 June 1966 and 30 June 1967, were:30.6.66 30.6.67
Approved HospitalsNumber Beds Approved Nursing HomesNumber Beds 14
1,109 72,335 1,059 33,075
1,098 73,644 -'
-
1,098 35,537
Medical Benefits There were no increases in 1966-67 in the rates of Commonwealth medical benefits or in the ceiling medical benefits tables operated by the registered medical benefits organisations. The proportion of the cost of services covered by Commonwealth benefits in 1966-67 was 32.2 per cent. Fund benefits covered 35.5 per cent of the cost and the share borne by the contributor was 32.3 per cent. Comparative figures for the previous year were 33.9 per cent, 35.7 per cent and 30.4 per cent respectively. The number of people covered by the Medical Benefits Scheme continued to grow. At 30 June 1967, 8,846,000 persons, or about 76.0 per cent of the population, were covered by the registered medical benefits organisations. Commonwealth medical benefits expenditure amounted to $43,841,000, an increase of $2,559,000 over the previous year. The increase was due mainly to an increase in the total number of professional services given and the greater number of people covered. Medical benefits funds increased their payments of benefits from :544,502,000 in 1965-66 to $48,941,000 in 1966-67. Statistics relating to medical benefits are set out in Tables 8 to 13 on pages 94 to 96.
I
I t-
Verification of Benefits Payments The verification by Departmental officers of Commonwealth benefits paid through registered hospital and medical benefits organisations to approved private hospitals and approved private nursing homes was continued during the year although, at times, considerable difficulty was experienced through shortage of inspections staff in some of the States. The State Auditors-General, on behalf of the Commonwealth, continued to undertake the verification of Commonwealth benefits paid direct to State controlled public hospitals and nursing homes.
Registration Committee The Registration Committee, which is constituted under Section 70 of the National Health Act, consists of the Commonwealth Actuary or his representative and two officers of the Department of Health. The functions of the Committee are to examine and to make recommendations to the Minister for Health in regard to applications for registration as medical and/or hospital benefits organisations and proposed changes to the rules of registered organisations. The Committee met thirty-three times in 1966-67 and made recommendations on 356 proposals submitted by organisations. During the year the Committee also considered applications by two organisations for cancellation of registration under the Act. The Minister approved the applications on the recommendation of the Committee.
..
Commonwealth Health Insurance Council The Commonwealth Health Insurance Council is constituted under Section 136 of the National Health Act. Its functions are to advise the Minister for Health on matters relating to the Hospital and Medical Benefits 15
Schemes and to recommend means by which improvements in methods and standards may be effected. The Council consists of the DirectorGeneral of Health as chairman, six members nominated by the State associations of registered organisations, five members representative of registered organisations generally and one member nominated by the Federal Council of the Australian Medical Association. The Council met in Canberra twice during the year, in December 1966 and March 1967. At these meetings the Council discussed a wide range of matters including the formulation of a code of ethics which all registered medical and hospital benefit organisations have been invited to adopt.
$ Million 150
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Cost of Medical Services Received by Contributors to Registered Organisations
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Pensioner Medical Service In October 1966 the National Health Act was amended by Act No. 44 of 1966. The definition of ' pensioner' under the Act was altered to permit enrolment in the Pensioner Medical Service of those persons who became pensioners as a result of increases in the pension rates. The date of effect of this Amendment was 30 September 1966. The definition of 'pensioner' in the National Health Act was again altered, with effect from 21 April 1967 by Act No. 14 of 1967. This enabled persons who qualify for an age, invalid or widow's pension under the Social Services Act, or a service pension under the Repatriation Act, by virtue of the relaxation of the pensions means test, and persons who became eligible for a sheltered employment allowance under the Social Services Act, to receive benefits under the National Health Act. This amendment to the National Health Act meant that up to 41,000 persons and their dependants would become eligible to enter the Pensioner Medical Service. However, as the general practitioner services under the Pensioner Medical Service are provided by doctors in accordance with an agreement between the Commonwealth and the Australian Medical Association, the agreement of the Association is necessary before these new pensioners may receive free general practitioner attention. As at 30 June 1967, the A.M.A. had deferred a decision on the admission of the new pensioners to the Pensioner Medical Service. The Act does, however, make provision for the new pensioners to receive free public ward treatment in public hospitals and free pharmaceutical benefits irrespective of whether an agreement can be made with the Australian Medical Association for the extension of free general practitioner services. The new pensioners have consequently been given special entitlement cards to enable them to receive these benefits. The number of pensioners and dependants enrolled in the Service continued to increase during the year, reaching 1,043,000 at 30 June 1967 compared with 1,006,000 at 30 June 1966. This represents 8.9 per cent of the population. Doctors participating in the Pensioner Medical Service are remunerated by the Commonwealth on a fee-for-service basis. As from 1 May 1967 these fees were increased from $1.60 to $1.70 for each surgery consultation and from $2.00 to $2.15 for each home visit. The number of doctors participating in the service increased during the year from 6,034 at 30 June 1966 to 6,175 at 30 .Tune 1967.
Payments to DoctoTs Total payments to participating doctors rose from $13,365,000 for 1965-66 to $14,351,000 for 1966-67. The 7.4 per cent increase in payments may be attributed mainly to the estimated 120,000 pensioners and 17,000 dependants who became eligible to receive medical services under the Pensioner Medical Service from 1 January 1966. The effect of providing services for these pensioners and dependants was felt for a fuE year for the first time in 1966-67. Statistics relating to the Pensioner Medical Service are set out in Tables 14 to 17 on pages 97 to 98. 17
Committees .of Inquiry Medical Services Committees of Inquiry, established in each State in accordance with Section 110 of the National Health Act, among other things, inquire into matters in respect of the services or conduct of medical practitioners in connection with the provision of medical services under the Pensioner Medical Service. During 1966-67, thirty references to these committees concerning the provision of medical services to pensioners were finalised. In twenty-five of these cases a total reduction of $28,725 to doctors' claims was made. Also, in two cases the medical practitioners were reprimanded by the Minister. No action was taken with regard to four cases. No. of Persons Enrolled 00,000
PENSIONER MEDICAL SERVICE
Number of Persons Enrolled and Average Number of Services per Enrolled Person-1951·52 to 1966-67
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Pharmaceutical Benefits The rate of prescribing pharmaceutical benefit prescriptions in 1966-67 increased by 7.4 per cent. This compared with a 5,1 per cent increase in 1965-66 over 1964-65. Some of this increase is the result of the addition to the list of benefits in recent years of new drugs that have come to be widely prescribed, for example in the diuretic and analgesic drug groups. HO'wever, increases alsO' occurred in the prescribing rates in other grO'ups such as tranquillisers, anti-histamines, antacids and cough suppressants which could not be explained either by the addition of new drugs or the rate of growth of the population. The volume of prescriptions for broad-spectrum antibiotics also showed a substantial rise but in this case the easing of restrictions on erythromycin would have contributed to the increase. Prescribing of penicillins fell substantially, partly as the result of restrictions applied during the year to the prescribing of oral forms of benzathine and benzyl penicillin. 18 "
A feature of the prescribing pattern is that comparatively recent, and relatively high cost, additions to the list of pharmaceutical benefits have attracted a steadily increasing number of prescriptions. At the same time there has been no comparable decrease in the prescribing of other drugs with similar therapeutic classifications. Mainly because of thi8 change in the prescribing pattern, the number of prescriptions per head of population rose to 4.61 compared with 4.36 in 1965-66. Similarly, because of the tendency to increased prescribing of relatively high cost drugs, the average cost per prescription rose from $1.89 in 1965-66 to 81.94 in 1966-67. This was despite the fact that significant price reductions were negotiated in some groups of widely used drugs. Examples of relatively new high priced drugs which have attracted heavy prescribing are shown in the following table:IVante of Thm'upe-1dic
Drug
Group
Date of L,:sting
Average P"ice of Other Pr-we .peT Drugs in Same Prescr,ptwn Therapeutic . G't'OHP
Indomethacin Frusemide Methyldopa
Antirheumatics Non-mercurial diuretics Drugs Acting on Blood Vessels
1.5.66 1.11.65 1.11.63
$3.11 84.86 $5.98
$1.99 $2.99 82.26
The three drugs in question now rank high on the list of the most frequently prescribed proprietary products, yet none were available as benefits four years ago. The following table illustrates the increase in prescribing within the respective drug groups after listing each new product:Annual Rate of Prescribing 0/ Therapeutic G,'oup Before Listing of Current Therapeut-ic Group New Drug
Anti-rheumatics Non-mercurial diuretics Drugs acting on blood vessels
1,414,000 1,745,000 2,112,000
2,477,000 2,197,000 2,868,000
Cost of Schellw Commonwealth expenditure on pharmaceutical benefits for the year totalled $101,280,799. This included $56,655,939 for prescriptions for the general public, $15,344,592 for benefits dispensed in public hospitals and miscellaneous services and $29,280,268 for prescriptions for pensioners. Expenditure on combined prescription benefits provided under the general benefit and pensioner benefit schemes increased by 11.4 per cent. This compared with a 9.4 per cent increase in 1965-66 over 1964-65. Prescription benefit expenditure exceeded the 1965-66 levels by $3,577,893 or 6.7 per cent in the case of general benefit prescriptions and by $5,209,141 or 21.6 per cent in the case of pensioner benefit prescriptions. An increase of $710,097, or 4.9 per cent was recorded for expenditure on benefits provided in public hospitals and miscellaneous services. Patient 19
contributions for general benefit prescriptions were $18,347,036 compared with $17,481,228 paid in 1965-66. Benefit prescriptions for the year totalled 53,687,342, including 36,750,907 for general benefits and 16,936,435 for pensioner benefit prescriptions. This represents an increase of 1,666,356, or 4.7 per cent in prescriptions for the general public and 2,028,042, or 13.6 per cent in prescriptions for pensioners. The proportionately higher increases in both pensioner benefit expenditure and prescriptions occurred because of the impact of the transfer of 137,000 people from general benefits to pensioner benefits on 1 January 1966 subsequent to the easing of the means test. In the previous year the effect of this transfer was confined to the second half of the year. PHARMACEUTICAL BENEFITS Average Cost per Prescription, Average Number of Prescriptions per Head of Population and Cost per Head of Population Average Cost per Prescription and Cost per Head of Population Average No. of Prescriptions per Head of Population
j
$ 10
No. - - Ave~age Cost per Pre~cnptlon - - - Average No. of Prescriptions per Head of Population - • - • Cost per Head of Population
1
1"
I I
10
,
,
s 1-.-'
-.- . -
_ 0 - __ 0_ •
-.- -.- . -'
. - .-
,
,
,
, 8
6
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,
,
/
6
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- --- - -' ----------
4 .
'.
2
2
o 1960-61 2()
o 1961-62 1962-63 I96l-64 1964-65 1965-66
1966-67
The following comparative table shows prescription volumes and costs for benefits provided in the more frequently prescribed therapeutic groups in 1965-66 and in 1966-67. Therapeutic CategoTY Year ended 30 June 1966 1967 Pre.eripExpendiPre.criptions ture tions 000'5 $000 000'5 Expendi't1l.1"e $000
Broad Spectrum 4,168 14,760 4,564 13.872 Antibiotics 4,392 11,045 4,216 9,500 Penicillins . Blood Vesselsdrugs acting 9,278 8,227 2,868 2,657 on. 6,893 6,914 6,792 Hypnotics 6,619 Diuretics - non2,197 7,365 6,096 1,956 mercurial .. 4,286 8,729 5,390 Analgesics 3,705 5,223 2,974 2,606 4,707 Anti-Histamines 2,339 803 707 2,036 Tranquillisers 1,856 1,538 1,329 1,563 Antacids. 1,307 966 1,055 1,481 Sulphonamides . Expectorants & Cough Sup973 1,167 1,044 894 pressants . The remaining expenditure was on a wide variety of drugs not so commonly used. Detailed information of financial and statistical aspects of the Pharmaceutical Benefits Scheme is given in Tables 18 to 28 on pages 98 to 102.
Changes in Listings As a result of recommendations by the Pharmaceutical Benefits Advisory Committee, forty new preparations were added to the list of pharmaceutical benefits in 1966-67. Among the most important additions were five anti-diabetics, four drugs for the treatment of heart conditions, two sulphonamides and a tetanus antitoxin for the treatment of persons sensitive to equine serum. In addition, fifty new forms and strengths of existing pharmaceutical benefits were made available during the year. The Committee also recommended that eighty-one preparations be deleted from the list of pharmaceutical benefits. In the main this followetl the normal, periodic reviews by the Committee aimed at maintaining the schedule of benefits as an up-to-date, effective range of drugs.
Price Negotiations As in past years, officers of the Department conducted negotiations with manufacturers and these resulted in reductions in the prices of drugs during 1966-67. It is estimated that, if the rate of prescribing of the particular drugs remained constant, these reductions would save the Pharmaceutical Benefits Scheme approximately $3,700,000 during a full financial year. The most significant price reductions related to antibiotics and diuretics, although most therapeutic groups of drugs were affected to some extent. 21
Joint Committee on Pricing Arrangements During 1966-67, the Joint Committee on Pharmaceutical Benefits Pricing Arrangements considered a number of aspects of pricing arrangements for pharmaceutical benefits. Its main activity during the past year, however, has been in connection with the survey of pharmacy earnings, costs and profits. The survey, which is being conducted by a firm of independent consultants on behalf of the Government and the Federated Pharmaceutical Service Guild of Australia, is intended to provide information to serve as a basis for negotiations in regard to chemists' remuneration for dispensing pharmaceutical benefits. It follows an application by the Guild for increased remuneration. The Joint Committee was concerned initially with drawing up suggested terms of reference for the survey and examining the consultants' proposed survey plan. During the past year the Committee has been maintaining liaision with the consultants in the conduct of the survey. In last year's Annual Report, reference was made to a pilot survey of a small group of pharmacies to test sample design and method. This pilot survey has been completed and the consultants have been accumulating information from the participating pharmacies for the main survey. At the close of 1966-67, the survey had not been completed, as a number of chemists, who had agreed to participate, had still not returned the questionnaires they had been asked to complete.
;(
Committees oj Inquiry The Pharmaceutical Services Committees of Inquiry considered eightyseven references during 1966-67 arising out of the services or conduct of chemists in connection with the supply of pharmaceutical benefits. The majority of these references concerned the supply of pharmaceutical benefits which did not conform to the required standards of composition or purity. The Committees' recommendations on these references resulted in sixty-three chemists being warned to exercise greater care in dispensing, fourteen being reprimanded and the suspension for two months of one chemist's approval to supply pharmaceutical benefits. Seven chemists gave satisfactory explanations to the Committees and two cases were not finalised at 30 June 1967. The Medical Services Committees of Inquiry considered two references involving the prescribing of pharmaceutical benefits. Following on the report and recommendations in these cases, one doctor had his authority to write pharmaceutical prescriptions revoked. No action was taken in the other case.
Court Proceedings Court proceedings were instituted against two doctors for breaches of the National Health Act. Both were convicted and fined and subsequently their authorities to write prescriptions for the supply of pharmaceutical benefits were revoked.
22
Tuberculosis
'-
The year 1966-67 can again be claimed as one of great success in the campaign against tuberculosis. Much has been achieved in recent years in the fight against tuberculosis but there is still no room for complacency. There are three considerations that must be kept in mind. Firstly, there were still 2,549 new cases notified in 1966, a fall of 354 compared with 1965, but still a large figure. Including old cases, there were some 2,500 known infectious patients in 1966. Secondly, tuberculosis is an infectious disease and, in the absence of a completely efficient immunising agent, any infectious disease can rapidly recrudesce. Thirdly, there are vast areas of the world where tuberculosis remains a scourge. The battle against tuberculosis in these areas is far from being won. In some of these countries the emergenc2 of drug resistant organisms has its implications and dangers for the countries with advanced tuberculosis control programmes like Australia. The final control of tuberculosis is not yet in sight. It may lie in the introduction of a more efficient immunising agent, the discovery of simpler and cheaper drugs, or the slower, year-to-year improvement which results from the application of the present methods of control. A reasonably, but not completely, effective immunising agent, BeG vaccine, is available and this is being used in larger quantities as the incidence of tuberculosis falls, because the decline in incidence also means a decline in immunity of the population. In the meantime it is necessary to intensify the campaign against tuberculosis until it can be reduced to the status of a minor disease. The number of new cases and the number of tuberculosis allowances fell in 1966 while the number of deaths was one of the lowest yet recorded. Details are given in Table 30 on page 103. Reactivated cases-patients with known old treated or untreated lesions who break down-now account for almost ten per cent of the total pulmonary notifications. This illustrates the importance of keeping the known cases under supervision indefinitely.
Special Pro.fects In conjunction with New South Wales authorities, an inaugural Australian Clinical Tuberculosis Conference was held in Sydney from 27 February to 3 March 1967. Delegates attended from all States, the Australian Capital Territory, the Northern Territory and the Territory of Papua and New Guinea. The objectives were to stimulate the exchange of ideas between States and discuss the future of tuberculosis control. Most of the papers were contributed by full-time medical officers in the State divisions of tuberculosis. The conference was highly successful in its objectives and several of its papers have been accepted in full for publication in the Medical Journal of Australia while others will appear in condensed form. In April 1967 a revised version of the document' Bacteriological Investigations for Mycobacteria Including Drug Sensitivity Tests' was produced.
23
Public Health
The volume of work undertaken by the Public Health Branch increased rapidly during 1966-67. This increase necessitated the creation of the position of Assistant Director-General to co-ordinate the functions of the various sections within the Branch. A position of Executive Officer, to supervise the clerical staff and to assist the First Assistant DirectorGeneral and Assistant Director-General, was also created during the year. All aspects of public health are the responsibility of the Branch. During the year special studies were made by officers of the Branch of the association of smoking with health, fluoridation of public water supplies, and the advertising of proprietary medicines in media other than radio and television.
Vaccination Against POliomyelitis The Australian States and Territories, with the exception of Victoria, have now implemented the change from Salk vaccine to oral Sabin vaccine in their campaigns against poliomyelitis. It is estimated that during the next year some eight million doses of Sabin vaccine will be administered throughout Australia. At the 64th SeRsion of the National Health and Medical Research Council in April 1967 a previous recommendation was re-affirmed in regard to the efficacy and safety of Sabin vaccine. Six suspected cases of poliomyelitis were referred to the Poliomyelitis Sub-Committee of the National Health and Medical Research Council. Only one of these cases was considered io be poliomyelitis. The case was due to type one poliomyelitis virus and was in an unvaccinated female aged sixteen years.
Broadcasting and Tele'vision Censorship The provisions of the Broadcasting and Television Act require the approval of the Director-General of Health for all medical talks and advertisements for medicines on radio and television. Details of the number of scripts examined during 1966-67 are given in Table 37 on page 106. In comparison with the previous year there was an increase of 45.8 per cent in the number of radio scripts examined. There was a decrease of 19.6 per cent in the number examined for television. The result was an overall increase of 27.6 per cent in the number of scripts examined. During the year the percentage of radio scripts amended and rejected showed very little movement when compared with 1965-66. The percentage amended increased from 29.0 per cent to 31.8 per cent while the percentage rejected rose only 0.1 per cent to 3.2 per cent. However, the numbers amended and rejected for television showed significant increases. Amendments increased from 30.5 per cent to 38.3 per cent of the number examined and rejections from 0.3 per cent to 5.5 per cent. These increases were due largely to amendments made to the standard guide for the preparation and censorship of medical talks and advertisements. 24
./
National. POU3ons Register The first supplement to the National Poisons Register Manual was issued in December 1966. This supplement covered approximately 3,500 additional substances not contained in the original manual and a second supplement, covering a further 3,500 substances is currently being prepared. A further issue of the Poisons Information Bulletin was also made during the year and it is anticipated that an increased number of supplements and bulletins will be issued next year. The States are co-operating with the Department in providing poison case reports. These reports will form the basis for statistics being compiled on cases of poisoning reported throughout Australia.
Joint FAO/WHO Food Standards Programme The Department continued to take an active interest in the proceedings of the Codex Alimentarius Commission during. 1966-67. A senior medical officer of the Public Health Branch represented the Department at the fourth session of the Commission in Rome, in November 1966, at the Food Hygiene Committee, in Washington, June 1967 and at the Food Labelling Committee in Ottawa, June 1967. The work in connection with the Commission and its committees was undertaken in collaboration with the Department of Primary Industry. The volume of work has increased as new standards are constantly being prepared and Australia will be expected to continue to play an active role in this field.
Nursing Section As in previous years, basic, post-graduate and ad hoc courses have been arranged for nurses from overseas countries under the Government sponsored schemes. At the end of 1966, thirty-five overseas nurses completed post-graduate courses at the Colleges of Nursing in Australia under technical assistance programmes. During 1966-67, there was a substantial increase in the number of ad hoc programmes arranged. The numbers of students from different countries involved in these programmes were Burma 1, Ceylon 1, India 2, Indonesia 1, Papua and New Guinea 1, Philippines 2, South Vietnam 3 and Thailand 6. Twenty-six students commenced post-graduate courses at the Colleges of Nursing in 1967. During the year, fifteen students completed their basic nursing training in Australia. As Malaysia now provides adequate facilities for basic training, the last of the students under the Malaysian Government Assistance Plan will complete their courses in 1968. Basic training has been commenced by one Colombo Plan student from the Maldive Islands. Ad hoc programmes have been arranged for holders of two WHO fellowships and basic training for a WHO scholar from the British Solomon Islands. Research into the services supplied by various public health nurses employed in the fields of occupational, medico-social and community health was undertaken and details of training compiled. Details of all post?asic courses conducted in Australia and of the content of basic training" In selected schools of nursing have also been compiled.
25
A questionnaire on the functions of home nursing services, designed to assess the extent of the service being given to the community was compiled and sent to all home nursing services in Australia which receive the Commonwealth home nursing subsidy.
Ccmmittees and Conferences The Public Health Branch is responsible for providing the secretariat for nine committees and six sub-committees of the National Health and Medical Research Council. Officers of the Branch act either as chairman or convener of these committees and sub-committee and the agenda and reports are prepared in the Branch.
Sabin vaccine has proved popular iu ."fehool raccilwtioH prr'ogramm€8
26
Therapeutic Substances
Commonwealth activities in the control of therapeutic substances are co-ordinated by the Therapeutics Substances Branch under the provisions of the Therapeutic Substances Act and Regulations and, in respect of certain items, the Third Schedule to the Customs (Prohibited Imports) Regulations. The Branch also maintains the Registry of Adverse Drug Reactions and provides the secretariat of the Australian Drug Evaluation Committee.
Standard of Therapeutic Substances A number of controlled therapeutic substances are subjected to examination in respect of packaging, labelling and conformity to standard for importation into Australia. To avoid undue delays to importers, the analyses are carried out by the Department of Customs and Excise Laboratories in the various States. The following table indicates the number of samples assayed by the Customs' Laboratories for the year ended 30 June 1967. Examination of the other categories of therapeutic substances is conducted by the National Biological Standards Laboratory and details of these examinations are outlined in the section of the report relating to that Laboratory. State o. of Sa mples Passed Failed
x
New South Wales Victoria Queensland South Australia Western Australia Tasmania
121 122 37 5 1
4 1
1
New TheTapeutic Substances Details of the information required from manufacturers and importers to allow adequate assessment of the safety of new therapeutic substances is outlined in a circular published by the Department. This circular, Form N.D.F.2, is distributed to drug manufacturers and importers and copies are available to interested persons. The data supplied is evaluated by the Department and assessments are circulated to the members of the Australian Drug Evaluation Committee for consideration. In some instances, however, the Department refers full details to the Committee for advice.
The Australian Drug Evaluation Committee Dr Edgar Thomson, Chairman of the Australian Drug Evaluation Committee since its inception, resigned on 31 December 1966, after three and a half years most valuable service, to take up the position of General 27
Secretary of the Australian Medical Association. Sir William Morrow, a distinguished physician and a member of the Committee, was appointed to the position of Chairman. Dr Stanley J. M. Goulston, honorary physician at the Royal Prince Alfred Hospital, Sydney, was appointed to fill the resultant vacancy. The Committee, which is composed of seven members eminent in the fields of clinical medicine and pharmacology, normally meets every two months and has met on twenty-one occasions since its inception in June 1963. Since that date the Committee has made 131 resolutions relating to drugs under its terms of reference. The first report of the Australian Drug Evaluation Committee, covering the years 1963-1966, was published in April 1967 and widely distributed to medical practitioners, hospitals and drug manufacturers.
Registry of Adverse Reactions There has been a continuing response by the medical profession in the reporting of adverse drug reactions by means of the voluntary reporting scheme. Since the scheme was introduced in August 1964, 870 reports have been received from the profession concerning adverse reactions. A major development in the reporting programme has been the feedback of information contained in the Registry. Cumulative lists of suspected adverse reactions have been forwarded to various professional colleges, teaching hospitals and medical institutions. In view of the favourable response, consideration is being given to distributing these lists to the entire medical profession. In the past year a new adverse drug reaction report form was distributed to the medical profession. This new form, designed to facilitate reporting of adverse drug reactions, will enable Australia to participate in the World Health Organisation drug monitoring pilot scheme. At the 20th World Health Assembly, in May 1967, the Director-General of WHO reported that negotiations with the Government of the United States of America had been completed and that funds to support the scheme were now available, together with suitable office space and equipment and data processing facilities. The accumulation of world-wide data on the adverse effects of drugs will undoubtedly result in a more efficient drug surveillance scheme which will lessen the probability of serious adverse reactions to therapeutic agents.
"
28
, Quarantine Human Quarantine The General Quarantine Branch carried out its functions efficiently in the past year and no cases of quarantinable disease entered Australia during this period. Quarantine officers at all first ports throughout Australia carried out inspections of incoming travellers and examinations of vaccination certificates and any necessary measures were implemented. In addition, quarantine stations throughout Australia were kept in a state of preparedness in case of any epidemic of a quarantinable disease such as smallpox, cholera, yellow fever or plague. General Quarantine Branch officers also handled a large volume of work at airports and sea ports throughout Australia on imports, in the inspection of ships and aircraft, the disinsection of aircraft and other related duties. During the year considerable attention was paid to forward planning in two fields. These were the possible introduction in the future of aircraft carrying up to 400 passengers and the. planned introduction of container handling of overseas cargo. Both of these developments may entail the adoption of new quarantine procedures and, on this account, every aspect of quarantine clearance is being critically reviewed. The numbers of vessels and persons being cleared through quarantine continues to increase every year. Over the past year 4,040 ships and 3,918 aircraft, carrying a total of 781,756 persons passed through quarantine. This compares with 3,488 ships, 3,297 aircraft and 733,815 persons during the 1965-66 period. To deal with these increases additional staff has been made available.
Smallpox The threat of the introduction of smallpox continues in view of its occurrence in countries to the north of Australia, Some 65,500 cases were reported throughout the world in 1966 and, of these, some 10,100 cases were in Indonesia. Because of this, particular attention is paid to the vaccination certificates of persons arriving in Australia from overseas. On 1 January 1967 a new format for these certificates was introduced by the World Health Organisation. This measure has been incorporated in the Australian vaccination requirements. Vaccinations performed since 1 January 1967 must be recorded on a form on which are indicated the origin and batch number of the vaccine used. In addition, the vaccine must be certified to conform to the recommended requirements of the World Health Organisation. The vaccine used in Australia is manufactured by the Commonwealth Serum Laboratories and meets the recommended requirements. In 1966-67 2,730 persons from overseas were vaccinated against smallpox on arrival by air because they did not have satisfactory vaccination certificates. The difficulties in this regard have continued despite 29
the efforts of the Department to inform airline operators of our requirements. Further measures to correct this situation are being examined. Seventy-one air travellers from abroad who were not vaccinated and who refused vaccination were quarantined in a quarantine station for the prescribed period. A group of six quarantine officers visited India in April 1967 for a two-week training course in the diagnosis of smallpox. On this occasion the instruction was at the Haffkine Institute and the Kasturba Infectious Diseases Hospital at Bombay. As in previous courses in India every facility was placed at the disposal of these officers by the Indian authorities and this is much appreciated. Subsequent to this course the Commonwealth Director of Health, Western Australia, visited New Delhi for discussions with officers of the Indian Ministry of Health concerning forthcoming training courses.
y.
Cholera The cholera situation continues to be unstable and there were epidemics in Burma, India, Pakistan, Indonesia, Nepal, the Philippines, Thailand and South Vietnam. Outbreaks also occurred in West Irian and Iraq. Steps were taken to proclaim Iraq as an infected area under the Quarantine Act until the disease came under control. Travellers from infected areas and proclaimed countries are required to be currently vaccinated against cholera for entry to Australia. It was necessary to vaccinate 1,064 persons who arrived by air without satisfactory international certificates of vaccination against cholera.
..
Yellow Fever Yellow fever occurs in the African and American continents and, as the mosquito vector exists in Australia, travellers coming from yellow fever areas must be currently vaccinated against yellow fever and hold international certificates; of vaccination against the disease.
Plague Concern has been expressed in international health circles at the incidence of plague throughout the world and in particular the plague epidemic occurring in South Vietnam. The exact extent of infection in Vietnam is not known, but epidemics have been reported from twenty-seven of the forty-four South Vietnam provinces. Plague has not occurred in Australia since 1923 and routine measures are taken to prevent the introduction of cases of the disease or of the animal vectors of the disease. These measures comprise the inspection by quarantine personnel of all incoming vessels and the requirement that all sea vessels arriving in Australia mnst be in possession of a current de-ratting certificate or an exemption certificate in the form prescribed by the World Health Organisation. The methods used in Australia in this aspect of quarantine have recently been reviewed and it is not considered that any change in procedures or legislation is at present warranted. Special attention is, however, being given to vessels arriving from Vietnam. 30
'.
The subject of plague was discussed at length at the First Regional Seminar on International Quarantine held by the World Health Organisation at Manila in March 1967. The Department was represented at the seminar by the Commonwealth Director of Health, New South Wales.
Facilitation in Quarantine Quarantine activities concern people, commercial interests, ships, aircraft and government departments. It has always been the intention of the Department of Health that its quarantine procedures should be carried out with every regard to these varied interests but without any diminution in the effectiveness of the controls. With this in mind new methods have been devised over the years. These include the method of granting radio pratique for ships in which the inspection of passengers is carried out by the ships' surgeons. More recently a method has been adopted of granting pratique to ships which, on arrival in Australia, are within fourteen days of departure from an overseas port and on which all persons are satisfactorily vaccinated. Both of these measures have worked successfully and have not resulted in any lowering of Australia's quarantine standards. The special factors associated with air travel are also kept in mind. Representatives of the Department confer regularly with airline operators in each State and with other government departments, with a view to diminishing delays and generally facilitating the passage of travellers through quarantine and other necessary formalities. At the national level, representatives of the Department attend meetings of the National Advisory Facilitation Committee to draw up and define overall policy. In the past year the Department was also represented at a combined meeting of the International Association of Travel Agents and the International Civil Aviation Organisation in Sydney.
Animal Quarantine Once again, in 1966-67, the Animal Quarantine Service achieved its objective of preventing the entry into Australia of the more serious animal diseases existing overseas. These diseases, once established in this country, would have serious economic effects on our livestock industries. A continuous, close vigilance is therefore maintained on all means by which exotic animal diseases could enter Australia.
I mpoTts Subject to Quamntine For some years there has been a complete ban on the importation of most species of animals from most parts of the world. Exceptions are poultry and other birds from New Zealand, horses, dogs and cats from the United Kingdom, Ireland and New Zealand and certain zoological animals imported into registered zoos where they are kept in permanent quarantine. Approved laboratories are also sometimes given permission to import small animals for scientific purposes and these institutions, together with circuses registered for the keeping of such animals, are kept under constant quarantine control. A variety of goods of animal origin such as hair, special types of wool. skins, hides, canned meat and other foodstuffs were admitted during the
31
year under quarantine control and, where necessary, these goods were subjected to special treatment on arrival. Continued control over the importation of cultures, vaccines, pathological specimens and biological products was also exercised in collaboration with the Therapeutic Substances Branch. This control covered the importation of therapeutic substances such as sera, vaccines and glandular extracts derived from animals. A standard form of application to import biological materials, laboratory animals and insects was introduced during the year, together with a standard form of printed permit to import and transfer these classes of quarantinable material. This innovation shows promise of reducing the time required to process applications. The number of animals imported decreased in 1966-67 when 2,797 animals were imported compared with 4,315 in 1965-66. Detailed statistics for 1966-67 are given in Table 40 on page 107.
~
~
Exports Subject to Quamntine The Animal Quarantine Service is responsible for issuing health certificates for the export of animals to overseas countries and for ensuring that any tests and health conditions specified by importing countries have been completed. Negotiations to ascertain the current requirements of a number of overseas countries continued during the year.
Disposal of Ships' Garbage Particular attention is paid to the disposal of ships' garbage in order to prevent the introduction of exotic diseases into Australia. An offer has been made by the Commonwealth Government to the State Governments to pay the full cost of building incinerators at selected ports. This offer has, to date, been accepted by the Governments of New South Wales, South Australia and Tasmania.
Meetings and Conferences The Director of Veterinary Hygiene attended meetings of the Standing Committee on Agriculture in July 1966 and February 1967 and a meeting of the Cattle Tick Control Commission, of which he is Chairman, in April 1967. In November 1966 the Director and a Senior Veterinary Officer attended an Exotic Diseases Committee Meeting, the Biennial Conference of Commonwealth and States' Veterinarians and the Chief Quarantine Officers (Animals) Conference. A further meeting of the Exotic Diseases Committee was arranged and attended in Melbourne in April 1967. Other meetings attended during the year by the Director were a Consultative Committee on Newcastle Disease, the Australian-New Zealand Technical Committee on Animal and Plant Quarantine and the Veterinary Public Health Committee.
Overseas Visits F?llowing an outbreak of foot and mouth disease in England in 1966 the DIrector of Veterinary Hygiene and the Assistant Principal Veterinary Officer (Disease Control) of the New South Wales Department of Agriculture spent ten days at the outbreak area in Northumberland. Here they 32
observed the proven methods and procedures carried out by the British Ministry of Agriculture and Food for the eradication of this disease. These observations provided valuable information for all States and Territories, who are now finalising reviews of plans for the control and eradication of foot and mouth disease should it ever enter Australia. In May 1967 the Director of Veterinary Hygiene attended the annual meeting in Paris of the Office International des Epizooties as the Australian delegate. During the course of this visit he also visited and conferred with the United Kingdom Ministry of Agriculture, Fisheries and Food, the Irish Ministry of Agriculture and the Food and Agriculture Organisation, Rome. In July 1966 a Senior Veterinary Officer visited Suva, Fiji, where he attended the Technical Meeting on Livestock Production and Health of the South Pacific Commission. While in this area, he visited Noumea where discussions were held with the New Caledonian authorities on items of mutual quarantine interest.
Plant Quarantine Active vigilance against the importation of plant pests and diseases was maintained during the year. The full and active co-operation in these activities of the State Departments of Agriculture, whose officers supervise plant quarantine activities in the States on behalf of the Commonwealth, was readily given at all times. In some cases the C.S.I.R.O., universities and other institutions such as the Waite Agricultural Research Institute assisted.
Legislation Three new plant quarantine proclamations came into force during the year. Proclamation 56P, gazetted on 27 October 1966, provides for the prohibition, except by permit, of eight tropical grass species and nine tropical legume species. Some of these species could possibly make a significant contribution to agriculture in the tropical areas of Australia but, as the introduction of large quantities of seed could be the means of introducing devastating seed borne diseases, it was considered necessary to limit the amount of imports. Proclamation 57P, which restricts more closely the importation of walnuts into Western Australia, was gazetted on 9 March 1967, and Proclamation 5SP, permitting the Department to approve the importation of harmless species of cacti, was gazetted on 29 June 1967.
International Meetings The fifth meeting of the Australian-New Zealand Technical Committee on Animal and Plant Quarantine took place in Canberra in February 1967. Discussions on matters of mutual interest included problems relating to nursery stock, seed, fruit and vegetables. The sixth meeting of the Plant Protection Committee for South East Asia and Pacific Region was held at Kuala Lumpur in March 1967. Australia was represented by the Director of Plant Quarantine as delegation leader, and the Chief of the Division of Plant Industry of the Department of Agriculture, Stock and Fisheries, Territory of Papua and New Guinea. Representatives of
33
fourteen countries attended, together with an observer from the South Pacific Commission. On technical matters the Plant Protection Committee approved recommendations relating to ten crops or groups of crops. A proposal to ext~nd the geographical scope of the Plant Protection Agreement, under whIch the Committee operates, was discussed and a recommendation made to the Food and Agriculture Organisation, which sponsors the Plant Protection Committee. Attention was focussed on losses caused by pests and .diseases in the region, training in plant quarantine, and the intensificatIon of research training and demonstration in the field of plant protection.
Meeting of Chief Quarant7:ne Officers The Chief Quarantine Officers (Plants) from all States and the Northern Territory met in Sydney in July 1966. Discussion took place on items of particular interest to plant quarantine, including bulk commodity imports, nursery stock policy, a course for plant quarantine officers and procedures to be followed when a new disease is discovered.
Course .tor Asian Students During September 1966 a course on plant quarantine for Asian students, arranged by Dr T. H. Harrison, former Director of Plant Quarantine, was held in Canberra. The course was made possible by an allocation of funds from the' Freedom from Hunger Campaign' and students came from Pakistan, India, Singapore, Thailand, Ghana, the Philippines, Mauritius and Fiji. Administrative arrangements for the course were made by the Overseas Training Section of the Department of External Affairs. Lectures were given by the staff of the Plant Quarantine Branch on plant quarantine conditions in Australia, fumigation of imported plants and plant products, quarantine in relation to seeds and weeds, and plant quarantine publicity. Some time was spent by the participants at the plant quarantine laboratory and quarantine glasshouse at Yarralumla Nursery, where the investigation work being undertaken and post-entry quarantine procedures were explained and demonstrated.
Plant Quarantine Officers' Course In May 1967 a course of one week was held in Melbourne for two plant quarantine officers from each State and the Northern Territory. This was the first course of its type and was considered a success. It was arranged by quarantine officers of the Canberra office with the full and ready co-operation of the Chief Quarantine Officer (Plants) for Victoria and his staff. Subjects covered included the principles and systems of plant quarantine, quarantine legislation, seeds and seed-borne diseases, weeds, treatment procedures for various plant items, soil, bags and packing material, nursery stock and a review of quarantine plant pathology and entomology. 34
_"
~i.
I
Container Cargo Handling The introduction of container handling of overseas cargo will present new problems to be overcome by the Plant Quarantine Service. Containers with a wood content will have to be examined by quarantine officers to ensure that the wood has not become infested while overseas. As there are a number of serious insect borers which attack seasoned timber, overseas organisations have been advised to treat all timber, including plywood, used in the construction of containers. The whole problem of quarantine with containerised cargo is under active study by the Department in collaboration with the Department of Customs and Excise.
Sirex Wasp The administration of the National Sirex Fund was transferred from the Department of Health to the Department of National Development on 1 July 1966, but this Department has continued to play its role in the eradication campaign by dealing with the quarantine aspects. The National Sirex Fund Committee continued its work during the year. Survey and control work in Victoria has been effective in checking the spread of Sirex and the Committee believes that the serious economic threat to pine plantations, which existed in 1962, has been reduced. However, it should be stressed that the pest has by no means been eliminated. At a meeting of State and Commonwealth Ministers in March 1967, a most encouraging report on the research work undertaken in Australia was received. At this meeting it was agreed to recommend to all governments that the campaign be continued in 1967-68.
Ca'rpenter Ants Early in June an unusually severe infestation of Carpenter ants was found on a vessel in the port of Sydney. Prompt action was taken to treat the cargo as it was discharged, as well as the dunnage, which is believed to have been the source of the infestation.
Subterranean Clover During the year advice was received that Australian produced subterranean clover seed of a new strain had been exported to India for multiplication in the Northern Hemisphere to gain one season. The resultant seed is to be returned in quantity for distribution in Australia. Because this type of clover develops its seeds underground, and because subterranean clover in Australia is relatively free of disease, there is a definite quarantine hazard from soil carried with the seed from India. Steps are being taken to prevent the introduction of plant and animal diseases with this seed.
Biological Control of Weeds Discussions have taken place with the C.S.I.R.O. and the Queensland Department of Lands on biological control of the weed 'Groundsel', which is a native of Florida, U.S.A. Following the procedure adopted for the screening of insect parasites of lantana, agreement was reached that an officer from the Queensland Department of Lands should carry 35
out screening tests in Florida with nominated parasites on certain plant hosts approved by the Department of Health. Carrying out screening tests overseas has advantages over attempting limited screening under quarantine in Australia.
Laboratory and Glasshouses For some time it has been recognised that there are many matters peculiar to plant quarantine which can only be resolved by the Plant Quarantine Branch carrying out its own investigations. During 1966-67, this type of work was begun with the development of laboratory and glasshouse facilities at Yarralumla Nursery, Canberra. Investigations have begun into various plant quarantine treatments including methyl bromide fumigation of plants, seed treatments for seed-borne diseases and effective means of establishing imported plants. In a co-operative venture with government authorities and private enterprise in the Territory of Papua and New Guinea, several hundred tea clones were grown in intermediate quarantine at Yarralumla before being forwarded on to the Territory. This was done to avoid the risk of introducing Tea Blister Blight, which could ruin the prospects of this newly developing and important industry in Papua and New Guinea.
Disease Outbreak The lucerne disease, bacterial wilt, was reported from the Gippsland area, and from Katunga, in the Goulburn Valley, Victoria. It is thought to have been present for some time, probably about fifteen years. No other State has reported its occurrence.
36
Management Services
When the administrative structure of the Department was reorganised in mid-1964 the Management Services and Benefits Division was established with three branches. These are the Establishments and Finance Branch, the Planning and Legislation Branch and the Medical and Hospital Branch. The activities of the Medical and Hospital Branch have been mentioned in previous Annual Reports under the general heading National Health Benefits, as they are again this year on page 13. No mention has been made previously, however, of the other two branches. As the volume and scope of their activities have increased year by year it is felt that details should be given in the Annual Report of the developments that have taken place during the year. This new section has, accordingly, been added to this report.
Establishments Reviews of Departmental establishments were undertaken throughout the year. These included a major review of the Administration and Finance Branches located in the State offices, as well as many minor variations to the establishments of the Medical and Hospital Branches throughout the States and in Central Office. The conversion to automatic data processing of the checking of pharmaceutical prescriptions in State offices involved a detailed and lengthy review of the establishments of the various sections in order to provide the necessary staff to ensure a smooth transition from one system to the other. During the year the medical establishment in the Northern Territory was considerably expanded. The situation has now been reached where specialist services are available to the population in almost all branches in medicine and surgery. The total number of staff in the Department increased by 159 in 1966-67 to 3,167. The most significant of these increases were sixty in Victoria and eighty-two in the Australian Capital Territory. In Victoria the rise in the number of staff was due, in part, to the need to employ additional staff to implement the processing of pharmaceutical benefit prescriptions on A.D.P. equipment. One factor in the A.C.T. was the improved recruitment situation in the professional and technical areas of the National Biological Standards Laboratory. Regular induction and Departmental orientation courses were conducted during the year, as well as a course for programmers-in-training on Departmental A.D.P. procedures and techniques. Considerable benefit was obtained by officers who attended an efficient reading course. As well as attending internal courses, Departmental officers were nominated for courses conducted by the Public Service Board and outside organisations. 37
A utomatic Data Processing The A.D.P. Section was mainly engaged during the year on the further implementation and development of automatic data processing in the pharmaceutical benefits area. The pharmaceutical benefits A.D.P. 'lystem is unique to Australia and has attracted considerable interest in overseas countries with similar health schemes. At 30 June 1967 approximately 4,620 chemists, or 82 per cent of the chemists throughout Australia, were submitting claims for computer processing. The remaining chemists, all in Victoria, will be introduced into the scheme by September 1967. Major components of the related management information system were developed and implemented during the year. All data preparation for the pharmaceutical benefits A.D.P. system is carried out in the State offices of the Department. When the remaining chemists in Victoria are brought into the system, A.D.P. data preparation sections in all States will be producing verified data at the rate of over 1,400 million characters yearly for this system. Stringent control measures have been adopted in all State offices and data preparation equipment has been maintained at a uniformly high performance level. In addition to work associated with the pharmaceutical benefits scheme, the A.D.P. Section has been able to maintain a system which regularly undertakes automatic analysis of the results of biological assays performed by the National Biological Standards Laboratory and to implement an automatic system for the continuing analysis of the dental health of A.C.T. school children. This latter system is of particular significance in the light of the introduction of fluoride to the Canberra water supply in 1964. The computing requirements of both these systems are small. The approval of the Public Service Board has been given to a substantial increase in programmer strength. The larger establishment will be engaged on the maintenance and further development of existing computer systems, development and implementation of A.D.P. systems in other areas of the Department and studies to determine, for the purposes of medium and long-term planning, the total computer requirements of the Department.
Organisation and Methods The work of the O. and M. Section of the Department falls into two categories. It undertakes cyclical reviews of sections within the Department to ensure that organisations are adequate and that methods are modern and efficient and it also examines those problems which arise from time to time outside the pattern of cyclical reviews, but which involve questions of organisation and methods. During the year a number of major organisation reviews were carried out. The areas covered where Pharmaceutical Benefits-A.D.P. in Brisbane, Adelaide and Perth and the A.D.P. Section in Central Office, the Accounts Section, Central Office, the A.C.T. Health Services Branch, the School of Public Health and Tropical Medicine, the Commonwealth Aco~s~ic L~boratories and Institute of Child Health, Sydney, and the admmlstratlOn and finance areas in the Brisbane and Adelaide divisional
38
offices. Most of these reviews have lead to staffing proposals being placed with the Public Service Board. A number of methods reviews were carried out covering the use of office communications equipment. A programme has been laid down for the next year to cover approximately twenty items by cyclical review and to examine a number of areas where major difficulties have been encountered. In addition, the Section will continue to examine and process all proposals for office machines, administer the suggestion scheme and undertake steps for the introduction and development of a forms control progTamme.
Heseanh The efforts of the Research Section during the year were mainly directed towards an examination of hospital and nursing home costs and utilisation in Australia. Progress was not as rapid as was hoped due to the lack of available information in many of the fields covel'ed. However. detailed investigations into State public hospital systems and private nursing homes have been brought to a successful conclusion and should provide the basis upon which investigations can be extended to other areas. The results of the completed investigations have been most informative and have provided the basis for both past and future articles in the quarterly journal 'Health '. At present a survey of patients in private nursing homes and a survey of uninsured patients in private hospitals, both in respect of the year 1966-67, are being conducted and it is proposed that the results of these surveys will also be published in the journal 'Health' as soon as they become available. Investigations carried out so far have been concentrated on the hospital sector, as a great deal of the information could be obtained from State hospital authorities or from Departmental records. The next stage of the Section's programme will involve investigations into fields where the basic information is less readily available .
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Small patients of the Northern TerTitm'Y A"'ial Medical Service
40
Northern Territory Health
The Health Department in the Northern Territory, in its continuing efforts to provide modern health services, is faced with the dual problems of a rapidly growing population, in both its major urban areas and rural districts, and the special difficulties of a race in transit from nomadic existence to urbanisation. In an effort to meet these problems in urban areas, it has become necessary to acquire additional land and to provide additional staff, equipment and civil works. This is a major task in the Northern Territory, with its particular difficulties in the fields of recruitment, transport, climate and availability of major works contractors and building materials. In rural areas the main problems are those of public health and quarantine services. With the beginning of overseas ore shipments from Groote Eylandt and its use as a first port of call it has become necessary to implement quarantine procedures and other important health measures at this previously undeveloped site. This and other rural areas experiencing rapid community expansion require diligent inspection and supervision. The problems of the Aboriginal continue and health education is playing an ever increasing role in the difficult transition period. In an effort to overcome the administrative difficulties associated with expansion, a Southern Regional Office has been established, embracing the area of the Territory south of Newcastle Waters. This office will eventually take over much of the responsibility previously borne by the Divisional Office in Darwin. There has been further progress during the year in building and equipment programmes and a general increase in staffing. It is notable that there are now positions for specialists in most of the major fields of medicine and the present staff establishment in the Northern Territory is 901 positions.
Communicable and Tropical Diseases Once again in the field of communicable disease, the greatest problem has been gastro-intestinal infections in the Aboriginal infant population in Central Australia. Infectious hepatitis, ancylostomiasis and leprosy still give cause for concern and there has been a notable rise in venereal disease. The occurrence of a case of malaria in Central Australia which does not appear to have been introduced from overseas was of great interest and is a cause for concern. The ancylostomiasis situation remains basically unaltered. This disease represents a general index of the state of hygiene in any community living in moist tropics. There was a definite increase in the incidence of venereal disease throughout the Territory in 1966-67. A total of 274 cases was reported 41
compared with 157 eases in 1965-66, and an active programme of patient treatment and follow-up, together with contact investigation, has been undertaken. The problem of contaet investigation is, of course, most difficult with a transient population. Venereal disease among the natives also has its own specific problems of patient identification and follow-up. However, every effort is being made through all the branches of the Department to combat this disease. Fifteen eases of malaria were reported during the year from a number of centres throughout the Territory including Darwin, Tennant Creek and Alice Springs. Most notable was a case diagnosed at Aliee Springs in a man who had been living in a settlement in Central Australia and who, after full investigation, was thought to have contracted the disease somewhere in Australia. This has highlighted the potential dangers of permitting persons from endemic zones to enter receptive areas without initial medieal interviews. Diseussions have been held with other Government departments and with airlines operating routine flights to Timor and it is intended that, in future, persons from endemic malarious areas will be interviewed by Departmental doctors. Work on tubereulosis surveys was hampered because of severe wet weather conditions and staff shortage and it was only possible to conduet twenty-seven chest clinics during the year. Initial examinations, in aceordance with the Silicosis and Tuberculosis (Mineworkers and Prospectors) Ordinanee, of the 1,500 mineworkers employed in the Territory are about to be completed. The world trend in leprosy control has become increasingly one in which only disabled and infectious patients are treated in hospital, while those who are not disabled are treated as outpatients. Treatment in the Northern Territory has followed this trend and, as a result, East Arm Leprosy Hospital has become less of a settlement and more of a hospital, with a decrease in the number of patients, but an inerease in their individual medical needs. One new ward of eight beds for female inpatients was opened during the year and this has made a great difference in treating patients who have orthopaedie complications or require reconstruetive surgery. At a meeting of the Tropieal Medicine and Health Committee of the National Health and Medical Research Couneil in Sydney in May 1967, which was attended by the Medical Superintendent of the East Arm Leprosy Hospital and representatives from other States, the desirability of a general liberalisation towards outpatient treatment was stressed. It is felt that sueh a policy will be of considerable benefit in attraeting the more timid people of Arnhem Land to come forward for treatment. A notable event at the East Arm Settlement during the past year was a sports meeting at which members of two Darwin amateur sporting clubs engaged in competition with inpatients at the settlement. This event may be taken as evidenee of a generally improved attitude by the public towards leprosy and it is hoped that similar events can be arranged in the future. 42
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School Health Services In the Northern Region, 1966-67 has seen a continued increase in school population, but a decrease in the number of school children examined. The reasons for this include an increase in the number of visits by the Commonwealth Acoustic Laboratories officers involving preparation and follow-up time; planning and preparation for the introduction of Sabin oral poliomyelitis vaccination into the Northern Territory; the introduction of the Sabin vaccine mass campaign at the end of May 1967 and shortage of medical staff at the Darwin Hospital and Divisional Office requiring the Schools Medical Officer to be seconded for other duties. The Sabin vaccine campaign in the schools and pre-schools has been progressing smoothly. Only urban children are being given doses this year. The campaign will be extended to rural areas-missions, settlements and cattle stations-next year. Some children have been sent to Adelaide, or other capital cities, for specialist treatment for ear complaints and others have been referred to the Social Welfare Branch to be sent to Adelaide for speech therapy. In the Southern Region, a medical officer officially attached to the hospital at Alice Springs has been released where possible to carry out school medical services. Activities in this field have included the general medical examination of school children, specific examination in relation to ear, nose and throat problems of Aboriginal and part-Aboriginal children and the supervision of the infant health and district nursing services. At Alice Springs the high school and infant schools were fully examined. The major problems found at these schools were in the area of eye and ear diseases. Areas examined outside Alice Springs included Finke Primary School, Ross River School, Barrow Creek School, Ernabella School and the Sunny Centre Sub-Normal Children's School. Again the major problems found in all these areas were particularly those relating to ear disease. Children in both the pre-school and the higher primary school were examined at Tennant Creek. In the same way as has been done in the Northern Region, ear clinics have been organised and run by the schools medical officer and sister.
Infant Health Service In the Northern Region, three sisters have been employed full-time in infant health work since August 1966. Since then the Peel Street centre has been opened an extra day, and is now open" three days each week. In September 1966 the Parap centre was moved to the Guides' Hall and opened for a full day each week. Increasing numbers in the Rapid Creek area have necessitated the centre there being opened one additional day each week. The general health of the children continues to be of a reasonable standard, although the incidence of gastro-enteritis remains high at certain times of the year. In the Southern Region, a sister was seconded from the nursing staff of the Alice Springs Hospital to provide home nursing services pending the provision of a permanent position. This permitted the infant health sister to extend her own activities and to begin planning for routine 43
examinations of two-year-old infants. She has also been able to increase her visiting of babies whose mothers require extra advice and to assist in the ante-natal clinics.
Home Nursing Service In the Northern Region, the number of visits made by the Home Nursing Service was considerably greater in 1966-67 than in the previous year. This was due to both an increase in population and greater utilisation of the service, particularly by private practitioners. Immunisation clinics, held twice weekly, were chiefly staffed by the Home Nursing Service. In the Southern Region utilisation of the Home Nursing Service has increased to a point where by the end of June 1967 up to thirty patients per day were being seen. A full service is being offered, covering both fractures, geriatric and general home nursing problems and extending over the week-end. This service has been utilised by the private practitioner at Alice Springs since mid-May.
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Aerial Medical Service With the addition of a further aircraft and provision for an extra pilot, there are now three Doves in service in the Northern Region with a pilot complement of four. The new aircraft, which was delivered in 1966, has been of great value and will no doubt prove even more valuable when servicing time comes up for the other aircraft in the Division. Routine medical trips to outlying areas have been maintained and, in addition, there has been a need to transport the aerial doctor to Groote Eylandt for quarantine duties. Vessels are now arriving at Groote Eylandt direct from South-East Asian ports. In association with these overseas arrivals, the smallpox vaccination programme in that area has been stepped up in an effort to fully protect the people. During the year the senior pilot in Darwin was accorded chief pilot rating and is now responsible for the activities, training and supervision of pilots operating Aerial Medical Service aircraft. The activities of the Aerial Medical Service in the Southern Region during the year were marked by a general increase in flying hours. This increase was due to a larger number of calls by people in the south-eastern sector of the region for routine trips and a rise in the number of interhospital evacuations between Tennant Creek and Alice Springs, particularly in the early months of 1967 when road transport was not possible because of heavy flooding of the Stuart Highway. A noteworthy improvement in 1966-67 was the installation of improved infant carrying facilities in the form of a humidicrib which works off the aircraft battery.
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Rural Public Health In the early part of the year, the measles epidemic which had swept through the Aboriginal population was abating and the results and complications of vaccinations of almost 1,000 Aboriginal children with living measles vaccine were recorded and are now being evaluated. J'~
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Systematic surveys at major settlements and missions in the northern part of the Territory to gather basic data on growth and health of Aboriginal children were conducted. This information, in conjunction with data on diet, water supplies and sanitation, will be used in planning to combat the ever present problems of sub-nutrition and infectious diseases. Investigation of two cases of diphtheria at Hooker Creek Settlement resulted in the detection of a carrier. The method of Schick testing and throat swabs demonstrated apparent susceptibility to diphtheria of a number of children previously immunised against this disease, and served to warn that diphtheria can still be a serious public health problem. The additional task of a mantoux and BCG campaign, in conjunction with the tuberculosis survey, was successfully introduced into the year's programme. Leprosy reviews covered the major rural areas by air and road, and smaller more scattered centres are at present being combed. There is a constant follow-up of contacts and suspects wherever the opportunity offers. At Warrabri Welfare Settlement a group under the leadership of Dr. F. W. Clements, of the Institute of Child Health, explored some of the problems of health education in Aboriginal communities. Emphasis was placed also on baby health surveys in the major settlements and mISSIOns. These were carried out by a two-person-doctor and sisterteam. The haemoglobin of children was checked as well as their heights and weights. Diet studies were undertaken and, with the help of the dietitian and Welfare Branch, some progress is being made in rectifying deficiencies in the rations given to certain Aboriginal communities. In the Darwin area, local camps, especially those formed in the 'wet' season, were visited. Special care was paid to the welfare of the children, who tend to become neglected in these areas, particularly with the easy availability of liquor for their parents. Bagot Settlement infant immunisations were kept up to date and haemoglobins checked regularly. The pre-school and school children were also surveyed. An attempt is being made to introduce Aboriginal mothers to personal immunisation cards for their children, particularly when they attend the general town immunisation clinics. In the Southern Region an ' adoption' system was introduced whereby one sister adopted one settlement and continued to follow up the general health status of the settlement over an indefinite period. It is felt that, by continued contact with the people of the settlement, the sisters are better accepted by the indigenous population. The staff of the Survey Section in the Southern Region are convinced of the need to speak the language of the people with whom they are dealing. They are all attending, in their own time, special classes in Pitjantjaljara, a local dialect widely understood in the area, so as to be able to communicate more freely with the Aboriginal population. This will be particularly valuable, especially in the field of health education. Much material has been collected from settlements during the year in the form of haemoglobins, weights and other useful information. It is hoped eventually to construct from this data some apparent normals for Central Australian Aboriginals. The Survey and Aerial Medical Sections combined to investigate health conditions in areas where no previous 45
medical visits had been made. The Utopia-McDonald Downs area, in the south-eastern sector, was investigated and immunisation campaigns have been started in these areas, which are now on routine visit schedules.
Rural Health Inspectors The general activities of the Rural Health Inspection Section continue to hinge on inspection of rural establishments, hookworm control and general health education of Aboriginal communities. The authorities responsible for the development of townships in the Groote Eylandt and the McArthur River areas have approached the Department for advice in the planning of health facilities both for the developmental and completed stages of their projects. It is felt that, with the Department's co-operation, potentially dangerous situations, particularly relative to the early camp sites, have been averted. Several classes have been held during the year for the training of hygiene supervisors drawn from the ranks of Aborigines resident in settlements and missions.
Urban Public Health Darwin continues to expand rapidly, but fortunately new subdivisions are sewered prior to the building of houses. A feature of the developing town is the accommodation problem and, as a result of this, caravan parks are springing up with temporary and sometimes permanent dwellings. These areas require close supervision to see that health standards are maint a i n e d . . . , Importation of milk from other States requires close supervision to maintain adequate standards of carriage. Locally produced milk also requires much careful supervision in its handling prior to distribution, and constant supervision of the dairymen is required to maintain adequate standards. Difficulties are still being experienced with food shipments, some of which, particularly when transported by road and sea, arrive in unwholesome condition. Problems exist, particularly at Alice Springs, in regard to the disposal of effluent. As yet, no solution to these problems has been found. because the effluent standards have not been satisfactory, but it is hoped that, with co-operation from the Works Department and Agriculture Division, the effluent will eventually be used for citrus growing or for forests.
Health Laboratories At the Darwin Health Laboratory the work load has shown a steady increase over the past twelve months. Two cases of meliodosis were reported during the year. In a fatal case the organism was isolated from blood culture. In the second, non-fatal, case the organism was isolated from an abscess on the forearm of an Aborigine at East Arm Leprosy Hospital. Salmonella isolation continued, but there was a Several notable drop in the number of shigella dysentery isolations. cases of malaria, from visitors to Timor and New Guinea, were reported. Blood transfusions showed a marked increase. Approximately 1.000 pints of blood were cross matched during the year. The laboratory service at Alice Springs was further diversified and extended. Besides regular clinical examinations, it performed work for
46
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the Aerial Medical and School Health Services, the periodic tuberculosis surveys and a malaria survey. It also provided further substantial support for a lactose tolerance research project among Aboriginal children being carried out in conjunction with the Department of Child Health of the University of Adelaide.
Quarantine There was a marked increase in 1966-67 in the number of service aircraft requiring clearance as a result of activities in South East Asia. Medical evacuation aircraft were cleared both in Darwin and Alice Springs for the New Zealand authorities. The volume of commercial aircraft traffic remained fairly static with the usual heavy load of midnight to dawn clearances for Quarantine officers. The use of disposable garbage bags is being tried by overseas and internal airlines, both of whom use the quarantine incinerator. A favourable response has been expressed and these bags may soon come into routine use.
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Dental Services Treatment given by the Dental Service was somewhat reduced this year despite an increase in popUlation. The number of dentists available was the critical factor, together with the loss of experienced dental officers and their replacement by new graduates. The present strength of six dental officers, out of an establishment of thirteen, reflects recruitment difficulties.
Pharmaceutical Secti.on An improvement in the staff situation during the year enabled increased activities in the pharmaceutical field. During the dry season most settlements, missions and stations with medical posts staffed by nurses were visited and also several smaller settlements. The contents of medical kits provided by the Department and conditions of storage were inspected and revised lists of contents were proposed. During the year a Poisons Information Centre was established at Darwin Hospital. Use of the Centre by private medical practitioners and the public is growing .
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Nutrition Section Activities by the Nutrition Section were wide and varied during the year. Surveys were made to assess the actual intake offered to pre-school children eating communally on a number of missions and settlements. Pin pointing of some deficiencies in their diets enabled the staff to take steps to improve the diets in all ways possible. A survey to assess the response to offering a self selection of vegetables to Aborigines eating communally at Warrabri Settlement was also undertaken prior to a health education workshop.
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Hospitals The hospitals in the Northern Territory have continued to function efficiently, despite the difficulties presented by the continuing building programme at Darwin Hospital and by staffing difficulties at some of the
47
smaller hospitals. Major works completed or nearing completion at the Darwin Hospital include a ninety-bed ward block, the new nurses home-a feature of which is the first lift in Darwin-a swimming pool, stage one of the administration block, a new kitchen and a system of covered ways which should be completed by the next wet season. Associated water supply, drainage, sewerage, road works and boiler house services are also nearing completion and a new oil-fired incinerator has been installed. At the Katherine Hospital the addition of one medical officer to the staff has enabled additional road trips to surrounding areas to be undertaken as welI as the performance of certain surgical procedures requiring general anaesthesia. At Tennant Creek considerable difficulties were once again experienced in recruitment of medical and nursing staff. A medical officer now spends one day a week at Batchelor Hospital and this, together with constant attention by the nursing sisters there, provides a continuing service for residents of Batchelor. At the Alice Springs Hospital there was an overall increase in activity, and in particular a rise in the number of surgical operations performed. Preliminary foundation surveys are now under way for the proposed new hospital development. The installation of an emergency power unit capable of providing all electrical needs for the present and proposed hospital was completed during the year and work was begun on professional officers' quarters to provide eight single fiats. Floods in the early part of the year slowed work on the building, but it is expected to be completed by the end of 1967.
New ward block at the Darwin H08pital
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Australian Capital Territory Health
The population of Canberra continues to expand rapidly and this has meant a corresponding increase in health service activities. Because of this expansion and the growing importance of many of the local health functions, the A.C.T. Health Services Branch was established during the year to co-ordinate and integrate the many services now available and to plan for future health needs.
Health Inspection, Infectious and Notifiable Diseases Health inspection activities in the A.C.T. are mainly concerned with supervision of the manufacture, storage and distribution of food supplies, with inspection of sanitary arrangements on construction sites and the examination of building plans to ensure that proper hygiene standards are observed. Inspections in the rural areas of the A.C.T. have increased with the establishment of the Tidbinbilla, Orroral Valley and Honeysuckle Creek satellite tracking stations and routine supervision of the catchment area and fauna reserve. The Medical Officer of Health for the A.C.T. receives reports of infectious and notifiable diseases and where necessary follow-up investigations are carried out. Details of diseases notified in the A.C.T. in 1966-67 are given in Table 34 on page 105.
Quarantine The number of overseas aircraft arriving at Canberra as a first port of entry has increased significantly. In 1964-65 a total of twelve aircraft received quarantine clearances at the Canberra Airport. In 1965-66 the number was nineteen and in 1966-67 it was thirty-six. Quarantine inspection of parcels arriving under bond at the Canberra Post Office is carried out by health inspectors.
School JIedical Service Medical examinations of children at both public and private schoolsincluding Jervis Bay and Wreck Bay-have continued during the year. Examinations requested by parents, teachers, medical practitioners, or in conjunction with the Commonwealth Acoustic Laboratories and the Educational Clinic of the New South Wales Department of Education have been undertaken. The number of school and pre-school children examined by the School Medical Service and defects noted are given in Table 46 on page 109. There was an' increase of 7.2 per cent in the number examined when compared with the previous year, while the number of personal interviews with parents increased 66.5 per cent to reach 821 in 1966-67. The total number of school children enrolled in the A.C.T. during term one, 1967 was 25,762, an increase of 2,678 over the number enrolled at the same time last year. 49
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Immunisation During 1966-67 the School Medical Service administered 10,311 inj~ctions of triple antigen in the continuing campaign against diphtheria, whoopingcough and tetanus. This compared with 9,690 injections in the previous year. In addition, an immunisation campaign against poliomyelitis was commenced throughout schools in the A.C.T. using Sabin oral vaccine. During the first three phases of this campaign 58,659 doses of the vaccine were administered by the School Medical Service to school children. A poliomyelitis clinic has been established and a further 22,156 doses of the vaccine were given here and in outlying clinics to babies and to some adults. The number of doses of Salk vaccine given was 2,223. A survey of blood antibody levels among children from four schools in Canberra was undertaken in conjunction with the Sabin immunisation campaign. This was done to assess the degree of protection given by previous Salk vaccinations and to ascertain the optimum time for administration of further booster doses of Sabin vaccine. The results of this survey, when available, will be of considerable interest to public health authorities throughout Australia.
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Child Dental Service Free dental treatment is available to children attending infants' and primary schools in the Australian Capital Territory. During 1966-67, 12,844 children were examined by the Child Dental Service compared with 11,259 in 1965-66. A progratnme to provide mouth guards for children involved in contact sports was carried out during the school holiday period in May 1967. This was done only in cases where requests had been received from parents. The project was well supported and 340 mouth guards were provided. In a similar programme in 1965-66, 147 mouth guards were provided. One additional position of dental officer was created during the year bringing the total to fourteen. However, recruitment has continued to be a problem and two positions could be filled on a part-time basis only. One new clinic was opened during the year in the Woden Valley district and the construction and equipping of five more clinics in new suburbs was begun. Since the fluoridation of Canberra's water supply in September 1964 there has been an improvement in the dental condition of children. Survey results to date show that children who were examined in 1966 and who had lived in Canberra since the beginning of fluoridation had 6 per cent less decayed, missing or filled permanent teeth than children examined before fluoridation was introduced. In terms purely of decayed permanent teeth the survey results indicate an improvement of 14 per cent.
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Child Guidance Clinic The Child Guidance Clinic has been in operation for eighteen months and during 1966-67 there has been a steady increase in the volume of work. A speech therapist joined the Clinic staff and speech therapy is now offered to children who have been investigated by a psychiatric team, of .~ 4
which the Bpeech therapist is a part. 50
Special rooms have been equipped for the purpose of conducting psychotherapy with disturbed children. These rooms give the children as much freedom as possible without risk of accident. In the treatment of disturbe. children it is important for the therapist to be free of anxieties concerning the child's safety or the safety of others. One of the main aims of the Clinic is to carry out preventive mental health work. In order to do this potential behaviour disorders must be detected as early as possible. A small pilot study, using an inventory for a detection instrument, was conducted and, an investigation made of the social adjustment of children attending pre-school in Canberra. The results obtained suggested that the particular inventory used would, in fact, be a useful aid in communicating between pre-schools and the Clinic. It is hoped that the Clinic will be able to collect some norms for the Canberra pre-school popUlation and thus be in a position to discover deviant children as early as possible. Consultative services have continued for private medical practitioners and bodies such as the Child Welfare Section of the Department of the Interior and the Educational Clinic of the New South Wales Department of Education. Advice has also been given to mothercraft nurses.
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Hospital Services /
Planning for two additional public hospitals in Canberra has proceeded during the year in accordance with the Government's decision to construct a 600-bed general hospital in the suburb of Garran, in the Woden Valley, and to provide Commonwealth assistance for the construction and operation of a 200-bed general hospital by the Order of the Little Company of Mary. The latter hospital will be erected on a site in the Belconnen district of Canberra, giving easy access to the existing northern suburbs of the city.
Nursing Home Accommodation The Canberra Regional Board of the New South Wales Baptist Homes Trust has commenced building operations to erect stage one of a nursing home in Canberra in the suburb of Red Hill. The Commonwealth is providing financial assistance towards the capital building cost of the home.
Ambulance Service Planning for a new headquarters for the A.C.T. Ambulance Service has advanced to the stage where full working drawings have been completed and tenders called. It is expected that a contract for stage one of this project, to cost approximately $70,000, will be let early in 1967-68. This will provide garage accommodation for six vehicles, an administrative area, a radio control and communication centre and staff amenitie8. The station will be located in the suburb of Dickson. ',,1
A new two-vehicle ambulance station was erected in the suburb of Griffith during the year. When the headquarters station at Dickson is completed the administration and control of the A.C.T. Ambulance Service
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will be transferred to the A.C.T. Health Services Branch. Both building projects have been undertaken by the National Capital Development Commission for the Department of Health.
Health Laboratory The Pathology Laboratory, which was transferred from the Institute of Anatomy to the Canberra Community Hospital in October 1965, occupied additional space in the hospital in May 1966. This area has been used for microbiology, virology and radio-isotope work. The Guthrie test for the early deduction of phenylketonuria is now being performed on babies born in the Northern Territory as well as on those born in the A.C.T. The statistics of the Laboratory show an increase of 26 per cent in the number of tests performed and of 20 per cent in the number of patients. This large increase in work volume is due to the improved facilities available and the more convenient location of the Laboratory at the hospital.
Registration Boards The secretariat of the A.C.T. Medical, Pharmacy, Dental, Optometrists', Nurses' and Veterinary Surgeons' Boards is now located in the headquarters of the A.C.T. Health Services Branch. Recent legislative changes have, with the exception of the Veterinary Surgeons' Board, transferred the position of chairman of the boards from the Director-General of Health to the Director of Health for the A.C.T. Other changes in legislation have given the Dental Board the power to review fees charged for dental services, and the Medical Board the opportunity to register medical practitioners for short-term periods and for special purposes, such as teaching or research. A substantial increase in the number of nurses seeking registration has occurred. Details of registration by each Board are given in Table 47 on page 109.
Veterinary Services A total of 2,053 dairy cattle in the A.C.T. were tuberculin tested during 1966-67. At the routine annual test sixteen reactors were detected in one herd and these reactors were ordered to be slaughtered under supervision by meat inspectors. At a re-test of this herd three months later there were no positive reactions, indicating that the disease had been eliminated. Advice was given to landholders on disease problems, and autopsies and specimen examinations performed in the field and laboratory. This included faecal examinations and worm egg counts to determine the presence of hidden infestations. Surveillance was kept over the movement of stock in the A.C.T. and health certificates issued after examination of stock and domestic animals leaving the A.C.T. both for overseas and other Australian States. Regular dairy inspections were made during the year to ensure the maintenance of a high standard of hygiene. Stock sales were attended and inspections made for the presence of notifiable diseases.
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National Fitness In January 1967 a National Fitness Officer, with specific A.C.T. responsibilities, was appointed. Thus, for the first time, the A.C.T. was recognised as a separate area for the promotion of youth services, recreational and fitness activities. The A.C.T. National Fitness Advisory Committee, at whose request the National Fitness Officer was appointed, is at present being reconstructed to provide a more effective controlling body in the A.C.T. Its associated Youth Committee is also re-constituting itself as the Youth Council of the A.C.T. Three scholarships were provided to the Australian Recreation Leadership Course at Narrabeen, New South Wales. Each scholarship entitled the holder to four weeks intensive training. In addition, grants were made to local sporting and youth organisations.
Canberra Mothercraft Society There are twenty-one mothercraft centres operating in the A.C.T. These are administered by the Canberra Mothercraft Society, a voluntary organisation subsidised by the Commonwealth, and are staffed by a total of ten triple-certificated nursing sisters. Advice is given to mothers on the care of their babies. The Society's nursing sisters also make an initial home visit to mothers following their discharge from hospital. The Queen Elizabeth II Home for Mothers and Babies, also operated by the Canberra Mothercraft Society, provides post-natal care for mothers and babies following their discharge from hospital. During the year 201 mothers and 299 babies were admitted to the home. In addition sixty-seven mothers attended as outpatients after having been referred to the home by doctors or the Society's sisters.
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District Nursing Service There has been a significant increase in the activities of the District Nursing Service as it continues to meet the expanding needs of the A.C. T. The Service, with the co-operation of other medical and social agencies, is enabling many sick people to remain in their homes and, in addition, is giving support to relatives and instructing them in the care of the patients. During 1966-67, district nurses also helped with various clinics and were members of the Sabin vaccine campaign teams. The number of patients visited in 1966-67 was 1,265 and the total number of visits made was 51,564. In preparation for their public health nursing duties a series of lectures, films and discussions have been held and attendance at a nursing seminar was arranged for several members of the staff. Two scholarships have been made available by the Public Service Board, one for a three months in-service public health nursing course conducted by the New South Wales Department of Public Health and the other for the Diploma of Public Health Nursing course held at the College of Nursing, Australia. In addition, observation periods have been arranged with other District Nursing Associations. Visits to the Rehabilitation Centre at the Canberra Community Hospital have been made by all district nurses and the Director of Rehabilitation has led discussion groups.
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National Fitness
There was a significant increase in the range and extent of national fitness activity during the year following the increased Commonwealth allocation Commonwealth assistance was to the National Fitness Movement. increased from $200,000 to $366,000 anually. State National Fitness Councils received a total increase of $96,000, which was distributed in the same proportions as previously applied. The allocations to the various States of the total amount of $224,908 is shown in Table 48 on page 110. A further $200,000 was made available over a three-year period to assist the development of capital programmes. This assistance was given on the basis of the Commonwealth contributing $1 for every $2 contributed by the States and the proceeds being available for State National Fitness Council projects. With the increased financial support, State Councils have been able to engage in a wider range of activities and to give increased services to the community. In addition to a variety of camping programmes for both young people and adults, assistance in various recreational activities and instruction through specialised sports coaching clinics have been provided. Field officers and, in certain States, regional national fitness officers have been responsible for developing programmes in widely scattered areas. Councils have continued their link with their youth work generally through associated youth committees or State youth councils.
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State Education Departments The Commonwealth grant to State Education Departments during the year was $34,000. Assistance was given for training of teachers in physical education and for publications, films and equipment. School camping has also been developed in most States as an integral part of the general education programme.
Universities Grants totalling $24,800 were paid during the year to universities to assist in the training of specialist physical education teachers. Physical education departments of the universities concerned also provided physical recreation activities for the general student body. The Universities of Melbourne, Queensland, Adelaide and Western Anstralia each received $4,200 and the Universities of Sydney and Tasmania each received $4,000.
Commonwealth Council for National Fitness The Commonwealth Council met on 24 and 25 August 1966 in Canberra in a session which marked the twenty-fifth anniversary of the passing of the National Fitness Act. Consideration was given to a wide variety of subjects affecting the development of the National Fitness Movement, particularly the possible development of sports councils and the need for national parks and adequate recreation areas in the future. 54
, Keeping Fit' During the year arrangements were made for the printing and distribution of the Commonwealth Council publication on exercise and diet, 'Keeping Fit '. The A.M.P. Society assisted the Council to achieve its aim of a wide distribution of the booklet throughout Australia by providing financial assistance for the project.
Recreation Leadership Course Now in its third year of existence, the Australian Recreation Leadership Course is making a major contribution to the promotion of health, physical education and recreation throughout Australia. The first group of students will graduate from the course early in 1968. In addition to the scholarships provided by the Commonwealth, certain State Councils have provided additional scholarships. Students have come from a wide variety of backgrounds and have included State Government employees engaged as psychiatric nurses and prison wardens and as recreation officers of the Department of Education. Professional and voluntary youth leaders also studied at the course. A total of 169 students received training at the Narrabeen Centre and extension courses were also provided by the National Fitness Council of New South Wales. An additional $4,000 was made available for the Australian Recreation Leadership Course. An annual grant of $2,000 was provided to assist with administrative costs involved in the course and $2,000 was apportioned between the States to provide scholarships for the course.
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Duke of Edinburgh's Award State National Fitness Councils have continued their active promotion of the Duke of Edinburgh's Award Scheme through State committees and the operation of field officers. A central award office has been established in Sydney and State Councils are contributing towards its operation and the salary of the central award organiseI'. At 30 September 1966, 3,311 young people were participating in the scheme throughout Australia. The Australian premiere of the film' So Few Dare' which was made for the Award Scheme, was held in Canberra on 25 August, 1966 and His Excellency the Governor-General presented twenty-nine gold awards at the conclusion of the screening. His Royal Highness, the Duke of Edinburgh, also presented thirty-one gold awards during his visit to Australia in March 1967. With increased promotion and publicity directed by active State Award committees, it is felt that the A ward Scheme will make an increasing impact on the young people of Australia .
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Commonwealth Health Laboratories
The volume of work performed at the Commonwealth Health Laboratories has continued to increase and the scope of the service has progressively widened with the demand for new procedures and the greater use by the medical profession of laboratory investigations as an aid to diagnosis, treatment and prognosis of disease. The Laboratories now provide services in haematology, histopathology, serology, biochemistry and bacteriology. This general expansion has led to the necessity for the recruitment and training of a staff of science graduates and medical technologists. Recruitment of technical staff during the year resulted in the appointment of some medical laboratory technologists and the transfer of the positions from Central Office to the Health Laboratories in the respective States. Four cadet biochemists completed their degree courses and have been posted to the Laboratories in the States. Six cadets in training are expected to complete their courses this year and it is anticipated that a further six undergraduates will then be recruited to the cadetship scheme. The lack of qualified pathologists to supervise the work performed at each of the Laboratories has been an ever-growing problem and, in an endeavour to overcome this, an intensified recruiting campaign was launched in the United Kingdom where interviewing committees were set up. Approval has been given for the provision of a scholarship for a health laboratory medical officer to attend the Diploma of Clinical Pathology Course at the London Postgraduate School of Medicine. A suitable applicant has already been selected and will begin this course in October 1967. At the same time the feasibility of training pathologists in Australia is being explored. The Canberra Health Laboratory has been enlarged by a further 2,464 square feet to provide additional facilities for the Microbiology Section. The total area occupied by the Laboratory, including the blood bank, in the Canberra Community Hospital is now 11,600 square feet. Building work at present in progress at the Albury Health Laboratory will provide increased working areas for three sections-the haematology and bacteriology departments and the sterilising and cleaning room. The Third Annual Conference of Pathologists was held in Mackay, Queensland during September 1966 in conjunction with the North Queensland Medical Conference. Pathologists from Queensland, Victoria and the Australian Capital Territory attended the Eleventh Congress of the International Society of Haematology and the Eleventh Congress of the International Society of Blood Transfusion, which were held in Sydney during August 1966. The Department was also represented at the annual meeting of the Haematology Society held in Canberra during May 1967. Statistics of tests performed and the number of patients who attended the Laboratories are given in Table 52 on page 111.
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School of Public Health and Tropical Medicine
The teaching, research and consultative activities of the School of Public Health and Tropical Medicine were maintained and extended in 1966-67. In the teaching field a variety of extra-mural activities were undertaken. A full-time course of one week on health hazards in industry was presented for managerial and technical staffs and a one-week course on ergonomics was given in association with the Department of Labour and National Service and the Productivity Group Movement. Various courses were also presented for the Australian School of Pacific Administration, the University of New South Wales and the New South Wales College of Nursing. The annual non-professional course in tropical medicine and hygiene for missionaries, nurses and tropical residents generally, now past its thirtieth year, was continued. Instruction was arranged for personnel of Commonwealth departments and organisations, the Armed Services and various institutions.
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Full-time courses were provided for graduates in medicine for the Diploma of Public Health and the Diploma of Tropical Medicine and Hygiene. Courses were also provided for various subjects of the postgraduate diploma courses in public health dentistry, clinical pathology and social work and for a course of three weeks in occupational health for medical practitioners.
Undergraduate Courses were given for medical students in preventive medicine (fifth year) and parasitology and malaria (fourth year) and in hygiene, industrial hygiene and safety, and protozoology for students of architecture, engineering and science respectively.
Research Microbiology A survey of human adult sera for antibodies against mycoplasma pneumoniae, an important cause of respiratory infection in the United States of America and Europe, has been reported. Of some 2,000 sera, 15 per cent had significant titres indicative of past infection. A survey of children with pneumonia is being continued. Only two cases of possible recent infection have been encountered. The work is being extended to study the possible association of other mycoplasmas with human disease.
Biochemistry An investigation of the quantitative aspects of protein fractions as estimated by dialophoresis, to determine the use of this method as a diagnostic clearing test and for studies on the so-called benign
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physiological or functional groups of albuminuria, was commenced. Investigations of copper metabolism and the presence of abnormal globulin patterns, to establish the nature of possible disturbances in copper metabolism occurring in leprosy and chronic liver damage, are continuing. The following projects, previously reported, have been completed and are being prepared for pUblication: serum protein studies in relation to malaria with Dr F. Schofield; correlation of electrophoresis quantitation methods; distribution of cholinesterase levels in the adult population; and significance of the cortisone provocative test with Dr A. Spears.
Environmental Health Work on the effect of thermal environment on the aged and infirm, being carried out in association with Dr F. Ofner at the Lidcombe State Hospital and Home, has been continued and a further paper on 'Temperature regulation on elderly men in bed' published. Statistical examination of recordings over a year of pulse rate, blood pressure and body temperature in a group of elderly men is nearing completion. The results indicate that tbere are marked seasonal variations in these measurements. Studies have commenced on the effect of the administration of anti-malarial drugs on heat tolerance. Statistical analysis of the extensive collection of measurements of blood pressure, weight, skinfold thickness, heart rate, oral temperature and thermal comfort, made in Antarctica over many years by medical officers of the Australian National Antarctic Research Expedition is proceeding in association with the C.S.I.R.O. Division of Mathematical Statistics. A study of the urinary excretion of adrenal hormones, before and after acclimatisation to cold in Antarctica, by assay of urine samples, is also proceeding. Members of the Antarctic Division, Department of External Affairs, were attached to the School staff while analysing the results of their work in Antarctica. Dr E. J. Elkington is investigating the effect of acclimatisation on finger blood flow. Dr K. E. Hicks has submitted for publication a paper on 'Changes in the blood-clotting mechanism, serum lipids and basal blood pressure in Antarctica' and is now completing the analysis of thermal comfort studies. A study of the relation of traffic accidents to the prevailing weather, previously reported, is proceeding.
Entomology The detailed investigation of unsolved problems associated with populations of 'filth-flies' in urban areas, which was initiated to provide biological information of possible value in the control of these flies is continuing. Statistical analysis of the data accumulating from exten~ive fly catches from selected sites has commenced.
Occupational Health Because of the health implications of exposure to asbestos dusts, a survey of asbestos industries was initiated. An extensive dust survey was made of an asbestos mine and mill in Western Australia with the 58
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co-operation of the Virestern Australian Departments of Health and of Mines. A detailed analysis of dust samples collected is proceeding. A survey of the health of workers, such as loggers, boilermakers, welders. fitters and others who have been intermittently exposed to asbestos while employed on ships at a dockyard, was also commenced. The procedures include chest radiographs, tests of lung function and sputum examination. The examination of sixty-eight long-term employees, the results of which have been compiled, is to be extended to other industries. A survey of the health of rotary machinists in the printing industry to determine the amount of ink and paper dust in the air of rotary printing departments and its possible effect on the health of operatives, is proceeding and will be completed in the next year. A clinical and environmental survey of the health of telegraphists has been completed and a report is being prepared.
Genetics
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Treatments of clinical, genetic and popUlation data in the following fields were completed in conjunction with colleagues in Oxford, Baltimore, Belfast and Adelaide: derivation and application of a linear discriminant function in phenotypes of inherited ichthyosis, derivation of correction for bias in estimation of linkage of two sex-linked loci and estimation of linkage and association for fifteen blood group or serum markers and the beta thalassaemia locus. An investigation was initiated, in conjunction with Dr F. Halliday, of inherited chorio-retinopathies in New South Wales. Clinical and genetic findings will be analysed together with ophthalmological and electrooculographic data. An investigation of inherited ataxias was commenced in association with Dr J. G. McLeod. Here clinical and genetic findings. will be analysed with electro physiological and histopathological data. In both these projects, the object is to discriminate between aetiologically distinct varieties and thus obtain information for assessing prognosis, management and hereditary counselling in a given case.
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Parasitology .
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Fieid work on the long-term study of the epidemiology and control of filariasis in New Guinea, undertaken in association with the Papua and New Guinea Department of Public Health, was completed with a final survey in the Sepik area, where the effect of residual insecticides on transmission was studied. Final laboratory work and preparation of a report are in progress. Results of the study indicate that a generalised filariasis control programme in New Guinea is not indicated, although delineation of hyperendemic areas, with intensive measures by drug administration and residual spraying for control of mosquito vectors, is suggested. A trichinosis survey, commenced in 1965, following a report from New Zealand that infestation with this parasite had been detected there in pigs, rats and cats, was continued. Examinations of 33 rats 44 cats and 2 pigs were negative in the present period. Investigation o~ helminthic infestation and treatment was undertaken on the Cocos Islands. 59
Preventive Medicine The six-year investigation of the efficacy of BCG vaccination in the prevention of leprosy, conducted in aNew Guinea area of high leprosy incidence in collaboration with the Papua-New Guinea Department of Public Health, was completed in September 1966 with a final survey of the test population. The results indicate the efficacy of BCG as a prophylactic. BCG was responsible for a 56 per cent reduction in incidence rates in the vaccinated group. In each decennial age group to thirty years and over the incidence rates were less in the vaccinated group than in the controls, but the differences were statistically significant only in the age groups 10 to 19 and 20 to 29. For both males and females of all ages, the decreased incidence in the vaccinated group was statistically significant. BCG does not appear to influence the type of leprosy or the age at onset of the new cases but preliminary results indicate that BCG may accelerate the natural healing process. An evaluated control programme will now be put into effect, with leprosy surveys at intervals to measure the decrease in incidence of the disease. A statistical study of breast cancer was commenced in association with the Tumour Clinic, St. Vincent's Hospital. Information on 2,000 cases has now been coded. A report covering the epidemiological and evaluational aspects of gynaecological cancer, in association with the New South Wales Gynaecological Registry, has been submitted for publication. A study of the symptomatology of specific histopathological types of lung cancer and the results of treatment for the period 1964-66, from data provided by the Lung Cancer Registry, has been published. A previously reported study, carried out at Fairfield in association with the New South Wales Public Health Department, to elicit the immunisation experience of infants born in 1964 and the educational and social status of their mothers, was completed. The results of interviews with 470 mothers were analysed and the findings will be considered by the New South Wales Public Health Department in its planning of health education programmes. A survey to determine a more accurate incidence figure for venereal infections in the Sydney metropolitan area was concluded and the results published. Information on 816 persons involved in traffic accidents in country areas of four States, collected by the Traffic Injuries Committee of the National Health and Medical Research Council, has been analysed and a report is being prepared for publication. The planning of a study to elucidate the difficulties experienced by asthmatics in obtaining employment was undertaken at the request of the Asthma Welfare Society. A questionnaire was designed and is being given to some 500 asthmatics by general practitioners and medical officers of large metropolitan hospitals. The results of a previously reported study of all cases of drowning which had occurred in the Sydney metropolitan area in the previous three years were published. The aim of this project was to determine the descr.iptive epidemiology of such accidents and to gain greater knowledge relatmg to their prevention. 60
Assistance is being given in statistical planning for the Australia-wide survey of smoking habits in school children which is being sponsored by the National Health and Medical Research Council. In a follow-up study of the individual problems and socio-economic adaptation of haemophiliacs in New South Wales, previously reported, comparisons are being made between the results of the present survey and data and conclusions from a major study undertaken six years previously.
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Radiation Biology In an investigation of prevention of radiation-induced leukaemia in mice, work has been done in cell transfer systems. When foetal haemopoietic tissue is used after radiation, either to impede the onset of radioleukaemia or in related experiments with resuscitation from the lethal effects of large doses of radiation, tests using cytogenetic methods and transplantation show that the leukaemia does not, for the most part, arise in donated tissue. Although administration of lymphoid tissue in dissociated form parenterally has not prevented the onset of leukaemia following a schedule of irradiation normally resulting in an incidence of 70 per cent, exclusion of a single lymph node from the radiation field results in well marked protection. Cases involving intersex states and chromosome trisomies continued to be referred for further investigation by tissue culture methods and autoradiography. Genetic counselling has been given where chromosome translocations were found to be responsible for inherited trisomic states such as mongolism. Further use has been made of the School's facilities to detect leukaemia cases in some haematological disorders. A survey of the presence of chromosome aberrations seen in polycythaemic patients treated by radiation or with radiomimetic drugs has been commenced.
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Tropical Medicine The study of the health of an Aboriginal community in a rural area of New South Wales has continued. All the children have been physically examined and some laboratory examinations made. Attention will also be directed to adults in the community. As a result of the findings in children, exploration of methods of remedial action, including a study of the employment of a public health nurse in such a situation, is projected. A statistical study on the mortality, morbidity and other aspects of the health of Australian Aborigines has been continued in association with the Social Science Research Council Project on Aborigines. Much vital statistical data has been collected and prepared for analysis.
Consnltative and Advisory Services Consultative services to various Commonwealth and State Departments, health authorities and institutions, provided by the School in its special subjects, were maintained. Members of staff served on a wide range of official bodies devoted to health or science and as honorary consultants to hospitals and other institutions.
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Institute of Child Health
Great encouragement has been given to the work of the Institute of Child Health by the start on construction of its new building. The building, which, in its first stage, will have two floors each of 6,000 square feet, is expected to be ready in the last quarter of 1967. There will be laboratories for biochemical and psychiatric research, office accommodation and a conference room. The new building will help the Institute to fulfil its functions, both in its role within the Commonwealth in relation to child health and as a focal point for paediatrics in South-East Asia. The work of the Institute is developing in three general directions: an increasing involvement in national and international advisory services related to child health and disease; a demonstration of the ways in which psychological adjustment to modern life can be assisted both individually, by the medical profession and, generally, by society; and attention to problems of certain specific illnesses in childhood. At the request of the Department of External Affairs, a special programme was arranged for Dr Asikin Hanafiah of the Department of Paediatrics of the University of Indonesia, Djakarta. His visit was an outstanding success. Short visits of this nature, made with adequate preparation, are felt to be one of the best ways of assisting paediatric developments in the countries of South-East Asia. Special advice was given on request to the Administration of Nauru in relation to health problems in children. Consultations were held during the year with a number of hospital authorities on the planning of accommodation for children. Expert opinion was given on the treatment of juvenile offenders and discussions continued with the New South Wales Child Welfare Department on the care of children in institutions.
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Child Psychiatry Associate Professor J. Katz has continued the teaching of child psychiatry to undergraduates, candidates for the Diploma in Psychological Medicine and social work students. Under the auspices of the Post-Graduate Committee in Medicine of the University of Sydney, addresses were given during the year to general practitioner groups in Sydney, Merrylands, Canberra and Kiama on various aspects of child psychiatry. The Canberra Child Guidance Clinic is now well established and has a fulltime psychologist and a social worker. Dr Katz has continued to make regular visits to advise staff and consult on patients.
Health Education During November 1966 Dr F. W. Clements visited the Northern Territ?ry to conduct an in-service training course in child health and health educatlOn for nurses. A visit was made to Oenpelli Mission Station to follow up
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studies commenced earlier. Dr Clements also conducted a pilot project in community health education at Warrabri Welfare Settlement in the Southern Region of the Northern Territory. In addition to the routine teaching of fifth year medical students, Dr Clements gave lectures on child development and nutrition for post-graduate students reading for the Diploma of Public Health and the Diploma of Tropical Medicine and Hygiene, to student dietitians, to students undertaking the Bachelor of Education course and to nurses doing post-graduate courses at the New South Wales College of Nursing.
Research
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A notable study on endemic goitre in Tasmania, carried out over many years, has been finalised and accepted for publication in the Bulletin of the World Health Organisation. A preliminary inquiry has begun into the needs of infants and children in day nurseries in Sydney . A long-term study of cretinism in fourteen children is being made. The principle criteria of progress used are measurements of height, span. weight and development quotient. An initial assessment of osseous age, cholesterol and protein bound iodine concentration in the serum is made. Serum calcium concentrations performed on all patients treated with thyroxin have been within normal limits.
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The long-term study of rheumatic fever and chorea, begun in 1952, has continued. The objects of this study are to determine the effectiveness of penicillin prophylaxis in preventing rheumatic recurrence and ultimate cardiac damage, and to study the history and course of the disease in as large a group of Australian children as possible. Since its commencement, 281 children have received regular oral penicillin prophylaxis, but thirtythree have been lost from the group during fifteen years, including four who have died. More than sixty of those remaining in the study are now over twenty years of age and are still attending for assessment at regular intervals. In addition to the 281 children receiving regular penicillin prophylaxis, a large number of rheumatic patients, initially attending the Royal Alexandra Hospital for Children, continued to be reviewed annually. The clinic, which is held weekly, also acts as a conSUltation centre for paediatricians and general practitioners who wish to refer children for opinion concerning diagnosis or management. The study of chronic urinary tract infections in childhood has also continued. During the year the introduction of a simplified technique of bacterial colony counts as part of the routine urine culture by the Bacteriology Department of the Royal Alexandra Hospital for Children has greatly simplified the interpretation of positive urine cultures.
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The care of children with rare inborn errors of metabolism detected by the screening survey of the New South Wales Department of Health has continued. From this survey, there are now twelve young children with phenylketonuria under dietary management. This low phenylalanine diet appears to protect affected children from further brain damage. There are eight children with cystinuria who are under regular supervision. Children with certain other rare metabolic errors have been investigated and their management supervised.
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National Biological Standards Laboratory
The past year was one of continued development and expansion at the National Biological Standards Laboratory. Sampling and testing of therapeutic products increased and the results obtained were an improvement on those for previous years. This improvement can be attributed to the growing awareness in the pharmaceutical industry of the need for strict quality control measures in production and the co-operation which exists between members of the National Biological Standards Laboratory staff and manufacturers. The need for additional staff to meet commitments in the various fields of research and testing has been recognised by the Public Service Board and increases in staff in several sections have been approved. RecrUitment of suitably qualified professional staff, particularly at higher levels, still presents some problems. These, however, are being gradually overcome by recruitment drives both in Australia and overseas. A symposium was held in Canberra on 30 March 1967 to outline to manufacturers of intravenous fluids and their users work carried out in the Laboratory which led to the preparation of draft standards for these
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Equipment developed at the National .Biologic~l Standards Laboratm'Y ior detecting pa'rticulate matter Ul tntravenous jlu,ds
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products and to demonstrate equipment and methods which were developed for detection of particulate matter. The symposium attracted representatives from leading hospitals in Australia and local and overseas manufacturers. The Laboratory combined with other organisations in collaborative studies on matters of common interest. It also combined with other sections of the Department in conducting an immunological survey during the Sabin vaccine campaigns in the Australian Capital Territory and the Northern Territory. Of particular interest was a survey of the level of immunity against poliomyelitis and diphtheria in the A.C.T. and, by extrapolation, elsewhere in Australia. This permitted estimates to be made of the proportion of school children who have been vaccinated and the improvement in protection offered by Sabin vaccine. To ensure the reliability of tests which require the use of experimental animals, infection free animals are needed. A colony of animals has been established under strict quarantine conditions in an attempt to eliminate the risk of infection from outside sources. When suitable accommodation becomes available, it is hoped to maintain strains of experimental animals free from the common diseases which affect the results of tests carried out in the Laboratory. The principal activities of the various sections of the Laboratory are outlined below, and statistics relating to tests carried out appear in Tables 53 and 54 on page 112.
Antibiotics Prodncts The programme of testing of all antibiotic preparations which are available as pharmaceutical benefits was completed by December 1966, and by June 1967 this survey had been extended to include all antibiotic preparations for human use available on the Australian market. Examination of bulk tetracycline imported for processing has been commenced and is continuing. This Laboratory has taken part in two world-wide collaborative assays to establish the second international standard for chlortetracycline and an international reference preparation of rolitetracycline. Research has been undertaken into the stability of cycloserine preparations and the influence of the container on the stability of these and other antibiotics.
Bacterial Prodncts The Bacterial Products Laboratory was enlarged during the year to enable a new microbial and immunological unit to be set up. This unit will carry out purification of bacterial toxins and develop' in vitro' tests for bacterial vaccines. The testing of veterinary clostridial vaccines is proceeding and expanding as suitable staff becomes available. In connection with the introduction of the Sabin vaccine in the Australian Capital Territory, the Laboratory carried out the collection of samples from some 450 donors. These samples were also examined for their diphtheria-antibody levels to determine the status of diphtheria immunisation in the community.
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Endocrine Products The Endocrine Products Laboratory moved from the Downer Laboratory into a section of the Australian Institute of Anatomy during the year. A complete survey of all heparin injections on the market has been carried out. Sampling of insulins and corticotrophins has been suspended pending the remodelling of the animal house at the Institute of Anatomy. The techniques of radio-immuno-assay of hormones are being developed. When fully developed these will reduce the time taken and increase the precision of a variety of hormone assays. This section also participated in an international collaborative assay on a new heparin standard. __ i
Viral Products Testing of Salk and Sabin poliomyelitis vaccines was continued during the year. Eight batches covering some five million doses were cleared for use in Australia. Minimum requirements for Sabin vaccine and live attenuated measles vaccine have been drawn up. Research into theoretical and practical analyses of the plaque counting technique is continuing, as is the question of local immunity in infectious laryngotracheitis and antibody production in cultured cells. J
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Pharmaceutical Chemistry Research work into detecting and counting particulate matter in intravenous fluid proceeded and modifications were made to draft standards as a result of research carried out. A collaborative study of the efficiency of drugs in tablet form was carried out in conjunction with a New Zealand scientist, Mr G. B. Engel of the Otago University, who spent fifteen weeks in Canberra for this purpose. Interesting and important discoveries were made on the method of release of active material in tablets and tablet disintegration generally. Sampling has shown an increase over the previous year and equipment has now been selected and purchased for a textile testing unit, which is taking an increasing number of samples for testing. A new technique for the determination of infra-red spectra of powders was developed. This involves the use of attenuated total reflection. The infra-red spectrum is the most valuable method of identification of drugs, but its use has been limited previously by the time involved in sample preparation. The new method reduces this time very considerably and it is now possible to carry out routine checks on bulk drugs and preparations containing more than about 25 per cent active material.
Pharmacology New drug applications submitted to the Pharmacology Section for preclinical evaluation are increasing and the Public Service Board has approved additional staff to assist in this work. Routine tes~ing for pyrogens, toxicity and histamine-like substances has been earned out, but this has been restricted during the latter part of the year because of modifications to the animal house at the Institute of Anatomy.
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Commonwealth Acoustic Laboratories
The most important development at the Commonwealth Acoustic Laboratories in 1966-67 was the expansion of clinical facilities into rural areas. The new, permanently-staffed laboratory at Newcastle and a visiting laboratory at Lismore were officially opened. A permanentlystaffed laboratory at Parramatta and visiting laboratories at Wollongong and Orange have been planned. The branch laboratories in Melbourne and Adelaide moved into new and larger premises and an extension of the Brisbane laboratory has been planned. The psychological staff was increased during the year to cope with the extra case load involved. The issue of the new subminiature in-the-ear hearing aid, Calaid E, to deafened ex-servicemen for the Repatriation Department and to children under the National Health Scheme has been an outstanding success. Production of the hearing aid commenced in June 1966 and to date nearly 3,000 have been produced and issued.
Services
Clinical Audiology and Psychology The clinical audiology and psychology services carried out through the Laboratories in the States continue to expand. Audiological services are now established in twelve country centres throughout Australia. There was a considerable increase in psychological staff during the year and intensive training was carried out. A pre-school officer has been appointed to work with the Chief Psychologist in planning a more comprehensive service for specialised guidance of parents, home training and educational follow-up of selected pre-school children. The Psychologist-in-Charge of the South Australian Laboratory visited Darwin and Alice Springs to carry out a regular hearing test and aid fitting programme in this area. The Psychologist-in-Charge of Audiology Services attended the 8th International Congress of Audiology, Mexico City, in November 1966 and a meeting of the Acoustical Society of America in Los Angeles. He also visited various audiological research and diagnostic centres in the U.S.A., U.K. and Europe. The second twoyearly conference of Psychologists-in-Charge of Laboratories was held in the Central Laboratory, Sydney, in March. Such conferences are proving an ideal means of keeping staff members informed on the latest developments in research and audiological psychology.
Hearing Aids and Hearing Conservation The Cal aid E programme is well under way and the scheme is now operating in all States. There has been continued progress in hearing conservation work with the Armed Services. Lectures were given at the Southern Command medical weekend on hearing conservation in Melbourne 67
and various types of apparatus that may be used for hearing conservation were demonstrated. A visit was also made to Canberra to carry out audiological testing at the Royal Military College, Duntroon. A hearing conservation training course for R.A.A.F. hygiene inspectors was held at Central Laboratory. This training will help the R.A.A.F. personnel concerned to set up hearing conservation programmes on their own bases throughout Australia.
Engineering During 1966-67 the Engineering Section supervised the completion of new laboratory premises in the Commonwealth Centre, Melbourne. Further planning was also done for new laboratories in Adelaide and Wollongong, and preliminary planning was begun for the proposed new laboratory at Parramatta, Sydney. In collaboration with a special committee set up by the Prime Minister's Department, acoustic advice was given in connection with the design of the' talking chair " part of Australia's contribution to Canada's' Expo 67 '. The N.S.W. Government Railways sought advice for the design of a locomotive engine test house with acoustical treatment to preserve hearing and reduce annoyance to nearby communities. Visits were made to Department of Supply establishments at Lithgow, Footscray, Maribyrnong and Bendigo to assist with hearing conservation programmes and give advice on the reduction of noise. Advice was also given to the Atomic Energy Commission, Australian Shipbuilding Board and contractors who operate noisy installations on Commonwealth land to minimise hearing damage to operators and avoid community annoyance.
Research
Acoustics and Electroacoustics The main efforts of the Acoustics and Electroacoustics Section during the year were concentrated on investigations into noise standards in ships of the Royal Australian Navy. A long-term investigation of communication in noise with particular reference to problems in the Armed Services has commenced with the evaluation of equipment. Measurements of the acoustic properties of communication headsets for the Army were completed and a relevant report was published. The efficiency of equipment currently in use in the Royal Australian Navy is being determined. Research on the acoustic properties of on-the-head hearing aids was continued and satisfactory methods were developed for the determination of the efficiency of microphone mountings under test conditions. Work on the isolation of vibration and shock provided by these mountings is continuing. The results of these investigations may increase the acoustic gain achieved in practice with the Calaid E and reduce maintenance costs.
A udiology-Psychowgy A pilot study for testing the hearing of six-months-old babies at seven baby health centres in the Sydney suburban area was ~ommen~ed. Preliminary results indicate that it is feasible to test babIes at thIs age for
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deafness and to detect those whose hearing is sufficiently impaired to be a serious handicap in language development. Babies who fail tests in a baby health centre and subsequently fail tests administered by paediatricians of the Maternal and Baby Welfare Division of the N.S.W. Department of Public Health are referred to the Commonwealth Acoustic Laboratories for further testing. Among other things, these tests include the use of encephalograph and computer to record auditory evoked cortical potentials. Research has continued on the use of this technique in audiological testing. The feasibility of measuring thresholds of hearing by detecting the evoked response to low level sound stimuli has already been shown. Good results are obtained with children but there are a number of problems still to be solved in applying the technique to babies, where, of course, it would be most valuable. The present research is aimed at using measurements of evoked response to sound well above threshold to show variations in the detection of loudness changes among people with sensorineural deafness. Present indications are that information of diagnostic significance can be obtained from tests of this nature. Studies of the effects on hearing of ultrasonic therapy for Meniere's disease are continuing. A comprehensive battery of audiological tests is being used on each patient prior to the operation and at follow-up. Another important research project, which was completed recently, dealt with deterioration that occurs in the hearing of children with sensorineural deafness. The results of this investigation confirmed previous findings concerning the deleterious effect of using high-power hearing aids.
Medical Ultrasonics There has been considerable progress in research in the application of ultrasonics to cardiology. This work has been carried out in conjunction with the Cardiology Clinic of Prince Henry Hospital. The work of the Ultrasonic Section has now been extended to Newcastle Hospital and C.A.L. staff members are co-operating in the establishment of ultrasonic investigation and research in this hospital. After preliminary clinical trials in the Ultrasonic Section at Central Laboratory, the breast echo scope has now been installed in the Royal North Shore Hospital, Sydney, for investigation of the structure of the human breast and analysis of lumps. Laboratory staff are working on this project in co-operation with medical specialists at the hospital. The C.A.L. abdominal echoscope is being regularly used in clinical diagnostic applications at the Royal Hospital for Women, Sydney. An investigation of the biological effects of ultrasonics has commenced in conjunction with the School of Pathology at the University of New South Wales. Work on the round window ultrasonic technique for the treatment of Meniere's disease has continued. The project, carried out in conjunction with the School of Veterinary Science, University of Queensland on the ultrasonic estimation of lean and fat has continued and work on the detection of minute air bubbles which cause 'bend' pains when divers come too quickly to the surface is being carried out in conjunction with the Aero Medical Research Laboratory of the University of Adelaide. 69
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Psychoacoustics Experiments on the effect of variation in rise time and repetition rate on the loudness and detectability of acoustical impulses were successfully completed. A paper entitled' Effect of spectrum of loudness of impulse noise' was presented to the International Meeting on Aerospace Medicine at Sydney in November 1966. This stressed the need for an agreed method of calculating the loudness of impulse noise. Preliminary analysis of data obtained from relevant experiments undertaken in the Laboratories suggests that it may soon be possible to provide such a method. The social importance of this study lies in the fact that it could help to rationalise legislation concerned with the annoyance due to such impulse ~ounds as the sonic boom.
Standards During the year a considerable amount of work has been done by C.A.L. staff members in connection with Australian standards in acoustics. The sub-committee on instrumentation and measurement techniques, of which the Physicist-in-Charge of the Electroacoustics Section is chairman, discussed the adoption of a new IEC standard on filters for analysis of noise and drafted a standard on the measurement of noise emitted by machines for use in Australia. The same sub-committee also finalised work on sound level meters, and two new Australian standards, AS Z371967, sound level meters, type I-general purpose, and AS Z38-1967, sound level meters, type 2-precision, have been published. The sub-committee on batteries has now finished discussions on an Australian standard for batteries and a draft standard has been published. A meeting of the bioacoustic and psychoacoustic sub-committee discussed draft international standards for noise rating with respect to annoyance and hearing conservation and considered their adaptation to Australian conditions.
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aid at Commonwealth Acoustic
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Commonwealth X-Ray and Radium Laboratory
Two important developments at the Commonwealth X-Ray and Radium Laboratory during the year were the introduction of an arrangement whereby the Laboratory supplies radon direct to New Zealand users and the decision to install a whole-body monitor at the Laboratory.
Commonwealth Radium The Laboratory continued to discharge its responsibility for the care and maintenance of the Commonwealth radium issued on loan to approved hospitals and research centres. The re-mounting of some of this radium in containers more appropriate to modern treatment techniques has continued. In addition, radium containers previously issued on loan have been progressively recalled for inspection and testing to ensure that they meet relevant standards. Following a request from the New Zealand Government, arrangements were made to supply radon to New Zealand users direct from the Laboratory. This service, which came into operation on 1 April 1967, replaces the service previously operated by the National Radiation Laboratory in Christchurch. The Laboratory manufactures the gold tubing required for use by all radon services in Australia. During the year 1,670 feet of gold tubing were constructed.
Diagnostic Radiology The Laboratory has continued to provide an advisory service to hospital authorities and to Government departments on technical aspects of diagnostic X-ray equipment, including that used by the States under the tuberculosis arrangement between the Commonwealth and the States. The arrangement under which the Laboratory provides a service to orthodontists by maintaining specially designed equipment for taking skull radiographs of a particular type has been continued. The same equipment is also made available to the Growth Unit of the Anatomy Department, University of Melbourne, in a co-operative, long-term investigation on the sequential developments of skull growth. Assistance with other special projects has also been given to Government instrumentalities, universities and similar organisations.
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Radiation Dosimetry As part of the programme relating to the provision of national radiation standards, the existing free-air chamber at the Laboratory will shortly be certified as the Commonwealth standard of exposure in the intermediate range of X-ray energy. A smaller free-air chamber, designed and built in the Laboratory, has permitted the investigation of problems arising in 71
the measurement of X-rays of low energy, with a view to extending the range of accurate measurement to X-rays of this type and ultimately to establishing a corresponding national standard. Work is also proceeding on the measurement of X-rays of very high energy, again with a view to establishing a suitable national standard of measurement. A smaIl cobalt-60 unit is being designed and constructed. This unit will provide a source of high-energy X-rays for experimental investigations. Concurrently with these new developments, the routine services relating to measurement of radiation output and associated characteristics of X-ray equipment, used for therapeutic purposes in hospitals and in private medical practices, have been maintained.
Radio-Isotopes The Laboratory provides an advisory service on physical aspects, including radiation safety, of the use of radio-isotopes in medical diagnosis, treatment and research. It also acts as the central procurement agency for purchasing and distributing all radio-isotopes used in Australia for these purposes. During the year, 2,401 shipments of radio-isotopes were procured by the Laboratory for medical use. This represents an increase of 12 per cent over the number of shipments for the previous twelve months. Of the total 266 shipments were procured from the Australian Atomic Energy Commission, compared with 156 shipments in the previous twelve months. The remainder of the shipments were from overseas sources, which included the United Kingdom, Holland, India and France. The total shipments included forty-nine different radio-isotopes in many different forms. A total of 37,548 individual issues of radio-isotopes were made in 1966-67, an increase of 52 per cent over the number for the previous year. These doses are made available without charge to all classes of patient through the National Welfare Fund. The marked increase in expenditure from the National Welfare Fund for radio-isotopes procured by the Laboratory for medical purposes over the past twelve years is shown in Table 58 on page 113. The Laboratory has responsibilities under the National Standards legislation and work is proceeding on setting-up equipment for the precise measurement of radio-isotopes in terms of the curie, with a view to establishing suitable national standards of measurement. ~
Protection Against Ionising Radia.tion Although legislative control in Australia of the use of ionising radiations from irradiating apparatus and radioactive substances is mainly the responsibility of the States, the Laboratory co-operates with State authorities and also maintains its own advisory function in this field. Technical assistance available from the Laboratory ranges from the detailed design of radiation protective shielding in X-ray departments and radio-isotope laboratories to the monitoring of radiation levels and the assessment of proposed safety procedures. During the year assistance was provided to Governme~t de?artment~ on matters relating to the safe transport and storage of radIoactive materIals. 72
Investigations into the technique and possible applications of thermoluminescent dosimetry, and into the measurement of power density of the intense beams of 'microwave' radiation emitted by radon installations, have continued. The Laboratory has also been consulted about hazards associated with the use of lasers.
Film-Badge Service The film-badge service continues to expand. In 1966-67, 74,711 individual monitoring films were assessed and reported on, compared with 66,528 for the previous year. The number of centres-hospitals, private medical and dental practitioners, research departments and industrial organisations-registered with the service rose from 956 at the beginning of the year to 1,063 at the end. The increasing demand for the film-badge service has made a review of its operation necessary. As space and staff are limited, it has become necessary to employ automatic techniques for assessment of the films and recording of the results.
Radiochemistry and 'Low-Level' Measurements As part of a continuing programme of monitoring global fall-out from nuclear weapons tests, radio-assays were made during the year of public water supplies for strontium-90 and caesium-137, of liquid milk for caesium-137, of ion-exchange fall-out collectors for caesium-137, strontium89 and strontium-90 and of air filter samples for strontium-89, strontium90, caesium-137, cerium-141, cerium-144, barium-140 and plutonium-239. In addition, naturally occurring radium D (Iead-210) has been determined in relevant samples. A total of 2,096 samples was chemically prepared and subjected to radio-assay in 1966-67. This continuing programme of monitoring is supplemented during periods of actual nuclear weapons testing in the atmosphere. The Laboratory is making relevant measurements for the Atomic Weapons Test Safety Committee and, through it, for the National Radiation Advisory Committee, during the series of nuclear weapons tests being conducted by France in the South Pacific Ocean. A programme of investigation into the assaying of radioactive substances in environmental samples is being continued and, during the year, this included the assay of plutonium in air, rainwater and biological material, the assay of radium D in human bone and of caesium-137 in meat. A series of computer programmes has been prepared to facilitate the complex calculations necessary in this work. A whole-body monitor, designed by the Laboratory, is being installed. This device is to be used for the detection and measurement of minute amounts of radioactive material in man. A steel-walled 'room' and ancillary equipment for the whole-body monitor is being built by the Laboratory staff.
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Commonwealth Bureau of Dental Standards
The Commonwealth Bureau of Dental Standards has reached the age of twenty under its present title, but its roots go back about another ten years to research done at the Australian College of Dentistry under the leadership of Dr Howard Worner, now a world leader on continuous production methods of metal extraction. Over the years, the Bureau has steered a course between the Standards Association of Australia, the Australian Dental Association, the Dental Colleges, the dentists, technicians, dental laboratories and traders and it has done this in such a way that it has earned the respect and appreciation of each by the services it has rendered. The Bureau provides independent and unbiased information on the quality of dental materials and has been instrumental in materially raising the quality of products available to dentists and of dental practice in Australia.
Preparation of Standards Apart from continuous research into more appropriate methods of testing dental materials and the revision of completed standards to accord more closely with clinical requirements, two new fields of standardisation have opened up. These are the orthodontic (movement of teeth) and the endodontic (treatment of the diseases of the tooth pulp). The standard T32 ' Resilient Orthodontic Wires' was completed in 1965 and now a sub-committee of the Standards Association for Orthodontic Materials has been set up. The Bureau has been asked to provide the data on the quality of elastic bands for the movement of teeth, metal bands for bonding teeth and cements for attaching the metal bands. These alone could provide a programme for a long time. The Australian Society of Endodontology has asked for preparation of standards for endodontic files and reamers and an international colour coding of endodontic instruments has been proposed. Hypodermic equipment for general medical use and a new restorative resin for posterior teeth are under consideration and the Australian standard T15 for alginate impression material has been revised. Over thirty standards have been completed.
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International Standards There is a great deal of international activity in the field of standardisation of dental materials led by the Federation Dentaire Illternatiollale (F.D.I.) and the International Organisation for Standardisation (I.S.O.). These two organisations are planning combined action. The Bureau has a member and adviser on the F.D.I. Committee. A number of standards have been approved and more are being prepared by correspondence and with the aid of research units throughout the world.
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Testing ,
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During the year there was a steady flow of requests by manufacturers and distributors for testing of products. The products comprised :-mineral products, 35; cements, 15; waxes and impression materials, 43; synthetic resins, 37; metals and alloys, 52; therapeutics, 31; instruments, 1; a total of 214. Although the majority were tested to completed standards, in many cases standards did not exist and tests for quality had to be devised. Since there is no organisation in Britain similar to the Bureau of Dental Standards, a leading manufacturer had his full range of products tested with a view to entering the Australian market. Other overseas firms have already found this a profitable course. In several cases Australian dentists and their patients have, by this means, been protected from inferior products. The materials tested have included denture base resins, artificial stone, casting investments, artificial teeth, orthodontic wires, impression materials, elastic materials, mouth washes, cements, mercury, waxes, cavity varnishes and local anaesthetics.
Meetings and Lectures The outstanding event of the year was the Dental Congress held at the Melbourne University in February-March 1967. The Officer-in-Charge of the Bureau presented one of the main lectures and the Bureau was represented by an extensive display and demonstrations by the staff on testing and handling of dental materials. In its advisory and teaching capacity, members of the Bureau have been involved in a large number of lectures to a wide variety of associations and groups connected with dentistry.
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Institute of Anatomy
A great deal of effort was devoted by the Nutrition Section of the Institute of Anatomy during the year towards assisting the Department of Territories to marshal and present the facts relating to diet and nutrition in connection with the 'basic needs' of local officers employed in public service in the Territory of Papua and New Guinea. At the request of the South Pacific Commission, and with the concurrence of the administering authorities of the Territory, the Institute is collaborating in a study with Professor H. A. P. C. Oomen, of the Institute of Tropical Hygiene, Amsterdam. The study is of certain aspects of the energy and nitrogen metabolism of New Guinea Highlanders, whose basic food is the sweet potato, compared with indigenous medical students and nurses in Port Moresby, whose basic foods now resemble those of Europeans. The staff of the Institute contributed papers to the 39th ANZAAS Congress and the 3rd Far East Symposium on Nutrition. As Chairman of the Standing Committee on Nutrition of the Pacific Science Association, the Medical Officer-in-Charge presented its report to the 11th Pacific Science Congress. The Committee expressed concern at the widening gap in food consumption between the poorly nourished and the wellnourished countries. In a paper contributed to the population symposium in the same congress, attention was drawn to the difficulties imposed by the climate and terrain of New Guinea in producing and transporting local food surpluses that could be used to support urban growth. This situation was compared with Australian conditions, which are very favourable to the production and transportation of large food surpluses. A paper entitled 'Nutrition Education and Ecological Awareness' was delivered at the 3rd Far East Symposium on Nutrition. This paper was orientated towards the concept that individual human organisms are part of wider biological organisms.
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Museum In the museum section of the Institute the exhibit on the ancestry of man was completed. Work on a display on the brain and nervous system has begun. By means of anatomical specimens, models and by two dimensional pictorial representations, it is hoped that it will prove possible to convey the idea of the brain and nervous system as the most highly developed integrative system of life. The compilation of the catalogue of the ethnographic collections is proceeding satisfactorily and a start has been made on entering the items in the accession register. Additional material is being obtained through the activities of the Australian Institute of Aboriginal Studies. 76
National Health and Medical Research Council
Two sessions of the National Health and Medical Research Council were held in 1966-67. The 63rd Session was held in Canberra on 4 November 1966, and the 64th Session in Perth on 18 April 1967. In addition, the committees and sub-committees reporting to Council held over eighty meetings. These committees and sub-committees include in their membership leading authorities in all fields of medicine and its related sciences.
Medical Research During the year a new organisation of the medical research functions of the Council was implemented. This has resulted in a strengthening of capacity for long range planning to determine the optimum utilisation of funds and for ensuring that the medical research activities and policies of the Council have the understanding and approval of the scientific and lay public. In recognition of the experience and efficiency of the Council as a grant giving authority, the Commonwealth Government approved an increase of 25 per cent in the appropriation to $1,065,000 per annum. Co-ordination with the Australian Research Grants Committee has ensured that duplication of Commonwealth support for research projects has been eliminated. Grants were made in 1966-67 to provide training in research and to support well over a hundred different research projects. Recipients of these grants have, during the year, published the results of their work in more than 550 scientific papers. To provide the necessary assurance that the Council's medical research work is being conducted with maximum effectiveness, regular qualitative evaluation is required. An extensive study of areas lacking support is being conducted with the co-operation of State health departments, universities, research institutes and professional associations and this has provided many excellent suggestions for increasing the effectiveness of the Council's research programmes. For many years the Council has subsidised with grants from the Medical Research Endowment Fund the publication of reports and monographs on research. The past year has seen the publication of two such reports, one on traffic injury in Brisbane and the other a summary of the results of a study of over 300,000 illness episodes seen by general practitioners. A detailed report of the work supported by National Health and Medical Research Council grants is presented to Parliament each year. Details of grants made from the Medical Research Endowment Fund during 1966-67 are given in Table 59 on page 114.
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Epidemiology The Council's recommendations for smallpox vaccinations have been enlarged by the inclusion of recommendations referring to the vaccination of pregnant women. The use of Sabin oral poliomyelitis vaccine in Tas77
mania and overseas has been carefully studied and the Council has issued a statement regarding the safety of this vaccine and made recommendations concerning the schedules of dosages and the optimum season for vaccination. The Council has also recommended that consideration be given to a joint Commonwealth-State clinical trial of measles vaccine in Victoria.
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Fats and Cardiovascular Disease After careful consideration of all the available evidence the Council has issued a statement supporting the recent conclusions of a sub-committee of the National Heart Foundation concerning the relationship of dietary fats to coronary heart disease.
Fluoridation of Water At its meeting in April 1967, the Council expressed concern at the delay in the introduction of fluoridation of public water supplies and pointed out that, as stated in its recommendation of November 1961, fluoridation is safe and has been shown to result in a significant reduction in dental caries. The Council strongly urged water authorities in Australia to give urgent consideration to the implementation of this important measure in the interests of the health of children. L
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Food Additives and Food Standards The necessity for additives of various kinds in foodstuffs for human consumption is under continuous review by the Council and further recommendations have been made. A table of suggested allowable tolerances for residues of agricultural chemicals in or upon vegetables, fruits and other foods has been prepared. Food standards have been recommended for baking compounds, dried milks, edible fats and oils, fish and meat products and a bacteriological standard for pre-cooked frozen prawns introduced. Codes of practice have been published for the 'Handling of Frozen Foods' and for the 'Sale, Service, Display and Transportation of Frozen Foods '.
Home Safety The Council has expressed its interest in the work carried out by the National Safety Council of Australia in the field of home safety and has offered its co-operation through appropriate committees. The Council has also stated that there is a need for effective legislation to reduce the incidence of accidental burns, including standards for flame resistance of fabrics, garment labelling and standards for guarding of heating appliances. , _~
Maternal and Child Health The Council has drawn the attention of medical practitioners to the effect of certain drugs upon the foetus and also to the effect of heavy smoking during pregnancy. A standard of antenatal care has been produced for distribution to medical practitioners. Steps have been taken towards the 78
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preparation, at regular intervals, of reports collating the findings of maternal mortality committees in all States and Territories on the factors responsible for maternal deaths in Australia.
Medical Research among Aborigines The Council has continued to examine all projects put forward to carry out medical research among the Aboriginal population of Australia. This service was initiated at the request of the conference of Commonwealth and State Ministers responsible for Aboriginal welfare. Approval is only given for a research proposal when it will benefit the health of Aborigines.
Medical Statistics The Council has taken steps to introduce the 8th Revision of the International Classification of Diseases into Australia both for mortality and morbidity statistics. A scheme has been prepared for the introduction of a uniform system of hospital morbidity statistics recording, and it is expected this will begin to operate in 1969. Attention has also been drawn to the contribution which can be made to the study of cancer aetiology by the development of cancer registries. The council has decided to set up a Standing Cancer Registration Committee which will advise on tabulations of cancer statistics and make recommendations to assist in the co-ordination of activities of existing cancer registries.
Mental Health A Mental Health (Standing) Committee has been set up and held its first meeting prior to the 64th Session of the Council. Through the work of this committee the Council has been able to make a number of recommendations in the field of mental health. These have included recommendations on the long-term care of cases of brain damage. research in mental health and uniform statistics of mental health. A glossary of mental disorders has been produced for use with Section 5, Mental Disorders, of the 8th Revision of the International Classification of Diseases.
Occupational Health Further recommendations in the field of occupational health have been approved. A recommended standard for paint has been published to apply to imported and locally produced paints. This includes recommendations on the content of scheduled poisons and insecticides, restrictions on the use of paints containing poisons, powers to order destruction and warning labelling. Recommendations have also been made concerning the licensing of users of ion smoke detectors.
Phenacetin and Nephropathy • >
In recent years considerable interest has been shown in the association between certain kidney diseases and the excessive taking of analgesic preparations containing phenacetin. The Council has recommended that a warning label should be required on such preparations. pointing out that the medication may be dangerous when used in large amounts or for a long period. '79
Radiation Health The Council is preparing codes of practice on the diagnostic use of X-rays in medicine and dentistry, safe use of radioactive luminous compounds and safe use of X-ray equipment for spectrographic analysis. It is also preparing a survey to assess the genetic and somatic doses to the Australian population from the medical and dental uses of ionising radiation and radioactive substances.
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Road Safety Recommendations have been made concerning resuscitation equipment which it is considered desirable to carry in ambulances. The Council has drawn attention to the need for a re-examination of the standards for motor cyclists' safety helmets. Attention has also been drawn to the need for co-operation between States in the collection of uniform statistics of road accidents.
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Scheduling and Labelling of Poisons The uniform schedules for the guidance of persons drawing up legislation on the scheduling and labelling of poisons have been further enlarged and amended by the addition of new compounds and by the inclusion of simple first aid directions and warnings for labelling. An index has also been included which indicates substances and compounds previously covered only by , blanket' entries in the schedules. A completely revised version of the schedules has been published in the Report of the 64th Session of the Council.
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Smoking Attitudes in Australia In response to a request by the conference of Commonwealth and State Ministers for Health, the Council recently set up a sub-committee to design a survey which would give data on the patterns of acquisition of the smoking habit, the attitudes of Australian children towards smoking and the social forces acting on children which tend to promote or inhibit the beginning of the smoking habit. The sub-committee's design for a survey has been approved and its organisation on a national scale has begun.
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World Health Organisation
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The 20th World Health Assembly was held at Geneva from 8 to 26 May 1967. One hundred and nineteen member and two associate member states were represented. Australia was represented by Dr A. J. Forbes, the Commonwealth Minister for Health, as Chief Delegate, Sir William Refshauge, as Deputy Chief Delegate, Miss June Barnett, First Secretary, Australian Consulate-General, Geneva, Dr J. Boxall, Director, International Health, Department of Health, Dr A. Johnson, Chief Medical Officer, Australia House, London, Dr R. Cumming, Medical Director, Australian Migration Office, Athens and Dr A. Tarutia, Medical Officer, Papua. Sir William Refshauge was elected a member of the Executive Board for three years. Australia has previously been represented for one year in 1949 and for a full three-year term in 1957-60.
Budget /
The Budget for WHO in 1966 was 21 per cent higher than that for the previous year. It is proposed that after 1967 the annual increase will be kept to about 9 per cent. Thus for 1968, the amount is $US56,123,000, and the proposed budget for 1969 is $US61,174,000. A joint inspection unit of eight inspectors, chosen from national inspection bodies and nominated by countries to be designated at the 21st World Health Assembly, is to examine matters bearing on efficiency and economy in the use of the organisation's resources.
Malaria While malaria is not a direct problem in Australia, in many countries, particularly in Africa, it is an important deterrent to the realisation of full economic and social development. Sufficient finance and trained manpower are often not available and the general administrative and health services cannot cope with full malaria eradication programmes. Delays in the global programme lead to further aggravation of problems such as resistance to insecticides. Notwithstanding these difficulties, more than 1,250 million people now live in areas where malaria has been eradicated, or where eradication programmes are in progress. Fields of research include chemotherapeutics, epidemiology, parasitology, study of the effects of new insecticides, and also the socio-economic effects of the disease. At the 20th World Health Assembly it was resolved to intensify fundamental research and to study how best to carry out a re-examination of the global strategy of malaria eradication.
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Smallpox A global programme for smallpox eradication was first launched by the 11th World Health Assembly in 1958. However, transport, equipment and vaccine are usually scarce in those countries where the disease is 81
endemic. In 1966 some 65,500 cases were reported compared with 64,300 in 1965. With a view to co-ordinating the eradication programme the 19th Assembly, in 1966, set up a ten-year plan to start in 1967. Meanwhile endemic regions persist in South-East Asia, Africa south of the Sahara and several countries of South America. Europe, North and Central America and the Western Pacific Region continue to maintain their status as non-endemic areas. WHO's contributions to smallpox eradication include preparation of a comprehensive manual setting out the principles and technical considerations of the eradication programmes, assistance in formulating plans of operations, health education, surveillance and health laboratory services, statistical methodology, promotion of vaccine production facilities, provision of consultant services and technical assistance, preparation of vaccine reserves, and establishment of training courses, fellowships and scientific and research groups. Vaccination is a safe and effective measure for the control of smallpox and is recommended at birth in endemic countries, particularly as differential diagnosis becomes more difficult as the incidence of the disease declines. Comparatively little is known about the smallpox virus and to aid in the eradication campaign a reference strain of vaccine for use in potency testing has been developed.
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t
Cancer Research The 18th World Health Assembly approved the establishment of the International Agency for Research on Cancer, with a view to promoting international co-operation in this field. The Agency has now been established in Lyon, France, and through the generosity of the French Government, a modern multi-storey building is to be built to replace the present temporary premises. The present programme includes the building of two regional laboratories, one at Singapore and the other at Nairobi. Fellowships are being offered to research workers throughout the world for periods of three months for senior research workers, and of one year for trainees. As one of the nine member states of the Agency, Australia contributes $134,398 per annum and sends a representative to the meetings of the Agency. (
Pharmaceutical Preparations There was considerable discussion at the 20th Assembly on quality control of pharmaceutical preparations, and particularly on measures to ensure stricter control in international commerce. An outline of a standard for the manufacture of pharmaceutical preparations had unanimous support and there was also support for the proposal to provide regional quality control laboratories to assist underdeveloped countries. A study is also to be made of the ethical and scientific criteria that should govern the advertising of drugs.
J- 1
Dependence-Producing Drugs
-~
.l
for eITective counter 82
As the increasing abuse of L.S.D. and related hallucinogenic substances, with their inherent risk to the health of the individual and society, calls memmre~, WHO re"olved that the Ug" of p",yehotropic
drugs be restricted to scientific and special medical purposes, that competent health authorities supervise production, distribution and conditions of use, and that suitable education programmes be sponsored. The feasibility of international control is also to be studied. It was also resolved that those drugs of the sedative and stimulant types which have been found to be dependence-producing should be restricted to prescription only, transactions should be supervised from production to retail sale. all producers should be licensed, trade should be limited to authorised persons and possession without authorisation should be prohibited.
Equivalence .of Medical Degrees Information on length of study for primary medical qualification, content of curricula, titles obtained on qualification and special requirements for the practice of medicine is to be sought by WHO. As each country has sovereign powers in setting standards, a study of relative equivalence of both basic and post-graduate qualifications will be a lengthy and difficult process.
The Challenge to Public Health of U1'banisation Over the last 100 years mankind has doubled in numbers but the world's city population has increased five times. A third of this urban population lives in slums and shanty towns. Even where basic physical requirements are met, the modern city threatens the health of its citizens in many ways, particularly in mental health. As counterpoints to the glamour of the city, its employment opportunities, educational wealth and cultural achievements there are delinquency, crime, prostitution, alcoholism and the excessive use of drugs. Technical discussions were held on these problems during the 20th World Health Assembly and it was accepted that there was a need for well planned and properly implemented urbanisation with health authorities and WHO accepting the challenge of urbanisation.
Regional Committee for the Weste1'n Pacific The 17th Session of the Regional Committee for the Western Pacific was held at Manila from 21 to 27 September 1966. The Australian delegation was headed by Dr H. E. Downes, Deputy Director-General of Health and included Dr Reuben Taureka, Department of Public Health, Territory of Papua and New Guinea, and Mr D. R. Argall, Third Secretary, Australian Embassy, Manila. Fifteen countries were represented at this Session as well as representatives of thirteen international organisations. The Regional Director, Dr Francisco Dy, referred to the importance of national health planning and of assistance at local levels in the South Pacific and stressed the importance of preventive rather than curative medicine. The communicable diseases, cholera, tuberculosis, filariasis, leprosy, encephalitis and haemorrhaegic fever were stilI present in the Region. Further efforts in environmental health were needed to reduce intestinal diseases.
,.
83
Commonwealth Grants
The Commonwealth Government, through the Department of Health, makes available grants to State Governments and non-profit making organisations to subsidise various schemes for the promotion and maintenance of health services for the community.
Australian Red Cross Society-Blood Transfusion Service The Blood Transfusion Service is possibly the most important of the services operated by the Red Cross Society in Australia and its Territories. Since 1954 the Commonwealth has made an annual grant to each State Government, equal to 30 per cent of the operating costs of the Blood Transfusion Service incurred by the Society in each State, provided that 60 per cent of the operating costs are met by the State concerned. This has left 10 per cent of the operating cost to be met by the Society. Grants made by the Commonwealth to the Society since 1953-54 are shown in Tables 60 and 61 on page 114. The Society also operates blood transfusion services in the Australian Capital Territory and Northern Territory, the Commonwealth making grants to the Society equal to 90 per cent of the certified operating expenses. Grants during 1966-67 were $10,566 for the Australian Capital Territory and $2,321 for the Northern Territory.
Royal Flying Doctor Service Since 1936 the Commonwealth has been making grants towards the operational and capital costs involved in conducting the Royal Flying Doctor Service. The operational grant during 1966-67 was $150,000 and the capital grant $86,350. The Commonwealth also continued to meet the cost of the contents of standard medicine chests, supplied for use in the various centres serviced by the Royal Flying Doctor Service. These medicine chests are used when doctors give medical advice by radio.
Home Nursing Subsidy Scheme The Home Nursing Subsidy Scheme, which began in 1957, was designed to assist in the extension of home nursing activities, either by the expansion of existing home nursing organisations or the formation of new ones. To be eligible for a subsidy, an organisation must provide a home nursing service, be non-profit making, employ registered nurses and receive assistance from a State Government or a local governing body established under a State Act. Subsidy payments are based on the number of nurses employed over and above the number employed during September 1956, in the case of existing organisations, and on the total number of registered nurses employed by organisations formed after that date. The present subsidy 84
rate is $2,200 per annum for each additional nurse employed in the first instance and $1,100 for each nurse employed by organisations which commenced after September 1956. The rates, which have increased gradually from $1,600 and $800 in 1957, are reviewed periodically. At 30 June 1967 there were sixty home nursing services employing approximately 600 trained nurses in receipt of the Commonwealth subsidy. Seventeen of those organisations were in existence when the scheme was introduced and at that time they employed about 200 trained nurses. Details of the annual subsidies paid by the Commonwealth since the inception of the Home Nursing Subsidy Scheme are given in Tables 62 and 63 on page 115.
l.
,
Free Milk jor School Children The Commonwealth grant for free milk for school children in 1966-67 was $9,020,990, which permitted the free distribution of one-third of a pint of milk on each school day to approximately 1,610,000 school children attending public and private primary schools, kindergartens, creches and Aboriginal missions throughout Australia. In the States, the detailed administration of the scheme is carried out by the State Governments. Distribution to children in the Australian Capital Territory is made by the Department of Interior and to children in the Northern Territory by the Department of Territories under conditions similar to those operating in the States. Expenditure by the Commonwealth on the Free Milk Scheme since its commencement is shown in Table 64 on page 115. However, these figures do not include amounts reimbursed to the States in respect of half of the cost of capital, administrative and incidental expenditure, which was $27,755 for 1966-67.
Mental Health Institutions The aministration and operation of mental health institutions is carried out by State Governments. However, over the years the Commonwealth Government has made substantial grants to assist the States in financing their responsibilities. This Commonwealth assistance began with agreements entered into with the States, as authorised by the Mental Institution Benefits Act 1948, and provided for Commonwealth subsidy of day-to-day running costs of mental health institutions. In 1955, following a survey which disclosed severe deficiencies in institutional accommodation throughout Australia, the subsidy was replaced by the States Grants (Mental Institutions) Act, which provided for grants of capital assistance on the basis of $1 contribution by the Commonwealth for each $2 contributed by the States. This legislation, which limited the grants to a ceiling of $20 million, to be divided between the States in accordance with their populations was later replaced by the States Grants (Mental Health Institutions) Act 1964, which removed the financial limit and substituted a time limit of three years. 85
The Commonwealth financial assistance provided under the 1955 and 1964 legislation has stimulated and encouraged the States to provide more accommodation of a considerably higher standard. In addition, it has, in more recent years, assisted the States in a building and conversion programme developed to provide institutions required for modern concepts of treatment of mental illnesses. Encouraged by the success of the grants made so far, the Government has announced its intention of extending the States Grants (Mental Health Institutions) Act 1964 for a further three years, concluding on 30 June 1970. Details of the total expenditure each year since the inception of capital assistance in 1955, together with amounts contributed by the Commonwealth and the States, are shown in Table 66 on page 116.
,,-'
Lady Gowrie Child Centres The Commonwealth has always had a very close interest in the Lady Gowrie Child Centres, having established in 1940 a Centre in each State capital and having provided since then a major part of the finance for their operation. The Centres were primarily created for the study of problems of physical growth, nutrition and development and to test and demonstrate methods for the care and instruction of the young child, but in more recent years the activities have included the mental development of children. The Centres are specialised demonstration and research centres which disseminate knowledge gained in this field. For some years the Commonwealth has also subsidised the activities of the Australian Pre-School Association which, in administering the Centres, has been of considerable assistance in developing these activities on a national basis. The total grant for 1966-67 was $134,800, comprising $120,000 paid to the six Centres in equal proportions and $14,800 to the Australian Pre-School Association.
} £
86
Contents Appendix 1-Statistics Table No. NATIONAL HEALTH.
Page.
NG.
1. 2. 3. I ,,. '
Departmental Expenditure-1962-63 to 1966-67 HOSPITAL BENEFITS.
91
,
4. 5. 6. 7.
Number of registered organisations, membership and coverage1952-53 to 1966-67 Number of registered organisations, membership and coverageby States-30 June 1967 Benefits paid to contributors by registered organisations-1952-53 to 1966-67 Benefits paid to contributors by registered organisations-by States-1966-67 Amount of Commonwealth and fund benefits paid-by States1966-67 Amount of Commonwealth nursing home benefit paid-by States1966-67 MEDICAL BENEFITS.
91 92 92 92 93 93
"
8. 9. 10. 11.
12. 13.
Number of registered organisations, membership and coverage1953-54 to 1966-67 Number of registered organisations, membership and coverageby States-30 June 1967 Medical services received by contributors to registered organisations-fee-for-service only-1953-54 to 1966-67 Medical services received by contributors to registered organisations-fee-for-service only-by States-1966-67 Cost of medical services to contributors to registered organ is ations-1953-54 to 1966-67 Cost of medical services to contributors to registered organisations-by States-1966-67 PENSIONER MEDICAL SERVICE.
94 94 95 95 96 96
14. 15. 16. 17.
Number enrolled, number of services received and average attendances per enrolled person per annum-1951-52 to 1966-67 Number enrolled, number of services received and average attendances per enrolled person per annum-by States-1966-67 Number of participating doctors, payments received and average annual payment per doctor-1951-52 to 1966-67 Number of participating doctors, payments received and average annual payment per doctor-by States-1966-67 PHARMACEUTICAL BENEFITS.
97 97 98 98
18. 19. 20.
21.
Cost of prescriptions-1960-61 to 1966-67 Cost of prescriptions-by States-1966-67 Dissection of benefit prescription costs into ingredient cost and chemists' remuneration-1960-61 to 1966-67 "" Dissection of benefit prescription costs into ingredient cost and chemists' remuneration-by States-1966-67 , ,"
98 99
99 99
87
CONTENTS-Appendix I-continued Table No. Page. No.
22. 23. 24. 25. 26. 27. 28.
Number of prescriptions and average cost per prescription1960-61 to 1966-67 Number of prescriptions and average cost per prescriptionby States-1966-67 Number of prescriptions per head of population and average cost per head of population-1960-61 to 1966-67 Number of prescriptions per head of population and average cost per head of population-by States-1966-67 Payments to hospitals and miscellaneous services-1966-67 Drugs dispensed by chemists-1966-67 Number of pharmaceutical chemists and medical practitioners dispensing pharmaceutical benefits prescriptions-1949-50 to 1966-67 TUBERCULOSIS.
100 100 100 101 101 101 102 102 103 103 104 104 105 105 106 106 106 107 107
29. 30. 31. 32. 33.
Number of allowances, notifications and mortality-1952 to 1966 Number of allowances. notifications and mortality-by Statesyear ended 31 December 1966 Expenditure under the Tuberculosis Act-1949-50 to 1966-67 Expenditure under the Tuberculosis Act-by States-1966-67 Results of mass X-ray surveys-by States-year ended 31 December 1966 PUBLIC HEALTH.
, '
34. 35. 36. 37. 38. 39. 40.
Notifiable diseases in the States of Australia-1966-67 .... Poliomyelitis-number of confirmed cases-by States-1957-58 to 1966-67 ... Infectious hepatitis-cases notified-by States-1961 to 1966 Radio and television scripts on medical matters examined-1966-67 QUARANTINE.
Vessels boarded and cleared-by States-1966-67 Infectious diseases on overseas vessels arriving in Australia1966-67 Animal importations subject to quarantine-1966-67 NORTHERN TERRITORY HEALTH.
41. 42. 43. 44. 45. 46. 47. 48. 88
Aerial Medical Service-1966-67 Health services provided at main Northern Territory hospitals1966-67 Dental services provided in the Northern Territory-1966-67 AUSTRALIAN CAPITAL TERRITORY HEALTH.
107 108 108 109 109 109 109
t _ ( -'
Licences issued under the public health ordinance-1966 Samples collected by health inspection section-1966-67 School medical service examinations-1966-67 . Registrations granted-1966-67 NATIONAL FITNESS.
-, •
Allocation of annual grant to State National Fitness Councils1966-67
110
CONTENTS-Appendix I-continued Table No. Page. No.
49.
Allocation of annual grants to State Education Departments1966-67 COMMONWEALTH MEDICAL OFFICERS.
110
50. 51.
Number of clinical examinations by Commonwealth Medical Officers-by States-1966-67 Number of vaccinations by Commonwealth Medical Officers-by States-1966-67 COMMONWEALTH HEALTH LABORATORIES.
111 111
l
52.
Number of pathological examinations and laboratory tests performed and number of patients-1966-67 NATIONAL BIOLOGICAL STANDARDS LABORATORY.
111 112 112 112 113 113
53. 54.
Summary of all samples examined-1966-67 Safety tests performed-1966-67 COMMONWEALTH ACOUSTIC LABORATORIES.
. /
55. 56. 57. 58.
Cases examined-1966-67 Calaid hearing aids fitted-1966-67 Calaid hearing aids maintained-1966-67 COMMONWEALTH X-RAY AND RADIUM LABORATORY.
Expenditure under the National Welfare Fund on radio-isotopes for medical purposes-1955-56 to 1966-67 NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL.
113 114 114 114 115 115 115 115 116
59. 60. 61. 62. 63. 64. 65. 66.
Grants made from the Medical Research Endowment Fund-1966-67 COMMONWEALTH GRANTS.
Red Cross Blood Transfusion Service-1953-54 to 1966-67 Red Cross Blood Transfusion Service-by States-1966-67 Home Nursing Subsidy Scheme-1956-57 to 1966-67 Home Nursing Subsidy Scheme-by States-1966-67 Free Milk for School Children-1950-51 to 1966-67 Free Milk for School Children-by States-1966-67 Mental health institutions-by States-1955-56 to 1966-67
Appendix 2-Publications School of Public Health and Tropical Medicine Institute of Child Health . . ..... ... National Biological Standards Laboratory Commonwealth Acoustic Laboratories ... .. Commonwealth X-Ray and Radium Laboratory Commonwealth Bureau of Dental Standards Institute of Anatomy .. .... .. Central and Divisional Offices National Health and Medical Resea~ch C~uncil 89 117 119 119 119 119 120 120 120 121
"~
~
,
Appendix 1 STATISTICS Table I
Departmental Expenditure 1962·63 to 1966·67 Year ended 30 June
1963 $'000
1964 $'000
1965 $'000
1966 $'000
1967 1'000 67,398 43,841 101,281 14,351 9,021 10,983 3,947 250,821 499 IO,677t 2,363 4,420:1= 3,291 1,096 .-~---~,----
------,------~
National Welfare Fund Hospital Benefits .. Medical Benefits
..
Pharmaceutical Benefits .. Pensioner Medical Service
Free Milk for School Children Tuberculosis*
l
Miscellaneous Total National Welfare Fund Consolidated Revenue Fund Tuberculosis capital reimbursement Administration
47,326 23,474 76,910 9,146 7,454 9,748 1,529 ~~-----~
175,588
60,743 56,216 58,791 41,282 24,848 35,277 78,839 82,203 91.784 13,365 9,531 9,320 7,775 8,059 8,493 13,379 10,473 10,146 1,785 2,859 3,453 ------ --------189,467 206,655 232,500 598 1,762 908 4,943 1,989 2,732 1,451 242 -------. 14,625 1,595 205,687 696 2,087} 1,078 4,817 2,152 3,136 1,916 869 16,751 2,504 225,909 696 8,836t 2,256 3,682:1= 2,388 1,105 18,962 4,539 256,001
Quarantine .. Health Services Subsidies and grants Northern Territory Austral ian Capital Territory Capital Works and Services Total Consolidated Revenue Fund ..
• Special Capital Grants to States for Mental Health Institutions Total Expenditure
984 1,596 838 4,843 1,852 2,500 1,350 1.248 _._----------15,211 1,590 192,389
22,346 4,973 278,141
..
Apparent minor errors in totals are due to "rounding off". * In addition to the amounts shown, allowances are paid by the Department of Social Services-see Table 31, page 103. t Under the new division of expenditure introduced by the Department of the Treasury, it is not now possible to derive separate figures for these three items. =1= Certain expenditure previously included in Administration is now included in this item.
Table 2
Hospital Benefits Number of registered organisations. membership and coverage-I 952-53 to 1966-67 No.
As at 30 June -----_. 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
registered organisations 139 127 128 124 122 119 116 115 115 113 110 112 III III 109
of
Membership' ODD's 1,500 1,865 2,111 2,247 2,373 2,514 2,749 2,908 3,044 3,130 3,176 3,286 3,407 3,489 3,657
Estimated coverage ODD's 3,413 4,601 5,121 5,499 5,878 6,195 6,774 7,208
Percentage of population covered -------
%
39 51 56 59 61 63 68
7,500 7,738 7,895 8,194 8,732 8,915 9,342
72 72 73 73 74 77 78 80
.-
~
* As advised 91
by the organisations.
Table 3
Hospital Benefits ..
~ ~
Number of registered organisations, membership and coverage-by States30 June 1967 State No. of registered organisations 32 43 3 13 9 9 109
Membership' OOO's
Estimated coverage OOO's 3,686 2,890 807 971 703 285 9,342
Percentage of papulation covered
I
I
New South Wales Victoria . .
Queensland South Australia Western Australia Tasmania . . Commonwealth
1,467 1,063 322 403 288 114 3,657
%
84 89 48 85 83 76 80
* As advised by the organisations.
/
~
I
Table 4
Hospital Benefits Benefits paid to contributors by registered organisations-I 952-53 to 1966-67
Year ended 30 June -------
No. of days fund benefic paid OOO's 1,874 3,413 4,642 4,808 5,492 6,215 7,049 8,937 9,740 10,341 10,419 9,576 9,988 10,252 10,444
Average daily benefic
No. of claims per 100 members 13.4 19.9 23.5 20.8 23.3 25.6 26.9 29.4 29.7 30.9 32.1 30.7 32.5 32.8 33.4
Average stay in hospical per claim
).
--_.,-----
1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
S 1.03 1.40 1.58 1.81 2.32 2.62 2.75 2.68 2.88 3.17 3.43 4.40 4.83 5.40 6.61
days 10.98 10.17 9.92 10.60 10.30 9.96 9.74 10.81 11.02 10.78 10.29 9.39 9.23 9.05 8.72
--• ,
.~
!.
Table 5
Hospital Benefits Benefits paid to contributors by registered organisations-by States-1966-67 State No. of days fund benefit paid ooo's 4,466 2,604 1,092 1,116 842 324 10,444
Average daily benefit 6.92 6.58 4.02 5.73 6.35 6.89 6.61
No. of claims per 100 members 35.1 27.8 38.7 33.5 39.9 32.9 33.4
Average stay in hospital per claim days 8.92 8.99 8.92 8.41 7.45 8.44 8.72 1 "
S
New South Wales Victoria . .
Queensland South Australia Western Australia Tasmania . . Commonwealth
92
Table 6
Hospital Benefits Amount of Commonwealth and fund benefits paid-by Commonwealth State States-1966~67
Fund Total Excluding ancillary Total Ancillary $'000 915 731 191 440 294 61 2,632
Uninsured patients $'000 753t 424 894 III 148 46 - - - - - - - - -..
Insured patients
Pensioner patients $'000 7,119t 4,164 3,506 1,582 1,787 572 18,731
Total $'000 31,799 17,870 4,579 6,835 5,638 2,290 69,011
/'Jew South Wales Victoria . .
Queensland South Australia Western Australia Tasmania . . ---
*$'000 10,639 5,736 2,348 2,218 1,913 670 23,524
--~-----.~-
~
Commonwealth
2,376
$'000 $'000 18,512 30,885 10,324 17,138 6,748 4,388 3,911 6,396 3,848 5,344 1,289 2,230 ----44,631 66,379
$'000 50,311 28,193 11,327 10,746 9,486 3,579 113,642
Apparent minor errors in totals are due to "rounding off".
* Includes payment of Special Account deficits of $3,784,000. t Includes A.C.T. and N.T.
r
Table 7
Hospital Benefits Amount of Commonwealth nursing home benefit paid-by State nursing State States-1966~67
homes $'000 1,698 2,337 1,700 355 825 333 .~~--~-
Private nursing homes $'000 7,833 2,547 1,848 1,654 1,209 428 15,518
Total $'000 9,531 4,884 3,548 2,009 2,033 761 22,767
~------
New South Wales Victoria
Queensland South Australia Western Australia Tasmania .. Commonwealth Apparent minor errors in totals are due to "rounding off",
7,249
93
Table 8
Medical Benefits Number of registered organisations, membership and coverage-I 953-54 to 1966-67 As at 30 June No. or registered ----------_.
Membership'
Estimoted coverage
organisations 79 80 82 81 81 82 83 83 82 78 81 80 80 78
Percentage or population covered
~-.------------
1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
- - - - ----_._-------------------OOO's OOO's % 39 1.358 3.502 4.154 45 1.666 51 1.901 4.806 5,715 60 2.229 63 2.422 6.148 67 2.667 6.713 72 2.908 7.311 7,I73t 2.850t 68t 7,'1.75 68 2.846 71 2,952 7.686 3,095 73 8.058 75 3.217 8.462 3.313 8.679 76 76 3.418 8.846
j
t Variation as compared with
* As advised
by the organisations. 30 June 1960 results from revision of membership figures in one of the major organisations.
Table 9
Medical Benefits Number of registered organisations. membership and coverage-by States30June 1967 State
No. or registered organisations
Percentage of
Membership' OOO's
Estimated coverage OOO's 3.498 2.642 823 925 682 276
population covered
% 80 81 49 81 80 74 -- - - - - >-
28 1.363 Victoria .. 19 969 324 Queensland 6 South Australia 373 8 279 8 Western Australia 9 110 Tasmania .. -------- ------ ------ ----- ----3.418 Commonwealth 78
New South Wales
)
--- --- - - - - - -
J. j
8.846
76
* As
advised by the organisations.
I
94
Table 10
Medical Benefits Medical services received by contributors to registered organisations-fee-for-service only-I 953-54 to 1966-67
Year ended 30 June
No. of services received ooO's 3.284 9,453 12,259 13,668 15,582 16.819 19,625 20,123 21,669 23,431 24.308 25,847 28,210 29.269
Percentage of G.P. to Total
Average No. of services per contributor 3.4 6.2 6.8 6.6 6.7 6.5 7.1 7.3 7.7 8.0 7.8 8.3 8.7 8.7
Average cost per service $ 2.85 2.91 2.91 3.10 3.24 3.28 3.30 3.56 3.64 3.69 3.85 4.02 4.20 4.48
--~-----------------~----~-
1954 1955 '1956 1957 1958 1959 1960 1961 1962 I' 1963
%
74 70 71 75 75 75 75 73
72 72 71 70 69 68
-1964 1965 1966 1967
Table II
Medical Benefits Medical services received by contributors to registered organisations-fee-for-service only-by States-1966-67 State No. of services received Percentage of G.P. to Total 66 69 69 70 64 64 68
Average No. of services per contributor 8.6 8.6 9.7 9.0 9.1 7.6 8.7
Average cost
per service $ 4.77 4.48 4.12 4.10 4.07 4.35 -~-------
-------------
000', 11,594 8.086 3.086 3,281 2,404 818 29,269
%
New South Wales Victoria . .
Queensland South Australia Western Australia Tasmania . .
,
Commonwealth
--4.48
95
Table 12
Medical Benefits
Cost of medical services to contributors to registered organisations-1953-54 1966-67 of services (fee-for-service and contract)
to.~,
/
Total cost
Percentage o( total cost met by-«(ee-(or-service only) Fund 31.7 33.9 35.0 34.1 33.9 34.4 35.4 36.0 36.9 37.1 36.8 35.2 35.7 35.5 Contributor Cwealth ---_._-----------
Year ended 30 june --1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
$'000 9,112 27,169 35,276 42,003 49,625 54,619 64,203 71,242 78,499 86,213 93,313 104,624 119,021 131,770
%
31.4 30.9 30.6 29.3 28.3 28.5 28.2 27.4 27.0 26.6 25.9 32.9 33.9 32.2
%
36.9 35.2 34.4 36.6 37.8 37.1 36.4 36.6 36.1 36.3 37.3 31.9
%
30..01 32.3
Table 13
Medical Benefits
Cost of medical services to contributors to registered organisations-by States1966-67 of services State (fee-(or-service and contract) $'000 55,500 36,372 12,727 13,441 10,100 3,631 131,770 Total cost
Percentage o( total cost met by(fee-far-service only) Fund Cwealth Contributor
Fund benents paid Excluding ancillary S'OOO 20,104 11,788 4,679
Ancillary S'OOO 1,104 328 192
New South Wales Victoria
%
Queensland South Austral ia
Western Australia
Tasmania -
..
36.2 32.3 36.8 38.2 37.8 36.8
%
30.3 31.9 33.8
%
33.5 35.8 29.4
35.3 37.8 32.9 32.2
26.5 24.4
5,128 3,850 1,350 46,899
236 106 76 ~
30.3 32.3
_ _ _ _ _ _0
r_
Commonwealth
35.5
2,042
Apparent minor errors in totals are due to "rounding off".
.''1;
96
Table 14 ..A
Pensioner Medical Service Number enrolled, number of services received and average attendances per enrolled person per annum-1951-52 to 1966-67 No. of pensioners and dependants enrolled 01 30 June OOO's 501 558 597
No.
of services OOO's 1,105 1,651 2,092 2,346 2,514 2,603 2,774 2,980 3.076 3,131 3,223 3,111 3,020 2,859 2,824 2,972
received
..
_
Year ended 30 June ... _---
Surgery OOO's 1,228 1,671 2,076 2,375 2,669 2,778 2,992 3,462 3,763 3,866 4,139 4,278 4,406 4,389 4,670 5,215
Domiciliary
Total OOO's 2,334 3,322 4,168 4,721 5,183 5,381 5,766 6,441 6,839 6,996 7,363 7,389 7,426 7,248 7,494 8,187
Average No. of services per enrolled person 5.0 6.2 7.2 7.6 7.9 8.0 8.3 9.0 9.4 9.4 9.3 9.0 8.9 8.6 8.4 8.0
l ~
1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
640 668 684 697 720 740 766 810 831 844 849 1,006 1,043
'/ Table IS
Pensioner Medical Service Number enrolled, number of services received and average attendances per enrolled person per annum-by States-1966-67 No. of pensioners and dependants enrolled at 30 June 1967 OOO's 404 260 168 100 77 34 1,043
No. Surgery OOO's
of services received Domiciliary ODD's 1,154 877 348 339 181 73 2,972
Siale
Total ooo's 3,267 2,109 1,197 789 597 228 8,187
Average No. of services per enrolled person 8.3 8.3 7.2 8.2 7.9 6.9 8.0
New South Wales Victoria . .
Queensland South Austral ia Western Australia Tasmania . . Commonwealth
2,113 1,232 849 450 416 155 5,215
Apparent minor errors in totals are due to "rounding off",
97
Table 16
Pensioner Medical Service Number of participating doctors. payments received and average annual payment per doctor-I 95 I-52 to 1966-67 Year ended 30 June
~
No. of participating doctors at 30 June 3,502 3,898 4,239 4,567 4,730 4,990 5,243 5,531 5,685 5,861 6,012 6,025 5,899 5,896 6,034 6,175
Payments to doctors
Average receipts
per annum 620 928 1,024 1,132 1,236 1,234 1,250 1,376 1,466 1,456 1,476 1,520 1,598 1.578 2,246 2,360
$'000 1952 .. 1953 .. 1954 .. 1955 .. 1956. 1957 .. 1958 .. 1959. 1960 .. 1961. . 1962 .. 1963 .. 1964 .. 1965. 1966 .. 1967 .. 2,070 3,480 4,231 5,032 5,749 5,998 6,398 7,613 8,225 8,401 8,796 9,146 9,531 9,320 13,365 14,351
I
1-
Table 17
Pensioner Medical Service Number of participating doctors. payments received and average annual payment per doctor-by States-I 966-67 No. of participating State doctors at 30 June 1967 2,384 1,733 819 590 461 188 6,175
"
Payments to doctors $'000 5,708 3,746 2,064 1,407 1,020 406 14,351
Average receipts per annum
New South Wales Victoria
I 2,404 2,211 2,577 2,439 2,261 2,197 ---
Queensland South Australia
Western Australia Tasmania .. Commonwealth . . Apparent minor errors in totals are due to "rounding off".
2,360
Table 18
Pharmaceutical Benefits
, Cost of prescriptions-I 960-61 to 1966-67 Payments by Commonwealth Patient
Year ended 30 June ---'
Excluding pensioners $'000 34,282 44,632 47,093 46,461 48,930 53,078 56,656
contribution
Pensioners $'000 14,677 18,195 19,831 20,602 21,564 24,071 29,280
Total 8'000 48,959 62,827 66,924 67,063 70,494 77,149 85,936
Total cost 3'000 59,284 75,835 91,666 82,637 87,336 94,630 104,283
8'000 10,325 13,008 14,742 15,574 16,841 17,481 18,347
1961 1962 1963 1964 1965 1966 1967
.... -
..
Apparent minor errors in totals are due to "rounding off".
98
Table 19
Pharmaceutical Benefits Cost of prescriptions-by States-I 966--67 Payments by Commonwealth Stote Excluding
Patient
Total
pensioners New South Wales Victoria ..
Pensioners $'000 12,305 6,933 4,546 2,705 1,989 802 29,280
contribution
Total
cost $'000 42,226 28,060 14,945 9,499 6,736 2,817 104,283
Queensland South Australia Western Australia Tasmania. Commonwealth
$'000 22,580 16,040 7,765 5,135 3,610 1,526 56,656
$'000 34,885 22,973 12,311 7,840 5,599 2,328 85,936
$'000 7,341 5,087 2,634 1,659 1,137 489 18,347
Table 20
Pharmaceutical Benefits Dissection of benefit prescription costs into ingredient cost and chemists' remuneration-1960-61 to 1966-67
;
Cost Year ended 30 june 1961 .. 1962 .. 1963 .. 1964 .. 1965 .. 1966 .. 1967 ..
and containers $'000 35,629 46,714 49,113 49,398 52,139 57,293 63,676
of ingredients
Chemists' remuneration
Total
cost $'000 59,284 75,835 81,666 82,637 87,336 94,630 104,284
$'000 23,655 29,121 32,553 33,239 35,197 37,337 40,608
Table 21
Pharmaceutical Benefits Dissection of benefit prescription costs into ingredient cost and chemists' remuneration-by States-1966-67 State Cost of ingredients and containers Chemists' remuneration Totol
cost $'000 42,227 28,060 14,945 9,499 6,736 2,817 104,284
New South Wales Victoria
Queensland South Australia Western Australia
Tasmania Commonwealth . .
$'000 25,776 17,243 9,000 5,803 4,124 1,730 63,676
$'000 16,451 10,817 5,945 3,696 2,612 1,087 40,608
Cost of ingredients and containers includes payments to chemists for wastages on broken quantities of ready-prepared items. Chemists' remuneration includes mark up on wholesale price and professional fees, but does not include discount allowed
to chemists by wholesalers and manufacturers.
99
Table 22
Pharmaceutical Benefits Number of prescriptions and average cost per prescription-1960-61 to 1966-67 No. of benefit prescriptions Average ('ost per benefit prescription*
Year ended 30 June
Popufat;on
Total population OOO's 31,217 37,714 42,192 44,357 47,556 49,993 53.687
excluding pensioners OOO's 20,489 26,050 29,518 31.040 33,715 35,085 36.751
Pensioner
population OOO's 10,728 11,664 12,674 13,317 13,841 14.908 16,936
Total population I 1.90 2.01 1.93 1.86 1.83 1.89 1.94
Population excluding pensioners $ 2.18 2.22 2.09 2.00 1.95 2.01 2.04
Pensioner
population $ 1.37 1.56 1.57 1.55 1.56 1.61 1.73
1961. 1962 .. 1963 .. 1964 .. 1965 .. 1966 .. 1967 ..
* Includes
patient contribut\on where applicable,
Table 23
Pharmaceutical Benefits Number of prescriptions and average cost per prescription-by States-I 966-67 No. of benefit prescriptions Stat. Population Total population OOO's 21,773 14,136 8.070 4.850 3.438 1,420 53,687 excluding
Average cost per benefit prescription* Population
pensioners OOO's 14.657 10,202 5,291 3,322 2,301 978 36,751
Pensioner population ODD's 7,116 3,934 2,779 1.528 1.137 442 16,936
Total population $ 1.94 1.99 1.85 1.96 1.96 1.98 1.94
excluding pensioners
Pensioner population I 1.73 1.76 1.64 1.77 1.75 1.81 1.73
,
I 2.04 2.07 1.97 2.05 2.06 2.06 2.04
New South Wales Victoria
Queensland South Australia Western Australia Tasmania .. Commonwealth . .
* Indudes
patient contribution where applicable.
Table 24
Pharmaceutical Benefits Number of prescriptions per head of population and average cost per head of population-1960-61 to 1966-67 Number of prescriptions per head of population Average cost per head of population* Total population Population excluding pensioners Pensioner population 19.86 23.08 23.95 24.38 25.88 26.45 28.68
Year ended 30 June Total Population 1961 .. 1962 .. 1963 .. 1964 .. 1965 .. 1966 .. 1967 .. 3.00 3.56 3.90 4.02 4.23 4.36 4.61
Population excluding penSioners 2.13 2.65 2.95 3.05 3.24 3.32 3.46
Pensioner population 14.25 14.80 15.45 15.91 16.35 16.38 16.59
S 5.70 7.20 7.48 7.51 7.93 8.25 8.95
S 4.62
S
5.92 6.12 6.10 6.47 6.68 7.06
* Includes
patient contribution where applicable.
100
Table 25
Pharmaceutical Benefits Number of prescriptions per head of population and average cost per head of population-by States-I 966-67 Number of prescriptions per head of population State Total Population Population exduding Pensioner
Average cost pe, head of population' Total population 9.67 8.64 8.92 8.34 7.92 7.54 8.95 $ Population excluding
Pensioner
Pensioners 3.69 3.41 3.51 3.19 2.97 2.87 3.46
Population 18.02 15.43 16.72 15.81 15.04 13.49 16.59
pensioners $
population $
New South Wales Victoria
Queensland South Australia Western Australia
Tasmania
..
4.99 4.35 4.82 4.26 4.04 3.80 4.61
7.53 7.06 6.89 6.52 6.13 5.91 7.06
31.17 27.19 27.34 27.98 26.31 24.49 28.68
Commonwealth . .
... Includes patient contribution where applicable.
Table 26
Pharmaceutical Benefits Payments to hospitals and miscellaneous services-1966-67 Hospitals -~----------- ..---
N.S.W. $'000 5,233
Vic.
Qld $'000 2,041
S.A.
W.A. $'000 1,100
Tas.
Miscellaneous se,vices' $'000 322 $'000 187 18 117
Cwealth $'000 15,344
$'000 5,000
$'000 1,110
$'000 538
'" Miscellaneous services expenditure consisted ofBiological products and prophylactic materials Commonwealth Medical Officers and Immigration Medical Service Miscellaneous (including bush nursing and testing expenses) ..
322
Table 27
Pharmaceutical Benefits Drugs dispensed by chemists-I 966-67 (Benefits dispensed in hospitals are excluded)
Therapeutic category
Percentage Percentage of total of total expenditure prescriptions 13.3 9.1 8.9 6.6 7.1 8.4
Therapeutic category
Percentage Percentage of total of total expenditure prescrjptions 5.0 2.2 1.8 1.3 sup0.9 35.4 2.2 39.6
..
Broad Spectrum Antibiotics .. Penicillins Blood Vessels-drugs acting on Hypnotics . Diuretics-non-mercurial Analgesics ..
%
.
8.5 7.9 5.3 12.7 4.1 8.0
%
Anti-Histamines . . Tranquillisers Antacids Sulphonamides .. Ex pectorants and cough pressants Other drugs
%
5.5 1.5 2.9 1.8
%
101
Table 28
Pharmaceutical Benefits "
Number of Pharmaceutical Chemists and Medical Practitioners dispensing pharmaceutical benefits prescriptions-I 949-50 to 1966--67 A. Pharmaceutical Chemists approved under Section 90 of the National Health Act 1953-1967 for the purpose of supplying pharmaceutical benefits. B. Medical Practitioners approved under Section 92 of the National Health Act 1953-1967 for the purpose of supplying pharmaceutical benefits in areas in which there are no other pharmaceutical services available.
As at 30 June 1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967
New South Wales A 1,200 1,252 1,323 1,368 1,452 1,519 1,574 1,615 1,681 1,763 1,818 1,877 1,933 2,008 2,065 2,101 2,140 2,204
Victoria A 1,038 1,054 1,070 1,102 1,170 1,206 1,245 1,284 1,299 1,348 1,383 1,402 1,414 1,445 1,482 1,520 1,545 1,583
Queensland
South Australia A 265 292 305 329 368 384 396 403 424 433 436 449 459 470 474 487 507 520
Western Australia A 202 208 212 221 232 243 261 270 282 292 296 311 312 325 338 354 363 370
Tasmania
Commonwealth A 3,080 3,231 3,353 3,502 3,754 3,923 4,093 4,227 4,368 4.552 4,696 4,838 4,941 5,100 5,243 5,375 5,501 5,638
8 2 25 26 29 31 32 31 27 28 30 29 34 36 32 31 32 33 34
8 6 6 7 8 8 5 6 7 7 6 6 6 6 6 7 7 6 5
A 285 332 348 388 437 476 520 554 571 603 645 676 696 721 750 775 805 818
8 3 4 5 5 6 7 8 8 8 9 9 7 6 7 6 5 6 4
8 27 30 29 24 25 20 20 19 18 16 17 14 13 14 12 10 9 9
B 12 12 12 10 II 12 II 12 12 II 10 7 6 7 8 8 5 5
A 90 93 95 94 95 95 97 101 III 113 118 123 127 131 134 138 I'll 143
8 7 8 10 II 12 II II II 12 12 12 II 10 12 12 12 13
B 50 84 87
86 92 88 87 84 84 84 83 80 78 76 76 74 71 70
~
,
Table 29
Tuberculosis Number of allowances, notifications and mortality-I 952 to 1966 No.
Year ended 31 December
Allowances Current 6,127 5,696 5,742 5,029 4,182 3,326 2,750 2,503 2,235 2,017 1,845 1,796 1,573 1,378 1,177
of
Notircations Incidence
Deaths per 100,000 all forms 54.8 55.9 54.5 49,4 46,4 41.4 37.2 35.2 39.2 34.0 35.3 35.2 30.6 25.3 21.8
No. pulmonary 4,761 4,787 4,650 4,360 4,169 3,762 3,632 3,160 3,556 3,239 3,503 3,574 3,113 2,624 2,276
No. all forms 4,786 4,979 4,952 4,602 4,419 4,035 3,708 3,582 4,084 3,570 3,825 3,883 3,446 2,903 2,549
No. pulmonary 1,165 879 823 672 663 543 501 509 447 412
No. all forms 1,290 974 897 729 724 585 538 549 489 447 475
Per 100,000 all forms 14.8 10.9 9.9 7.8 7.6 6.0 5,4 5,4 4.7 4.3 4.4 4.0 3.7 2.6 2.8
1952 .. 1953 .. 1954 .. 1955 .. 1956 .. 1957 .. 1958 .. 1959 .. 1960 .. 1961. . 1962 .. 1963 .. 1964 .. 1965 .. 1966 ..
448 410 388 259 303
440 413 294 321
102
Table 30
Tuberculosis Number of allowances, notifications and mortality-by States-year ended 31 December 1966 Notifications State
,
Deaths Incidence per 100,000 all (arms 21.4 19.9 34.7 11.9 15.8 16.8 6.0 122.4 21.8
No. of Allowances current 381 217 352 123 51 53
No. pulmonary 830 571 552 106 102 50 6 59 2,276
No. all forms 915 649 581 131 134 63 6 70 2,549
No. pulmonary 92 119 39 23 19 9 2 303
No. all (arms 94 127 43 25 19 II 2 321
Per 100,000 all (arms 2.2 3.9 2.6 2.3 2.2 2.9 2.0 2.8
New South Wales .. Victoria
Queensland South Australia Western Australia Tasmania ..
I
Aust. Capital Territory
t •
,
Northern Territory Commonwealth . .
t
*
1,177
t Included
* Included
in New South Wales figure. in South Australian figure.
,
Table 31
Tuberculosis Expenditure under the Tuberculosis Act-I 949-50 to 1966-67
Year ended 30 June
Capital reimbursements to States $'000 472 809 1,290 2,327 2,591 3,422 3,495 4,757 4,257 2,822 1,458 776 756 984 598 703 689 499 32,707
Maintenance reimbursements to States
Allowances paid to sufferers $'000 2,690 3,555 3,816 3,753 3,809 3,380 2,921 2,509 2,125 2,051 1,893 1,746 1,607 1,593 1,458 1,286 1,193 41,385
Total $'000 1,165 5,386 9,074 12,107 13,822 14,832 14,976 17,289 15,905 14,636 12,262 11,142 11,302 12,523 12,861 12,497 15,552 12,930 220,260
$'000 692 1,887 4,229 5,965 7,478 7,601 8,101 9,610 9,138 9,688 8,753 8,473 8,800 9,932 10,669 10,337 13,577 11,238 146,168
~
1950 1951 1952 1953 1954 1955 1956 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 1967 ,
Total
Apparent minor errors in totals are due to "rounding off".
103
Table 32
Tuberculosis Expenditure under the Tuberculosis Act-by States-I 966-67 State Capital ,fOOD 356 110 28 5
Maintenance
Allowances
Total $'000 4,742 3,747 2,564 831 641 404 12,930
$'000 4,012 3,374 2,196 708 589 360 11,238
$'000 374' 263 340 119t 53 44
New South Wales Victoria . .
Queensl.nd South Australia
Western Australia Tasmania . . Commonwealth
499 Capital Territory.
1,193
Apparent minor errors in totals are due to "rounding off".
t
* Includes the Australian
Indudes the Northern Territory.
Table 33
Tuberculosis Results of mass X-ray surveys-by States-year ended 31 December 1966 No. No.
Rate per 1,000
No.
State
Rate per 1,000
examined
active
T.B. New South Wales Victoria
inactive T.B. 4,203 2,363 1,298 851 41 30 191 8,977
Suspect active T.B. at 31.12.66 54 336 n.a. 26 2 27
Rate per 1,000
) .
Queensland South Australia Western Australia Tasmania Australian Capital Territory Northern Territory . . Commonwealth .. n.a.-Not available. • Excludes Queensland.
742,104 662,576 304,128 82,345 57.291 95,580 3,528 1,947.552
164 204 96 10 13 20 27 534
0.22 0.31 0.31 0.12 0.23 0.21 7.65 0.27
5.66 3.57 4.27 10.33 0.72 0.31 54.14 4.61
0.07 0.51 n.a. 0.32 0.03 0.28 2.55 0.23'
9 454'
104
,
Table 34
Public Health Notifiable diseases in the States of Australia-I 966-67t Disease N.S.W. Vic.
Qld 79 6 6 16
S.A. 5
W.A.
Tos.
AC.T.
N.T.
Aust.
Acute Encephalitis ... Acute Rheumatism Amoebiasis
Ancylostomiasis Anthrax .. Bilharziasis Breast Abscess Brucellosis . .
* * * * 17
26
I 5 oi'
*
26
2 266
138 8 278 33 65 4 1,517 10 " 589 14 83 48 10,139 v 2 43 91· 10 125 166 7 16 4 9 25 257 2,147 271 1,096 41 34 2,630 19 5
Chorea (St Vitus Dance) .. Dengue
* 394 5
16 38 4 803 4
8 III 212 17 6 1,234 2 3 80 49 116 3 II 134 5 12
* * I 123
* 16
* 122 12 23
,
Diarrhoea. Infantile Diphtheria .. Dysentery, Bacillary Erythema Nodosum Encephalitis
*
* *
* * *
* 28
80 9 24 12 2,638 I 2 10 25 28 4 I 4 3
5
* * * * 5
Filariasis Homologous S. Jaundice .. Hydatid Infective Hepatitis Lead Poisoning
13 4,417
*
1,232
I 92 16 2
14 275
* 141
2 110 23 15 4
Leprosy Leptospi rosis Leukaemia . .
*
* 6 6
Malaria Meningococcal Infection
27
* * * * 3 I
* *
* 7 14
2 5
*
* * * *
".
/ Neonatal Infection* Ophthalmia .. Ornithosis . .
* *
*
* * I 2
2
*
Paratyphoid Puerperal Fever Q. Fever Rubella Salmonella Infection Scarlet Fever Tetanus Trachoma Trichinosis . .
6
* * * * * *
1,464 638 13 I
I 16 251 185 134 13 557
2 2
* * * * * 3 2 I 7
* *
* * * 3 3
10
269 117 67 2 I 134 I
*
115 37 2 225
* * * 2
222 206
*
5 38 7 I 32 83
*
Tuberculosis Typhoid Fever Typhus (flea, mite or tick borne)
851 5
710
63
7
7
*
t The
* Not
notifiable. No caSes. figures shown in this table are the number of cases notified by individual medical practitioners to State Health Departments.
In Victoria notified as acute infection in the newborn, and in Queensland as Neonatal Infections.
Details of the one case of poliomyelitis confirmed are given on page 105. No case of cholera, plague, smallpox, epidemic typhus or yellow fever.
Table 35
Public Health Poliomyelitis-number of confirmed cases-by States-1957-58 to 1966~7 N.T.
Year ended 30 June 1958 .. 1959 .. 1960 .. 196\. . 1962 .. 1963 .. 1964 .. 1965 .. 1966 .. 1967 ..
N.S.W.
Vic. 3 78 10 80 21
Qld 3 3 4 19 157
S.A 5 I 7 22 19 17 2
W.A 2 I 6 6 2 2
Tos.
AC. T.
Cwlth 37 102 60 178 572 35 25 4 2 1
.
21 18 17 8 367 5 2 4
3 I 2 46
II 19
14 3 2
105
Table 36
Public Health
Infectious Hepatitis-cases notified-by States-I 961 to 1966 State New South Wales Victoria
"
1961 6,025 3,515 1,022 1,406 262 304 281 61 12,876
1962 3,358 3,533 885 504 117 630 88 100 9,215
1963 2,822 3,840 1,433 293 145 856 20 104 9,513
1964 2,667 2,705 1,148 277 101 638 12 57 7,605
1965 3,299 1,988 511 413 86 199 51 128 6,675
1966* 4,417 2,638 1,234 1,232 92 275 141 110 10,139
Queensland South Australia
Western Australia Tasmania Australian Capital Territory
Northern Territory Commonwealth
* Figures in
this column are subject to confirmation.
Table 37
Public Health
Radio and television scripts on medical matters examined-196b-67 Type of script Radio Television
Approved Number examined 1,448 308 1,756
Approved as amended Number 461 118 579
Rejected Number 47 17
Number 940 173 1,111
Per cent 65.0 56.2
Per cent 31.8 38.3 33.0
Per cent 3.2 5.5 3.6
'.
Total
63.4
64
Table 38
Quarantine
Vessels boarded and deared--by States-1966-67 Surface State Vessels New South Wales Victoria
Air Passengers
Crew 64,048 29,887 46,912 17,123 74,160 5,437 3,266 240,833
Vessels 2,031 20 372 3 613 879 3,918
Crew 22,164 145 3,596 31 6,242 7,138 39,316
Passengers 145,076 168 15,653 189 42,322 59,553 262,961
Queensland South Australia Western Australia Tasmania " Northern Territory Commonwealth
1,136 411 923 338 1,014 121 97 4,040
44,579 42,352 14,256 4,895 130,636 1,818 110 238,646
106
Table 39
Quarantine
Infectious diseases on overseas vessels arriving in Australia-1966-67 Diseose Chickenpox Dysentery .. Infectious Hepatitis
No.
of coses 174 I 5 320
Disease Scarlet Fever Tuberculosis Venereal Disease
No. of cases 2 I 158 695
Measles Mumps Rubella
32 2
Total
Table 40
Quarantine
Animal importations subject to quarantine-I 966 to 1967 Type Horses--from United Kingdom from New Zealand Dogs and cats-from United Kingdom from New Zealand
Number 141 631 738 460 ..
..
Small laboratory animals for scientific institutions
680 30 117 2,797
Monkeys from Malaysia and U.S.A. for Commonwealth Serum Laboratories Animals for permanent quarantine in registered zoological gardens and circuses ..
Total ..
Table 41
Northern Territory Health
Aerial Medical Service-1966-67 Darwin Emergency flights Routine flights Hours flown .. Miles flown .. Patients carried Patients carried by charter and commercial services Radio medical consultations
Alice Springs 176 614 85,730 280 276 2,821
191
222 1,509 208,600 788 1,699 1,740
107
Table 42
Northern Territory Health Health services provided at main Northern Territory hospitals-1966-67 Darwin
Alice Springs 34,959 2,815 95.7 261 81 68 210 770 28,620
Tennant Creek 5,093 881 14.0 53 19 26 283 12,412
Katherine 13,151 1,238 36.0 126 27 31 32 250 10,431
Batchelor
Total No. of daily occupied beds Total No. of admissions Average daily No. of patients Total No. of births ..
Total No. of deaths in hospital Total No. of major operations
..
88,421 7,161 242.3 851 106
Total No. of post mortem examinations .. Total No. of minor operations Total No. of outpatients treated
84 645 2,168 70,681
1,508* { 4,732t
DispensariesPrescriptions dispensed .. Average No. of prescriptions dispensed per working day
X-ray Department-t No. of exposu res
Ambulance ServicesNo. of trips No. of patients carried No. of miles travelled
Physiotherapy Department-t No. of patients .. No. of treatments ..
1,322 6,314
634 3,874
:f: Inpatients
t
* Doctor's clinic. Daily clinic. and outpatients.
Table 43
Northern Territory Health Dental services provided in the Northern Territory-I 966-67 Darwin
Dental Clinic -----------_. Examinations Extractions .. Porcelain restoration
Aerial Mobile (operating Darwin)
from
Overland Mobile (operating from Darwin) 1,996 515 175 1,241 22 7 4 27 90 I 12 36 2 17 2 595
Darwin
Schools
Alice Springs (including Mobiles and Schools) 1,864 1,946 280 3,006 64 28 4 282 767 31 18 103 119 34 8 1,583 97 79 331 91
Nightclif( Clinic
Amalgam restoration
Inlays Crowns
Bridges Dressings X-rays G.A.'s hospital Root treatment
Scale and clean Infective Gingivitis
Orthodontist Oral su rge ry Jaw fracture Other treatment
Dentures-Full Partial Repair .. Remodel
5,350 3,196 398 2,349 105 50 9 1.393 589 59 23 44 10 848 64 17 2.262 276 104 562 55
821 454 227
618 75 144 712
790 I, 167
2
21 85
326 1,897 21 6 5 357 153 I 21 45 6 14 I 1,007 61 58 81 22
15
80
48 28 41 8
108
Table 44
Australian Capital Territory Health Licences issued under the Public Health Ordinance-1966
Barber shops Eating houses Boarding houses
Ice cream vendors
61 73 63 13
Meat vendors .. Milk distributors
Milk vendors Prepared meat vendors
54 71 169 212
Table 4S
Australian Capital Territory Health Samples collected by Health Inspection Section-1966-67 For bacteriological examination For chemical
examination
Milk Cream Ice cream
1,266 89
471 97 5
2 9
Meat Other foods Water-City supply Swimming pools Picnic resorts and other supplies Sewerage ..
12 1,397 38 88 199 2
Lake Burley Griffin and Molongo River
30 795 135 175 18 632
5
Table 46
Australian Capital Territory Health School medical service examinations-1966-67 School
Pre-School
No, of children examined Defects notifiedEye Ear, nose and throat Hearing loss ..
6,832
183 5 I 5 5 3 2
Speech Cardiac abnormality
Hernia ..
Orthopaedic .. Miscellaneous ..
326 71 210 107 26 8 54 180
Table 47
Australian Capital Territory Health Registrations granted-1966-67 Type Number 41 5 192 43 Pharmacists ..
Type Optometrists Veterinary Surgeons
Number 15
Medical Practitioners Dental Practitioners
Nurses Nursing Aides
3
109
Table 48
National Fitness Allocation of annual grant to State National Fitness Councils-I 966--67 Item
N.S.W. $
Vic.
Qld
SA $
WA $
Tos. I 9,124 9,/24 1,564
Cwlth
Wages, salaries. allowances. overtime and services not otherwise provided for .. Services to associated groups, including leader training
S 10,646 12,/78
S 9,124 9,124
$
10,646 12,/78
9,124 9,/24
9,124 9,/24
57,788 60,852 15,672 23,458 6,286 60,852 224,908
Grants to voluntary youth organisations .. Subsidies to local national fitness committees Services to sports organisations Development of camps and hostels
3,034 4,572 1,476
3,034 4,572 1,476 12,178 44,084
2,680 3,986 908 9,124 34,946
2,680 3,986 908 9,124 34,946
2,680 3,986 908 9,/24
12,178 44,084
2,356 610 9,124 31,902
Total
34,946
,
Table 49
National Fitness Allocation of annual grants to State Education Departments-1966--67 Item
N.S.W. $
Vic. $ 1,000
Qld
S.A. $
W.A. $
Tos.
Cwlth
Training of gener.1 teachers in physical education(a) Short courses (b) Residenti.1 courses Provision of bursaries to enable selected teachers to undertake university courses Development of health and physical education in practising schools and teachers colleges<a) Equipment .. .. .. .. (b) Camps for teachers college students Publications, films, records, etc. Development of school camping and hostelling-(0) Equipment of camps and schools .. (b) School camping and hostelling
$
S 600 1,000 1,200
S 4,800 6,000 3,600
..
1,000 1,000
1,000
1,000 1,000
600 1,000
600 1,000
1,200
1.200
600 500 968 1,000
600 500 968 1,000 600 5,668
600 500 966 1,000 600 5,666
400 300 966 800 400 5,666
400 300 966 800 400 5,666
400 300 966 800 400 5,666
3,000 2.400 5,800
5,400 3,000 34,000
600 5,668
Total
110
Table 50
Commonwealth Medical Offi Number
cers by Commonwealth Medical Officers Seamen 1,226 205 145 89 241 2 4 1,912 Pensioners
1966-67 of clinical examinations
by States
State New South Wales Queensland South Australia Victoria
Departments 28,197 14,751 6,212 4,478 2,814 1,337 5,654 1,441 64,884
Others 8 16
Total 35,579 18,714 8,559 6.897 4.686 1.809 7,409 1,852 85,505
Western Australia Tasmania Australian Capital Territory Northern Territory . .
6,148 3,742 2,202 2,330 1,631 369 91 59 16,572
101 1,664 348 2,137
Commonwealth .. ~
Table 51
Commonwealth Medical Officers Number of vaccinations by Commonwealth Medical Officers-by States-1966-67 Yellow State Smallpox 25.830 2.607 4.694 3.231 2.591 1.590 2.776 2.531 45.850 Fever
Cholera 32.009 3,715 5.457 2.546 2,979 2,067 4.708 2,536 56.017
T.A.B. 992 1.286 316 12 215 509 4,312 838 8.480
Tetanu~
Plague 72 5 2 2 2 5 91 6 185
Total 60,333 8,434 10.758 6,002 6.223 4.2IT 12.079 6,668 114.IT4
New South Wales Victoria
Queensland South Australia Western Australia
Tasmania Australian Capital Territory Northern Territory ..
1.069 622 184 211 176 34 69
361 199 105 260 72 123 733 1,853
24 2,389
Commonwealth ..
Table 52
Commonwealth Health Laboratories Number of pathological examinations and laboratory tests performed and number of patients-I 966--67 Health laboratory
Examinations and tests* 118,688 43.124 163.767 378.161 567.116 172.327 169.689 45,761 66.982 264.218 70.010 409.398 225.267 257.596 386.738 3,338.842
No.
of patients 20.824 8,780 26,131 52,294 112,435 40,265 18,526 9,352 13.527 36,268 14.235 60.904 34.604 39.574 57,309
j
Albury Alice Springs Bendigo Cairns Canberra Darwin
..
Hobart Kalgoorlie .. launceston lismore Port Pirie ..
,
Rockhampton Tamworth Toowoomba Townsville . .
Total ..
545,028
* N uffield 111
points score.
Table 53
National Biological Standards Laboratory Summary of all samples examined-1966-67 Type
No. examined I, III
Percentage
of
Foi}ures 265
foilures -----23.9 22.6 24.4
%
Therapeutic Substances Act--Official samples
National
Health
Scheme-Pharmaceutical
benefits 380 287 13 1,791 421
samples "
86 70
Other Departments and authorities
Item 28A-Customs (Prohibited Imports) Regulations and miscellaneous samples
Total
23.5
Table 54
National Biological Standards Laboratory Safety tests performed-1966-67 Type
No. examined 553 120 64 163 148
Passed
Failed 18 I
Suspected foiluresnot confirmed 7 3
SterilityStandard test technique Millipore technique .. Histamine-like substances Toxicity Pyrogens ..
528 119 64 160 148
Table 55
Commonwealth Acoustic Laboratories Cases examined-I 966-67
New cases attending laboratories Repatriation ..
N.S.W.
Vic. 695 1.128 137 31 12 210 51 128 2.392 755
Qld 532 1.603 I 102 6 I
S.A. 438 874 74 30 40 21 103 1.580 259
W.A.
Tos. 80 488 I I
Cwlth
Children Social Services Army .. R.A.A.F. Navy .. Directors of Health .. Commonwealth compensation State compensation . . Miscellaneous . .
2.354 2.135 4 246 9 55 114 64 76 5.057 577
262 594 2 I 42 1/
142 4
8 23 139 304 2.719 207
15 9 96 1.032 129
65 781 15
4.361 6.822 8 561 260 79 391 168 139 772 13.561 1.942
-
1
Total Civil Aviation referrals
112
Table 56
Commonwealth Acoustic Laboratories Calaid hearing aids fitted-I 966-67
I.
Calaids fitted ------_.
N.S.W. 759 325 29 6
Vic. 737 280 58 22 2
Qld 425 173 41 10
S.A. 297 114 12 I
W.A. 220 57 9 8
Tas. 136 21 II
Cwlth 2,574 970 160 47 I 4 I I 15
Repatriation
.Children Health Adolescents Social Services Army .. R.A.A.F. Navy Commonwealth compensation
I 2 1,122
9 1,108 650
4 428 295 170
Total
3,n3
I. ,.
Table 57
Commonwealth Acoustic Laboratories Calaid hearing aids maintained-1966-67 Ca/aids Maintained N.S.W. 4,647 1,161 1.969 II 27 3 3 13 -------Vic.
Qld 1,853 527 901 2 7 2
S.A. 1,687 354 828 I 7 3 4
W.A. 1.447 249 445 4 2
Tas. 507 88 239 5 I
Cwlth 14,713 3,035 6,271 35 58 15 5 27 24,159
, / Repatriation .. Health Children Social Services
Army .. R.A.A.F. Navy Commonwealth compensation
4,572 656 1,889 12 14 7 2 9 7,161
Total
7,834
3,292
2,884
2,148
840
Table 58
Commonwealth X-ray and Radium Laboratory Expenditure under the National Welfare Fund on RadiO-isotopes for medical purposes1955-56 to 1966-67
r, 1956
Year ended 30 June
Expenditure $ 6,172
Year ended 30 June 1962 1963 1964 1965 1966 1967
Expenditure
$ 28,988 35,936 55,874 67,942 81,755 132,201
1957 1958 1959 1960 1961
13,900 15,954 21,382 19,368 27,736
113
Table 59
National Health and Medical Research Council Grants made from the Medical Research Endowment Fund-1966--67* Maintenance
Universities, institutions and hospitals
Research workers $
Scholarships
Technical
and
Total
assistance $ 14,140 9,880 8,340 2,336 3,820 3,300 990 $ 26.050 72,115 20.400 15,900 12,638 28,042 35,341 7,000 89,965 3,915
equipment $
$ 86.320 8.500 212,559 62,590 34,603 52,718 103,830 2,000 56,620 85,800 225.095
Universities University of Adelaide Flinders University University of Melbourne
22.810 91,828 22.350 16.367 14,760 52,724 11,079 68,910 1\8,250 1,750 16.367 420,828
Monash University University of New South Wales University of Queensland
23,320 8.500 38,736 11,500 21,500 19,764 2,000 9.210 9,890 7,900
University of Sydney
..
University of Tasmania .. University of Western Australia
Institutions and hospitals New South Wales Victoria . .
8.980
Queensland South Australia
7,700 4,881 22,500 74,286 311,366 164,901
9,450 8,796 22,500 971,381
Travelling Fellowships Total
..
• The above figures are not Strictly comparable with those in Table 59 in the 1965-66 Annual Report as the method of allocation of grants has been revised.
,
Table 60
Commonwealth Grants Red Cross Blood Transfusion Service-J953-54 to 1966--67
Year ended 30 June 1954 1955 1956 1957 1958 1959 1960
Commonwealth grant $'000 88 138 172 214 251 263 282 1961 1962 1963 1964 1965 1966 1967*
Commonwealth
Year ended 30 June
grant
$'000 315 349 369 402 435 490 974
• The figure for this year reflects an alteration in accounting procedures during 1966--67, when annual payments were replaced by quarterly payments. The grant relates to expenditure incurred by the Society during the period I July 1965 to 31 March 1967.
Table 61
Commonwealth Grants Red Cross Blood Transfusion SerVice-by States-I 966--67 *Payments State
1966-67 $'000 231 276 215 123 92
*Payments
State Tasmania Australian Capital Territory Northern Territory ..
1966-<'7 $'000 24 II 2
New South Wales Victoria
Queensland .. South Australia Western Australia
Commonwealth ..
974
* These
payments relate to expenditure incurred by the Society during the period I July 1965 to 31 March 1967.
114
Table 62
Commonwealth Grants Home Nursing Subsidy Scheme-I 956-57 to 1966-67
Year ended 30 June
Annual subsidy $'000 4
Year ended 30 June
Annual subsidy $'000
1957 1958 1959 1960 -1961 1962
36 69 107 156 215
1963 1964 1965 1966 1967
289 372
465 546 664
Table 63
Commonwealth Grants Home Nursing Subsidy Scheme-by States-I 966-67 State Payments 1966-67 $'000
State Western Australia Tasmania Commonwealth . .
Payments 1966-67 $'000
New South Wales Victoria
Queensland .. South Australia
175 237 86 29
128 10 664
The apparent minor error in the total is due to "rounding off",
,/ Table 64
Commonwealth Grants Free Milk for School Children--1950-5 I to 1966-67 Year ended 30 June Commonwealth Gront $'000 72
Year ended 30 June
Commonwealth Gran! $'000
1951 1952 1953 1954 1955 1956 1957 1958 1959
1,630 3,043 3,999 4,475 4,811 5,214 5,511 6,137
1960 1961 1962 1963 1964 1965 1966 1967
6,719 7,120 7,483 7,454 7,775 8,059 8,493 9,021
Table 65
Commonwealth Grants Free Milk for School Children-by States-I 966-67 No. State As at 30 June 1967
of children' 000'5
Payments 1966-67 $'000
_ _ _ _ _ _ _ _ _ _0
_ _ __
New South Wales Victoria Queensland .. South Australia Western Australia Tasmania Australian Capital Territory Northern Territory .. Commonwealth ..
620 475 260 191 137 63 17 II
3,067 2,391 1,396 857 698 442
93 77
1,774
9,021
'These figures represent the approximate number of school children eligible to participate in the Free Milk Scheme.
115
Table 66
Commonwealth Grants Mental health institutions-by States-1955-56 to 1966-67 N.S.W.
Vic. $'000 892 1,783 2,674 1,054 2,109 3,163 1,091 2,181 3,272 1,239 2,478 3,718 1,036 2,073 3,109 168 335 503
Qld
S.A.
W.A.
Tas.
Cwlth
.~~---~~------"-----~-~'-
$'000 1955-56 Commonwealth grant
$'000 133 266 400 176 352 528 228 456 685 237 474 711 149 298
$'000 24 49 73 257 514 771 304 609 913 245 489 734 184 367 551 91 183 274 56 III 167 104 208 313 173 345 518 265 530 794 242 484 726 193 385
$'000 20 40 60 104 207 311 58 117 175
$'000 59 119 179 138 276 414 183 366 548 92 184 275 134 268 402 104 208 312
$'000 1,546 3,093 4,639 2,496 4,993 7,489 2,513 5,026 7,538 2,241 4,482 6,722 2,295 4,590 6,885 1,454 2,909 4,363 1,648 3,297 4,945 1,590 3,181 4,771 1,595 3,189 4,784
Net State expenditure Total expenditure ..
418 835 1,253 767 1,534 2,301 648 1,297 1,945 394 787 1,181 718 1,436 2,154 866 1,732 2,597 1,297 2,595 3,892 1,295 2,590 3,885 982 1,964 2,947 659 1,319 1,978 1,717 3,434 5,151 2,217 4,434 6,652 11,979 23,957 35,936
1956-57 Commonwealth grant Net State expenditure Total expenditure .. 1957-58 Commonwealth grant Net State expenditure Total expenditure . . 1958-59 Commonwealth grant
34 69 103 74 147 221 31 61
Net State expenditure Total expenditure ..
1959-60 Commonwealth grant
Net State expenditure Total expenditure . . 1960-61 Commonwealth grant Net State expenditure Total expend itu re . .
448 195 391 586 141 283 424 75 150 226 108 216 324
92 154 308 462 116 232 347 332 663 995 447 893 1,340 338 675 1,01l 260 521 781 1,967 3,933 5,900
1961-62
Commonwealth grant Net State expenditure
Total expenditure .. 1962-63 Commonwealth grant
Net State expenditure Total expenditure .. 1963-64 Commonwealth grant
Net State expenditure Total expenditure .. 1964--65 Commonwealth grant Net State expenditure Total expenditure .. 1965-66 Commonwealth grant Net State expenditure Total expenditure .. 1966-67 Commonwealth grant Net State expenditure
711 1,423 2,134 1,567 3,134
225 449 674 146 293 439 288 576
197 394 591 529 1,058 1,586 823 1,646
2,504 5,007 7,511 4,539 9,078 13,617 4,973 9,947
4,700 1,192 2,385 3,577 8,951 17,901 26,852
Total expenditure ..
863 2,103 4,205 6,308
578 2,1l7 4,275 6,412
2,469 2,259 4,518 6,776
14,920 19,395 58,790 88,184
/
~
Total Commonwealth grant
Net State expenditure Total expenditure ..
Apparent minor errors in totals are due to "rounding off".
116
Appendix 2-Publications • SCHOOL OF PUBLIC HEALTH AND TROPICAL MEDICINE Adams, A. 1.-' The Descriptive Epidemiology of Drowning Accidents', (1966), Med. J. Aust., 2, 1257. Adams, A. 1.-' Prospects for the Control of Venereal Disease in New South Wales', (1966), Public Health (N.S.W.), No. 10, 11. , Adams, A. 1.-' Venereal Disease in an Australian Metropolis " (1967), Med. J. Aust., 1, 145. Adams, A. 1.-' Parental Apathy and the Non-immunized Child', (1967), Pediatrics Digest, 9, 45. Atkinson, L., Booth, K., Cooke, R. and Scott, G. C.-' Cancer in the Territory of Papua-New Guinea " East African Med. J. (in press). Atkinson, L. and Scott, G. C.-' Cancer of Nasopharynx in Australia, 1953-62: 2. Some Clinical Features and Results' (in press). Bearup, A. J.-' Ancylostoma brazili.nse', Trap. geogr. Med. (in press). Bearup, A. J. and Howell, M. J.-' The Life Histories of Two Bird Trematodes of the Family Philophthalmidae' Linn. Soc. N.S. W. Proc. (in press). Black, R. H.-' Tropical Illness and Blood Transfusion " (1966), 4th Int. Red C"oss Seminar, Sydney, mimeographed. Black, R. H.-' Pig-bel-Summing Up' (1966), Papua and New Guinea Med. J., 9, 73. Black, R. H.-' God's Gift to the Ham: The XYL', (1967), Amateur Radio. Black, R. H.-' The Health Implications of the Relationships between Australia and Asia', (1967), A/asian. Ann. Med., 16, 1. Black, R. H.-' Malaria in Medical Practice in Australia', Med. J. Aust. (in press). Black, R. H. et al.-' W.H.O. Expert Committee on Malaria-Tbirteenth Report', (1967), Wid., Hlth. Org. techno Rep. Series, No. 357, 1. Black, R. H., Dew, Barbara B., Hennessy, W. B., McMillan, B. and Torpy, D. C.-' Studies on Depot Antimalarials: 1. The Effect of a Single Injection of the Depot Antimalarial CI-501 (" Camolar ") on Relapsing Vivax Malaria Acquired in New Guinea', (1966), Med. J. Aust., 2,588. Black, R. H., Hennessy, W. B., McMillan, B., Dew, Barbara B. and Biggs, J. C.-' Studies on Depot Antimalarials: 2. The Effect of a Single Injection of tbe Depot Antimalarial CI-564 on Relapsing Vivax Malaria Acquired in New Guinea', (1966), Med J. Aust., 2,808. Budd, G. M.-' Skin Temperature, Thermal Comfort, Sweating, Clothing and Activity of Men Sledging in Antarctica', (1966), J. Physiol., 186, 201. Budd, G. M. and Warhaft, N.-' Body Temperature, Shivering, Blood Pressure and Heart Rate During a Standard Cold Stress in Australia and Antarctica " (1966), J. Physiol., 186, 216. Budd, G. M. and Warhaft, N.-' Cardiovascular and Metabolic Responses to Noradrenaline in Man, Before and After Acclimatization to Cold in Antarctica', (1966), J. Physiol., 186,233. Campbell, C. H.-' Tuberculoma of the Liver: An Important Consideration iu the Differential Diagnosis of Primary Carcinoma of the Liver', (1966), Papua and New Guinea Med. J., 9, 152. Campbell, C. H.-' The Death Adder, Acanthopis anta,'cticus: The Effect of the Bite and its Treatment', (1966), Med. J. Aust., 2, 922. Campbell, C. H.-' The Taipan, Oxyuranus soutellatus, and the Effects of its Bite', (1967), Med. J. Aust., 1, 735. Campbell, C, H.-' Antivenene in the Treatment of Australian and Papuan Snake Bite " Med. J. Aust. (in press). Clements, F. W.-' The Geography of Hunger', (1967), Aust. J. Sci., 29, 206. Davidson, Eileen M.-' Haemophiliacs in New South Wales', (1966), Health in New South Wales, 7, 13. Ford, E.-' Three Australian Medical Historians: Leslie Cowlishaw, John Lidgett Cumpston and William Stewart McKay', Med. J. Aust. (in press.) Hansman, D., Murphy, A. M., Wannan, J. S., Woolard, T. J. and Boger, J. R. F.-' Q Fever, Brucellosis and Leptospirosis Among Abattoir Workers in New South Wales', (1966), Med. J. Aust., 2, 20. Hobbs, J. R., Slot, G. M. J., Campbell, C. H., Clein, G. P., Scott, J. T., Crowther, D. and Swan, H. T.-' Six Cases of Gamma-D Myelomatosis', (1966), Lancet, 2, 614. Ilbery, P. L. T.-' Prevention of Radioleukaemia by Lymph Node Shielding', Nature (in press). Ilbery, P. L. T. and Alexander, J. M.-' An Inherited Translocation Trisomy C/E with Partial Trisomy 17', (1966), Austr. Paed .. 2, 180 . Ilbery, P. L. T. and Williams, D.-' Evidence of the Freemartin Condition in Capra hircus " (1967), Cytogenetics, 6, 276. Kariks, J. and McGovern, V. J.-' Heart Disease in the Territory of Papua-New Guinea: A Preliminary Report Based on a Necropsy Study'. (1967), Med. J. Aust., I, 176. Kariks, J. and McGovern, V. J.-' Glomerulonephritis in the Territory of Papua-New Guinea: A Preliminary Report Based on a Necropsy Study', (1967), Med. J. Aust. 1,331. Kerr, C. B.-' X-chromosomal Inactivation: Evidence from X-linked Dern'!atological Ocular and Dental " (1966), Aust. Soc. Med. Res. Proc., 2, 28. ' Kerr, C. B.-' Linkage Relationships between Xg and other X·chromosomal loci', (1966), Aust. Soc. Med. Res. Proc., 2, 34.
•
117
Kerr, C. B.-' Genetical Aspects of Carrier Detection in Haemophilia: Current Studies in Haemophilia', (1966), Bibliothec. Haem., 26, 4. Kerr, C. B.-' The Role of the Medical Adviser in an Association of Haemophiliacs: Current Studies in Haemophilia', (1966), Bibliotkec. Haem., 26, 128. Kerr, C. B.-' Genetics in Medical Practice, 1 " (1967), Med. J. Aust., 1, 778. Kerr, C. B.-' Genetics in Medical Practice, 2', (1967), Med. J. Aust., 1, 828. Kerr, C. B.-' The Detection of Carriers of Haemophilia', (1967), World Federation Haemophilia Proc., Sydney, 29. Kerr, C. B.,-' Genetics and Community Health', (1967), Health, 17, No.1, 8. Kerr, C. B.-' Introduction to Medical Genetics: 1. Molecular and Chromosomal Aspects', POBt- .. Graduate Committee in Medicine University of Sydney Bull. (in press). Kerr. C. B.-' Introduction to Medical Genetics: 2. Mendelian Genetics: Theory and Application " Post-Graduate Committe. in Medicine University of Sydney Bull. (in press). Kerr, C. B.-' Introduction to Medical Genetics: ~. Population Genetics: Environmental andGenetic Interactions', Post-Graduate Committee in Medicine University of Sydney Bull. (in press) . Kerr, C. B.-' Observations on the Management of Haemophilic Arthritis in Australia and Europe " Rehabilitation in Australia (in press). Kerr, C. B.-' X-linked Haematological Traits', XIth Congr. IntM·nat. Soc. Blood Transfusion Proc., Basel, S. Karger, (in press). Kerr, C. B.-' Genetic Counselling in Hereditary Disorders of Blood Coagulation' Modern Treatment, (ed.) O. Ratnoff, New York, Harper and Row (in press). ' Kerr, C. B.-' Studies on X-linked Human Variation', London, Oxford University Press (in press) . Kerr, C. B.-' Inactive X-Chromosome Hypothesis', Ann. hum. Genet. (in press). Kerr, C. B. and Davidson, Eileen M.-' Individual Problems and Social Adaptation of Haemophiliacs in New South Wales', Canberra, Australian National University Press (in press). Kerr, C. B., Merrett, J. D., Wells, R. S. and B.lrl', A.-' Discriminant Function Analysis of Phenotype Variates in Ichthyosis', Am. J. hum. Genet. (in press). Kerr, C. B., Preston, A. E., Barr A. and Biggs, Rosemary-' Further Studies on the Inheritance of Factor VIII', (1966), Brit. J. Haemat., 12,212. Kerr, C. B., Welch, J. P. and Wells, R. S.-' Ancell-Spiegler Cylindromas and Brooke-Fordyce Tricoepitheliomas: Evidence for a Single Mutation', J. med. Genet. (in press). Kerr, C. B., Wells, R. S. and Cooper, K. E.-' Gene Effects in Carriers of Anhidrotic Ectodermal Dysplasia', (1966), J. med. Genet., 3, 169. Lee, D. J.-' The Fly Problem (2)', (1966), Health in New South Wales, 7,5. Lee, D. J. 'The Fly Problem (3)', (1966), Health in New South Wales, 7, 5. McGarrity, K. A. and Scott, G. C.-' A Review of Cancer of the Cervix in New South Wales: Part I', (1967), Med. J. Aust., 1,214. McGovern, V. J. and Kariks, J.-' Liver Disease in the Territory of Papua-New Guinea: A Necropsy Study', (1966), Med. J. Aust., 2,441. McMillan, B.-' Highlands Region Survey of Intestinal Parasites', (1966), Med. J. Aust., 2, 1121. McMillan, B.-' Is Filariasis Endemic in the Northern Territory of Australia? ' Med. J. Aust. (in press) . McMillan, B.-' Observations on Strongyloidiasis in Australia and New Guinea', South Pacific Commission Seminar on Helminthiasis and Eosinophilic Meningitis, Noumea, New Caledonia, 5-16 June 1967, (in press). McMillan, B. and Kelly, A.-' Ovale Malaria in Eastern New Guinea' Trop. geogr. Med. (in press) . Macpherson, R. K.-' Physiological Adaptation, Fitness and Nutrition in the Peoples of the Australian and New Guinea Regions', (1966), The Biology of Human Adaptability, (ed.) Paul T. Baker and J. S. Weiner, Oxford, Clarendon Press, pp. 431-468. Macpherson, R. K.-' Housing and Human Welfare', (1966), Architecture in Australia, 55, 106. Macpherson, R. K. Ofner, F.-' Temperature Regulation in Elderly Men in Bed', (1967), Med. J. Aust., 1, 889. Macpherson, R. K., Ofner, F. and Welch, J. A.-' The Effect of the Prevailing Air Temperature on / Mortality', (1967), Brit. J. prevo and soc. Med., 21, 17. Scott, G. C.-' Leprosy in the International Classification of Diseases ", (1966), Int. J. Leprosy, 34,71. Scott, G. C.-' Assessment of Results of Cancer Control', (1967), Post-Graduate Committee in Medicine University of Sydney BUll. 22, 238. Scott, G. C. and Atkinson, L.-' The Demographic Features of the Chinese P?pulation in. Austra1!a and the Relative Prevalence of Nasopharyngeal Cancer among CaucasIans and Chmese (m press) . Scott, G. C., Wigley, S. C. and Russell, D. A.-: The Karimui :rri~l of BCG: II. Tuberculin Reactions in a Leprosy-Endemic but TuberculOSis-Free PopulatIon, (1966), Int. J. Leprosy, 34. 139. Smee, L.-' A Revision of the Subfamily Leptoconopinae Nor, Diptera: Cera,topogonidae in Australasia', (1966),14,993. . ' Stevenson, A. C. and Kerr, C. B.-' On the Distribution of Frequencies of MutatIOn to Genes Determining Harmful Traits in Man', (1967), Mutation Research, 4, 339. . Wannan, J. S.-' A Survey of Human Sera in Sydney for Antibodies to Mycoplasma pneumomae (Eaton Agent)', (1967), Med. J. Au.t., 1.113.
'1
118
INSTITUTE OF CHILD HEALTH ~
Clements, F. W.-' The Geography of Hunger', (1967), Aust. J. Sci., 29, 206. Clements, F. W. and Robers, Josephine F.-' Diet in Health and Disease' (1967) A. H. & A. W. Reed, Sydney. ' , Katz, J.-' Adolescents and Anti-Social Behaviour " (1967), Med. J. Aust. 1 252. Katz, J.-' Behaviour Disorders in General Practice " (1966), New Zealand Med. J. 65 411. Mortimer, J. G. and Rudd, B. T.-' Cushing's Syndrome in a Young Girl' (1966) Au;t. Paed. J 2, 119. " .,
Stapleton T. and Katz, J.-' Non-directive Psychotherapy: A Little Girl Talks to Herself " (1967), Med. J. Augt., 1, 1166. Stapleton, T.-' Children-The Future Nation', (1967), Med. J. AU8t., 1, 1049. Stapleto~, T.-' Spotlight on the Battered Child Conference-Psychiatric Aspects " (1966), University of Queensland.
NATIONAL BIOLOGICAL STANDARDS LABORATORY Atkinson, F. F. V. and Hard, G. C.-' Chronic Fluorosis in the Guinea-Pig', (1966), Nature, 211, 429. Hard, G. C. and Atkinson, F. F. V.-' "Slobbers" in Laboratory Guinea·pigs as a Form of Chrome Fluorosis', (1967), J. Path. Bact., 94" July. Hard, G. C. and Atkinson, F. F. V.-' The Aetiology of "Slobbers" (Chronic Fluorosis) in the Guinea-Pig " (1967), J. Path. Bact., 94, July.
COMMONWEALTH ACOUSTIC LABORATORIES Carter, N. L.-' The Effect of Spectrum on the Loudness of Impulse Noise " (1966), Paper No. 23 presented at Internat. Meeting on Aerospace Med., Sydney. Cordell, Joan-' 20 Years of Achievement by C.A.L.', (1967), Health, 17, No.1, 14. Garrett, W. J., Robinson, D. E. and Kossoff, G.-' Ultrasonic Echoscopy in Transverse Lie " (1966), J. Ob8tet. Gynaecol. Brit. Cwlth., 73, 679. Kossoff, G.-' Diagnostic Applications of Ultrasound in Cardiology', (1966), AU8trala8. Radiol., 10 (2), 101. Kossoff, G.-' A Transistorised Preamplifier for the Recording of Nystagmus', (1966), Proc. fREE AU8t., 27 (9), 264. Kossoff, G. and Khan, A. E.-' Treatment of Vertigo Using the Ultrasonic Generator', (1966), Arch. Otolaryngol., 84 (2), 181. Kossoff, G., Robinson, D. E. and Garrett, W. J.-' Two Dimensional Ultrasonography in Obstetrics', in Grossman, C. and others (eds.), Diagnostic Ultrasound, Proceedings of First International Conference, University of Pittsburgh, 1965, New York, Plenum Press, 1966, pp. 333347. Kossoff, G. and WiIcken, D. E. L.-' The C.A.L. Ultrasonic Cardioscope', (1967), Med. and Bioi. Engng., 5, 25. Murray, N. E.-' Hearing Conservation in Aviation', (1966), Paper No. 22 presented at Internat. Meeting on Aerospace Med., Sydney. Robinson, D. E., Garrett, W. J., Kossoff, G. and Little, K. J.,-' Ultrasonic Examination of the Uterus', (1967), Med. J. Aust., 1, 1202. Robinson, D. E., Kossoff, G. and Garrett, W. J.-' Artifacts in Ultrasonic Echoscopic Examination " (1966), Ultrasonic8, 4 (4), 186. REPORTS Donald, G. and Piesse, R. A.-' Tests on the Performance of David Clark Co. Inc. Headset 15BM', (1966), C.A.L. Report No. 38, 24 pp. Kossoff, G. and Robinson, D. E.-' Essential Basic Physics in Diagnostic Ultrasound', (1966), C.A.L. Report No. 39, 22 pp. Robinson, D. E., Garrett, W. J. and Kossoff, G.-' Ultrasonic Echoscope in Clinical Obstetrics and Gynaecology', (1967), C.A.L. Report No. 40, 24 pp. Tonkin, E. J.-' Overseas Observations on Recent Developments in Audiological Psychology and Audiology', (1967), C.AL. Report No. 41, 34 pp.
COMMONWEALTH X-RAY AND RADIUM LABORATORIES Bonnyman, J.-' Determination of Strontium-90 and Caesium-137 in Drinking Water', CXRL Tech. Rep. No.3 (in press). Bonnyman, J.-' Determination of Strontium in Calcium Oxalate by Atomic Absorption Spectrometry', CXRL Tech. Rep. No. " (in press). Bonnyman, J.-' Radio-Assay of Strontium-89, Strontium-90, Caesium-137 and Radium D in Fallout in Exchange Collectors " CXRL Tech. Rep. No.6 (in press).
119
Bonnyman, J. and Duggleby, J. C.-' Iodine-131 Levels in Milk in Australia During the Period July-December 1966' (1967), Aust. J. Sci., 29, 402. . ., . Bonnyman, J. and Molina-Ramos, J.-' Strontium-90 and Caesium-137 m some AustralIan Drmkmg Water Supplies 1961-1965', Aust. J. Sci. (in press). Duggleby, J. C. and Seebeck, R. M.-' Potassium and Caesium-137 Distributions in Angus Steer Careases', J. Ag. Sci. (in press). Hargrave, N. J.-' A Free-Air Chamber for Measurement of X-Ray Exposure Below 50 kvp', (1967), Aust. Bull. Med. Phys. and Biophys., No. 32,1.6.67. Leith, 1. S.-' Biological Effects of Microwave Radiation', (1967), Aust. Bull. Med. Phys. and Biophys., No. 31, 1.2.67. . Stevens, D. J., Fletcher, W., Gibbs, W. J., Moroney, J. R. and Titte~ton, E. W.-' StrontIUm-90 in the Australian Environment During 1965', (1967), Aust. J. Sm., 29, 319. . Stevens D. J., Gibbs, W. J., Moroney, J. R. and Titterton, E. W.-' Fallout Over Austraha from·.·· Nu~lear Weapons Tested by France During July 1966', (1966), Nature, 212,1562. . Stevens, D. J., Gibbs, W. J., Moroney, J. R. and Titterton, E. W.-' Fallout over Australia from Nuclear Weapons Tested by France in Polynesia from July to October 1966', (1967), Aust . .7. Sci., 29, 407.
COMMONWEALTH BUREAU OF DENTAL STANDARDS Chong, Joan A., Chong, M. P. and Docking, A. R.-' The Surface of Gypsum Cast in Alginate Impressions', (1967), Proc. Brit. Soc. Study of Pros. Dent., 49. Chong, Joan A.-' The Laboratory Testing of Fluoride Tooth Pastes', (1965-66), Year Book of Dentistry, 119. Ware, A. L.-' Mechanical and Hand Preparation of Amalgams', (1965-66), Year Book 0/ DenNstry, 335. Ware, A. L.-' A Study of the Physical Properties of Resilient Orthodontic Wires', (1967), Aust. Orthodontic Bull., 5 (2), 3. Ware, A. L.-' Notes on the Wilcock Orthodontic Wires', (1967), Aust. Orthodontic Bull. 5 (2),11. Illustrated Pamphlet---' The Way to Better Amalgams', (1967). Illustrated Pamphlet-' The Way to Better Silicates', (1967). Pamphlet-' Repair Technique for Acrylic Resin Denture Base Materials " (1967). Current Notes No. 51-' A New Direct Filling Resin', (1966), Aust. Dent. J., 11 (4),274. (Also (1967), Dent. Abs., 12 (4),221.)
INSTITUTE OF ANATOMY Hipsley, E. H.-' The Relationship between Energy Utilisation and Food Production-the Examples of New Guinea and Australia', (1965), Paper read at 11th Pacific Science Congress, Food and Nutrition Notes and Reviews, 24, 6. Hips]ey, E. H.-' Nutrition Education and Ecological Awareness', (1967), Proceedings of the 3rd Far East Symposium on Nutrition, Manila. Food and Nutrition Notes and Reviews-Vol. 23, Nos. 7-12, Vol. 24, Nos. 1-6. Pamphlet-' The Australian Institute of Anatomy'. Pamphlet-' Keep Fit with Food '.
CENTRAL AND DIVISIONAL OFFICES Boxall, J. S.-' Ideal Poisons Information Centre', (1966), Health, 16, No.3, 28. Carr, L. M.-' Fluoridation in Canberra, Part I-Prefluoridation Data: Dental Caries and Mottled Enamel', (1966), Aust. Dent. J., 11, 248. Edmondson, K. W.-' H. Fever-A Threat to Australia?', (1966), Health 16 No.4 23. Edmondson, K. W.-' Evaluating Mortality Shtistics', (1966), Health, 16, 'No.' 3, 14.' Elliott, R. B., Maxwell, G. M. and Vawser, N. D.-' Lactose Maldigestion in Australian Aboriginal Children', (1967), Med. J. Aust., 1, 46. Green, A. and Spears, A. ~.-' Sabin 9~mpaign in the A.C.T.', (1966), Health, 16, No.4, 5. McCahey, P. F.-' The NatIonal MorbIdIty Survey', (1966), Health, 16, No.4, 16. McIntosh, K. S.-' Lessons from Disease Outbreak', (1967), Health, 17, No.1 28. Morey, B. J. W.-' Recreation Leadership Course', (1966), Health, 16, No. 3, ~i7. Morschel, J. R. G.-' Plant Smuggling Problem Increasing', (1966), Health, 16, No.3, 29. Powell, B. J.-' Private Nursing Home Costs', (1967), Health, 17, No.1, 11. Rofe, R. B.-' Medicare and the P.M.S.', (1965), Health, 16, No.3, 25. Wells, R . H. C.-' The Support of Medical Research in Australia 1962-1964', (1966), Med. J. AUst., 2,430 . Wells, R. H. C. and Kupkee, L.-' Lost Years-The Important Causes of Death in Australia 1963' (1966), Med. J. Aust., 2, 466. ' Wells, R. H. C.-' Safety Zones-Differential Mortality Rates in Australia 1961-1963', (1966), Med. J. Aust., 2, 573.
120
NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL , • Dietary Allowances for Australians '. Reprinted from Report of 60th Session, October 1965. Reprinted from Report of 60th Session, October 1965. • Dental Auxiliary Personnel '. Reprinted from Report of 62nd Session, May 1966. • Statement on Human Experimentation '. • Code of Practice for the Safe Handling of Corpses Containing Radioactive Substances'. Reprinted from Report of 62nd Session, May 1966. • Principles to be Applied in Minimising Radiological Hazards to Patients from the Diagnostic Use of X-Rays in Medical Practice '. Reprinted from Report of 62nd Session, May 1966. Reprinted from Report of 62nd Session, May • Poisoning by Organo-Phosphorus Compound,s', 1966. Jamieson, K. G. and Tait, I. A.-' Traffic Injury in Brisbane '. Special Report Series No. 13 1966. Report on a National Morbidity Survey, February 1962-January 1963, Part I.
121
Commonwealth Department of Health
Central Office Director-General Sir William F.R.A.C.P. Refshauge, C.B.E., E.D., M.B., B.S., F.R.C.O.G., F.R.A.C.S.,
Deputy Directors-General Dr H. E. Downes, O.B.E., M.B., B.S., D.P.H. Dr G. M. Redshaw, O.B.E., M.B., B.S., D.P.H. Management Services and Benefits Division FIRST ASSISTANT DIRECTOR-GENERAL: D. G. Dunlop, B.COM., D.P.A., F.A.S.A., F.C.I.S., F.C.A.A. ESTABLISHMENTS AND FINANCE BRANCH: ASSISTANT DIRECTOR-GENERAL: M. Carroll, B.COM., A.A.U.Q. FINANCE SECTION: Director: L. B. Holgate, B.COM., A.A.S.A. A.D.P. SECTION: Director:
R. H. Searle, B.EC., DIP.COM., A.A.TJ.Q., A.A.S.A.
ESTABLISHMENTS SECTION: Director: H. W. Farr O. AND M. SECTION: Senior Inspector:
J. G. Burt, B.EC. (Acting)
PLANNING AND LEGISLATION BRANCH: ASSISTANT DIRECTOR-GENERAL: L.
J. Daniels, B.EC., A.A.S.A.
POLICY AND LEGISLATION SECTION: Director: D. Corrigan RESEARCH SECTION: Director:
R. B. Rofe, B.EC.
DEFENCE AND CIVIL DEFENCE SECTION: Director: T. H. Betts MEDICAL AND HOSPITAL BRANCH:
122
,
ASSISTANT DIRECTOR-GENERAL: A. A. M. Kelly, D.P.A., A.A.S.A. INSURED BENEFITS AND INSPECTIONS SECTION: Director:
J. L. Hayes, DIP.COM., F.A.S.A.
UNINSURED BENEFITS AND REVIEW SECTION: Director: L. W. Lane, A.A.S.A. National Health Division FIRST ASSISTANT DIRECTOR-GENERAL: Dr J. B. Mathieson, M.B., B.S., D.T.M. PHARMACEUTICAL SERVICES BRANCH: ASSISTANT DIRECTOR-GENERAL:
R. M. W. Cunningham, PH.C., M.P.S.
Directors:
J.
G. G. Kelleher, M.B.E., M.P.S. H. West, B.COM., A.A.S.A., A.C.l.;,
THERAPEUTIC SUBSTANCES BRANCH: ASSISTANT DIRECTOR-GENERAL: Dr A. D. Spears, M.B., B.S., D.T.M. & H.
Medical Officer: Dr R. A. J. McGregor, M.B., B.S. PUBLIC HEALTH BRANCH: ASSISTANT DIRECTOR-GENERAL: Dr A. C. Green, M.B., B.S., D.D.M., D.T.M. & H., D.P.H. TOXICOLOGY SECTION: Dr A. M. Walshe, M.B., B.S., B.SC. GENERAL SECTION: Dr D. B. Travers, M.B., B.S. NURSING SECTION: Principal: Miss I. M. Copley, DIP.N.AD., F.C.N.A. Assisstant Principal: Miss M. Wilks, DIP.N.AD., F.C.N.A. Laboratory Services and Quarantine Division FIRST ASSISTANT DIRECTOR-GENERAL: Dr. R. W. Greville, M.B., B.S., B.V.SC., F.F.A.R.A.C.S., D.A. INTERNATIONAL HEALTH SECTION: Dr
J.
S. Boxall, M.B., B.S., M.R.A.C.P.
GENERAL QUARANTINE BRANCH: Dr F. S. D. Thompson, M.R.C.S., L.R.C.P., D.P.H.
123
ANIMAL QUARANTINE BRANCH: ASSISTANT DIRECTOR-GENERAL (DIRECTOR OF VETERINARY HYGlENE) : K. S. McIntosh, B.V.SC., H.D.A.
,
Senior Veterinary Officers: H. R. Peisley, B.V.SC., D.P.A. I. D. Cameron-Stephen, M.R.C.V.S. PLANT QUARANTINE BRANCH: ASSISTANT DIRECTOR-GENERAL (DIRECTOR OF PLANT QUARANTINE) : J. R. G. Morschel, B.SC.AGR., H.D.A. Principal Plant Quarantine Officer: J. O. Smith, B.SC.AGR., H.D.A. National Health and Medical Research Council Division FIRST ASSISTANT DIRECTOR-GENERAL: Dr R. H. C. Wells, M.D., B.S., B.SC., M.R.C.P., D.T.M. & H., D.C.T.M. Medical Officer: Dr K. W. Edmondson, M.B., CH.B., D.P.H. Tuberculosis Division FIRST ASSISTANT DIRECTOR-GENERAL: Dr G. Howells, M.D., B.S., M.R.C.P., M.R.A.C.P. Specialist: Dr A. J. Proust, M.B., B.S., M.R.C.P., M.R.C.P.E. Administrative Officer: R. C. West, DIP.COM., A.A.S.A.
l
State Offices SydneyCOMMONWEALTH DIRECTOR OF HEALTH: Dr L. J. Wienholt, M.B., B.S.
Assistant Directors: Medical: Dr B. E. Welton, M.R.C.S., L.R.C.P., D.T.M. Administration and Finance: J. L. Cockburn, B.A. General Benefits: A. B. McDonald, A.A.S.A. Pharmaceutical: K. J. Kelly, PH.C., M.P.S. MelbourneCOMMONWEALTH DIRECTOR OF HEALTH: Dr. H. M. Franklands, M.B., B.S., D.T.M.
&
H.
Assistant Directors: Medical: Dr A. V. M. Cocks, M.B., B.S., M.P.S. Administration and Finance: K. F. Delaney, F.A.S.A. General Benefits: M. J. Carlson Pharmaceutical: L. L. Lock, PH.C., n.p.A.
124
BrisbaneCOMMONWEALTH DIRECTOR OF HEALTH: Dr A. H. Humphry, M.B., B.S., D.T.M. &
H.
Assistant Directors: Medical: Dr H. B. Cumpston, M.B., B.S., D.T.M. & H. Administration and Finance: A. J. Lavercombe, M.B.E., A.A.S.A. General Benefits: A. E. Garske, A.A.U.Q. Pharmaceutical: K. L. Bate, PH.C. AdelaideCOMMONWEALTH DIRECTOR OF HEALTH: Dr C. S. Barbour, M.B., B.S.
Assistant Directors: Medical: Dr R. B. Lapedus, M.B., B.CH., B.A.O., B.A. (T.C.D.) Administration and Finance: A. S. W. Arnold, O.B.E., E.D., A.A.S.A. General Benefits: N. J. Gluyas, A.U.A. (COM.) Pharmaceutical: A. P. BrammaIl, PH.C., M.P.S. PerthCOMMONWEALTH DIRECTOR OF HEALTH: Dr R. C. Webb, M.B., B.S., D.T.M. & H.
Assistant Dir'ectors : Medical: Dr W. H. Young, M.B., CH.B. Administration and Finance: F. G. Dienhoff General Benefits: A. J. Wilson, A.A.S.A. Pharmaceutical: A. T. Stocker, PH.C., M.P.S. HobartCOMMONWEALTH DIRECTOR OF HEALTH: Dr C. W. Phillips, M.B., B.S., D.T.M. & H.
Assistant Director's: .: Administration, Finance and General Benefits: R. J. Boxhall Pharmaceutical: K. R. Heferen, PH.C., M.P.S. DarwinCOMMONWEALTH DIRECTOR OF HEALTH: Dr W. A. Langsford, O. ST. J., M.B., B.S., D.T.M. &
H.
Assistant Dir'ectors : Medical: Dr C. W. Ramsay, M.B., B.S., D.P.H., D.P.A. Public Health: Dr B. L. Kirkup, M.B., B.S. Tuberculosis: Dr E. G. Wilson, M.B., B.S., D.A. Public Health & Medical Services (Southern): Dr N. D. Vawser, M.B., B.S., D.T.M. & H. Administration and Finance: H. C. Harrison
125
Darwin Hospital: Medical Superintendent: Dr A. H. Dunnet, D.P.H. Matron: Miss A. K. L. Brennan, DIP.N.AD. Secretary: D. A. Hyde, L.H.A.
M.B., CH.B., D.T.M. & H.,
,""
Alice Springs Hospital: Medical Superintendent: Dr G. E. E. White, M.B., B.S., PH.C. Acting Matron: Miss L. R. John.ston Secretary: E. C. Milgate
Tennant Creek Hospital: Medical Superintendent: Dr C. W. Wright, M.B., B.S. Acting Matron: Miss M. Maher Secretary: R. S. LisBon
Katherine Hospital: Medical Superintendent: Dr P. D. Short, M.B., B.S. Acting Matron: Miss C. 1. McMahon Secretary: J. M. Palmer
East A I'm Leprosy Hospital: Dr J. C. Hargrave, M.B.E., M.B., B.S., D.T.M. & H.
Dental Services: Senior Dental Officer: W. C. Gadd, B.D.S.
CanberraCOMMONWEALTH DIRECTOR OF HEALTH: Dr W. F. H. Crick, M.B., B.S. Medical Officer of Health: Dr M. Ryan, L.R.C.P. & s.l., D.P.H.
Assistant Director: General Services: K. W. Arscott, A.A.S.A., A.C.I.S.
, .
School Medical Service: Senior Medical Officer: Dr A. S. Cumming Thorn, M.B., B.S., D.T.M.& H.
School Dental Service: Senior Dental Officer: L. M. Carr, M.D.S., D.P.D., F.A.C.D.S.
Child Guidance Clinic: Psychiatrist: Associate Professor Dr Julian Katz, M.B., B.CH., D.P.M.R.C.P. & s., M.A.N.Z.C.P. Psychologist: D. J. McKenzie, B.A., DIP.PSYCH., M.A.P.S.
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Laboratories and Research Organisations School of Public Health and Tropical MedicinePRINCIPAL: Sir Edward Ford, O.B.E., M.D., D.P.H., D.T.M., F.R.C.P., F.R.A.C.P., F.Z.S.
T1'opical Medicine: Director: Professor R. H. Black, M.D., B.S., D.T.M. & H., F.R.A.C.P., DIP .ANTHROP. Associate Professor C. H. Campbell, M.B., B.S., D.T.M. & H., M.R.C.P., M.R.C.P.E., F.R.A.C.P. Entomology Sub-Section: Chief Entomologist: Associate Professor D. J. Lees, B.SC. Environmental Health: Director: Professor R. K. Macpherson, M.D., B.S., M.SC., M.R.A.C.P. Industrial Health Section: Principal Medical Officer: Dr G. C. Smith, M.B., B.S., D.P.H., M.R.A.C.P. Institute of Child HealthDIRECTOR: Professor Thomas Stapleton, M.A., D.M., M.R.C.P., D.C.H. (R.C.P. & s.) Associate Professor of Child Psychiatry J. Katz, M.B., B.CH., D.P.M., R.C.P. & s., M.A.N.L.C.P. Principal Medical Officer: Dr F. W. A. Clements, M.D., B.S., F.R.A.C.P., D.T.M., D.P.H. National Biological Standards LaboratoryDIRECTOR: Dr L. F. Dodson, M.B., B.S., DIP.CLIN.PATH., D.PHIL.
Assistant Directors: Bacterial Products: Dr V. P. Ackerman, M.B., B.S., B.A., PH.D. Endocrine Products: Vacant Viral Products: Dr D. W. Howes, M.SC., PH.D. Pharmaceutical Chemistry: Dr F. E. Peters, M.SC., PH.D. Pharmacology: Dr C. G. Haining, B.PHARM., PH.D. Antibiotics: N. M. Semple, B.SC. Medical Administration: Dr J. Raby, M.B., B.S., B.SC. (MED.), M.C.P.A. Commonwealth Acoustic LaboratoriesDIRECTOR: N. E. Murray, O.B.E., B.E., B.SC. Chief Physicist (Ultrasonics) : G. Kossoft', M.E., B.SC. Principal Physicist (Acoustics and Electroacoustics) : R. A. Piesse, B.SC., A.A.J.P. Principal Psychologist (Clinical Audiology and Psychology Services) : E. J. Tonkin, B.A.
127
Commonwealth X-Ray and Radium LaboratoryDIRECTOR: D. J. Stevens, O.B.E., B.SC., F.C.R.A. (HONS.), HON.F.I.R. /. ,
Assistant Directors: Principal Physicist (X-Rays): J. F. Richardson, M.SC., F.INST.P., F.A.I.P., HON.M.I.R. Principal Physicist (Radioactivity): D. W. Kearn, M.SC. Bureau of Dental Standards-DIRECTOR: A. R. Docking, M.B.E., M.SC., F.R.A.C.I. Institute of AnatomyMEDICAL OFFICER-IN-CHARGE: Dr E. H. Hipsley, M.B., B.S.
Overseas Posts London: CHIEF MEDICAL OFFICER: Dr A. Johnson, M.B., B.CH., B.A.O., D.P.H. The Hague: MEDICAL DIRECTOR: Dr J. M. Thompson, M.B., B.S., M.R.C.S., L.R.C.P., M.C.P.A. Athens: MEDICAL DIRECTOR: Dr R. W. Cumming, M.B., B.S. Cologne: MEDICAL DIRECTOR: Dr J. L. Pring, M.R.C.S., L.R.C.P. Rome: MEDICAL DIRECTOR: Dr P. Dawes, M.R.C.S., L.R.C.P. Malta: MEDICAL DIRECTOR: Dr J. BOYD, L.R.C.P.
&
S.
Beirut: MEDICAL DIRECTOR: Dr C. E. A. Mason, M.R.C.S, L.R.C.P.
D. E. WILKINSON, Government Printer, Tasmania.
COMMONWEALTH OF AUSTRALIA
A,
'I
MEDICAL RESEARCH 1966 -¥.:
REPORT UPON THE WORK DONE
" ~; .",.
UNDER THE MEDICAL RESEARCH ENDOWMENT ACT DURING THE YEAR 1966
NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL
r
1967
In accordance with the provIsIOns of the Medical Research Endowment Act 1937, this Report upon the work done under that Act during the year 1966 has been prepared and is now presented to Parliament. A. J. FORBES Minister for Health
4275/67
ii
National Health and Medical Research Council, Commonwealth Department of Health, Canberra, A.C.T. Sir, The National Health and Medical Research Council has the honour to present the Twenty-Ninth Annual Report of work done under the Medical Research Endowment Act 1937. This Act provides for the establishment of a fund, known as the Medical Research Endowment Fund, which consists of such amounts as are appropriated from time to time by Parliament and of income derived from the investment of these amounts; and gifts or bequests given or made for the purposes of the Fund and the income derived therefrom. The appropriation by Parliament to the Fund in 1965-66 was $878,000 and in 1966-67 $959,000. The balance in the Fund at 31 December 1966 was $72,377. Section 6 of the Medical Research Endowment Act states: " (1.) The Fund shall be applied to provide assistance(a) to Departments of the Commonwealth or of a State engaged in medical
...
research; to Universities for the purpose of medical research; to institutions and persons engaged in medical research; and in the training of persons in medical research. (2.) Assistance under the last preceding sub-section shall be provided in such cases and subject to such conditions as the Minister, acting upon the advice of the Council, determines. " (b) (c) (d)
This report sets out the work done in a wide field of medical research with the support of grants approved by you in accordance with the terms of the Medical Research Endowment Act 1937. Yours sincerely,
Chairman The Han. A. J. Forbes, M.C., M.P., Minister of State for Health, Parliament House, Canberra, A.C.T.
iii
'f!'
CONTENTS Reports of Work Done in 1966 byUniversity of Adelaide .. University of Melbourne Monash University University of New South Wales .. University of Queensland University of Sydney .. University of Tasmania University of Western Australia .. Institutes, New South Wales Institutes, Queensland .. Institutes, South Australia Institutes, Victoria e. J. Martin Overseas Travelling Fellowship-Report N.H. & M.R.e. ScholaiShips Other Grants Wolfson Foundation Bowling Bequest " Renewals and New Grants .. AppendicesI. Appropriations by Parliament II. Grants made from the Medical Research Endowment Fund, 1965-66 III. National Health and Medical Research Council Salary Scales and Scholarship Stipend Rates IV. Conditions Associated with National Health and Medical Research Council Grants for Medical Research, C. J. Martin Travelling Fellowships and Public Health Travelling Fellowships V. Members of Medical Research Advisory Committee VI. Members of Standing Grants Committees VII. Members of National Health and Medical Research Council Page I
12
48 69 83 95 121
123 136
154 160
164
175 178 180
181 181
182 192
193 194
195 202 203 204
.f.
v
INTRODUCTION It is now thirty years since legislation was introduced in the Commonwealth Parliament for the establishment of the Medical Research Endowment Fund. Today the Fund has an annual appropriation of more than a million dollars and this is used to provide training in research - and to support well over a hundred different research projects. During the past year the recipients of these grants have published the results of their work in more than 550 scientific papers. The field of studies supported by these grants is very wide, ranging from basic research in molecular biology and cellular immunology to studies in cancer therapy and organ transplanta,...- tion which have an immediate practical application. But all these studies, however remote some of them may seem from everyday medical care, have one basic aim in common, to improve the health and happiness of the nation. To achieve this aim more knowledge about the function of body in health and disease is constantly needed, and this new knowledge can only be found through research. Much of this research, particularly on local medical problems, can only be done in Australia. However much medical research is carried out in Australia it is still true that most of the new knowledge needed to improve the national health will be discovered elsewhere and will have to be imported to this country. This new knowledge mostly becomes available in published scientific papers and other forms of scientific communication which can only be fully understood and reliably assessed by other scientists working in the same field. New medical knowledge discovered elsewhere can only be applied rapidly and efficiently to Australian problems if there are competent well trained medical scientists here who can appreciate its significance and use it. The National Health and Medical Research Council in recent years has therefore given increased emphasis in its grant recommendations to the award of fellowships and scholarships which will provide research training for medical and dental students ;cnd graduates. Most of the results of this programme do not appear in this report but they are incr<:asingly apparent in the lists of Australian trained medical scientists who reach high academic and clinical distinction. For many years the Council has subsidised with grants from the Medical Research Endowment Fund the publication of reports and monographs on research. The past year has <pen the publication of two such reports on research work that had been supported by Council grants. The first of these was a report on traffic injury research in Brisbane by Dr K. G. Jamieson and Dr I. A. Tait giving the results of studying a series of 1,000 hospital admissions or deaths resulting from 822 traffic accidents. The second report summarised the results of a study of over 300,000 illness episodes seen by general practitioners. This National Morbidity Survey was carried out by the Council with the assistance of the College of General Practitioners, and it is a most important addition to our knowledge of illness patterns in Australia. The following pages describe areas of interesting and encouraging research now under wav. The new knowledge gained by this work when translated into better methods of treatment, new drugs and improved procedures and tests will help bring about further progress in the control of the major health problems.
vii
REPORTS OF MEDICAL RESEARCH WORK DONE DURING 1966 WITH THE SUPPORT OF GRANTS UNDER THE MEDICAL RESEARCH ENDOWMENT ACT 1937 UNIVERSITY OF ADELAIDE DEPARTMENT OF HUMAN PHYSIOLOGY AND PHARMACOLOGY Professor R. F. Whelan, M.D., Ph. D., D.Sc., F.R.A.C.P., F.AA Dr J. A. Walsh, M.B., B.S., Temporary Lecturer in Physiology Project Nervous and humoral control of blood vessels. Report Study of the effects of various procedures, such as muscular exercise, and of various drugs and hormones on the circulation in man is of importance not only for the understanding of the normal physiological control of the circulation but also for an understanding of disease processes. Exercise of the forearm muscles in normal subjects results in an increase in the muscle circulation. Previous studies had shown that no vasodilator substance could be detected in the muscle blood, but that small amounts of acetylcholine were found in certain circumstances which contributed to a minor degree to the increased circulation. Investigation of the effect of adrenaline blockil}g agents on the hyperaemia of exercise has shown that in the majority of subjects there appears to be release of sufficient adrenaline into the circulation during the forearm exercise to have a significant dilating effect on the muscle vessels. However, the effects of acetylcholine and adrenaline were not su fficient of themselves to account for more than a small part of the muscle dilation in exercise and the chief cause of the effect remains to be determined. Studies of the actions of alcohol and of nicotine on the blood vessels in man have been completed. Alcohol was shown to be a constrictor of peripheral blood vessels when applied directly. When taken by mouth the increased blood flow that occurs in the arm and hand has been found to occur only in skin and to be due to an action of alcohol in releasing sympathetic tone centrally. Intra-arterial administration of alcohol is contra-indicated in the treatment of peripheral vascular disease. While oral administration may cause dilatation of skin vessels, an accompanying constriction of muscle vessels could prove to be a disadvantage where muscle ischaemia is present. Nicotine has a complex action on blood vessels, the predominant effect being to cause a long-lasting dilatation of muscle and skin vessels. A slight and transient degree of vasoconstriction may occur which is due to stimulation of the peripheral sympathetic nerve fibres. Both constrictor and dilator effects of nicotine are abolished by administration of hexamethonium bromide, but the mechanism of this action is not known. Angiotensin is a hormone formed in the blood when renin is released into the blood from the kidney. This occurs particularly with certain kinds of kidney disease and is the cause of the accompanying high blood pressure. An action of angiotensin on the central sympathetic nervous system has been demonstrated. However, studies in normal subjects in?i.cate that this sympathetic effect does not play an important part in the blood pressure ral5lng effect of the hormone. Patients with high blood pressure associated with kidney disease are also b.eing studied as the relationship of angiotensin to the sympathetic nervous system and particularly of its effect on the sensitivity of vessels to adrenaline and noradrenaline may have therapeutic importance.
-;/-
2
University of Adelaide
Publications BRANDON, K. W., COOPER, C. J., FEWINGS, 1. D., and WALSH, J. A. 'Some aspects of post-exercise hyperaemia in man.' Aust. 1. expo Bioi. med. Sci., 1966, 44, 379. FEWINGS, J. D., HANNA, M. 1. D., WALSH, J. A., and WHELAN, R. F. 'The effects of ethyl alcohol on the blood vessels of the hand and forearm in man.' Brit. 1. Pharmacal., 1966, 27, 93. FEWINGS, J. D., RAND, M. J., SCROOP, G. G., and WHELAN, R. F. 'The action of nicotine on the blood vessels of the hand and forearm in man.' Brit. 1. Pharmacal., 1966, 26, 567. FEWINGS, 1. D., and WHELAN, R. F. 'Differences in forearm blood flow measured by capacitance and volume plethysmography.' 1. appl. Physiol., 1966,21, 334. SCROOP, G. C., and WHELAN, R. F. A central vasomotor action of angiotensin in man.' Clinical Science, 1966, 30, 79. WHELAN, R. F. 'Adrenergic drugs on the systemic circulation.' Physiological Pharmacology. (In press.) WHELAN, R. F. 'The control of the peripheral circulation in man.' Monograph, C. C. Thomas. (In press.)
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Dr I. S. de la Lande, M.Sc., Ph.D., Reader in Pharmacology. Mrs J. C. WanstaH (nee Lewis), B. Pharm. (Hons.), Research Assistant, N.H. & M.R.e. Project Pharmacological analysis of insect venoms.
Report The work on the venom of the bulldog ant (Myrmecia pyriformis) was a continuation of a study which showed that hymenoptera venoms (bee, wasp, hornet) are a rich source of physiologically active amines and hitherto unknown polypeptides. The present work was undertaken several years ago to establish the nature of the physiologically active substances present in the venom of the Myrmecia ants (bulldog ants), which are indigenous to Australia and renowned for their ferocity and painful sting. Several physiologically active fractions from the venom of Myrmecia pyriformis have been isolated, including histamine and a proteinaceous fraction, probably polypeptide, which combined pain-producing properties, smooth and skeletal muscle stimulation, histaminereleasing activity, and red cell lysing activity, also phospholipase A, which is associated with and probably responsible for additional histamine-releasing activity, and finally hyaluronidase activity. The separate identity of the above fractions has been established by a combination of the following techniques; paper chromatography, low and high voltage electrophoresis, dialysis, sensitivity to heat, sensitivity to proteolytic enzymes, and partial isolation using long sephadex columns. Emerging from this work is the implication that, when compared with other hymenoptera venoms, there is a striking similarity between the composition of the bull ant-venom and bee-venom. Both make use of a single low molecular amine (histamine) to cause immediate inflammation, together with a proteinaceous material which causes pain and Drolonged inflammation. This is likely to be associated with a direct effect on. cell membranes as manifested by contraction of smooth and skeletal muscle, and haemolysls of red cells a~d an indirect effect involving histamine-release. Both venoms utilise phospholipase A, which adds further to release of histamine, and hyaluronidase to assist spreading of the venom in the tissues at the site of its injection.
University of Adelaide
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During the final stages of the project it is proposed to further purify and compare in detail, the pharmacology of the proteinaceou3 smooth muscle stimulant with that of the corresponding fraction (mellitin) in the bee venom. Publication LEWIS, J. C., and de la LANDE, I. S. 'Pharmacological and enzyme constituents of the venom of an Australian bulldog ant, Myrmeda pyriformis.' Toxicon. (In press.)
Dr S. L. Skinner, M.D., Research Fellow, N.H. & M.R.e. Dr E. R. Lumbers, M.B., B.S., Medical Postgraduate Research Scholar. Project Physiology of the renin-angiotensin system. Report Renin, an enzyme hormone secreted by the kidney, is known to be the cause of certain rare forms of high blood pressure in man. Renin acts on a protein substrate in blood to form a peptide end-product called angiotensin which raises blood pressure by constricting blood vessels and increases the secretion of the salt retaining hormone aldosterone from the adrenal gland. Inaccurate measurement of renin has hindered research in this area and during the past twelve months an investigation was undertaken into the problems of renin assay and, as a result of this, a new system was developed which overcomes many of the criticisms of older assays. On the basis of this work a travelling fellowship was awarded by the Australian Nephrological Society to present the assay system at the Third International Congress of Nephrology in Washington, D.C., September 1966. Using the assay, renin levels have been measured in blood, urine and amniotic fluid of man, sheep and rabbits, and the following findings have clearly emerged. Firstly, the assay is suitable for mass screening of the hypertensive population as an aid to the diagnosis of high blood pressure. Secondly, the differentiation between primary and secondary aldosteronism can be clearly established. Thirdly, oral contraceptives have an interesting effect on the reninangiotensin system since the oestrogen component enhances the reaction between renin and its substrate with formation of more angiotensin from the same amount of renin. This alteration in the kinetics of the system is being followed because of its possible effect in provoking hypertension in certain women. Also, renin in urine has been measured in a variety of normal and abnormal situations and its diagnostic potential is being investigated. Further, renin has been found to occur in high concentration in amniotic fluid. The origin of this renin and its role in foetal physiology is being studied with the co-operation of the Department of Obstetrics and Gynaecology at the University of Adelaide. The renin levels in sheep drinking rain water versus salt water are being studied in collaboration with the C.S.I.R.O. Falls in plasma renin are seen on salt water and this has relevance to the understanding of the ability of sheep to survive on a remarkably high salt intake. Further studies are indicated along the lines of all the projects listed above and several of these have possible direct application to clinical medicine. Publication SKINNER, S. L. 'Improved assay methods of renin concentration and activity in normal human plasma using selective denaturation of renin substrate.' Circulat. Res. (In press.)
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University of Adelaide
DEPARTMENT OF MEDICINE Professor B. S. Hetzel, M.D., M.R.C.P., F.R.A.C.P. Dr B. F. Good, Ph.D., C. J. Martin Fellow, N.H. & M.R.C. Dr M. J. Holfmann, M.D., Lecturer in Medicine, University of Adelaide. Dr I. H. Buttfield, M.D., Research Fellow, University of Adelaide. Miss E. K. Mason, B.Sc.(Hons), Technical Officer. Projects Studies of the control of the overactive thyroid gland and of endemic goitre in the Huon Peninsula of New Guinea. Report Studies of the abnormal thyroid stimulating substance characteristic of the overactive thyroid gland in man have been continued. Previous evidence from this laboratory indicates the importance of this agent known as the long acting thyroid stimulator (LATS) in relation to the various clinical features of the disease including the size of the goitre, the tendency to recurrence and the presence of exophthalmos and pretibial myxoedema. An improved method has been developed for measurement of the mouse thyroid stimulating effect of this agent. It has been possible to show a fall in the level following the usc of the immunosuppressive drug lmuran indicating that the agent is probably produced by antibody producing cells. This is one of the first examples of an antibody causing an increase rather than a decrease in organ function. This may be due to the antigen being a natural repressor of the thyroid which is destroyed by LATS causing hyperfunction of the gland. Recent studies in our laboratory show a striking increase in LATS following a therapeutic dose of radioactive iodine which would largely desuoy the thyroid gland. This suggests that there is a relation between the thyroid gland and LATS production as well as the effect of LATS and that the antigen may therefore be of thyroid origin. Further studies of endemic goitre in the Huon Peninsula of New Guinea have been conducted. The Public Health Department of the Territory has now undertaken an extensive mass injection campaign of iodised oil, following our demonstration of its value in correcting iodine deficiency. The oil is to be given as a prophylactic to women of reproductive age and children. It will also be given to men with established goitre. Recent observations by Dr Ian Buttfield indicate that this oil' is still present in the body five years following administration. Elevation of plasma PBI persists while the 1-131 uptake is still within the normal range. These findings fit in with the previous epidemiological observation of the successful preventive effect of the oil on the development of goitre for five years. In collaboration with the Public Health Department, Dr Buttfield has carried out surveys of iodine nutrition in various parts of the Territory in the light of the previous finding that many natives living in the coastal area of Lae are probably iodine deficient. It seems likely that approximately 50% of the native population in New Guinea is to some degree iodine deficient. The question of prophylactic measures involving iodised salt is becoming an urgent consideration. . I An area on the Jimi River in the Mount Hagen Sub-District of the Western Highlands has been selected for the control trial of the effects of oil in preventing the occurrence of various neurological defects such as deaf-mutism, mental deficiency and spastic paraplegia, which occur in association with endemic goitre and severe iodine deficiency. There are 20,000 na tives in this area and a preliminary survey reveals a high incidence of these defects amongst children in the area. It is hoped that this experiment will provide a definite answer to the relation of these defects to iodine deficiency within three to five years.
University 0/ Adelaide
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Publications BUTTFIELD, I. H., HOFFMANN, M. J., MASON, E. K., WELLBY, M. L., GOOD, B. P., and HETZEL, B. S. 'Studies of the control of thyroid function in endemic goitre in Eastern New Guinea.' I. CUn. Endocr. and Metab., 1966, 26, 1201. GOOD, B. F., HETZEL, B. S., HOFFMANN, M. J., WELLBY, M. L., BLACK, M. L., POTTER, H. A., and BUTTFIELD, I. H. 'Studies of the effects of salicylate in hyperthyroidism.' Aust. Ann. Med., 1966, 15, 143. GOOD, B. F., and STENHOUSE, N. S. 'An improved bio-assay for TSH by modification of the method of McKenzie.' Endocrinology, 1966, 78, 429. HETZEL, B. S., and FORBES, I. J. 'Thyroid disease in pregnancy.' S.A. Clinics, Queen Victoria Maternity Hospital Commemorative Issue, 1966,2, 135. HOFFMANN, M. J., and HETZEL, B. S. 'The clinical significance of plasma thyroid stimulating activity in hyperthyroidism.' Aust. Ann. Med., 1966, 15,204. HOFFMANN, M. J., HETZEL, B. S., and MASON, E. K. 'Neonatal thyrotoxicosis: report of three cases involving four infants.' Aust. Ann. Med., 1966, 15, 262. SCOTT, T. W., GOOD, B. F., and FERGUSON, K. A. 'Comparative effects of LATS and pituitary TSH in the intermediate metabolism of thyroid tissue in vitro.' Endocrinology, 1966, 79, 949.
Dr Ian J. Forbes, M.D., M.R.A.C.P. Project Studies of human lymphocyte function. Report Using 'pure' lymphocyte suspensions, contaminated only by erythrocytes, quantitative and qualitative measurements of protein synthesis have been made on lymphocytes from persons with chronic lymphatic leukaemia, the para- proteinacmias and infectious mononucleosis. Measurements of total protein synthesis (as compared with globulin synthesis in previous studies) has shown diminished protein synthesis in some, but not all of the cases of leukaemia and paraproteinaemia. Abnormalities of glob ulin synthesis have been revealed by the qualitative technique. Increased protein synthesis occurs at some stage in infectious mononucleosis. The effects of drugs on protein synthesis have been studied extensively. All anti-inflammatory drugs in clinical use which have been tested so far have a potent inhibitory action on protein synthesis. Various drugs used to depress auto-immune activity and homograft rejection have also been shown to be inhibitory in this system. It is believed that the system represents a major step forward in the study of drugs of this sort. It should enable plasma binding of drugs to be studied, and will be most valuable for investigating the effeets of metabolites of the drug under study. There is a great deal to be done to study individual drugs, now that the system has been developed. Developmental work has been carried out on eleetron microscopy of lymphocytes, and analysis of the protein products by immunoelectrophoresis and autoradiography using different immunoelectrophoresis antisera. Evidence confirming that lymphocytes synthesise antibody was obtained, but lymphocytel' from persons with thyrotoxicosis could not be shown to synthesise the long-acting thyroid stimulator.
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University of Adelaide
Publications FORBES, I. J. 'Studies of human lymphocyte metabolism.' South Aust. Clinics, 1966,2, 21. FORBES, I. J. 'Mitosis in mouse peritoneal macrophages.' I. Immunol., 1966,96,734. FORBES, I. J., and HENDERSON, D. W. 'Globulin synthesis by human peripheral lymphocytes. In vitro measurements using lymphocyte from normals and patients with disease.' Ann. Int. Med., 1966, 65, 69. HETZEL, B. S., and FORBES, I. J. 'Thyroid disease in pregnancy.' S.A. Clinics, Queen Victoria Maternity Hospital Commemorative issue, 1966,2, 135. TURNER, K. J., and FORBES, I. J. 'Synthesis of protein by human lymphocytes in vitro. II. Analysis of proteins synthesised.' I. lmmunol., 1966, 96, 926.
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DEPARTMENT OF MICROBIOLOGY Professor D. Rowley, B.Sc., Ph.D., M.D. Dr K. J. Turner, B.Sc., Ph.D., Research Fellow, N.H. & M.R.e. Project Studies on the kinetics and formation of immunoglobulins. Report The isolation of substances having antibody-like actlVlty from invertebrates has been accomplished in the laboratory. The albumen gland of the snail Helix pomatia contains a component which agglutinates mammalian red blood cells to high dilution. Erythrocytes from several animals have been tested but the highest titres were obtained against the human A group cells. The agglutination could be inhibited by the prior addition of blood group A substance and more specific inhibition studies showed that the activity is directed against N acetyl galactosamine present in the blood group substance. This agglutinating system does not fix complement and requires the presence of divalent cations since ethylene diamine tetra acetate (EDTA) inhibits the reaction. There is good suggestive evidence that this antibody-like agglutinin is able to opsonise red blood cells allowing more rapid phagocytic removal. Attempts to purify this substance are in progress. Study on the synthesis of proteins by circulating leukocytes has continued. Human peripheral leucocytes in tissue culture under stimulation with phytohemagglutinin synthesise a spectrum of serum proteins including the immunoglobulins IgG and IgM. The proteins were characterised by the techniques of DEAE cellulose chromatography, immuno- and starch gel electrophoresis. Calculations have shown that the amount of IgG synthesised by circulating leucocytes does not exceed 0.1 per cent of the total IgG in circulation. Hence the contribution by the leucocyte is small yet significant. The leucocyte preparations used in these studies generally contained, in addition to lymphocytes, platelets, monocytes and granulocytes. Mixtures of cell types in optimal preparations are more efficient than lymphocytes alone in synthesising protein. Publications ROWLEY, D. 'The central role of phagocytosis in immune reactions.' Experientia, 1966,22,1. ROWLEY, D. 'The kinetics of phagocytosis.' Experientia, 1966,22, 5. ROWLEY, D. 'The carrier state and cellular immunity.' Experientia, 1966,22,9.
University of A de!aide
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ROWLEY, D. 'The relationship between immunity and the reticulo endothelial system.' Proc. IVth. Int. Congress of Infectious Diseases, Munich. ROWLEY, D., and TURNER, K. J. 'Number of molecules of antibody required to promote phagocytosis of one bacterium.' Nature, 1966, 210, 496. SCHWAB, G. E., REEVES, P. R., and TURNER, K. J. 'Bactericidal activity of serum of the Yabbie (Parachaeraps bicarinatus).' Brit. 1. Exp. Path., 1966, XLVII, 266. TURNER, K. J., and FORBES, 1. J. 'Synthesis of proteins by human leucocytes in vitro. II. Chemical characterisation.' 1. Immunol., 1966, 96, 926.
Dr P. C. Reade, F.D.R.C.S., M.D.S., Ph.D., Research Fellow, N.H. & M.R.C. Project The ontogeny of immune responsiveness. Report Investigations concerning the functional development of the immune response in animals as they mature from foetus to adult have previously demonstrated that there is an increasing bactericidal competence of the fixed hepatic macrophages. Studies have continued with the free macrophages of the peritoneal cavity of rats. Using this system it has been demonstrated that while phagocytosis by the cells from foetal and neonatal animals appears similar to that seen in cells from older animals the bactericidal efficiency of the cells from the very young rats is notably deficient when a similar comparison is made. The importance of the intracellular events which occur following phogacytosis by macrophages has been highlighted recently by the strong suggestion that it is these events which are of primary importance in the subsequent steps leading to antibody production. The working hypothesis has been that the relative macrophage incompetence demonstrated in foetal and very young rats could be a reason for the immuniological deficiency and the ease of tolerance induction in young animals. Further studies were consequently carried out to determine the reasons for the variation in bactericidal ability. It has been shown that the macrophages from young animals vary from these cells from older animals in some morphological characteristics in the relative numbers of some intra-cytoplasmic organelles and acid phosphatase levels. The latter variation In enzyme incidence has been taken to indicate low levels of lysosomal enzymes in cells from foetal animals varying to high concentrations in cells from older animals. This change in enzyme levels could explain the lack of bactericidal ability in young cells and also the deficient antibody formation of young animals if intracytoplasmic degradation is necessary for this process. In addition to this study, investigations into the transfer of isotopically labelled IgG from maternal to foetal and newborn rats have been continued and have demonstrated rapid transfer of isologous IgG in an antigenically and probably chemically unchanged state and marked concentration in the gut. Studies have also been continued into the effect of a thorium dioxide preparation on antibody production and animals' resistance to infection in an attempt to understand the way in which this rapidly phagocytosed particle alters the pattern of the immune response to produce a long term adjuvant effect to the macroglobulin antibody response. Publication JENKIN, C. R., AUZINS, lEVA, and READE, P. C. 'The synthesis of macroglobulin antibody to a bacterial antigen in mice after treatment with Thorotrast.' Aust. 1. expo Bioi. med. Sci., 1965,43,607.
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University of Adelaide
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY Dr R. I. Cox, B.Sc., Ph.D., Reader in Endocrinology. Professor L. W. Cox, M.B., Ch.B., F.R.C.S., F.R.A.C.S., F.R.C.O.G., Professor of Obstetrics and Gynaecology. Dr R. N. Munday, M.B., B.S., M.R.C.O.G., Honorary Assistant Obstetrician. Dr T. L. Black, M.B., B.S., Research Fellow. Project Studies in the control of ovarian, adrenocortical and pituitary function. Report Investigations have been carried out on ovarian and testicular function in selected patienIs with infertility. New procedures to control and test gonadal, adrenocortical and pituitary function have been investigated. A safe effective test for ovarian function and responsiveness has been developed using human menopausal gonadotrophin. The change in oestrogen output following three injections of gonadotrophin is measured. The procedure has been used with thirty-five infertile women, and has given useful data on potential ovarian activity for their fUrther treatment. Results 'of the stimulation test enable patients to be grouped into three main divisions, those with unresponsive ovaries, with potentially normally responsive ovaries, or with polycystic ovaries. Further subdivisions are becoming evident as treatment of the patients continues and their results are observed. Where a patient has given a satisfactory response in the ovarian function test it has been found that a subsequent dose of human chorionic gonadotrophin, suitably timed, can trigger ovulation. The function test can be usefully extended in this way. Ten patients have ovulated with such treatment and two have conceived, each in one course only. This extension of the function test has now led to much simpler courses of ovulation induction with gonadotrophin, based on 3-4 days of menopausal gonadotrophin in place of the usual 7-14 days treatment. Ovarian function testing has proved a useful preliminary to ovulation induction with both gonadotrophins and clomiphene citrate. Most of the patients not responsive to clomiphene citrate have been responsive to gonadotrophin treatment. From these various procedures, eighteen previously infertile women have achieved pregnancy in 1966. From the treatment of infertile patients, data has been obtained on the mechanism of action of clomiphene citrate. This, in some patients, involves a sensitfsation of the ovary. Preliminary work has been carried out on a pituitary gonadotrophin reserve test and a testicular function test. In the gas-liquid chromatographic analysis of steroids, further studies have been made of methods of analysis of pregnanediol, 17-oxosteroids and oestrogens. Variations in column preparation were investigated.
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Publications COX, R. I., COX, L. W., and BLACK, T. L. 'A test for ovarian function and responsiveness leading to ovulation induction.' Lancet, 1966, ii, 888. SHEARMAN, R. P., and COX, R. I. 'The enigmatic polycystic ovary.' Obstet. and Gynaec. Survey, 1966, 21, 1.
University of Adelaide DEPARTMENT OF PAmOLOGY Dr A. W. J. Lykke, M.D., M.e.Path., Senior Lecturer in Pathology. Project Investigation of the thymus as a source of a factor capable of increasing the vascular endothelium.
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tl¥: permeability of
Report An investigation was carried out to determine whether the cells of the thymus contained a factor capable of increasing the permeability of the vascular endothelium, similar to the factor which has been isolated from lymph node cells (lymph node permeability factor). It was found that thymocytes teased from the thymuses of freshly killed rats after ultrasonication liberate a potent permeability factor which is non dialysable and which is active after freeze drying. This heat labile factor was called thymic permeability factor. The intradermal inoculation of this factor into the skin of the ra t causes an immediate exudation of fluid and an emigration of leukocytes. The time course of the exudation and the histological appearances of the inflammatory emigration are almost identical to that produced by the intradermal inoculation of lymph node permeability factor (extracted from animals in this laboratory) except that the depoSition of fibrinoid which has been described after inoculations of this latter factor was not seen. Using a number of anti-inflammatory agents it was possible to demonstrate that the thymic and lymph node factors shared identical inhibition reactions; inhibition was produced by salicylate, indomethacin, guinea pig serum and pyridinol carbamate, whereas antagonists of histamine, serotonin and bradykinin failed to diminish exudation. Both agents were found by the carbon technique to increase the permeability of both venules and capillaries although the former effect was dominant: almost all other factors known to increase the permeability of the vascular endothelium act upon the venular end of the vascular bed. It was found that thymic permeability factor could be eluted from Sephedex G25 and 75 in an identical position to lymph node permeability factor and both factors showed maximum ultravoilet absorption at a wave length of 259 m.,... Antisera produced in the rabbit by inoculation of these factors failed to produce a biologically antagonistic effect, nor was it possible to inoculate neonatal rats with either factor so as to produce a state of biological unresponsiveness similar to that described by workers from St. Bartholomew's Hospital, London, using lymph node permeability factor. A factor with similar biological activity was extracted from the thymus of one human neonate who died from birth injuries. It is concluded that thymic permeability factor and lymph node permeability factor are the same substance.
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Publications LYKKE, A. W. J., and KOSCHE, E. R. 'The effect of traumatic shock on metabolism of alcohol in mice.' Aust. I. Exp. Bioi. Med. Sci., 1966,44,601. SPECTOR, W. G., and LYKKE, A. W. 1. 'The cellular evolution of inflammatory granulomata.' I. Path. Bact. (In press.) SPEC':t:'OR,. W.. G:, WILLOUGHBY, D. A., and L YKKE, A. W. J. 'The sustained cellular emigratIon m mflammatory granulomata.' I. Path. Bact. (In press.) 4275/67-'1.
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University oj Adelaide
DEPARTMENT OF SURGERY Dr J. S. Charnock, B.Sc., Ph.D., Senior Lecturer in Biochemistry. Mr L. J. Opit, M.B., B.S., F.R.C.S., F.R.A.C.S., Reader in Surgery. Miss H. Trebilcock, B.Sc., Postgraduate Scholar, N.H. & M.R.C• Project Further studies on the mechanism of cation transport. Report Further studies have been carried out OJ the mechanism of (Na + K) - activated ATPase and the role of this membranous enzyme system in active cation transport across cellular membranes. Progress has been made with the kinetic examination of the reaction mechanism and supporting evidence obtained for the reality of a phosphorylated enzyme protein as the carrier complex. Further studies will be required to unequivocally establish the precise role of this transition complex in the overall mechanism. The influence of cellular anions on the function of this system has been suggested by experiments on fluoride inhibition of this reaction system and this aspect of the work will be continued and enlarged. To examine a more organised cellular form than the isolated membrane system used in the studies cited above, a preparation of red cell membranes was developed which contains a functional enzyme system and from this evolved a satisfactory localisation of the reaction sites of enzyme (ATPase) activity. This study has involved a critical re-examination of the usual methods of electron-microscopical subcellular enzyme localization and exposed technical short-comings unsuspected in previously accepted procedures. Collaboration with Dr J. R. Casely-Smith has evolved a further electron microscope technique which has enabled absorption of ions on to particulate membrane fragments to be demonstrated. With some modifications it is proposed to apply this technique to a more detailed quantitative study of ion adsorption in the intact red cell membrane. Publications CHARNOCK, J. S., OPIT, L. J., and CASELY-SMITH, J. R. 'Cation accumulation by microand K activated ATPase.' Biochim. Biophys. Acta. 1966, 126, 350. somal Na OPIT, L. J., POTTER, H. A., and CHARNOC K, J. S. 'The effect of anions on (NA+ K+)activated ATPase.' Biochim. Biophys. Act'l, 1966, 120, 159.
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Dr J. D. Sallis, B.Sc., Ph.D., Queen Elizabeth II Fellow. Project Investigation of the mechanism of action of parathyroid hormone. Report . The role of the parathyroids in the regulation of calcium and phosphorus metabolism has been recoQTIised for many years. Both the bone and kidney have clearly been shown to be the sites of di~ect action of the hormone. Despite the intensive investigations which h~~e been pursued within the past decade, little progress has been made towards determmmg the
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University of Adelaide
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mechanism of action of this hormone. This may be partly attributable to the fact that the majority of investigators have been obliged to work with crude extracts of the hormone. Such preparations have limited the nature of the research undertaken. To overcome this problem in the present studies, the preparation of purified hormone was investigated. A technique has now been developed to enable easy location and collection of bovine parathyroid glands from the abbatoirs. By suitable modifications to established fractionation techniques currently employed in the processing of these glands, it has been possible to achieve a purified hormone preparation. The potency of the material, assessed through a method of bioassay utilising the calcium mobilising response of parathyroidectomised 'rats, has been found to be highly satisfactory for most studies. With the availability of the purified hormone, studies were undertaken to investigate more closely, the mechanism of hormone-induced phosphate excretion. A technique has now been developed in the rat whereby it is possible to detect early kidney responses to the hormone. The system utilises a convenient method of rat anaesthesia which is extremely useful for long term studies. It also permits the introduction of the hormone directly into the kidney and by the insertion of a cannulae into the bladder it allows continuous monitoring of urinary phosphate changes. As a result, it has been possible to demonstrate an immediate and dramatic excretion of phosphate following the direct renal infusion of the hormone. Further important information has also been gained from investigation of the dose-level response, sepcificity and time-course of the response. The rat is a most suitable animal for such studies in that a number of physiological states can readily be induced in these animals, thus broadening the scope of the investigations. Apart from its obvious important function in parathyroid hormone work, the method could be used extensively in testing drug action on the kidney. Utilising this rat preparation, studies have been initiated to examine, with the aid of an electron microscope, early changes in the ultrastructure of the kidney following hormone infusion. The results of such a study should prove helpful in interpreting recent data from in vitro studies, which have suggested extensive parathyroid hormone-induced swelling changes in mitochondria. Further investigations of the actions of the hormone on the transport of other ions will also be undertaken.
UNIVERSITY OF MELBOURNE DEPARlMENT OF ANATOMY Dr A. F. Roche, M.B., B.S., Ph.D., D.Sc., Reader in Anatomy. Mrs A. Cahn, B. Agr. Sci., Dip. Diet., Senior Lecturer, Department of Biochemistry. Dr J. J. M. O'Neill, M.B., B.S., Part-time Senior Research Officer, N.H. & M.R.C. Mr F. S. Seward, B.D.S., M.S. (ill.), Part-time Senior Research Officer, N.H. & M.R.e. Dr Joan Towns, MB., B.S., Part-time Senior Research Officer, N.H. & M.R.C. Project The physical growth of normal and abnormal children.
Report An attempt was made to interpret the prenatal and postnatal changes as positive and negative phases of growth and development. A critical review of the elongation of the mandible included a discussion of the present state of knowledge of the sites of elongation of this bone and drew attention to the complete lack of knowledge regarding its maturation after the age of one year. Attention was drawn to the types of studies required before reliable predictions of the elongation of this bone will become possible. A review has been prepared dealing with skeletal maturation and elongation in mongolism. There has been a great deal of recent work in this important field. Mongolism presents unrivalled opportunities for the study of the effects of an additional chromosome on the structure and function of the body. Standardised photographs, in a large number of slightly varied positions, have been used to study the importance of fixing the positions of other parts of the body during the clinical examination of children with possible kyphosis or lordosis. It was shown that it is important to standardise the positions of the pelvis, shoulders, arms and head and also the inclination of the body. After this investigation had been completed, the analysis of growth changes in the lateral silhouette of the trunk was resumed. The earlier study was necessary as a guide to the omission of unsatisfactory records. About 500,000 items of data relating to skeletal maturation in normal children have been punched on cards and a programme has been written to allow their analysis using a computer. This analysis will provide findings relating to the rates of maturation in Melbourne children and the differences between estimates of maturity made according to several methods. Records are still being made of children who are unusually tall or short. In some cases this is clinically helpful but the prime purpose is to obtain data from divergent children that will allow more accurate predictions of mature stature. Long term studies of children with unequal extremities are in progress. These may allow more accurate choices by orthopaedic surgeons of the ages and sites at which operations should be performed. The findings in four recent papers from the study have been analysed again in a review of the mongoloid dentition with special reference to the congenital absence of teeth and the ages of eruption. In the deciduous dentition, congenital absence was limited to t~e lateral incisors but in the permanent dentition the dis tribution of absence was the same as In normal children although it was more common in mongoloids. The eruption of most teeth was delayed to a statistically significant extent. . . . Attention has been directed to a large scale study of dental eruption published In 1837. A statistical analysis of the published data provides evidence of a secular acceleration of the eruption of permanent teeth.
University of Melbourne
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The serial records have been analysed in respect of the development of malocclusion during the change from the deciduous to the permanent dentition. In many children, a malocclusion may result from the movement of the permanent teeth into the excess space resulting from the replacement of the lower deciduous molars by their smaller permanent successors. An analysis is being made of age changes in dental arch measurements to determine the increments in individuals between the ages of two and fourteen years. This information, together with data delating to tooth size, should allow more accurate predictions relevant to crowding in young children. Preliminary findings indicate that cross-bites develop when the -lower dental arch width increases in the absence of corresponding changes in the upper arch. A statistical analysis has been made of serial weights, statures, calorie intakes and skeletal ages in normal children with particular reference to those who were markedly above the mean in one or more of these measurements. The investigation of the nutrient intakes and food habits of normal children has been continued. Assessments have been made also of the nutrient intakes and food habits of some short children. An investigation is being made of the diets of an additional sample of children of similar ages to those studied serially. The aim is to determine whether there are differences in food habits between the two groups that might be attributed to the information and advice supplied to parents after the serial dietary assessments. Publications BARKLA. D. H., ROCHE, A. F., JAGO, J. D., and MARITZ, J. S. 'Possible sex differences in incidence of caries in deciduous cuspids and molars.' Arch. Oral Bioi., 1966, 11, 20 l. BOWDEN, B. D. 'A longitudinal study of digital and dummy sucking.' Aust. Dent. I., 1966, 11, 184. CAHN, A. 'Growth and caloric intake in heavy and tall children.' 1. Arner. Diet. Ass. (In press. ) ROCHE A. F. 'The sites of elongation of human metacarpals and metatarsals.' Acta Anal., 1965, 61, 193. ROCHE, A. F. 'The cranium in mongolism.' Acta Neurol. Scandinav., 1966, 42, 62. ROCHE, A. F. 'The stature of mongols.' Arch. Mex. Anat., 1966,6,3. ROCHE, A. F. 'An early study of dental eruption.' Aust. Dent. 1. (In press.) ROCHE, A. F. The elongation of the mandible.' Arner. 1. Orthodont. (In press.) ROCHE, A. F. 'Skeletal maturation and elongation in Down's Disease (Mongolism).' Eugenics Rev. (In press.) ROCHE, A. F. 'Aging in the human skeleton.' Med. 1. Aust. (In press.) ROCHE, A. F., and BARKLA, D. H. 'The level of the larynx during childhood.' Ann. 0101. Rhin. Laryngol., 1965, 74,645. ROCHE, A. F., and BARKLA, D. H. 'The development of the dentition in mongols.' Ausl. Dem. 1. (In press.) ROCHE, A. F., TOWNS, J. W., and SMITH, E. D. 'Body positioning for clinical assessment of kyphosis or lordosis.' Aust. Paed. 1. (In press.) SEWARD, F. S. 'The development of malocclusion associated with change to the permanent dentition.' Angle Orthodonl. (In press.) TOWNS, J. W., JOHNSON, J. M., and ROCHE, A. F. 'The age of menarche in Melbourne schoolgirls.' Aust. Paed. 1., 2, 67. WETTENHALL, H. N. B., and ROCHE, A. F. 'Tall girls. Assessment and management.' Ausl. Paed. I., 1965, 1, 210.
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THE RUSSELL GRIMWADE SCHOOL OF BIOCHEMISTRY Professor V. M. Trikojus, D.Sc., D.Phil., M.Sc., F.A.A. Dr Mary T. McQuillan, M.Sc., Ph.D., Senior Lecturer. Dr Pamela E. E. Todd, RSe., Ph.D., Lecturer. Miss Paula .Jablonski, M.Sc., Research Assistant, N.H. & M.R.e. Mr G. D. Smith, M.Sc., Postgraduate Scholar. N.H. & M.R.C. Mr N. W. Dunn, Graduate Research Student. Project Studies on the thyroid gland. Report Pig thyroid acid proteinase has now been purified to 3,500 units/mg. compared witb a value of 1,800 units/mg. previously obtained. The highly active preparation is homogeneous in the ultracentrifuge. An important discovery has been that of an inhibitor of the acid proteinase, namely diazoacetylnorleucine methyl ester, after many negative attempts to pinpoint groups in the enzyme which might be part of an 'active centre'. This means that at least one carboxyl group is part of the 'active centre' of this enzyme, which appears to be critical in the intrathyroidal degradation of thyroglobulin. Studies are continuing on the effect of the enzyme and the inhibitor on 131J-labelled thyroglobulin in both the rat and the pig. The initial results of these experiments will be sent forward as a short communication in the near future. It has been shown that the purified pig enzyme, which is active against partially purified rat thyroglobulin at pH 5.2, is practically completely inactivated following prior incubation with inhibitor, but not if the inhibition is carried out in the presence of the thyroglobulin. Similarly, the pig enzyme can be inhibited with regard to its action on pig thyroglobulin where the enzymic activity is optimal at pH 3.5 Modification of the method of preparation of the peptidase acetyl-L-phenylalanyl-Ltyrosine hydrolase (APATase) has resulted in 1,200-fold purification of the enzyme and removal of contaminating acid proteinase and L-cysteinyl-L-tyrosine hydrolase (CTase). APATase has been found to be inhibited by L-tosyl-amido-2-phenylethyl chloromethyl ketone indicating that histidine is involved in the active centre. The leucine aminopeptidase activity of thyroid homogenates has been studied using two characteristic substrates, L-leucine amide and L-Ieucyl-,B-naphthylamide. From the results it appears that there are at least two enzymes with leucine aminopeptidase activity in the thyroid gland. The distribution of proteolytic activity in subcellular fractions of thyroid homogenates has been investigated. APATase and CTase are predominantly particulate whereas acid proteinase (and acid phosphatase, the lyosomal marker) are equally distributed between particulate and soluble fractions. Carboxypeptidase and leucine aminopeptidase are mainly soluble. The effect of thyroid status on the distribution of these enzymes in the rat thyroid has also been studied. The most notable results were a considerable decrease in the total acid phosphatase activity following inhibition of thyrotrophic hormone secretion in low dosage and an increase in the percentage of total acid proteinase activity found in the particulate fraction three hours after injection of thyrotrophic hormone. Publications DOPHEIDE, T. A. A., and TRIKOJUS, V. M. 'Hydrolysis of the A and B chains of oxidized insulin by thyroid acid proteinase.' Biochim. Biophys. Acta, 1966, 118, 435.
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JABLONSKI, PAULA, and McQUILLAN, MARY T. 'The distribution of proteolytic enzymes in the thyroid gland.' Biochim. Biophys. Acta. (In press.) McQUILLAN, MARY T., and TRIKOJUS, V. M. 'Thyroglobulin in glycoproteins: their composition, structure and function.' Elsevier Publishing Company, Amsterdam, 1966, p. 516. MENZIES, CATHERINE A., and McQUILLAN, MARY T. 'Partial purification and properties of a peptidase from thyroid glands.' Biochim. Biopilys. Acta. (In press.)
Dr F. D. Collins, M.Sc., Ph.D., F.RI.e., Senior Research Fellow, N.H. & M.RC. Dr G. G. de Pury, B.Agr.Sci., Ph.D., Research Assistant, N.H. & M.RC. Mr A. J. Sinclair, B.Agr.Sc., Graduate Research Student. Miss Chor Sang Lim, B.Sc., Graduate Researca Student. Mr M. A. TrewheIla, B.Sc., Graduate Research Student. Project Studies on phospholipids. Report The project is concerned \I ith the structure and function of certain phospholipids and with the biochemical role of the essential fatty acids. In recent years there has been much controversy on whether a deficiency of the essential fatty acids is connected with ischaemic heart disease. This has obscured the fact that these fatty acids are necessary in man and it is important that their role in metabolism should be studied in greater detail irrespective of an',' possible connection with atherosclerosis . . The turnover times of the lecithins and phosphatidyl ethanolamines in liver, kidney and heart have been measured in normal rats and in rats deficient in essential fatty acids. The turnover times in liver were less in deficient animals; no difference was found in the other tissues except for the phosphatidyl ethanolamines in heart muscle which had a greater turnover time in deficient animals. It is concluded that the change found in liver phospholipids is connected with fat transport and is associated with the accumulation of triglycerides found in rats deficient in essential fatty acids. The effect found in heart muscle is probably connected with the turnover of the lioprotein membranes. Rats were placed on diets containing no fat, saturated fat, and fat containing adequate linoleic acid and, after ten weeks, killed and the concentration of triglycerides and free fatty acids in serum measured. In addition the rates of fatty acid synthesis in the livers were determined and from these results it was concluded that a decreased secretion of lipoprotein from the liver to the plasma was the likely cause of the fatty liver. Pure linolenic acid was prepared from linseed oil and this, together with arachidonic acid (a gift from Hofmann La Roche, Switzerland), will be used for feeding experiments. After administering acetate-l-C14 to a rat an unidentified fraction was detected in liver lipids which had a greater specific radioactivity than either the triglycerides or the free fatty acids and appeared not to be a diglyceride. Work is continuing on the development of methods for the determination of the specific radioactivity of individual lecithins (characterized by their fatty acids). A method for gas chromatography of triglycerides has been used and modified for the analysis of diglycerides derived from lecithins. The phosphatidic acids derived from the lecithins can be fractionated on thin layer chromatography in the presence of silver nitrate. In this manner a number of
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fractions can be obtained with varying specific radioactivities. It is hoped that further development of this procedure will result in a successful evaluation of the specific radioactivities of the main molecular species of lecithin. The study of lipo-protein membranes was continued. The reaction of mitochondrial protein with lecithins, prepared from normal rats and from rats deficient in essential fatty acids, has been studied in greater detail and the data fitted to theoretical models using both analogue and digital computers. By varying the temperature and by isolating the lecithins from rats fed linolenic acid it is hoped to obtain a greater insight into the mode of reaction of lecithin and protein and in this way to study the role of the essential fatty acids in lipo-protein membranes. Phospholipids are synthesised in the endoplasmic reticulum and may be exchanged, by collision reactions, with the lipo-protein membranes throughout the cell. Experiments are in hand to test this idea. PublicatioDS COLLINS, F. D. 'The counter-current distributions of lecithins.' Chern. Phys. Lipids. (In press.) de PURY, G. G. and COLLINS, F. D. 'The influence of fatty acid composition on the rate of binding of lecithin by extracted mitochondria.' Chern. Phys. Lipids, 1966, 1, L de PURY, G. G., and COLLINS, F. D. 'The influence of fatty acid composition on the restoration of succinate-cytochrome c reductase activity by phospholipids in extracted mitochondria.' Chem. Phys. Lipids, 1966, 1, 20.
DEPARTMENT OF DENTAL PROSTHETICS Professor H. F. Atkinson, M.B.E., M.Sc., D.D.S., M.D.Sc., F.D.S.R.e.s. Dr R. W. Shepherd, D.D.Sc., Reader. Dr C. G. Dennis, D.D.Sc., Senior Lecturer. Dr E. Marks, D.D.Sc., Senior Demonstrator. Mr H. I. Gill, M.D.Sc., Senior Lecturer. Mr K. Johnson, M.D.Sc., Senior Demonstrator. Dr A. A. Grant, D.D.Sc., Senior Lecturer. Mr J. K. Harcourt, M.D.Sc., Senior Lecturer. Projects Muscle activity, mandibular movement and intra-oral forces during speech and mastication; alveolar bone resorption and muscle activity; the development of an intra-oral radio transmitter for the telemetering of the preceding events. Speech variations in the normal, the surgically treated and the untreated cleft palate patient. Report The study of mandibular movement in a group of young dentate students has been continued by using improved cine photographic methods. A more precise measurement has been possible by cementing extra-oral indicators directly to the anterior teeth of the subjects investigated. It has been found that the angle between the paths of approach and departure of the mandibular teeth from the contact point was always less than the included angle of the molar teeth; that there is a definite period during which the teeth remain in contact in which
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no movement could be detected; and that there was no gross sliding of the occlusal surface of the teeth one over the other during mastication. These are significant findings and added to the knowledge of the masticatory process and the movements of the mandible. In associated experiments in which pressure sensitive recorders were incorporated in teeth it was shown that forces were not developed until the teeth were virtually in contact and that such forces increased rapidly and were maintained during the period when movement of the mandible had ceased. There appears to be a definite relationship between the duration of each chew and the period in which the teeth are in contact when movement has ceased. Investigations have continued in the use of radio transmitters mounted in teeth or dentures to give a readout of pressure and position and while investigating some of the problems associated with temperature stability variations in signal strength were detected that appeared too great to be caused by slight rises in temperature. A study of some of the thermal properties of the denture base material (polymethyl methacrylate) was therefore undertaken which led to the finding of a new second order phase transition point at approximately 32' C. At the present time the transmitters are powered by miniature mercury cells which apart from creating problems of incorporation in the denture or tooth have a comparatively short life. Work is proceeding on a method of powering the transmitters from an external source. The investigations on mandibular movement have been extended to include certain clinical groups of subjects for whom major operative procedures have been necessary. Comparisons have been made between normal patients and those who have suffered the loss of a major part of the mandible or maxilla together with the temporomandibular joint. It has been found that the masticatory pattern in these patients after operation is considerably disturbed but after appropriate dental treatment, a pattern can be developed which enables the patient to lead a normal life. This work is of value in the treatment of patients and is being extended to include a study of muscle action in the subjects of this group. The equipment for the separation of speech into its nasal and oral components has been completed and analysis of recordings if proceeding to determine the significance of each factor. The two sounds are recorded on separate tracks on a twin-track tape recorder together with an appropriate synchronizing signal which later allows a precise analysis to be made. Athletes participating in contact sports in the U.S.A. have recognized the need for the protection of the mouth and face against injury. Mouth guards have been developed and appear to be effective but their use in Australian sport has not yet been evaluated. It was the possibility of making improvements in the design of mouth guards from the point of view of speech production and the protection of the face that aroused interest in this problem. A speech and e1ectromyographic analysis has been carried out for a group of athletes for whom mouth guards have been prepared in order to determine the effect of these when worn during contact sports. Full clinical examinations have also been made and the group will be reviewed and compared with similar groups who have not received mouth guards. The study of the activity of the muscles of the face has been continued by detecting the electrical changes which accompany their contraction. Signals have been recorded from both the skin overlying the muscle and also from within the muscle by means of needle electrodes. The latter method detects activity from a localized volume of the muscle surrounding the end of the needle and enables the behaviour of the individual basic functional units to be studied. This has provided information about the neuro-muscular basis of the postural position of the mandible and has disclosed the manner in which muscle activity is graded during the development of force with the teeth in contact. Although surface electrodes attached to the skin are more convenient and comfortable to the subject, the comparison of records obtained during the simultaneous use of both types of electrodes has indicated the necessity for caution when interpreting results obtained with surface electrodes. For example, experiments have shown that the resting lips are influenced by the spread of electrical activity from neighbouring active
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muscles, e.g., the contraction of the muscles of mastication when the teeth ate clenched, and tongue movement to moisten the lips. This w')Ik is of considerable imporance in interpreting myograms when the technique is used for treatment planning in the field of orthodontics. A related histological investigation into the number and structure of stretch receptors in the muscles of mastication has been undertaken. Preliminary findings indicate that muscle spindles in the human masseter muscle exhibit marked morphological differences. Those present in the deep portion of the muscle are greater in length and cross-sectional area, and possess more intrafusal fibres than the spindles of the more superficial part. The collection, measurement and analysis of material associated with changes in the alveolar bone after tooth loss has been continued and records are now available for up to four years. The results indicate a continuing bone loss which is greater in the width than the height of the alveolar ridge. However, an extrapolation of the figures indicates that for most subjects stabilization of the bony base occurs three yeats after the time of tooth loss. The measuring technique which has been developed involves the use of an instrument in which both vertical and horizontal micrometer readings are taken on an appropriately angled cast. This is a tedious and time-consuming procedure and in order to improve the method a semi-automatic electronic contour producing machine has been developed and a prototype made. In this apparatus a stylus is made to follow a pre-determined bone contour on the dental cast and a readout obtained by means of an XY record:r. To further a knowledge of the resorption process bone samples obtained at the time of tooth extraction have been examined by both histological and micro-densitometric methods. In an attempt to evaluate the degree of mineralisation of the bone the absolute tubecular volume has been examined by studying undecalcified sections by means of a microsco)e fitted with an integrating eyepiece. Since dental decay is essentially a destruc':ive disease of the hard tissues of the teeth this section of the work is concerned with the nature of the attack and the reactions of the tooth to this and other forms of injury. As differences in the degrees of mineralization occur in both the destructive and reparative processes, conta~t micro-radiography has been used in conjunction with standard histological techniques to s'udy, firstly normal enamel and ~econdly, tissue changed by disease. The development of a hyp~rmineralized peritubular translucent zone surrounding each dentinal tubule has been shown to be a part of the normal maturation process and changes in this zone are seen to take placc in reSDonse to injury. The changes appear to be directed towards the sealing of the injured dentinal tubules with hypermineralized plugs and so protecting the tooth from further external attack. It is anticipated that the use of the electron microscope together with diffraction te~hniques will sUf)plemimt the data obtained by micro-radiography and lead to a better understanding of the mechanism of the defence reaction of the tooth to dental decay.
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Publications ATKINSON, H. F., and GRANT, A. A. 'Exothermic reaction of polymethyl methacrylate.' Aust. dent. J. 11, 1966, 38. ATKINSON, H. F., and GRANT, A. A. 'A lower transition point for polymethyl methacrylate at 30-320 C.' Nature, 1966, 21, 5049. ATKINSON. H. F. 'The physical principles of impression techniques.' Aust. Dent. J., 1966, 11, 3, 145. ATKINSON, H. F., and SHEPHERD, R. W. 'Masticatory movements and the resulting force.' Arch. oral Bioi. (In press.) ATKINSON, H. F., and SHEPHERD, R. W. 'Masticatory movement and tooth form.' Aust. Dent. J. (In press.) DENNIS, C. G. 'Cleft palate speech. Part I, General considerations.' Aust. Dent. J., 1966, 11,13.
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DENNIS, C. G. 'Cleft palate speech. Part 11, A study of speech sounds.' Aust. Dent. I., 1966, 11, 16. DENNIS, C. G. 'Speech studies on adult male cleft palate patients.' (Abstract) I. Dent. Res. (In press.) GILL, H. I., and GRANT, A. A. 'The anatomy of the pterygoid region of the cat, sheep, goat and monkey.' Aust. J. Zool., 1966, 14, 265. GILL, H. I. 'Action potentials of muscles about the face.' (Abstract) J. Dent. Res. (In press.) GILL, H. I. 'An Electromyographic investigation of motor unit activity in some muscles of mastication.' Aust. Dent. J. (In press.) HARCOURT, J. K. 'The significance of the peritubular translucent zone in human dentine.' Proceedings of Conference on Calcium Metabolism conducted by the Post Graduate Committee in Medicine, University of Sydney, October 1965 . HARCOURT, J. K. 'Tooth structures, micro-radiography and the electron microscope.' (Abstract.) 1. Dent. Res. (In press.) JOHNSON, K. 'A clinical evaluation of upper immediate denture procedures.' J. prosth. Dent., 1966, 16, 5,799. JOHNSON. K. 'A three-year study of the dimensional changes occurring in the maxilla following immediate denture treatment.' Aust. Dent. I. (In press.)
DEPARTMENT OF CONSERVATIVE DENTISTRY Professor E. Storey, D.D.Sc., Ph.D. Dr H. A. McIntosh, B.D.Sc., D.D.S., Senior Lecturer. Mr A. S. Malcolm, M.D.Sc., Senior Lecturer. Project Factors effecting the development and metabolism of hard tissues. Report The investigation of the development of natural and experimentally induced osteoporoses was continued and in order to assess the nature of osteoporoses new methods are being evolved to study the rate of resorption and formation of bone matrix. One method utilises chemicals which become localised in the skeleton of growing animals and which can be identified under ultraviolet light by their chctracteristic fluorescent colours. Administered sequentially these substances demonstrate the growth pattern in bone and can be used to give an index of the rate of removal and addition of bone matrix in normal and rarefying skeletons. Preliminary studies show that rates of bone turnover differ greatly in the rabbit skeleton. Some structural elements in long bones are not replaced for a period of 210 days in contrast to the skull, where more than half the bone formed is removed during this time. This project is being extended to study other bone in the skeleton such as the mandible and vertebral column and to investigate the pathogenesis of osteoporosis in rats fed a calcium deficient diet. While seeking additional bone labelling substances a considerable amount of work has been completed on the nature of labelling of calcifying bone matrix and elastic tissues with some bisazo dyes. It has now been found that some of these stain elastic tissue in blood
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vessels and, following a single dose, are still detectable after six months. The nature of the material being stained in bone and blood vessels in the living animal is being studied by different histochemical methods. This may be of some significance for at least one bisazo dye is known to greatly affect blood coagulation. In order to study mineral metabolism during the development of osteoporoses stable strontium has been used as a tracer for calcium. The validity of using strontium in this way has been explored both in vitro and in vivo. Although there is discrimination against strontium in favour of calcium by bone mineral, it can still be used as a tracer substance to study mineral behaviour in the osteoporoses. Here the release of strontium from bone will be used as an indicator of the behaviour of the mineral component of bone during rarefaction. Present work now shows that this discrimination by bone against strontium is extremely sensitive to pH changes. Consequently the preferenthil removal of radioactive strontium from the skeleton may be possible, for an increase of only 0.2 pH units increases strontium release relative to calcium from bone by a factor of 3. It is intended to explore this possibility in the living animal by use of radioactive tracers. The previous work on the effect of tetracycline antibiotics has been continued. Tetracycline antibiotics stain teeth and bone in man and animals. Techniques have been developed now which permit study of extremely thin histological sections of undecalcified enamel. It has been confirmed that continuous injection of tetracycline colours enamel slightly, whereas a single injection produces little staining. Only if animals lose weight do teeth become deformed and hypoplastic during tetracycline administration. This supports previous conclusions that tetracycline antibiotics do not induce tooth defects, other than staining, unless given in toxic doses which interfere with general growth and enamel matrix formation. Work is continuing also on the effect of mechanical force on bone and bones. Previous work showed that enlargement of the skull could be induced by increased tensile forces applied to the parietal bones. Further study has shown that under increased mechanical pressure cranial sutures are united prematurely by bone formed in the suture space. Further studies on the effect of high levels of fluoride administration on bones and teeth have continued. Although it is well known that high levels of fluoride administration induce osteosclerosis, little detailed work has been done on the pathogenesis of the condition. The present study shows that as early as seven days after fluoride administration at a dose level of 500 p.p.m. in drinking water, metaphyseal fractures have been observed in bones which are becoming denser in the diaphysis. Later, general sclerosis develops and newly formed bone remodels extremely slowly, resorption being confined largely to bone formed prior to fluoride administration. Micro-X-ray, hardness measurements and chemical studies show that fluoride induced bone is abnormal in structure, less dense and more insoluble than normal bone. Using newly developed histological techniques changes in the organic substances of bone can be detected as early as seven days after fluoride administration. This, together with a striking affinity of fluoride bone for both matrix and mineral staining dyes in vivo, suggests that a primary effect of fluoride is on the matrix and that bone crystal changes may be secondary. Further work will be directed towards elucidating the nature of bone matrix and crystal changes during fluorosis by the use of electron microscopic studies. Following previous experiments showing the effects of intermittent administration 01 various hormones and vitamins, fluoride has been administered intermittently to growing rabbits. Even at high doses which induce resorption as well as sclerosis, the resorption phase of remodelling is not obvious and osteosclerotic bone coats the majority of endosteal margins. Microradiographic and histological studies show the intermittent accumulation of sclerotic bone. After nine months, osteosclerosis in these animals is much more pronounced than in rabbits given continuous administration of fluoride. Further work will be directed towards the effect of fluoride administration on experimental osteoporoses.
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Publications HINRICHSEN, O. J. 'The effect of m{;chanical stress on bone.' I. Dent. Res. (Abs.) (In press.) MALCOLM, A. S. 'The study of permeable osteones and their distribution in the tibia.' I. Dent. Res. (Abs.) (In press.) STOREY, E. 'The rarefaction of bone: with particular reference to endosteal bone margin changes.' I. Dent. Res., 1965, 44, 1192. (Abs.) STOREY, E., and McINTOSH, H. A. 'Studies with tooth and bone labelling substances.' I. Dent. Res. (Abs.) (In press.)
DEPARTMENT OF MEDICINE, THE ROYAL MELBOURNE HOSPITAL Dr Priscilla Kincaid-Smith, B.Sc., M.B., B.Ch., M.R.C.P., M.R.A.C.P., D.C.P., Senior
Research Fellow, N.H. & M.R.C. Projects
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The etiology and treatment of renal infection. Correlation of structure and function in renal disease. The treatment of chronic uraemia by diet, dialysis and renal transplantation. Analgesics and the kidney. Hypertension in pregnancy. Report
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The controlled trials of treatment in renal infection have been continued. Results so far indicate that there is no significant difference between two weeks treatment compared with six weeks treatment. A comparison of one and two weeks treatment shows no overall difference in results. However, it seems likely that there is a difference with certain drugs, particularly those related to penicillin. This possibly reflects the mode of action of these drugs and may be due to persistence of abnormal forms of organisms such as L forms and protoplasts and the reversion of these to pathogenic bacteria after completion of treatment. The study on the correlation of structure and function in renal disease has continued. The results in J ,200 renal biopsies have been submitted to a detailed analysis and the results were presented at the International Congress of Nephrology in Washington. Several large groups of cases were analysed. Eighty biopsies done in acute renal failure showed the value of histological lesions in predicting whether or not renal function would return. One hundred and fifty biopsies in the nephrotic syndrome were analysed in relation to the response to steroid therapy. This showed that onJy patients with relatively normal light microscopy findings and fusion of foot processes on electron microscopy responded to steroid therapy. Those with any significant changes on light microscopy, including focal, proliferative and membranous nephritis, were unlikely to respond although a few patients in the focal group showed a complete response. Of sixty-five patients with proteinuria in pregnancy who were studied by renal biopsy the majority showed an underlying focal glomerulonephritis. One could predict the outcome of pregnancy from the severity of the changes and detect those cases in which termination of pregnancy was advisable because of serious underlying disease. Several other groups of cases were analysed.
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Active research in the treatment of chronic uraemia by diet, dialysis and renal transplantation has also continued. A modification of Giordano's low protein diet has now been used with excellent results in over 100 patients with chronic renal disease. Some patients have now survived for over two years having presented with apparent terminal chronic renal failure. Long term Kiil haemodialysis with a view to renal transplantation is now in regular use and over the past year eleven patients with terminal renal failure have been prepared by this method and received cadaveric homografts. Ten of the eleven patients are alive and well with functioning homografts. Sixty per cent of the patients who received homografts in 1965 are alive and well. These results make cadaveric renal transplantation a promising means of treatment. The mechanism of rejection in homografts is being studied by light and electron microscopy on renal biopsy specimens. The results of clinical studies of analgesic abuse and renal disease have been published. Biopsy and autopsy studies of kidneys in cases of analgesic abuse show that the relevant lesion in these cases is papillary necrosis and that this leads to changes of so called chronic interstitial nephritis. The importance of this form of renal disease in Australia warrants further work in an attempt to elucidate the relationship between analgesics and the kidney. The controlled trial of treatment of pregnancy hypertension will probably be completed within six months. Publications KINCAID-SMI11I, PRISCILLA. 'Pyelonephritis and hypertension.' Accepted as part of a book on Renal Hypertension to be published jointly by the American Council jor High Blood Pressure Research and the Cleveland Clinic. (In press.) KINCAID-SMI11I. PRISCILLA. 'The clinical value of renal biopsy.' Proceedings oj Third International Nephrology Symposium, Washington, 1966. (In press.) MARSHALL, V. c', KINCAID-SMI11I, PRISCILLA, YOFFA, D. E., MATHEW, T. H., JOHNSON, V. C., McKENZIE, I. F., ALLCOCK, E. A., LOVELL, R. R. H., and EWING, M. R. 'Experiences with cadaveric renal transplantation with a report of 11 patients.' Med. I. Aust., 1966,1,921.
Dr J. R. E. Fraser, M.D., B.S., F.R.A.c'P., M.R.c'P., Assistant Director and First Assistant. Dr K. D. Muirden, M.D., B.S., M.R.A.C.P., Second Assistant. Mr B. Clarris, B.Agr.Sci., Dip.Ed., Research Officer, N.H. & M.R.c' Project Studies of human synovial cells in vitro, and the ultrastructure of rheumatoid synovial cells. Report The heat-labile inhibition of cell growth previously found in human serum was further studied. The difference in the sensitivity of synovial cells before and after attachment in a culture vessel was confinned by a different technique. It was possible to show that the inhibitor acts against synovial cells derived from the same donor, i.e. in the autologous situation. The relative insensitivity of the cells after attachment could not be fully corrected by the elimination of hyaluronic acid with hyaluronidase.
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platelets produced a sustained increase of glycolytic activity to a period of one hour. These results suggest that there is a relationship between platelet aggregation and platelet glycolysis. Platelets were incubated at 37° C and the nucleotide content assayed. There was a gradual and slight fall in platelet ATP content and a slight increase in platelet ADP content. The addition of thrombin to the platelet suspension resulted in a rapid fall in platelet ATP, ADP and AMP into the supernatant fluid. When small concentrations of thrombin were added to the platelet suspension, and the nucleotide in the total suspension, in the platelet aggregates, and in the supernatant analysed within thirty seconds of the addition of thrombin, it was found that there was a significant release of ADP without any fall in ATP. These results suggest that initially the release of platelet ADP occurs independently of ATP dephosphorylation. They are also consistent with previous reports that thrombin stimulates a platelet ATPase and thus leads to the dephosphorylation of platelet ATP. The addition of collagen to the platelet suspension produced a different pattern of nucleotide change. There was an initial and consistent slight increase in total ATP for up to ten to fifteen minutes and then a gradual fall in A TP. Analysis of the supernatant revealed a release of ADP at a time when there was no fall in ATP. These results suggest that the release of ADP by collagen occurs independently of ATP dephosphorylation. It is of interest that the increase in ATP corresponded to and may have occurred as a result of an increase in glycolytic activity. The results of both the thrombin and collagen nucleotide release experiments suggest that these agents influence more than one nucleotide pool and that the released ADP, initially at least, is not derived from dephosphorylated ATP. Studies on the effect of pyrazole compounds on the platelet collagen reaction were continued. It is known that phenylbutazone is able to suppress the platelet collagen aggregation reaction; the mechanism of this suppression is unknown. It has been investigated by studying in parallel, platelet nucleotide release and platelet aggregation with collagen, before and after the administration of phenylbutazone. It was found that phenylbutazone inhibited the platelet collagen reaction by inhibiting the release of ADP from platelets by collagen. Work on red cell metabolism in congenital haemolytic anaemias continued. Three further families with pyruvate kinase (PK) deficiency haemolytic anaemia have been investigated. The results indicate that there is an overlap between the PK values found in clinically affected homozygous subjects and clinically unaffected heterozygote subjects. In particular, it has been found that a homozygous subject in one family may have higher values than heterozygotes in another family; in these homozygotes PK values may be only slightly reduced, and in such circumstances the demonstration of an increase of 2,3 diphosphoglycerate is an important supportive diagnostic feature. -
-.;....-
Publication LODER, P. B., BABAROZY, C., and de GRUCHY, G. C. 'Red cell metabolism in hereditary spherocytosis.' Brit. J. Haematol. (In press.)
DEPARTMENT OF MICROBIOLOGY Professor S. D. Rubbo, M.D., Ph.D., M.C.P.A., D.Sc. Miss J. C. Franklin, B.Sc., Hons., Research Assistant, Grade II. Miss C. Noble, Technical Assistant. Project
Studies of the prevention of tetanus. 4275/67-3
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University of Melbourne
Report Two major lines of investigation were studied during the past year. The first dealt with '" the rate of disappearance of human tetanus immune globulins in different racial groups, and the second with the extent of immune response in individuals previously immunised to tetanus toxoid. The first study was initiated because of a previollS observation that serum antitoxin levels in Indian volunteers receiving human anti tetanus globulin of European origin were· lower than those in Europeans given the same dose per kg. body-weight. It has now been conclusively demonstrated, however, that the antibody globulin from a particular racial group disappears at the same rate in individuals of the same or different groups living in similar conditions and having the same diet. It would seem, therefore, that the rapid elimination of antibody in Indian subjects, living in India. was due to metabolic rather than immunological causes. The second line of study concerned the antitoxin response to a booster injection of toxoid ~ in individuals who had received a course of active immunisation twenty years previously. It was established that 49 per cent of such individuals had serum antitoxin concentrations exceeding the accepted protective level of 0.01 units/mI and that more than 90 per cent resl)onded to a booster injection. These results have been incorporated in an article entitled: 'New Approaches to Tetanus Prophylaxis', which has attracted international attention. Publications RUBBO, S. D. 'New approaches to tetanus prophylaxis.' Lancet, 1966, ii, 449. RUBBO, S. D. 'Prophylaxis against tetanus.' Proceedings ot the International Conference on __ Tetanus, Bern. July 15th-19th, 1966. f'
Professor F. Gibson, D.Phil., D.Sc., Professor of Chemical Microbiology. Mr G. B. Cox, B.Sc., Technical Officer, Science, N.H. & M.R.C.
in association with Mr Mr Mr Mr R. G. H. Cotton, B.Ag.Sci., Graduate Student. A. F. Egan, M.Sc., Graduate Student. I. G. Young, M.Sc., Graduate Student. R. K. Lnke, B.Ag.Sci., Graduate Student.
Project Studies on the metabolism of aromatic compounds by bacteria. Report Work has continued on the biosynthesis and function of aromatic compounds and several aspects of the work have been studied in detail. The purification and kinetics of the enzyme carrying out the reaction on the formation of 4-hydroxyphenyJpyruvate from chorismate, the first specific reaction in tyrosine biosynthesis, has received further study. The results obtained so far support the idea advanced previously that one protein carries out the two reactions involved in the complete sequence, namely chorismate to prephenate and prephenate to 4-hydroxyphenylpyruvate. Solutions of the enzyme lose activity when diluted and regain activity when concentrated. This observation together with a study of the kinetics of enzyme action suggest that the protein is one of the group of so-called allosteric proteins, the activity of which is markedly affected by end-products of metabolism.
University oj Melbourne ~
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platelets produced a sustained increase of glycolytic activity to a period of one hour. These results suggest that there is a relationship between platelet aggregation and platelet glycolysis. Platelets were incubated at 37° C and the nucleotide content assayed. There was a gradual and slight fall in platelet ATP content and a slight increase in platelet ADP content. The addition of thrombin to the platelet suspension resulted in a rapid fall in platelet ATP, ADP and AMP into the supernatant fluid. When small concentrations of thrombin were added to the platelet suspension, and the nucleotide in the total suspension, in the platelet aggregates, and in the supernatant analysed within thirty seconds of the addition of thrombin, it was found that there was a significant release of ADP without any fall in ATP. These results suggest that initially the release of platelet ADP occurs independently of ATP dephosphorylation. They are also consistent with previous reports that thrombin stimulates a platelet ATPase and thus leads to the dephosphorylation of platelet ATP. The addition of collagen to the platelet suspension produced a different pattern of nucleotide change. There was an initial and consistent slight increase in total ATP for up to ten to fifteen minutes and then a gradual fall in ATP. Analysis of the supernatant revealed a release of ADP at a time when there was no fall in ATP. These results suggest that the release of ADP by collagen occurs independently of ATP dephosphorylation. It is of interest that the increase in ATP corresponded to and may have occurred as a result of an increase in glycolytic activity. The results of both the thrombin and collagen nucleotide release experiments suggest that these agents influence more than one nucleotide pool and that the released ADP, initially at least, is not derived from dephosphorylated ATP. Studies on the effect of pyrazole compounds on the platelet collagen reaction were continued. It is known that phenylbutazone is able to suppress the platelet collagen aggregation reaction; the mechanism of this suppression is unknown. It has been investigated by studying in parallel, platelet nucleotide release and platelet aggregation with collagen, before and after the administration of phenylbutazone. It was found that phenylbutazone inhibited the platelet collagen reaction by inhibiting the release of ADP from platelets by collagen. Work on red cell metabolism in congenital haemolytic anaemias continued. Three further families with pyruvate kinase (PK) deficiency haemolytic anaemia have been investigated. The results indicate that there is an overlap between the PK values found in clinically affected homozygous subjects and clinically unaffected heterozygote subjects. In particular, it has been found that a homozygous subject in one family may have higher values than heterozygotes in another family; in these homozygotes PK values may be only slightly reduced, and in such circumstances the demonstration of an increase of 2,3 diphosphoglycerate is an important supportive diagnostic feature. Publication LODER, P. B., BABAROZY, C., and de GRUCHY, G. C. 'Red cell metabolism in hereditary spherocytosis.' Brit. J. Haematol. (In press.)
~,
DEPARTMENT OF MICROBIOLOGY Professor S. D. Rubbo, M.D., Ph.D., M.C.P.A., D.Sc. Miss 1. C. Franklin, B.Sc., Hons., Research Assistant, Grade II. Miss C. Noble, Technical Assistant. Project Studies of the prevention of tetanus. 4275/67-3
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University oj Melbourne
Report Two major lines of investigation were studied during the past year. The first dealt with -, the rate of disappearance of human tetanus immune globulins in different racial groups, and the second with the extent of immune response in individuals previously immunised to tetanus toxoid. The first study was initiated because of a previous observation that serum antitoxin levels in Indian volunteers receiving human antitetanus globulin of European origin were lower than those in Europeans given the same dose per kg. body-weight. It has now been conclusively demonstrated, however, that the antibody globulin from a particular racial group disappears at the same rate in individuals of the same or different groups living in similar conditions and having the same diet. It would seem, therefore, that the rapid elimination of antibody in Indian subjects, living in India, was due to metabolic rather than immunological causes. The second line of study concerned the antitoxin response to a booster injection of toxoid in individuals who had received a course of active immunisation twenty years previously. It was established that 49 per cent of such individuals had serum antitoxin concentrations exceeding the accepted protective level of 0.01 units/ml and that more than 90 per cent reslJonded to a booster injection. These results have been incorporated in an article entitled: 'New Approaches to Tetanus Prophylaxis', which has attracted international attention. A
Publications RUBBO, S. D. 'New approaches to tetanus prophylaxis.' Lancet, 1966, ii, 449. RUBBO, S. D. 'Prophylaxis against tetanus.' Proceedings of the International Conference on __ Tetanus, Bern. July 15th-19th, 1966. .
Professor F. Gibson, n.Phil., D.Sc., Professor of Chemical Microbiology. Mr G. B. Cox, B.Sc., Technical Officer, Science, N.H. & M.R.C. in association with Mr Mr Mr Mr
R. G. H. Cotton, B.Ag.Sci., Graduate Stu?ent. A. F. Egan, M.Sc., Graduate Student. I. G. Young, M.Sc., Graduate Student. R. K. Luke, B.Ag.Sci., Graduate Student.
Project Studies on the metabolism of aromatic compounds by bacteria. Report Work has continued on the biosynthesis and function of aromatic compounds and several aspects of the work have been studied in detail. The purification and kinetics of the enzyme carrying out the reaction on the formation of 4-hydroxyphenylpyruvate from chorismate, the first specific reaction in tyrosine biosynthesis, has received further study. The results obtained so far support the idea advanced previously that one protein carries out the two reactions involved in the complete sequence, namely chorismate to prephenate and prephenate to 4-hydroxyphenylpyruvate. Solutions of the enzyme "_ lose activity when diluted and regain activity when concentrated. This observation together with a study of the kinetics of enzyme action suggest that the protein is one of the group of so-called allosteric proteins, the activity of which is markedly affected by end-products of metabolism.
University of Melbourne
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Purification of anthranilate synthetase has continued and it has been possible to show that the protein is more complex than hitherto thought, in that the same protein appears to carry out not only the conversion into anthranilate but also carries out the subsequent step in the formation of tryptophan, that is the condensation of anthranilate with ribose phosphate to give phosphoribosyl anthranilate. The two reactions carried out by this protein may be shown as follows: glutamine phosphoribosylchorismate ) anthranilate ) phosphorisbosylanthranilate Mg++ pyrophosphate Mutants with blocks in the common pathway of aromatic biosynthesis have been found previously to respond generally to a mixture of phenylalanine, tyrosine, tryptophan, 4-aminobenzoate and are sometimes stimulated by 4-hydroxybenzoate and 3,4-dihydroxybenzaldehyde. However, it has been observed that some mutants only grow poorly when all these additions are made and it has been found now that the required bacterial growth factor for such strains is 2,3-dihydroxybenzoate. 2,3-dihydroxybenzoate appears to be concerned with metal metabolism since it is formed in very large amounts in supernatants of cultures grown in an iron deficient medium and in one mutant iron or manganese will replace 2,3-dihydroxybenzoate as a growth factor. The enzyme system converting chorismate into 2,3-dihydroxybenzoate has been examined and it has been found that this system may be controlled over a greater than fifty-fold range by varying the concentration of iron in the growth medium. It has also been found that the conversion of chorismate into 2,3-dihydroxybenzoate takes place in at least two steps. Cell extracts also convert 2,3-dihydroxybenzoate to 2,3-dihydroxybenzoylserine. A mutant has been isolated which requires 2,3-dihydroxybenzoate. The recent work on the biosynthesis and function of ubiquinone has continued. Attention has been focused on the enzyme which converts chorismate into 4-hydroxybenzoate, this reaction being the first specific reaction in ubiquinone biosynthesis in some organisms. Reliable assay methods have been worked out for determining the activity of this enzyme, the enzyme purified about 100-fold and some of its properties determined. 4-hydroxybenzoate synthetase appears to be a small protein. A mutant of E. coli has been examined which did not form ubiquinone (see later) and one of the mutations in this organism was found to have affected 4-hydroxybenzoate synthetase activity. It has been possible to determine that the gene coding for this enzyme on the E. coli chromosome is close to the galactose region. Another mutation also affecting ubiquinone biosynthesis has been approximately mapped on the chromosome and found to be in quite a different region from the gene for 4-hydroxybenzoate synthetase. A study has been made of the function of Ubiquinone in malate oxidation in collaboration with Dr A. Snoswell of the Veterinary School of the University of Melbourne. By comparing the rate of oxidation of malate by whole cells and particulate preparations from cells of normal E. coli and the E. coli mutant unable to form ubiquinone together with the effect of various inhibitors on the oxidation, it has been possible to demonstrate that malate oxidation takes place by at least two pathways. One of these is dependent on Ubiquinone, which is presumably part of the electron transport system. This work was complicated by the fact that the original strain unable to form ubiquinone was found to contain several different mutations. This necessitated a lengthy genetic analysis so that the Ubiquinone mutation could be transferred to another strain to make comparisons between the mutant and the wild type valid. In the course of this analysis it was found that the original mutant probably has two mutations affecting ubiquinone biosynthesis, one of them being mentioned above in relation to 4-hydroxybenzoate synthetase and at least one mutation affecting malate oxidation as such. The approximate position of each of these mutations on the E. coli chromosome is known. As previously reported, a mutant which will not form vitamin K has been isolated. Preliminary examination of this mutant shows that certain oxidative activities are affected and further experiments will be carried out when the mutation has been transferred to a new
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cell line. Preliminary experiments carried out in conjunction with Dr Snoswell have shown that this organism may prove a useful tool in making a re-appraisal of the action of vitamin " K antagonists such as dicoumarol. A series of experiments has been carried out in collaboration with Professor L. M. Jackman and Mr I. O'Brien of the Chemistry Department of the University of Melbourne to ascertain the source of the methyl groups in ubiquinone and vitamin K, by a combination of the use of auxotrophic mutants, nuclear magnetic spectroscopy and mass spectrometry. In • these experiments a mutant requiring methionine of E. coli was grown in a medium containing methyI-deuterated methionine. Ubiquinone and vitamin K were isolated and the spectroscopic techniques applied. It was possible to show that the ring methyls in both cases and that the methoxy groups of ubiquinone were derived from methionine by consideration of the NMR spectra of the compounds when measured in suitable solvents. Determination of the molecular weight of the normal and deuterated quinones by mass spectrometry showed that no appreciable amount of deuterium was incorporated elsewhere into the quinone molecules. This technique of tracing the source of methyl groups has the great advantages over the use -:'r of radioactive tracers, in that the molecules do not have to be degraded and this, together with the lack of isotopic dilution when an auxotroph is used, means that the results are easily interpreted and the technique requires relatively small amounts of material. During the last year work on the biosynthesis of the aromatic amino acids has continued, but emphasis has been placed on the biosynthesis and function of aromatic vitamins. As well as the work on ubiquinone and vitamin K, a new bacterial vitamin, 2,3-dihydroxybenzoate, has been discovered and considerable progress made in studying its route of biosynthesis and function in the cell. The role of this compound in cells other than bacterial cells is a -'"7problem for the future. Extremely fruitful joint projects have been carried out with the Organic Chemistry Department and the Biochemistry Department of the Veterinary School in the University of Melbourne, as well as with Dr A. J. Pittard of the School of Microbiology. The work of Dr Pittard and Miss Huang on the mutations affecting the biosynthesis of 4-aminobenzoate is described elsewhere by Dr Pittard. This study is the first part of a joint project combining a genetic and biochemical attack on the problem of 4-aminobenzoate synthesis. In all of these joint projects problems have been approached in a way which would not have been possible if the various groups concerned had been working separately. Publications
COX, G. B., and GIBSON, F. 'The role of shikimic acid in the biosynthesis of vitamin K2 .' Biochem. J., 1966,100,1. COX, G. B., and GIBSON, F. '2,3-dihydroxybenzoic acid-a new growth factor for multiple aromatic auxotrophs.' J. Bacteriol. (In press.) EGAN, A. F., and GIBSON, F. 'Anthranilate synthetase and PR-transferase from Aerobacter aerogenes as a protein aggregate.' Biochim. Biophys. Acta, 1966, 130, 276.
Dr B. W. HoRoway, D.Sc., Ph.D., Reader in Microbial Genetics. Mr B. Rolfe, B.Agr.Sc., Research Student, N.H. & M.R.e. Miss 1. WaItho, B.sc., A.S.T.C., Research Student. Miss V. Stanisidl, B.Sc., Research Student Projects
Gene distribution in Pseudomonas aeruginosa and its relation to enzyme control. Genetic basis of DNA specificity in Pseudomonas aeruginosa.
University of Melbourne Report
29
:;..
~
Genetics studies on the bacterium Pseudomonas aeruginosa have continued to provide new and different information from that found in the more popular bacteria of the Enterobacteriaceae. The information acquired has now reached the point where it can be applied to certain practical aspects of Pseudomonas infections, particularly the renowned drug resistance of this bacterium. There are two aims of the primary research project. Firstly, to establish the nature of sexual reproduction in Pseudomonas aeruginosa and compare and contrast the findings to the situation known in other bacteria. Secondly, by using this system, and that of phage mediated transduction, the gene distribution of Pseudomonas can be compared to that of other organisms. It is now amply confirmed by conjugation experiments that for biosynthetic pathways there is only rare clustering of related genes in Pseudomonas. The experiments on interrupted matings in which various lengths of male chromosome are permitted to enter the female cell, have shown that the genetic elements controlling chromosome mobilisation in Pseudomonas have fewer points of homology with the chromosome than occurs with E. coli. Considerable effort has been expended in trying to find a stable attachment of sex factor to the chromosome (Hfr mutant), because of the great value of such a mutant not only in detailed linkage studies but also in determining the mechanism of chromosome transfer. As yet no such stable mutant has been found but the search is continuing.
Genetic basis of DNA specificity in Pseudomonas aeruginosa Since deoxyribonucleic acid (DNA) is the storage centre of genetic information in the cell, it is obvious that any factors that can change the specificity of this substance or alter the information it imparts, are immediately of medical and biological interest. The specificity of the DNA may be considered to be at three levels. Two of these can be expressed in chemical terms-the base composition of the DNA, and the order of the bases on the phosphate backbone. These are obviously subject to biological control. The third level can as yet only be defined by a biological test, that of host controlled modification. It is postulated that the bacterium possesses two sets of enzymes which impart this specificity. One imposes the relevant specificity on the DNA being synthesised, be it viral or bacterial, while the second set of enzymes is involved in the recognition of incoming DNA as self or non-self. If the DNA is non-self it is rapidly destroyed. It is obvious that such a mechanism of production and recognition of specificity has a profound effect on many cellular properties particularly genetic ones. Attempts to investigate the genetic basis of this whole phenomenon in P. aeruginosa have shown it to be remarkably complex. Several genetic factors affecting DNA specificity have been identified. Firstly, native genes, different from strain to strain and recognised by the segregation patterns of intra-strain crosses. Secondly, temperature induced differences, following ""-- growth at 43° C. When the strains are returned to growth at 3r C these effects persist for sixty to seventy generations. They are postulated to be caused by an episome and slight evidence to support this view has been obtained. Thirdly, intra-strain genes. These can be mutated, give different phenotypes to the 'native' genes and map at different locations. Other factors identified included pleiotropic effects on host specificity following mutations to fluorophenylalanine resistance, and similar effects following mutations at the streptomycin resistance locus. Interactions of some of these genetic factors have been studied and clearly demonstrate the non-clustering of related genes characteristic of Pseudomonas. Apart from the genetic mechanisms of this control this study raises the more general problems of the evolutionary significance of DNA specificity. It obviously provides a mechanism by which a cell can prevent itself from invasion from foreign DNA, particularly that of episomes.
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Publications HOLLOWA Y, B. W. 'Mutants of Pseudomonas aeruginosa with reduced recombination ability.' Mutation Research, 1966, 3, 452. ROLFE, B., and HOLLOWAY, B. W. 'Alterations in host specificity of bacterial DNA following increased growth temperature of Pseudomonas aeruginosa.' J. Bacteriol., 1966, 92, 43. WALTHO, J. A., and HOLLOWAY, B. W. Suppression of fluorophenylalanine resistance by mutation to streptomycin resistance in Pseudomonas aeruginosa.' J. Bacteriol., 1966, 92, 35.
Dr I. H. Holmes, B.Sc., Ph.D., Lecturer. Dr D. O. White, M.B., B.S., Ph.D., M.Sc., M.C.P.A., Reader. Mr I. M. Cheyne, B.Sc., Research Assistant, Comtnonwealth Serum Laboratories. Mrs Marilyn Shew, B.Sc., Research Assistant, N.H. & M.R.C. Projects Electron microscopy of hepatitis viruses. Delay in initiation of viral infection. Viruses in keratoconjunctivitis. Report The search for the elusive virus of infectious hepatitis is being pursued in two systems using the electron microscope. Firstly, biopsies of liver from patients with hepatitis are being examined and compared with controls. Secondly, human cell cultures which have been inoculated with serum from infectious hepatitis cases are being examined at various times after inoculation. No particles resembling those of any known virus have been seen in either liver or cell cultures. However, crystals of what could possibly be an extremely small spherical virus have been seen both in liver and, rather rarely, in the cultured cells. Attempts at purification of these small particles have so far been unsuccessful, probably because they are present in only small numbers. The type of crystal seen in the liver of hepatitis patients has been reported by various workers to occur in a proportion of healthy people. Efforts are now being made to establish whether they are in fact related to hepatitis, that is to determine whether healthy people carrying the crystals are carriers of the virus. For most of the year Dr White was abroad, working at the Albert Einstein College of Medicine, New York, on the biochemistry of adenovirus infection. Meanwhile, in Australia, Mrs Shew has continued her work on keratoconjunctivitis. She has now perfected a highly sensitive technique for the rapid isolation of herpes simplex virus from a majority of the acute cases of this disease presenting to the Royal Victorian Eye and Ear Hospital. The results of the study will shortly be written up in collaboration with Dr K. G. Howsam and Dr I. F. Robertson, who have been carrying out ophthalmological observations. Mr Cheyne, continuing his experiments on delay in initiation of viral infecton, has made a very interesting finding. Cells from which the nucleus has been removed by micromanipulation, appear to support the multiplication of para-influenza virus. This would indicate that cell-coded information is not required for any step in the replication of this virus.
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Publications WHITE, D.O., and CHEYNE, I. M. 'Stimulation of sendai virus multiplication by puromycin actinomycin D.' Nature, 1965,208, 813. WHITE, D.O., and CHEYNE, I. M. 'Early events in the eclipse phase of influenza and para-influenza virus infection.' Virology, 1966, 29, 49. WHITE, D.O., and SOLOMON, J. R. 'Adenovirus and intussusception.' Med. J. Aust., 1966, 1,447.
Dr A. J. Pittard, Dip. Pharm. M.Sc., Ph.D., Senior Lecturer. Mr B. J. Wallace, Dip. Pharm., B.Sc., N.H. & M.R.e., Post Graduate Scholar. Miss M. Huang, M.Sc., Research Assistant.
'-
Project A genetic and biochemical investigation of aromatic biosynthesis in Escherichia coli K-12. Report The work to be reported is a continuation and extension of a project which commenced about two and a half years ago. It is the aim of this project to provide a comprehensive understanding of the regulation of aromatic biosynthesis in Escherichia coli in terms of both genetic and biochemical mechanisms. During the first two years, mutants were isolated blocked in seven of the ten reactions leading to the biosynthesis of phenylalanine and tyrosine. Genetic and biochemical analyses of these strains have been reported. Most of the work during the last year has been concerned largely with studying the first reaction of the aromatic pathway, but in addition an investigation of the biosynthesis of p-aminobenzoic acid from chorismate has also been started. Isolation oj mutant strains lacking one or more of the isoenzymes which carry out the fir,t reaction in aromatic biosynthesis The enzymic reactions leading from erythlOse-4-phosphate and phosphoenol pyruvate 10 chorismate form the common pathway of aromatic biosynthesis. Chorismate is converted via a number of different pathways into three aromatic amino acids, phenylalanine, tyrosine and tryptophan, and into a variety of aromatic vitamins and co-factors. The first reaction of the common pathway, the condensation of erythrose-4-phosphate and phosphoenolpyruvate to give 3-deoxy-D-arabino-heptulosonic acid-7-phosphate (DAHP) is a key reaction from the point of view of control of the synthesis of chorismate. Control is exerted at this point in the following manner. The reaction is carried out by three isoenzymes, the formation of each one being controlled by the intracellular concentration of a particular aromatic amino acid. These three isoenzymes have been referred to as DAHP synthetase (tyr), (that activity repressed and inhibited by tyrosine), DAHP synthetase (phe) (that activity repressed and inhibited by phenylalanine), and DAHP synthetase (try) (that activity repressed by tryptophan). By making use of the known sensitivity of these isoenzymes to repression and inhibition, it has been possible to isolate mutant strains lacking particular isoenzymes. e.g. A strain which lacks DAHP synthetase (tyr) was isolated on the basis of its ability to grow on minimal medium but not on minimal medium supplemented with phenylalanine and tryptophan. In a similar manner mutant strains were isolated lacking DAHP synthetase (phe) or DAHP synthetase (try) or various combinations of the three isoenzymes. Separation and identification of DAHP synthetases on DEAE cellulose Previous workers investigating DAHP synthetases of E. coli have used ammonium SUlphate precipitation to separate DAHP synthetase (phe) and DAHP synthetase (tyr). There are
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University of Melbourne
some drawbacks to this method, in particular it does not allow the separation of DAHP synthetase (try) from the other two isoenzymes. A complete separation of DAHP synthetase (try) from the other isoenzymes has been obtained during this work by using gradient elution from a DEAE cellulose column. In all, four peaks of activity have been identified. Two of these at the moment show the characteristics expected of DAHP synthetase (try) while the other two are readily identifiable as DAHP synthetase (phe) and DAHP synthetase (tyr). Chromatography of cell free extracts from mutants has confirmed the loss of the various isoenzymes predicted as a result of their growth characteristics. Furthermore, the study of these extracts has suggested the possibility that what has been referred to as a single isoenzyme may be a polymer formed from the products of two distinct genes. This possibility is currently being investigated. Genetic analysis oj isoenzyme mutants The mutations carried by these strains have been mapped. The genes for the DAHP synthetases are not grouped together on the chromosome but each one is widely separated from the others. The mapping of these genes was carried out by interrupted mating and by phage PI and A mediated transduction. Aro F, the structural gene for DAHP synthetase (tyr) is cotransducible with both Phe A and Tyr A genes. Aro G, the structural gene for DAHP synthetase (phe) is cotransducible with genes of the Galactose Operon and aro H, the structural gene for DAHP synthetase (try) is cotransducible with aro D. The isolation of mutant strains with properties of altered regulation The isolation of these strains has been greatly facilitated by the availability of the isoenzyme mutants. For example, AB2900, a strain lacking DAHP synthetase (tyr) cannot grow on minimal medium supplemented with phenylalanine and tryptophan, as both these end products effectively shut off the first reaction, hence preventing the essential synthesis of tyrosine. A number of derivatives of strain AB2900 have been obtained that are able to grow on media supplemented with phenylalanine and tryptophan. A genetic and biochemical analysis of one of these strains has revealed that it possesses a mutation in the aro G gene which renders the DAHP synthetase (phe) insensitive to inhibition by phenylalanine. The DAHP synthetase (phe) activity is still however repressible by phenylalanine. In spite of this repression, a strain possessing this altered DAHP synthetase (phe) and inactive forms of the other isoenzymes is still resistant to phenylalanine growth inhibition. Such a strain, in fact, excretes phenylalanine into the growth medium. This result indicates that phenylalanine exerts its control on the first reaction primarily through end product inhibition. A variety of other strains selected in the same manner from AB2900 including some showing resistance to 4-amino-phenylalanine (a tyrosine analogUe) have still to be examined. The biosynthesis of p-aminobenzoic acid The investigation of this problem is being carried out by Miss M. Huang under the joint supervision of Professor Gibson and Dr Pittard. Future studies will be continued by Miss Huang in Canberra. Three mutants have been isolated in a poly auxotrophic female strain of Escherichia coli K-12 that show a strict growth requirement for p-arninobenzoic acid. Special precautions in the isolation and characterisation of these strains have been necessary as it requires only very low levels of p-aminobenzoic acid to support growth of these mutants, and wild type E. coli cells growing on the same plate excrete enough p-aminobenzoic acid to feed the mutants. The mutations carried by these strains have been mapped by interrupted mating and by transduction. Two distinct genes appear to be involved. The precise location of one of these genes, pab A has been determined by transduction. It is situated between the genes for streptomycin resistance str and the aro B gene. The second gene pab B is separated from the first and is found in the chromosomal region between aro D and the tryptophan Operon.
University oj Melbourne
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Future Work There are three major lines of investigation to be pursued with regard to the common pathway. Firstly, cell free extracts will be prepared f rom cells grown under various conditions in which there are limiting concentrations of particular aromatic amino acids. These extracts will be dialysed and chromatographed on DEAE cellulose and the repression and derepression of the four isoenzymes will be compared with the repression and derepression of the two chorismate mutase enzymes and anthranilate synthetase. Two or three of the other reactions in the common pathway will be studied at the same time. Such a study should help to determine whether the system of repression controlling the formation of enzymes after the branch point is identical with the system involved in the repression of the DAHP isoenzymes. Secondly, the two peaks of activity currently regarded as DAHP synthetase (try) will be purified further. Approximate molecular weight determinations will be made by filtration through Sephadex gels. Kinetics of the reaction will be measured for each enzyme and in collaboration with Professor Gibson in Canberra, amino acid analyses of each of these purified enzymes will be carried out. Thirdly, using the isoenzyme mutants that have already been isolated, further mutants will be obtained showing properties of altered regulation. These, in addition to the strains that have already been isolated will be investigated biochemically and genetically. Finally, the study of the synthesis of p-aminobenzoic acid will be continued. The mutations affecting p-aminobenzoic acid biosynthesis will be transferred into an E. coli strain blocked in the three major reactions after chorismate and a biochemical investigation of the reactions converting chorismate to p-aminobenzoic acid will be studied. An attempt to isolate mutant strains which are derepressed for p-aminobenzoic acid biosynthesis will involve the isolation of strains resistant to the p-aminobenzoic acid analogue, sulphadiazine. This work will be part of a continuing collaboration with Professor Gibson at the Australian National University. Publications PITTARD, J., and WALLACE, B. J. 'Distribution and function of genes concerned with aromatic biosynthesis in Escherichia coli.' J. Bacterial., 1966, 91, 1894. PITTARD, J., and WALLACE, B. J. 'A gene controlling the uptake of shikimic acid in Escherichia coli.' I. Bacterial., 1966, 92, 1070. WALLACE, B. J., and PITTARD, J. 'A biochemical and genetic analysis of the isoenzymes concerned in the first reaction of aromatic biosynthesis.' I. Bacterial. (In press).
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY Dr J. B. Brown, M.Sc., Ph.D., First Assistant (Endocrinologist).
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Dr N. A. Beischer, M.B., B.S., F.R.C.S., M.G.O., M.R.C.O.G., First Assistant Dr D. F. Lawson, M.B., B.s., D.G.O., F.R.C.S., F.R.A.C.S., F.R.C.O.G., Director of the Endocrine Clinic, Royal Women's Hospital. Dr J. H. Evans, M.B., B.S., M.R.C.P., M.R.CO.G., Research Fellow. Dr H. P. Taft, M.D., F.R.A.C.P., Endocrinologist Miss M. A. Smith, B.Sc., Assistant Lecturer. Miss S. Barrett, B.Sc., Assistant Lecturer. Miss B. Smyth, B.Sc., Assistant Lecturer. Projects Study of the normal menstrual cycle and of gynaecological disorders having an endocrine basis: treatment of ovarian dysfunction.
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Use of urinary oestriol and pregnanediol measurements in the assessment of placental function and as guides in the management of pregnancy, particularly prolonged pregnancy. Development of rapid methods for the measurement of oestrogen and progesterone metabolites in urine for use in tracking ovarian and placental function. Development of sensitive methods for measuring oestrogens and progesterone or their metabolites in body tissues and fluids. In vitro studies on steroid biosynthesis in ovaries. Report
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The two important aspects of the work are laboratory and clinical investigations, although the two are very closely interrelated. One of the main projects during the past year has been to exploit as completely as possible the analytical procedures referred to in the previous Report. There is a considerable demand from overseas for details of these methods and the manuscripts are being prepared for publication. Rapid methods oj laboratory investigations The rapid methods are six to nine times faster than the standard methods for measuring oestrogens in urine and three times faster for measuring pregnanediol. Applications can now be considered which would otherwise have been impossible because of the labour involved. Their most important application has been to the tracking of ovarian and placental function. Normal values have been accumulated daily throughout 10 ovulatory menstrual cycles, and at intervals during more than 200 pregnancies; normal values have also been obtained for postmenopausal women and men. Because of their greater convenience to the patient and gynaecologist and greater accuracy in interpretation, the assays have now largely replaced other procedures such as endometrial biopsy, vaginal cytology, and culdoscopy in the assesment of ovarian function in patients attending the Endocrine Clinic. This applies both in the initial investigative period when the urines are collected weekly, and during treatment with clomiphene and gonadotrophins. Large numbers of pregnant women are being screened to discover the rarer conditions in which placental insufficiency is an important complicating factor during pregnancy. Sensitive methods of laboratory investigation Sensitivity has been increased 500 times for oestrogens in urine and 20 times for pregnanediol. This sensitivity re-opens lines of investigation in which the earlier methods failed. Perhaps the most important application is to study the effect of ablative therapy in the suppression of oestrogen and progesterone production in women with metastatic breast cancer. This study is being performed in collaboration with the Peter McCallum Cancer Clinic and the Austin Hospital. Preliminary experiments indicate that this is a project worthy of increased resources in the near future. Preliminary experiments have shown that the new levels of sensitivity are sufficient for the measurement of oestrogens and progestet;one in the blood of several species. Blood has been collected throughout the menstrual cycles of five normal women; this is a unique study since plasma levels of follicle stimulating hormone and luteinising hormone will be measured and comparison with urinary levels is being made. Ovarian vein blood has been collected throughout the oestrous cycle in the ewe, and peripheral blood has been collected during pregnancy in this animal. This is part of a project to study ovarian and placental function in the ewe being carried out in collaboration with the Department of Animal Husbandry, University of Sydney. The method has been used for studying the biosynthesis in vitro of oestrogens in the ovaries of the human and pig. The results have emphasised the importance of the oestrogen sulphates as secretory products and this information is being applied in the studies on blood. The application of these sensitive procedures will be greatly extended in 1967.
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Clinical investigations The main aim of the laboratory and clinical investigations is to study disorders of reproduction in the human, to treat these disorders and at the same time to gain as much fundamental information as possible about the many factors involved in normal fertility. The clinical work is progressing on a broad front and depends on the availability of suitable patients for study. Approximately 500 patients with ovarian hypofunction have attended the Endocrine Clinic of the Royal Women's Hospital since 1963. Many complain of infertility. A plan of study and treatment has been instituted for the majority to provide the maximum information about their disorders. Treatment starts with placebo, and according to the response, progresses to cyclical hormone therapy, then clomiphene and finally gonadotrophin, tests of ovarian and pituitary response being performed throughout. In an effort to restart the cycling centres in women with amenorrhoea and oligomenorrhoea, exogenous oestrogen and progestogen are given in such a manner as to simulate the normal cyclical production of these hormones by the ovaries. Over fifty patients have been treated, spontanous cycles have followed in twenty-eight and pregnancy in ten. This simple therapy is being extended to other types of infertility and its mechanism studied. By the monitoring of ovarian response with hormone assays and persevering with treatment in even the most difficult cases five interdependant factors have been discovered which are important in the induction of single fertile ovulations. These include dose of HPG (human pituitary gonadotrophin), timing of HPG, dose of HCG for ovulation, timing of HCG in relation to the last dose of HPG and support of the corpus luteum with further HCG. The difficult cases, or those delivering multiple pregnancies (three), or aborting (three) have provided information of particular importance and the general findings have an application not only in the correct use of these hormones, but also in the further understanding of the processes involved in the normal ovulatory cycle and in abortion. Seventeen patients have received treatment, and at present sixteen pregnancies have resulted in fourteen women. The patients not yet pregnant are still being treated, and the control achieved in the therapy is illustrated by one patient in whom a twin pregnancy was successfully induced by request. This compares favourably with the overseas fignres in which the pregnancy rates have generally been approximately 50%; in these, 50% have been multiple, and the abortion rates have been high. Approximately 4,000 doses of HPG have been prepared in the laboratory during the year. A large part of this has been used in a project to increase spermatogenesis in men; the effect has not yet been completely assessed but the results have been disappointing in terms of pregnancies achieved. The value of urinary oesthiol output as a measure of placental function has been established. The test is being used in the management of pregnancies in which placental insufficiency is suspected in order to determine whether the foetus is in jeopardy and termination is indicated or whether the pregnancy can be allowed to continue without danger to the foetus. Proof that such management results in a decreased perinatal mortality may be difficult to establish; however, the feasibility of a project designed to test this is under consideration. The emphasis in this study has shifted from the more obvious causes of placental insufficiency such as hypertension and renal disease to the less appreciated causes such as antepartum haemorrhage, anaemia and foetal abnormalities. The work on prolonged pregnancy is the largest single research project being undertaken by the Department. The study is prospective and involves all pregnant women presenting at the Royal Women's Hospital before fourteen weeks and in whom the period of gestation can be assessed with some certainty (approximately 1,500 per year). Those managed bv the Professorial Unit have further tests performed at twenty, thirty and forty weeks. All those women who go beyond forty-two weeks are studied intensively both clinically and by
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University oj Melbourne
placental function tests until they deliver. These tests include the examination of the liquor and the measurement of liquor volumes and frequent urinary oestriol and pregnane~ol assays. Almost 150 women have reached this category and the ~esul~ are pres~nt1y bemg analysed. It is expected that a series of 300 prolonged pregnancies will be req~ed b~~ore definite conclusions can be made about the best methods to assess and manage thiS condiuon. PUbUcatiODS
BEISCHER, N. A., BROWN, J. B., MacLEOD, S. C., and SMITH, M. A. 'The value of urinary oestriol measurements in patients with antepartum haemorrhage.' I. Obstet. Gynaec. Brit. Cwlth. (In press.) MacLEOD, S. C., BEISCHER, N. A., BROWN, J. B., and SMITH, M. A. 'The value of urinary oestriol measurements during pregnancy.' Aust. and N.Z. I. Obstet. Gynaec. (In press.) TOWNSEND, S. L., BROWN, J. B., JOHNSTONE, J. W., ADEY, F. D., EVANS, J. H., and TAFf, H. P. 'Induction of ovulation.' I. Obstet. Gynaec. Brit. Cwlth., 1966,73,529.
DEPARTMENT OF PAmOLOGY Dr I. K. Buckley, M.B., B.S., Ph.D., Research Fellow, N.H. & M.R.C. Project
Mechanisms of heat damage to living tissues. Report The mechanisms by which heat damages living tissues have yet to be fully elucidated. Previous microscopic studies indicate that following a single bum the extent and degree of overt tissue damage increases progressively for some hours. This phenomenon is being further studied in the expectation that a better understanding of the mechanisms involved may lead to therapeutic measures capable of controlling the spread of damage. To analyse this phenomenon of increasing tissue damage a microscopic study is being made of experimentally induced discrete thermal injuries in living tissue which is grown as a thin layer in a transparent chamber inserted in the rabbit's ear. Tiny discrete heat injuries are induced by a predetemllned pulse of high frequency electric current conducted to the tissue by a stainless steel electrode, the tip of which is positioned to lie above the selected target area. Accurate observation of the results obtained is facilitated through the use of a cine camera: movie film sequences showing the appearance of the living tissue are made before, during and after injury, so that the various changes induced may be recorded photographically over many hours. In this way permanent records are produced for subsequent detailed study and analysis. Rabbit ear chambers are now in operation. Preliminary movie records of heat-injured tissues have been made and an edited film dealing with various aspects of injured tissue has been prepared. Pub6catiOD
BUCKLEY, I. K., and PORTER, K. R. 'A light and electron microscopic study of cytoplasmic fibrils in cultured cells.' Protoplasma. (In press.)
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HOWARD FLOREY LABORATORIES OF EXPERIMENTAL PHYSIOLOGY Dr Derek A. Denton, M.B., B.S., Principal Research Fellow, N.H. & M.RC. Dr John Blair-West, Ph.D., Research Fellow, N.H. & M.RC. Miss Elspeth Bott, B.Ag.Sc., M.Sc., Research Associate. Mr Michael Cain, B.Sc., Research Associate. Dr John Coghlan, Ph.D., Research Fellow, N.H. & M.RC. Dr James R. Goding, M.B., B.S., Senior Research Fellow, Wool Industry Fund. Mr Jolm S. McKenzie, M.Sc., Senior Lecturer, Department of Physiology. Mr Bruce Scoggins, M.Ag.Sci., Research Associate. Mrs Sigrid Weller, M.Sc., Research Associate. Miss Marelyn Wintour, M.Sc., Lecturer, Department of Physiology. Professor R. Douglas Wright, M.B., M.S., D.Sc., F.R.A.C.P., Professor of Physiology. Collaborators: Dr J. F. Tait, F.R.S., Mrs S. A. S. Tait, F.R.S., Miss Angela Hartley, Ph.D.-The Worcester Foundation for Experimental Biology, Massachusetts, U.S.A. (Biosynthesis investigation.) Dr Ralph Peterson, Professor of Medicine, Cornell University Medical School, New York.
(Renin programme.) Professor Bryan Hudson, Professor of Medicine, Monash University. (Androgen investigation.) -Project
The control of the salt balance of the body. Report Disorders of fluid balance of the body are a common mode of clinical presentation of disease states of the heart, kidney and liver. Disorders of the physiology of these organs induced by diverse diseases may result in accumulation of fluid in the body (dropsy and ascites). An understanding of the intrinsic and endocrine mediated processes involved in the normal regulatory processes function of these organs is essential to elucidation of the sequence of events in the disease state and to effective treatment of the disorders. Following the evidence from this laboratory and the National Heart Institute, United States of America that secretion of aldosterone, the salt-retaining hormone of the adrenal gland, is controlled by a humoral agent there has been intensive investigation of the question of whether the renin-angiotensin pressor system deriving from the kidney is the principal control system involved. The precise evaluation of the role of the renin system in control of secretion of salt retaining hormone in various conditions has great potential clinical importance since the knowledge will also further understanding of the role of this system in both renal and essential hypertension, and in hypertension attributable to tumours of the adrenal gland. The first stage of the study in hypophysectomised anephric animals to determine the site of origin of aldosterone-stimulating hormone has been completed. Aldosterone secretion continued at a high level in sodium-depleted anephric sheep for six hours after nephrectomy in most experiments, but by twelve hours aldosterone secretion had fallen to sodium replete levels. This result is not consistent with the results of other workers using dogs, and this rate of fall of aldosterone secretion is slower than would be expected on current estimates of the halving-time of renin in vivo. It was much slower than the rate of reduction of aldosterone output observed when an intravenous infusion of sheep renin was stopped. In view of the possibility that the rate of disappearance of exogenous renin might not adequately describe the
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University of Melbourne
disappearance rate of endogenous renin after nephrectomy, renin levels were measured after nephrectomy in sodium-depleted sheep. The plasma renin disappearance curve has two components. The first exponential has a halving-time of approximately one hour, the second exponential has a halving-time of approximately eight hours, which may be due to the existence of extravascular stores of renin. This pattern of decay of renin blood levels is not compatible with the observed rate of fall of aldosterone secretion following nephrectomy in hypophysectomised sheep, and supports the suggestion that a factor other than the renin-angiotensin system is involved in the maintenance of aldosterone secretion in sodium-depletion. The partially purified sheep renin, prepared as described in the 1965 report, has been used as a standard reference for the assay of renin in the kidney and in peripheral plasma. This renin preparation has been shown to produce antibodies in the rabbit, and the antirenin titre of the antiserum is being determined by in vivo and in vitro methods. It is intended to use antirenin antibody to eliminate renin effects in sodium deficiency and other conditions associated with increased aldosterone secretion. A method has been developed for assay of the renin content of kidneys in the sheep and other species. A small wedge of kidney cortex is homogenised in normal saline and diluted in phosphate buffer. The diluate is incubated with a renin substrate prepared from dialysed, lyophilised sheep plasma. The reaction is stopped by heating and the incubate centrifuged. The supernate is assayed for angiotensin activity in a vagotomised, pentolinium-treated rat. The method has high reproducibility and the dispersion of recovery of added renin is from 80% to 105%. The renin content of the renal cortex of Na-replete and Na-deprete sheep has been measured. The renin content is increased in sodium-depletion, but it is not consistently elevated in late pregnancy. In collaboration with Myers of C.S.I.R.O. Wildlife, Canberra, and Junqueira of San Paolo, Brazil, the relation has been studied between the metabolic state of the animal and salt appetite in native and introduced species of animals in the Snowy Mountains of Australia. The results have been compared with findings in a continental desert or a sea coast region where soil and plant sodium content was vcry high. The very low sodium content of grass in the alpine region contrasts with the very high content in the continental desert. On a grassy plateau area near Canberra there was an intermediate low sodium content. Urinary sodium excretion was consistently very low in alpine rabbits in contrast to high levels in desert animals. Peripheral blood aldosterone concentration was high in the mountain animals. Low values were seen in the desert animals with intermediate values for the plateau grassland animals. Renin content of the kidney cortex was highest in the mountains with low levels in the sodium-loaded desert animals. The mean width of zona glomerulosa of alpine rabbits was two and a half times greater than the desert animals. The urine of kangaroos and wombats in the alps contained less than 1 mEq/l of Na+, whereas the sea coast kangaroos and wombats had very high outputs. Peripheral blood aldosterone concentration was usually higher in the mountain animals, and also the area of the zona glomerulosa was increased two- to three-fold. Concurrent with these metabolic observations, it has been shown that these wild alpine rabbits show an avid specific appetite for sodium salts. When wooden pegs impregnated with various salts are placed in the alpine forest, the animals gnaw NaCI and NaHC03 pegs, and largely ignore KCl, MgCh, CaCl2 and distilled water washed pegs. Salt appetite was not seen in the desert rabbits. A novel feature which has emerged is the Na-deficiency caused striking changes in the salivary glands of the marsupials-proliferation of intralobular ducts, increased epithelial height and hypervascularity of the duct region. Summarising, these comparative data have demonstrated circumstances in nature where aldosterone plays an important role in the whole organism adaptation to ecological conditions involving severe sodium deficiency. The concentration of renin in peripheral plasma is being measured by an enzyme kinetic method. Briefly, the method consists of dialysis of the plasma sample against EDTA solution at low pH to destroy angiotensinases and endogenous substrate. The plasma is incubated with a renin-substrate prepared from nephrectomised sheep plasma and the renin concentration is
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determined from the rate of production of angiotensin. The reaction between renin and renin substrate is first order, i.e., dependent on renin concentration only. The reproducibility of the method is high, and the recovery is within +20%. The specificity of the method is still under investigation. When sheep renin is infused intravenously the rate of infusion is proportional to the peripheral concentration of renin as measured by the method outlined, blood pressure and the aldosterone secretion rate. During the course of sodium-depletion by loss of parotid saliva, aldosterone and renin concentrations in peripheral blood increased progressively with sodium deficit. The concentration of renin was elevated following acute surgery or haemorrhage, but was only high normal in late pregnancy. The specificity of the assay was demonstrated by the observation that renin level was zero in nephrectomised sheep, and was not elevated by acute haemorrhage or sodium depletion in these circumstances. The~:e results with direct measurement of renin in plasma, in so far as they permit inference of a corresponding elevation of angiotensin II in blood, are strong evidence that the reninangiotensin system plays an important physiological role in stimulation of aldosterone secretion. However, other recent data suggest that the control system may be quite complex. Infusion of sheep renin at 4 U/hr for 12-16 hours caused substantial elevation of blood pressure but aldosterone secretion, initially elevated, fell to basal levels in 10-14 hours. The result indj~ates that conditions other than entry of renin into the circulation are necessary at the andrenal level to reproduce the physiological response to sodium deficiency. Furthermore, infusion of angiotensin II intravenously, or into the adrenal arterial supply of moderately sodium-depleted sheep, failed to augment aldosterone secretion significantly, which suggests that a factor other than angiotensin is necessary for the full functional response of the adrenal glomerulosa to severe sodium depletion. Studies have been commenced in experimental renal hypertension. Partial occlusion of one renal artery by a clip resulted in an in<:rease of blood pressure and plasma renin and aldosterone concentration within twenty-four hours. Usually within seven days renin and aldosterone levels in peripheral plasma were within the normal range, whereas the hypertension was sustained. These preliminary results suggest that although activation of the reninangiotensin-aldosterone system is associated with the onset of this hypertensive state, the mechanism is not essential for the maintenance of it, unless the physiological conditions produced also involve a large increase 'n sensitivity of vascular tissue to circulating
i
angiotensin. It has been shown previously that the contractile action of angiotensin on ileal smooth muscle preparations is potentiated by high environmental sodium concentration. The site of action of high sodium has been determined by comparing the contractile response, DMPP, acetylcholine and electrical stimulation in the presence of ganglion-blocking agents, nerveblocking agents and atropine, with varying sodium concentration in the media. High sodium concentration potentiates the action of angiotensin in the presence of effective doses of tetrodotoxin and atropine. The results indicate that high sodium potentiates the direct action of angiotensin at the smooth muscle cell, and not at a site in the intramural nervous element. In collaboration with the Tait group at the Worcester Foundation of Experimental Biology, investigations have been made on the in vivo biosynthesis of aldosterone. Using conscious sheep with transplanted adrenal glands, 3H corticosterone has been infused into the adrenal arterial supply for thirty minutes, during which time all the adrenal venous effluent has been collected. 4- 14 C-aldosterone has been used as an internal indicator in the rigorous purification and isolation procedures which have been used to determine the amount of labelled aldosterone produced. The aldosterone secretion rate was determined by modified double isotope dilution procedures, as allowance had to be made for 3H in the steroid ring. In the six sheep used, conversion to aldosterone of the 3H corticosterone substrate introduced into the artery occurred. Adrenal arterial infusion of 3H corticosterone was begun at zero time, and blood collected in five minute intervals during 25-30 minutes. 3H aldosterone appeared in the first period (0-5 minutes) and, in five of the six animals studied, steady state
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University of Melbourne
conversion occurred from ten minutes onwards. In other experiments the adrenal venous effluent was allowed to recirculate after the fifth or sixth five minute period, with the 3Hcorticosterone infusion continued. Further adrenal venous samples were taken at 60, 120 and 180 minutes. This is sufficient time for any other labelled steroids produced by the adrenal under these experimental conditions to have reached a plateaued level in peripheral blood. Any further utilisation of these products by the adrenal was not apparent. There was no significant trend in % -conversion during the recirculation period. The percentage conversion and aldosterone secretion rate when Na replete and at levels of Na-deficiency was studied. There was a progressive increase in percentage conversion with sodium deficiency. The mean percentage conversions at aldosterone secretion rates of 4-5.99, 6-7.99,8-9.99 and 10-11.99 ",g./hour are highly significantly increased over the mean of the replete level. At higher secretion rates the increase disappears. It could be postulated therefore that two mechanisms may be involved. One acts in early sodium deficiency, and is such that an increase in the % -conversion of corticosterone to aldosterone occurs. At higher secretion rates this mechanism is either inhibited or obscured by another, or both. A method for the measurement of aldosterone in the peripheral blood of the human and the sheep has been established. Based on the principle of double isotope dilution, 0.5 ng./sample can be measured with good accuracy. The blank of the method has been controlled by microdistillation of the radioactive reagents prior to use. The actual blank of the procedure ;s 0.2 ng./sample. The mean aldosterone level in recumbent human subjects on 80 mEq/day Na + intake is 6 ng./IOO m!. This method will allow exploration of the factors which affect metabolic clearance rate and secretion rate of aldosterone in the conscious human subject. The collaborative programme on metabolism of testosterone in the human, with Professor Bryan Hudson and colleagues, at the Medical Research Centre, Prince Henry's Hospital, forms the basis of a separate report from that department. Publications BLAIR-WEST, J. R., BOrr, E., COGHLAN, J. P., DENTON, D. A, MYERS, K., SCOGGINS, B. A., WINTOUR, M., and WRIGHT, R. D. 'Salt deficiency and salt appetite of mountain animals.' Proc. International Congres~Psychol. Sci., Moscow, 1966. (In press.) BLAIR-WEST, J. R., BOYD, G., COGHLAN, J. P., DENTON, D. A., WINTOUR, M., and WRIGHT, R. D. 'The role of circulating fluid volume and related physiological parameters in the control of aldosterone secretion.' Ausi. J. expo Bioi. med. Sci. (In press.) BLAIR-WEST, J. R. COGHLAN, J. P., DENTON, D. A., GODING, J. R., ORCHARD, E., SCOGGINS, B. A, WINTOUR, M., and WRIGHT, R. D., 'Mechanisms regulating aldosterone secretion during sodium deficiency.' Proc. III Internat. Congr. Neprol., Washington, 1966. (In press.) BLAIR-WEST, J. R., COGHLAN, J. P., DENTON, D. A. GODING, J. R., WINTOUR, M., and WRIGHT, R. D. 'The direct effect of increased sodium concentration in adrenal arterial blood on corticosteroid secretion in Na deficient sheep.' Aust. J. expo Bioi. med. Sci., 1966, 14, 455. BLAIR-WEST, J. R., COGHLAN, J. P., DENTON, D. A, and WRIGHT, R. D. 'The effect of endocrines on salivary glands.' Handbook of Physiology (Chapter in the volume on Alimentary Canal). American Physiological Society, Washington, 1966. (In press.) BLAIR-WEST, J. R., and McKENZIE, I. ,So 'So?iu~ concentration and the effect Df giotensin II on the ileal smooth muscle. ExpeTlentta, 1966,22,291. BO~~, G. W. 'The reproducibility and accuracy o~ plasma volume. estimation .in the sheep with both 1311 gamma globulin and Evan's blue. Aust. I. expo BioI. med. SCI. (In PIe5I!·)
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CATT, K., and COGHLAN, J. P. 'The generation and use of antibodies to angiotensin II.' Aust. !. expo Bioi. med. Sci. (In press.) COGHLAN, J. P., CAIN, M., DUMANIS, A, HUDSON, B., and SCOGGINS, B. A 'The measurement of concentration and metabolism of steroids in body fluids by application of double labelling procedures with special reference") aldosterone.' Proc. 2nd International Congr. Hormonal Steroids, Milan, 1966. E{erpta Medica Series No 111, Abstract No. 52. COGHLAN, J. P., WINTOUR, E. M., and SCOGGINS, B. A. 'The measurement of corticosteroids in adrenal vein blood of sheep.' Aust. !. expo Bioi. med. Sci. (In press.) DENTON, D. A 'Salt appetite.' Handbook of Physiology (Chapter in the volume of Alimentary Canal). American Physiological Society, Washington, 1966. (In press.) DENTON, D. A 'Some theoretical considerations in relation to innate appetite for salt.' Conditional Reflex. (In press.) GODING, J. R. 'Ovarian autotransplantation with vascular anastomoses, and its application to the study of reproductive physiology in the ewe.' J. Physiol. (Lond.), 1966, 186, 86. GODING, 1. R., and McCRACKEN, J. A. 'Preparation of a jugulo-carotid ovarian autotransplant in the sheep.' Proc. 2nd International Congr. Hormonal Steriods, Milan, 1966, Exerpta Medica Series No. Ill, Abstract No.472. HUDSON, B., and COGHLAN, J. P. 'The androgens.' In Endocrine Laboratory Diagnosis, ed. J. B. Brown. (In press.) HUDSON, B., and COGHLAN, J. P. 'Testosterone secretion.' In Clinical Endocrinology, ed. Astwood and Cassidy. Cmne & Stratton. (In press.) HUDSON, B., COGHLAN, J. P., DULMANIS, A., and WINTOUR, M. 'Measurement of androgen production in the normal subject.' Aust. Annals Med. (In press.) HUDSON, B., COGHLAN, J. P., and DULMANIS, A 'Testosterone function in man.' Ciba Colloquia in Endocrinology-The Testis. (In press.) McCRACKEN, J. A., and GODING, J. R. 'Progesterone secretion by the jugulocarotid ovarian autotransplant in the sheep.' Proc. 2nd International Congr. Hormonal Steroids, Milan, 1966, Exerpta Medica Series No. 111, Abstract No. 473.
DEPARTMENT OF PHYSIOLOGY ,K"
Dr D. J. Dewhurst, B.A., M.Sc., Ph.D., Reader in Biophysics. Mr A. H. WRcock, M.Sc., Research Student. Project The precise control of human muscular movements. Report The performance of highly skilled muscular movements by a human subject requires the production of sequences of contractions at a rate far greater than can be produced by deliberate conscious control of each separate movement. There has been considerable speculation by various scientific workers over the past twenty years as to the degree and kind of information which is required to be fed back from the active muscle groups to the brain to allow 4275/67-4
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University of Melbourne
preCISIOn of this sort, and hypotheses involving almost complete dependence on fed back information have been advanced. The work carried on in this Department and supported by the N.H.M.R.e. over the past two years has shown that this view is unlikely to be true, and that the control is exercised almost wholly by volleys of descending responses, in sequences which have been found by previous training and experience to be most appropriate to the situation. Information fed back as a result of the action, unless it is performed very slowly, will be available in the brain too late to modify the course of the action, but will be used to modify future actions of the same type. Work is at present in progress in studying the structure of these bursts of impulses, and investigating how they can be modified by training, and the manner in which a programme of teaching rapid skilled movements can best be implemented. This study is of the utmost importance in all situations in which a human operator is controlling a machine, and is also of vital interest in the re-education of patients who have suffered motor nerve injuries. It is proposed to continue this work with an investigation of the way in which the control volleys are varied following nerve injury, using the apparatus already developed and in use, including the PDP-8 digital computer recently acquired for use in this Department. Publications DEWHURST, D. J. 'Precise control of human muscular movements.' Proceedings of the Australian Association of Neurologists. (In press.) DEWHURST, D. J. 'Physical instrumentation in medicine and biology.' Pergamon Press, Oxford, 1966, pp. 201 and index. DEWHURST, D. J. 'Neuromuscular control systems.' Proceedings oj Second International Biophysics Congress, Vienna, 1966, 504.
Dr A. Shulman, B.Sc., M.B., B.S., A.R.I.C., F.R.A.e.I., Senior Medical Research Fellow, N.H. & M.R.C. Miss G. M. Laycock, M.Sc., Postgraduate Scholar, N.H. & M.R.e. Projects The action of metal chelates in biological systems. The mode of action of central nervous system stimulant and depressant drugs in the intact animal. Report The action of metal chelates in biological systems It has been shown, in collaboration with Mrs A. Cade, that the dermatophytes Candida albicans and Trichophyton mentagrophytes do not develop significant resistance when subcultured repeatedly in synthetic medium in the presence of selected metal chelates to which they show considerable sensitivity. This has considerable importance in the treatment of topical infection due to such organisms. A chemotherapeutic trial, carried out in collaboration with Dr T. R. Bradley, has demonstrated that selected metal chelates are ineffective in preventing tumour growth in mice innoculated with P388 lymphocytic leukaemic cells although the cells were killed when incubated with the chelates in vitro. It has been shown by the use of a fluorescent metal chelate that this may be due to the much slower in vivo penetration of the compound into these cells
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University oj Melbourne
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than into Landschiitz ascites tumour cells, the growth of which is prevented in mice by the chelates. Preliminary studies in collaboration with Mrs H. Cooper have shown that certain metal chelates modify the normal rhythm and tone of guinea-pig ileum as well as its response to certain neurohumoral substances. It is hoped to extend these studies to provide information concerning the nature of the drug receptors and the functional organisation of the ileum.
The mode oj action oj central nervous system stimulant and depressant drugs in the intact animal It has been shown by titration against a homologous series of , - dialkylglutarimides with agonist, partial agonist and antagonist action that a variety of central nervous system stimulant and depressant drugs most likely act at common sites in the central nervous system, sites which are capable of mediating both stimulation and depression. The responsive neuronal surface seems to be non-specific with respect to the types of drugs to which it will respond while the nature of the pharmacological response appears to depend on the physio-chemical properties of the drug molecule as a whole. Physico-chemical studies and organic syntheses have been undertaken in collaboration with Professors A. S. Buchanan and L. M. Jackman to determine the important steric, hydrophilic and hydrophobic characteristics of the drug and surface concerned in producing the pharmacological response. Publications DOlG, A. G., GRENOT, J., LAYCOCK, G. M., SHULMAN, A., and WERNER, A. 'An analysis of selected drug action in the central nervous system.' Symposium on the use of computers in Medicine and Biology, Melbourne, 1965. (In press.) SHULMAN, A., and LAYCOCK, G. M. 'A reappraisal of drug action in the central nervous system.' The Pharmacologist, 1966, 8, 183. SHULMAN, A., and LAYCOCK, G. M. 'A molecular basis for the action of certain drugs in the central nervous system.' 3rd Int. Pharmacal. Congr., Sao Paulo. Abstracts, p. 8.
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DEPARTMENT OF ZOOLOGY Professor G. Bumstock, M.Sc., Ph.D. Mr A. G. Willis, M.Sc., Senior Lecturer. Dr D. C. Rogers, Ph.D., Lecturer. Dr G. Campben, Ph.D., Lecturer. Mr P. M. Robinson, B.Sc., Senior Demonstrator (and Ph.D. student). Mr J. R. McLean, B.Sc., Demonstrator (and Ph.D. student). Mr M. R. Bennett, B.E., M.Sc., Research Student. Mr C. Bell, M.Sc., Research Scholar, N.H. & M.R.e. Miss S. Kirby, B.Sc., Research Student. Miss J. Read, B.Sc., Research Student. Mr V. ZawaIinski, B.Sc., Research Student. Professor R. S. Orlov, D.Med.Sci., University of Melbourne Senior Research Fellow.
University of Melbourne
Dr A. Yamauchi, M.D., University of Melbourne Research Fellow. Professor I. Singh, Ph.D., L.R.c.P., M.R.C.S., Leverhulme Visiting Fellow. Dr R. Bagby, Ph.D., N.I.H. Research Fellow. Project Autonomic nerve and smooth muscle physiology. Report Studies of the electrophysiological features of transmission from intramural excitatory and inhibitory neurones to the smooth muscle of the guinea-pig taenia coli have been continued. The problem has been extended to include the identification of the chemical transmitter released from the inhibitory nerves, and serial light and electronmicroscope studies of the pattern of innervation. A quantitative correlation of the electrophysiology and electronmicroscopy of the guineapig vas deferens has shown that only those axons within 1,OOOA of a muscle cell could be effective during transmission and that the long time course of the excitatory junction potential is probably due to the time taken for transmitter action on the muscle membrane. Comparative electrophysiological studies of the time course of junction potentials and miniature junction potentials in the rat, mouse and guinea-pig vas deferens have been continued and correlated with electronmicrosco/ic examination of the density of innervation. An ultrastructural study of the distribution of acetylcholinesterase in the areas of close contact between autonomic nerves and smooth muscle has been made in the toad bladder and vas deferens, and correlated with electrophysiological observations. The form and size of intra-axonal granular and agranular vesicles has been examined in the amphibia where fluorescent histochemical studies have shown that the sympathetic transmitter is adrenaline and in the mammals and reptiles where it is noradrenaline. Nicotine has been shown to increase the discharge of minature junction potentials in the guinea-pig vas deferens, which supports the view that its primary action is to release noradrenaline from sympathetic nerve terminals. Comparison of the maguitude and pattern of the responses of the guinea-pig vas deferens to stimulation of the hypogastric nerves 'loaded' either by in vitro or in vivo methods with noradrenaline, a-methyl noradrenali['e or adrenaline are being made. Spectrofluorometric assay and fluorescent histochemical localisation of tissue catecholamines before and after 'loading' "re also being carried out. The effects of the cholinergic ;!rugs, atropine and physostigmine on transmission to the guinea-pig vas deferens have bee.! examined. The results have been interpreted as evidence for the existence both cholinergic and adrenergic innervation. An intracellular electrode investigation of the role of the enzymes monoamine oxidase and catechol-o-methyl transferase, which metabolise catecholamines, in sympathetic nerve transmission are being carried out. Two smooth muscle cell types have been identified in the guinea-pig vas deferens in terms of the response of their membranes to current flow. One cell type gives passive electronic responses, the other non-propagating regenerative depolarisations. The effect of calcium and sodium on these responses, has been examined. A method of using the sucrose-gap technique to determine the ionic basis of the membrane potential of smooth muscle has been published and applied to the gu~ea-pig ~reter.. . Experiments are in progress to determine the threshold pulse duratIOn for direct stimulation of smooth muscle. Comparative physiology and morphological st~dies of visceral ~nd car?iovascular systeD?s in vertebrates and invertebrates have been contmued. Adrenergtc termmals about entenc ganglion cells have been demonstrated in the mammal gut and with the fluorescent
University of Melbourne
45
histochemical method and their role in peristalsis examined physiologically. Similar studies are being carried out on the intestines of lower vertebrates and molluscs. Examination of the effects of physostigmine on the toad bladder has shown that in addition to a low level of inhibition of tissue cholinesterases, this drug has atropine-like blocking action on smooth muscle receptors and also causes release of acetylcholine from nerve endings. The rate of contraction of a number of ditIerent vertebrate smooth muscles has been . measured and correlated with cell size and degree of development of the endoplasmic reticulum. The histology, electrophysiology, electronmicroscopy and pharmacology of the intestine and rectum of various molluscs has been studied, and remarkable similarities with the innervation of the vertebrate gut revealed. Comparative pharmalogical studies of the innervation of the lung and bladder of the lizard and toad have been completed and correlated with fluorescent histochemical localisation of monoamines in these tissues. The effect of seasonal changes, temperature and humidity on catecholamine levels in toad viscera have been measured. The distribution of adrenaline and noradrenaline in neurones of the sympathetic chain of Jish and amphibia is being studied. The effects of vasoactive agents on the smooth muscle of aortic spiral strips of reptiles, amphibians and teleosts are being studied and compared to mammalian species. Changes in arterial and venous blood pressure in the presence of these drugs are also being measured in the anaesthetised animals. The fine structure and histochemistry of the fish heart is being examined in relation to the question of whether or not it is supplied by sympathetic nerves. The development of autonomic innervation of smooth muscle has been studied. The electronmicroscopy of developing mouse vas deferens I to 180 days after birth has been examined, with particular reference to the ratio ofaxons to muscle cells. The results are being correlated with the histochemical localisation of monoamines and cholinesterases and with the biophysics of the transmission process at the different developmental stages. Stages in the development of sympathetic innervation of blood vessels of the vertebratl.! bladder are being examined with the fluorescent histochemical method. Several departments of the Medical Faculty are assisting with the project. Electronmicroscope and fluorescent histochemical studies of the innervation of the sheep parotid gland have been made (in collaboration with Professor R. D. Wright, Department ;)f Physiology) . Histochemical and electronmicroscope studies of cardiac tissue taken from patients suffering from cardiomyopathy have been undertaken and will be continued. Control tissue will also be examined when it becomes available (in collaboration with Dr G. Sloman, Royal Melbourne Hospital) . It has been suggested that angiotensin exerts its action on vascular smooth muscle via the nerves. Studies of the effect of angiotensin on isolated strips of human umbilical artery are being carried out. This artery provides an ideal preparation for studying the direct action of drugs on vascular muscle, uncomplicated by the presence of nerves. It is intended to extend these studies of the cardiovascular system of lower vertebrates where the results can be related to the evolution of the kidney and the nature of salt balance (in collaboration with Professor A. E. Doyle, Department of Medicine). Investigations of the role of noradrenergic terminals on ganglion ceIls in Auerbach's plexus and the pharmacology of intramural inhibitory enteric neurones are being carried out (in collaboration with Professor M. J. Rand, Department of Pharmacology). Electronmicroscopic examination of the innervation of the vas deferens and the snail rectum is being correlated with eIectrophysiological data on these organs (in collaboration with Dr N. C. R. Merrillees, Department of Anatomy).
46
University 01 Melbourne
Two review articles on autonomic neuromuscular transmission and drug action have been written during the year (in collaboration with Dr M. Holman, Department of Physiology). Histochemical and pharmacological studies of the innervation of the human uterus are being made (in collaboration with Professor C. Wood, Department of Obstetrics and Gynaecology) . Publications BELL, C. 'Effects of physostigmine on smooth muscle.'. Biochem. Pharmacol., 1966, 14, 1085. BELL, C. 'A histochemical study of the esterases in the bladder of the toad (Bulo marinus).' Compo Biochem. Physiol. (In press.) BELL, C. 'An electrophysiological study of the effects of atropine and physostigmine on transmission to the guinea-pig vas deferens.' I. Physiol. (In press.) BELL, C. 'Use of the 'direct-coloring' thlocholine technique for demonstration of intracellular neuronal cholinesterase.' I. Histochem. Cytochem., 1966, 14, 567. BENNETT, M., BURNSTOCK, G., and HOLMAN, M. E. 'Transmission from perivascular inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.' I. Physioi., 1966, 182,527. BENNETT, M., BURNSTOCK, G., and HOLMAN, M. E. 'Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.' I. Physiol., 1966, 182,541. BENNETT, M., and BURNSTOCK, G. 'Application of the sucrose gap method to determine the ionic basic of the membrane potential of smooth muscle.' I. Physiol., 1966, 183, 637. BENNETT, M. R., and BURNSTOCK, G. 'The electrophysiology of the innervation of intestinal smooth muscle.' In: 'Handbook of Physiology'. (In press.) BENNETT, M. R. 'Transmission from intramural excitatory nerves to the smooth muscle cells of the guinea-pig taenia coli.' I. Physioi., 1966, 185, 132. BENNETT, M. R. 'Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves.' I. Physio/., 1966, 185, 124. BENNETT, M. R. 'A model of the membrane of smooth muscle cells of the guinea-pig taenia coli during transmission from inhibitory and excitatory nerves.' Nature, 1966, 211, 1149. BENNETT, M. R., and MERRILLEES, N. C. R. 'An analysis of the transmission of excitation from autonomic nerves to smooth muscle.' I. Physio/., 1966, 185, 520. BENNETT, M. R. 'The effect of cations on the electrical properties of the smooth muscle cells of the guinea-pig vas deferens.' I. Physiol. (In press.) BURNSTOCK, G., and HOLMAN, M. E. 'Junction potentials at adrenergic synapses.' Pharmacol. Revs., 1966, 18, 481. BURNSTOCK, G., and HOLMAN, M. E. 'Effects of drugs on smooth muscle.' Ann. Rev. Pharmacal, 1966, 6, 129. BURNSTOCK, G., and WOOD, M. E. 'Innervation of the urinary bladder of the sleepy lizard (Trachysaurus rugosus). II Physiology and pharmacology.' Compo Biochem. Physiol. (In press.) BURNSTOCK, G., CAMPBELL, G., and RAND, M. J. 'The inhibitory innervation of the taenia of the guinea-pig caecum.' I. Physiol. 1966, 182, 504. CAMPBELL, G., and BURNSTOCK, G. 'The comparative physiology of gastrointestinal motility.' In: 'Handbook of Physiology'. (In press.)
University oj Melbourne
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CAMPBELL, G. 'Nerve-mediated excitation of the taenia of the guinea-pig caecum.' I. Physiol., 1966, 185, 148. McLEAN, J. R., and BURNSTOCK, G. 'Histochemical localisation of catecholamines in the urinary bladder of the toad (Bujo marinus): I. Histochem. Cytochem., 1966,14,538. McLEAN J. R., and BURNSTOCK, G. 'Innervation of the urinary bladder of the sleepy lizard (Trachysaurus rugosus). I Fluorescent histochemical localisation of catecholamines.' Compo Biochem. Physiol. (In press.) ROBINSON, P. M., and BELL, C. 'The localisation of acetylcholinesterase at the autonomic neuromuscular junction.' I. Cell. BioI. (In press.) ROGERS, D., and BURNSTOCK, G. 'The interstitial cell and its place in the concept of the autonomic ground plexus.' J. Compo Neurol., 1966, 126, 255. ROGERS, D., and BURNSTOCK, G. 'Multi-axonal autonomic junctions in intestinal smooth muscle of the toad (Bujo marinus).' J. Compo Neurol., 1966, 126, 625. ROGERS, D. C. 'A histological and histochemical study of the carotid labyrinth in the anuran amphibians (Bujo marinus, Hyla aurea and Neobatrachus pictus).' Acta anal., 1966, 63, 249.
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MONASH UNIVERSITY
DEPARTMENT OF ANATOMY Professor G. C. Schofield, M.D., D.Phil. Dr D. G. Silva, B.D.S.,F.D.S., R.C.S., M.R.e.S., L.R.e.P., F.A.C.D.S. Mr A. K. S. Do, M.Sc., Research Assistant, N.H. & M.R.e. Mrs J. M. Southwell, B.Sc., Research Assistant. Dr R. M. Alexander, B.Sc., M.B., B.S. Project The ultrastructure, cultural characteristics, and secretory properties of intestinal cells. Report The main ohjective of the project has been to extend earlier studies on the distribution and structure of the enterochromaffin cells in the intestine of rodents and to determine the nature of the secretions manufactured by the cells. The mouse has continued to be the main animal studied because of the unusual form of the enterochromaffm cells in the large intestine of this species. Morphological studies on normal animals have established that the number of enterochromaffin cells in the large intestine varies markedly in different animals. Two types of enterochromaffin cell have been identified and the detailed form of each has been examined by electron microscopy; one type of cell has cytoplasmic inclusions resembling those described by other workers as characteristic of the enterochromaffin cell and some cells of this type have an intimate association with enteric nerve fibres; the other type, which contains unusual crystal inclusions, does not appear to have been describrd previously. Most previous studies on enterochromaffin cells have suggested that they are involved in the production of the biologically active amine, S-hydroxytryptamine (SHT). During this year, using sensitive techniques for assaying the content of SHT in the large intestine of normal mice on which counts of enterochromaffin cells were also made, it was established that there is no consistent relationship between the numbers of enterochromaffin cells and the SHT content. Further, the administration of a drug, reserpine, which is known to deplete SHT from tissues, has not resulted in any alteration of the numbers or histochemical properties of the enterochromaffin cells in the large intestine even although the 5HT content of the large intestine was significantly reduced in treated animals. At least nine biologically active substances incorporated in gelatin models have been found to show fluorescent and historchemical properties similar to those of SHT. Chromatographic examination of extracts of large intestine in mice has established the presence of unknown and as yet unidentified substances which may be amines or their metabolites and which possibly confer on enterochromaffin cells their characteristic histochemical reactions. The structural association between enteric nerve fibres and one of the varieties of enterochromaffin cell requires much more detailed study before its Significance can be established. It seems likely, however, that at least one variety of enterochromaffin cell is involved together with nerve cells in regulating movements of th e intestine. Publications ALEXANDER, R. M. 'Enterochromaflin cells in developing mice.' I. A nat. (Lond.). (In press.) HO, A. K. S. 'Counts of enterochromaffin cells in chicks.' I. Anat. (Lond.). (In press.) HO, A, K. S., SOUTHWELL, J. M., and SCHOFIELD, G. C. 'Histochemical and pharamcolOgical studies on the S-hydroxytryptamine content of the colon in mice.' I. Anat. (Lond.). (In press.)
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I
UNIVERSITY OF MELBOURNE Howard Florey Laboratories of Experimental Physiology
Dr J. R. Blair-West, Research Fellow (N.H. & M.R.C.), examining a sheep with an adrenal transplant
Miss C. Oddie, Research Biochemist, with vacuum apparatus and chromatography systems used in the laboratory studies of biosynthesis
.. Professor R. D. Wright operating with the assistance of Sister S. van Holst
MON ASH UNIVERSITY
Department of Biochemistry
Professor J. Bornstein measuring oXYl'cn consumption of tissues in a vibrating reed oxy/?en polarograph
Department of Physiology
Professor A. K. McIntyre and Dr J. L. Veale, Senior Lecturer, examining results of computer operations produced by a direct writing recorder
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Monash University
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SCHOFIELD, G. c., HO, A. K. S., and SOUTHWELL, J. M. 'Enterochromaffin cells and 5hydroxytryptamine content of the colon of mice.' I. Anat. (Land.). (In press.) SCHOFIELD, G. C. 'The enteric plexus of mammals.' Int. Rev. Gen. Exp. Zool. (In press.) SCHOFIELD, G. C. 'The anatomy of muscular and neural tissues in the alimentary canal.' In Handbook of Physiology. (In press.) SILVA, D. G. 'Ultrastructural observations on multivesicular cell in the epithelium of the intestine.' I. Anat. (Land.). (In press.) SILVA, D. G. 'Ultrastructural observations on crystal-containing cells in the epithelium of the large intestine of the mouse.' I. Anat. (Land.). (In press.) SIL VA, D. G. 'Quantitative ultrastructural studies on the nerve fibres in the mucous membrane of the colon.' I. Anat. (Land.). (In press.) SILVA, D. G. 'The fine structure of multivesicular cells with large microville in the epithelium of the mouse colon.' I. Ultrastruct. Res. (In press.) SILVA, D. G. 'Crystal-containing cells in the intestinal epithelium of the mouse.' Sixth International Congress for Electron Microscopy, Kyoto, Japan, 1966. SILVA, D. G. 'The ultrastructure of crystal-containing cells in the colonic epithelium of mice.' I. Ultrastrucl. Res. (In press.) SILVA, D. G., and SCHOFIELD, G. C. 'The ultrastructure of argentaffin cells in the distal part of the mouse colon.' I. Anat. (Land.). (In press.)
DEPARTMENT OF BIOCHEMISTRY Professor J. Bomstein, D.Sc., M.D. Professor M. E. Krahl, Ph.D., University of Chicago---Visiting Professor 1966. Dr J. McD. Annstrong, Ph.D., Senior Lecturer in Biochemistry. Dr M. K. Gould, Ph.D., Lecturer in Biochemistry. Mr K. M. Ayadurai, B.Sc., Research Scholar. Mr R. E. H. Wettenhal1, B.Sc., Research Scholar. Project Insulin antagonism. Report Studies on the insulin antagonist previously isolated from pituitary glands and pituitary growth hormone had indicated that the material was homogenous in nature and it was proposed to commence sequence analysis. A critical study, however, showed that the previous ultracentrifuge and electrophoresis data was not correct and that samples prepared in the manner reported in fact had three components of which one, that present in minimal concentration, was active. As the quantity recoverable was minute, a fresh approach to preparation was developed and by the use of prolonged treatment with dilute acetic hydrochloric acid mixtures at 0° C. followed by chromatography of the extract on phenol sulphonic resin a highly active crude material was obtained. This material contained eight separable components, of which only one was active. Further purification was achieved by chromatography on a carboxylic resin and a very highly active material obtained. This proved to contain three polypeptides of which the major component was active.
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Monash Dniversity
Simultaneously with purification procedures, experiments on the localisation of site of action were commenced. Using fatty acid synthesis by liver slices as the criterion of activity, it was shown that the reciprocal of the inhibition was proportional to the logarithm of the concentration of polypeptide and that the concentration required to produce a minimal significant inhibition (20 per cent) 2.5 X 1<rB gm/ml. Analysis of slices for intermediates of the glycolytic pathway showed a significant diminution of concentration of 2-phosphoglycerate, enolphosphopyruvate and pyruvate suggesting that the polypeptide was acting in the area of triosephosphate dehydrogenase. Further experiments showed that fatty acid synthesis was also inhibited in liver homogenates and analysis of glycolytic intermediates showed an accumulation of fructose 1-6 diphosphate, dihydroxyacetone phosphate and glyceraldehyde 3 phosphate with a marked diminution of 2-phosphoglycerate, enolphosphopyruvate and pyruvate. thus accurately localising a site of action at triosephosphate dehydrogenase. Experiments were then carried out with crystalline triosephosphate dehydrogenase isolated from rabbit muscle and it has been shown that the polypeptide produces inhibition of the enzyme irrespective of the concentration of the enzyme substrates, thus indicating a direct effect on the enzyme. Kinetic and physical studies are now proceedi1!g to determine the nature of the inhibition. As the enzyme is a dimer there is strong possibility of an allosteric mechanism being involved. A further study has commenced to determine whether the gross effect on fatty acid synthesis is entirely due to the inhibition of triosephosphate dehydrogenase or whether there is a second locus of action. The work on slices and a preliminary account of the effect of the polypeptide on crystalline triosephosphate dehydrogenase are at present being prepared for publication.
Professor A. W. Linnane. M.Sc., Ph.D., Professor of Biochemistry. Dr H. B. Lukins, M.Sc., Ph.D., Lecturer in Biochemistry. Dr G. D. Clark-Walker, B.Sc., Ph.D., Senior Teaching Fellow. Mr D. JoHow, M.Sc., Senior Teaching Fellow. F. Firkin, M.B., B.S., B.Sc. (Med.). Post-graduate Student. Mr D. R. Biggs, B.Sc., Technical Officer, N.H.& M.R.C. M. Duncan, B.Sc., Research Student, N.H. & M.R.C. Mr P. J. Rogers, B.Sc., Research Student. R. Yu, B.Sc., Research Student. G. Saunders, B.Sc., Research Student. Dr D. Willde, B.Sc., Ph.D., Reader in Genetics, University College, London. Project The origin and mechanism of formation of mitochondria together with the manner of organisation and synthesis of the mitochondrial enzymes. Report The yeast cell offers a unique biological system for the study of the biogenesis of mitochondria. Thus the aerobic yeast cell contains mitochondria with apparently classical properties. However, under certain specific anaerobic conditions the cells appear to be free from recognisable mitochondria but their formation· is induced on oxygenation of the cells. Under both aerobic and anaerobic growth conditions the formation of the mitochondria and
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Monash University
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associated enzymes are under the influence of a catabolite (glucose) repression. Certain lipid components, namely, ergosterol and unsaturated fatty acids are required both for anaerobic growth and the formation of mitochondrial profiles. The previous studies have shown that the antibiotic chloramphenicol inhibits the formation of the cytochromes a-aa by the cell and this observation was described in the 1965 report. During the past year, the investigations have centred mainly on a continuation of the work on the mechanism of action of chloramphenicol and the lipid requirements for membrane formation. Sterol requirements for membrane formation Cellular organisation is a function of membranes. An understanding of development, in its very simplest terms-the differentiation of a cell into its various membrane-bound compartments-requires some insight into the manner in which membranes are assembled from their protein and lipid components, and of the factors which direct this assembly. Under anaerobic conditions S. cerevisiae is unable to synthesise sterols but the growth of the organism can be initiated by a supply of exogenous sterol, leading to the development of a 'primitive' system of intracellular membranes, as judged by electron microscopy. The structural parameters in the sterol requirement for anaerobic growth and thus membrane formation has been investigated. It has been found that the response to sterol is all-or-none, that is the growth-promoting sterols are all equally effective in supporting growth. Some basic structural features are as follows:A side-chain at carbon-14 of the steroid nucleus is necessary. This may be modified slightly (unsaturation or methyl substitution) but may not be cyclised. Unsaturation within the steroid nucleus is not required, although this typically occurs in natural sterols, such as cholesterol, ergosterol and stigmasterol; more surprisingly, the hydroxyl substituent at carbon 3 may be in either the alpha or beta configuration, i.e., either above or below the plane of the steroid ring system, although the beta configuration is not found in natural sterols. The hydroxyl substituent may not be replaced by a carbonyl group. Thus the ability of a sterol to support growth shows no stringent structural requirements. A further features, now being examined, is whether the junction of the A and B rings of the nucleus may be only in the transconfiguration, as it is in most natural sterols. How do these findings bear on the problem of membrane assembly? A minimum of structural specificity can be envisaged, in order that the sterol supplied to the organism can fit within the native lipoprotein framework. Current speculation on membrane assembly views this process as being organised by a structural protein, which binds specific lipids and catalytic proteins, to form a sub-unit which may then vesicularise, or aggregate spontaneously to a sheated lipoprotein framework. The question of fitting, therefore, involves the possibility of interaction of sterol with one or more of these components and the manner in which it may influence the assembly of the sub-units, vesicularisation or the viability of the final structure. In vivo differentiation of yeast cytoplasmic and mitochondrial protein synthesis with antibiotics When S. cerevisiae is grown in the presence of an excess of fermentable substrate and chloramphenicol the extent, and rate, of its growth is unaffected, but the formation of the cytochromes a, a3, band Cl are all inhibited as is the formation of the mitochondrial cristae. On the other hand, the synthesis of cytochrome c is unimpaired and electron microscope studies show that the formation of the outer mitochondrial membrane appears normal. The experiments are interpreted to indicate that the classical cytoplasmic ribosomal protein synthesising system is unaffected in vivo by chloramphenicol and that the outer mitochondrial membrane and cytochrome c are formed by this system. Also it seems clear that the protein synthesising system of the mitochondria is inhibited by chloramphenicol and it evidently synthesises the
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Monash University
cristae of the mitochondria and cytochromes a, a3, band Cl. We have considered that the results have a wider significance and that based on its sensitivity to chloramphenicol the mitochondrial system of yeast and presumably that of other more highly evolved organisms have properties similar to that of bacteria. Conversely as the yeast cytoplasmic ribosomol system is insensitive to chloramphenicol this system evidently differs in a number of respects from that of bacteria and mitochondria. It follows that antibiotics which inhibit bacterial protein synthesis would be expected to inhibit in growing yeast cells, the same system as chloramphenicol. This proposition was tested and erythromycin, the tetracyclines and carbomycin all completely inhibited the formation of cytochromes a and a3 by growing yeast while spiramycin, oleandomycin and lincomycin all partially inhibited the system. As in this experiment the organism was cultured on growth limiting amounts of fermentable substrate some affect on growth was also observed. The specificity of the action is illustrated by the effect of cycloheximide on the yeast. This antibiotic is lethal to yeast and higher organisms and it is known to inhibit the protein synthesising system of the cytoplasmic ribosomes. However, unlike the other antibiotics cycloheximide had no selective effect on the synthesis of cytochromes a, a3 by the yeast. These results suggest some important conclusions, namely, that as all of these compounds with the exception of cycloheximide, are clinically useful systemic antibiotics, they are useful because they do not inhibit the major protein synthesising system of the hosts' cells, the cytoplasmic ribosomes. Such antibiotics as inhibit the cytoplasmic ribosomal system will be very toxic compounds, e.g., cycloheximide. In highly evolved organisms such as the mammal the turn-over of the mitochondria is very slow compared with that of the sytoplasmic ribosomes and hence antibiotics which inhibit mitochondrial protein synthesis will be comparatively non-toxic. It is intended at some future time to test this idea further with a mammalian system.
A comparison between wild type and cytoplasmic respiratory deficient mutant yeasts inhibited by chloramphenicol The formation of mitochondria by yeast is under both cytoplasmic and nuclear genetic control. The cytoplasmic respiratory deficient mutant, the so-called cytoplasmic petite, is phenotypically characterised by a lack of the mitochondrial enzymes, cytochromes a, a3, b and Cl. The effect of the cytoplasmic mutation appears to be confined to the insoluble enzymes of the mitochondrial cristae while cytochrome c and a number of other readily solubilised enzymes of the mitochondria are still formed by the organism. Non-chromosomal mutations affecting cytochrome c do not appear to exist but chromosomal mutations affecting all of the cytochromes, collectively or separately are known. The characteristics of wild type cells inhibited with chloramphenicol and the cytoplasmic petite grown in the presence and absence of chloramphenicol have been studied. No effect of chloramphenicol on the cytplasmic petite was detected and the chloramphenicol inhibited wild-type cell was found to have properties very similar or identical to that of the petite. The observations suggested that chloramphenicol affects the same system as that affected by the cytoplasmic mutation. Thus chloramphenicol appears to reversibly inhibit the translation of the specific genetic information for particular mitochondrial proteins at the level of the mitochondrial ribosome, while the mutation resulting in cytoplasmic respiratory deficient yeast either eliminates or permanently prevents the transcription of this genetic information. Publications CLARK-WALKER, G. D., and LINNANE, A. W. 'In vivo differentiation of yeast cytoplasmic and mitochondrial protein synthesis with antibiotics.' Biochem. Biophys. Res.
Commun., 1966,25,8.
Monash University
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CLARK-WALKER, G. D., and LINNANE, A. W. 'The biogenesis of mitochondria in Saccharomyces Cerevisiae. A comparison between cytoplasmic respiratory deficient mutant yeast and chloramphenicol inhibited wild type cells.' I. Cell. Biol. (In press.) HUANG, M., BIGGS, D. R., CLARK-WALKER, G. D., and LINNANE, A. W. 'Chloramphenicol inhibition of the formation of particulate mitochondrial enzymes of saccaromyces cerevisiae.' Biochim. Biophys. Acta, 1966, 114, 434. LUKINS, H. B., THAM, S. H., WALLACE, P. G., and LINNANE, A. W. 'Correlation of membrane bound succinate dehydrogenase with the occurrence of mitochondrial profiles in saccharomyces cerevisiae.' Biochim. Biophys. Res. Commun., 1966, 23, 363.
Dr P. R. Davoren, B.Sc., Ph.D. Mr R. Hosken, B.Sc. Project The biosynthesis of insulin in calf pancreas pieces. Report In all species of animals so far studied the molecule of insulin consists of two polypeptide chains joined by disulphide bridges. The aim of the project is to determine the means by which the insulin molecule is assembled, and in particular, whether or not the chains are separately synthesised. The approach has been to incubate pieces of calf pancreas with radioactively labelled amino acids and to isolate the insulin from the tissue at the end of the incubation. The labelled insulin is then cleaved into its constituent chains and the extent of the incorporation a number of amino acids into each of the chains is determined. Initial results indicated that one of the chains was preferentiallytabelled, and this finding together with other evidence was interpreted to mean that the chains were separately synthesised. Some anomalous results indicated, however, that the procedures used, although accepted by a number of other workers, may not have been adequate for separation of the constituent chains of insulin in a state of radiochemical purity. A systematic study of the cleavage of insulin and the separation of the reaction products was undertaken. It was found that the radioactive insulin isolated from the pancreas, although acceptably pure by normal criteria, was contaminated with several compounds present in very small amounts, but highly labelled with radioactivity. The chemical nature of these materials is at present being studied. These components are of considerable interest as their demonstration may invalidate most of the studies carried out by ourselves and other workers on the relative rates of incorporation of amino acids into the two chains of insulin. The properties of these components elucidated to date make them excellent candidates for the postulated, but as yet undiscovered. bio<v,,thetic precursor of the insulin molecule.
Dr D. A. Lowther, B.Sc., Ph.D., Reader in Biochemistry. Mrs A. T. W. Goh, B.Sc., Research Student. Miss E. Baxter, B.Sc., Research Student. Projects An investigation of the macromolecular structure of cartilage. An investigation of the structure of intervertebral disc cartilage.
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Report The mechanical properties of cartilage depend on a complex interaction between a fibrous collagen network and a hydrated gel containing acid mucopolysaccharide protein complexes. In general a histological examination of ageing changes in cartilage show an increased fibrous network and decreased gel phase resulting in varying degrees of impairment of mechanical function. Chemical studies have shown major changes in the composition of the acid mUCDpolysaccharides as reported in December 1965, and the purpose of this project has been to examine the nature and physiological significance of these changes. The two projects are complementary in that the changes with age occurring in two distinct bovine cartilages have been examined; bovine nasal cartilage representing a tissue which is not normally subjected to mechanical trauma, whereas bovine intervertebral disc is subject to considerable mechanical strain throughout life. Preliminary results suggest that the qualitative chemical changes occurring during ageing are independent of mechanical stress, although the rate at which these changes occur may be affected by such stresses. As summarised in the 1965 report, the acid mucopolysaccharide protein content of the nasal cartilage from embryonic, young and old steers shows only a slight decrease with age, however the keratan sulphate content increases markedly whilst the chondroitin sulphate content decreases with age. An examination of the physical properties of these preparations showed that they were composed of large molecules in which the polysaccharide chains were covalently linked to protein and the properties of the molecules depended on the intactness of this structure. From electrophoresis studies on the native molecules it seems likely that each preparation contains two interacting components which have not as yet been separated. The simplest interpretation of these results would be that a separate chondroitin sulphate protein complex and keratan sulphate protein complex exist and that during ageing there is a decrease in the biosynthesis of chondroitin sulphate but continued biosynthesis of keratan sulphate. Metabolic studies on the incorporation of HC glucose into the two mucopolysaccharides present in cartilage slices incubated in vitro show that contrary to this the rate of formation of keratan sulphate is low even in adult tissue, whereas there is still a considerable synthesi, of chondroitin sulphate. Thus it seems that there may be a real difference in the rates of degradation of these two mucopolysaccharides in intact cartilage. Further experiments are in progress to examine this question. It has been shown, as reported in December 1965, that both acid mucopolysaccharides behave as though they are covalently linked to protein and the protein content and its amino acid composition does not change appreciably with age. Thus current investigations include experiments designed to examine the biosynthesis of the protein part of the acid mucopolysaccharide protein ::omplex. These studies may be of considerable interest since it has been shown that in a closely related group of compounds, the glycopr;)teins, that polysaccharide synthesis depends on the continued biosynthesis of the protein moiety, Intervertebral disc cartilage has proved to be remarkably similar to nasal cartilage in that the same AMPS components are present and can be extracted, purified and shown to be high molecular weight compounds in which the AMPS are covalently linked to protein. Again there is a distinct ageing pattern in which there is a progressive increase in keratan sulphate and decrease in chondroitin sulphate content of these compounds with increasing age. Initially no obvious difference could be detected in the physical properties of the molecules when examined in the analytical ultracentrifuge or free boundary electrophoresis apparatus despite the large changes in chemical structure. However, it is now known that considerable changes in physical properties can occur during isolation procedures without change in gross chemical composition and a milder method for the isolation of these molecules has been devised.
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Initial experiments in the formation of collagen fibres from soluble collagen have suggested that the AMPS-protein complexes may modify the rate and type of fibres formed. There is some tentative evidence that the AMPS-pro tein complex from older animals promotes collagen fibre formation and this in turn may correlate with increased fibre deposition in the disc cartilage from older animals. There appears to be no chemical difference in the AMPS-protein cOlhplexes isolated from the nucleus pulposus or annulus fibrosus portions of the intervertebral disc, both appear to change with increasing age. Attempts are being made to examine the mechanical properties of the intervertebral disc in the hope that the chemical changes in the AMPS-protein complex during ageing may affect the flow properties of the nucleus pulposus gel. There is considerable circumstantial evidence in the literature to suggest that this is likely to occur and several authors have suggested a correlation between impaired mechanical properties and histological changes in the nucleus pulposus gel. Publications GOH, A. T. W., and LOWTHER, D. A. 'The effect of age on the composition of bovine nasal cartilage.' Nature, 1966, 210. 1270. LOWTHER, D. A., and BAXTER, E. 'The isolation of a chondroitin sulphate-protein complex from bovine intervetebral discs.' Nature, 1966, 211, 595. LOWTHER, D. A., GOH, A. T. W. and BAXTER, E. 'The structure of mucopolysaccharide-protein complexes from bovine cartilage.' A ust. !. Sci. (In press.) LOWTHER, D. A., TOOLE, B. P. and MEYER, F. A. 'Extraction of the acid mucopolysaccharides of bovine heart valves.' Arch. Biochem. Biophys. (In press.) TOOLE, B. P., and Lowther, D. A. 'Organisation of hexosamine-containing compounds of bovine skin.' Biochim. Biophys. Acta, 1966, 121, 315.
DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY Professor E. C. Wood, M.B., B.S., M.R.C.O.G., F.R.C.S. Dr H. Nakanishi, M.D., Doctor of Medical Science. Dr H. Wansbrough, M.B., B.S., Teaching Fellow. Project Influence of the autonomic nervous system on the human uterus and Fallopian tube. Report Previous investigation of the influence of the autonomic nervous system on the uterus has been limited by the lack of suitable techniques to study this and also by acceptance of the concept that steroid control is the main influence on myometrial activity. With the development of new autonomic drugs more interest has been shown in the effects of these on the autonomic nervous control of the uterus and Fallopian tube.
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Postganglionic sympathetic nerve innervating the human Fallopian tube-in vitro studies Studies were made of effects of perivascular nerve stimulation on the mechanical activity of the human Fallopian tube in vitro. The contraction followed by spontaneous movement was observed during repetitive stimulation of perivascular nerve. The optimal stimulation
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frequency was between 30/sec. and 70/sec. The contractile response to perivascular nerve stimulation was not affected by ganglionic blocking agents hexamethonium (4 X 10-5 to 4 X 1Q-4 g/ml) and pentolinium (2 X 10-5 to 2 X 10-6 ). Cholinergic blocking agents (atropine (1.2 X 1Q-6) and Hemicholinium (lQ-6) had no effect on the contraction, also. Moreover, the contraction in response to the lower frequency stimulation (lO/sec.) and the higher frequency stimulation (30/sec.) of perivascular nerve was not affected by physostigmine (2 X 10-6 ). On the contrary, the contraction in response to perivascular nerve stimulation was abolished by treatment with alpha-blocking agents (phentolamine (l0-7 to 10-5), phenoxybenzamine (l0-7 to 1Q-5) and yohimbin (10-7 to 10-5 ). Particularly, in the presence of phenoxybenzamine (10-" to 10-5 ), the contractile response was converted into relaxation (sympathetic reversal). The optimal stimulation frequency of the inhibitory response was also between 30/sec. and 70/sec. The inhibitory response was abolished by beta-blocking agents (propranolol (l Q-5) and dichloroisoproterenol (10-5 ). The potentiating action of adrenaline (2 X 10-7 ) on the contraction in response to perivascular nerve stimulation was also reversed to one of depression in the presence of phenoxybenzamine (2 X 1Q-6). It was concluded that the nerve supplying the human Fallopian tube was predominantly adrenergic. Because of the frequency with which tubal spasm is associated with infertility this work may also have relevant clinical implications.
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Uterus-in vivo studies Studies are carried out on patients admitted to the gynaecological ward and on normal pregnancy patients admitted at term in early labour. Uterine activity is measured by means of a small balloon inserted into the uterus which connects through a closed fluid system to a strain gauge and pressure monitor. Drugs are given by intravenous injection or infusion and the change in uterine activity compared to spontaneous uterine activity which has been measured over two hours. Autonomic drugs have been used to try and establish the presence of sympathetic a and fJ tone in the uterus and their influence on uterine motility patterns. In the uterus fJ sympathetic tone is excitatory and fJ sympathetic tone is inhibitory, and these effects are thought to be mediated by catecholamines via nerve endings and the vascular system. Noradrenaline produces an excitatory effect on uterine contractility which is blocked by administration of phenoxybenzamine, an a receptor blocking drug, and augmented after administration of Inderal, a (3 blocking drug. Phenoxybenzamine blocks the a excitatory tone of the uterus over a period of three to four hours producing gradual decrease of activity. In the pregnant uterus a similar response is obtained with noradrenaline at comparable doses but the effect of a blocking agents has not been studied in vivo due to the danger of complications to the foetus. Stimulation of the f! receptors with a new drug Cc-25 produces complete inhibition of uterine activity in the non-pregnant uterus and the pregnant uterus in labour. This response is completely blocked by giving Inderal, a f3 blocking drug, despite a fivefold increase in the dose of Cc-25. Inderal alone blocks the fJ inhibitory tone of the uterus and produced an increase in activity probably due to the a excitatory tone becoming predominant. Much work has been done on the contractile response of the uterus to syntocinon. The relaxant effect of this drug has been observed in con junction with in vitro studies by Dr Nakanishi, the relaxant effect of certain doses of syntocinon on the uterus under certain hormonal influences is being studied. Adrenaline produces inhibition of uterine activity in vivo in pregnant and non-pregnant uteri. It is thought to stimulate the fJ receptors which is consistent with these results. The excitatory effect produced on non-pregnant uterine muscle in vitro could be explained by a drug dose effect, or by lack of nervous and humoral control in vitro.
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The response to adrenaline in vivo is markedly augmented after blocking .. receptors with phenoxybenzamine and is reversed after f3 receptors with Inderal, an excitatory response similar to that produced by noradrenaline is seen. Corresponding changes in cardiovascular response to adrenaline are obtained. These results suggest that adrenaline stimulates both a and p. receptors of the uterus, but the f3 effect is normally dominant. Fallopian Tube In vivo studies of the motility of the Fallopian tube and the effect of autonomic drugs on this have not been made previously. Measurement of this by means of a microballoon inserted into the Fallopian tube at operation and connected to a sensitive pressure recorder are being attempted. Further studies are planned to investigate the relation of sympathetic nervous control of uterine function to cyclical changes of hormone activity and to estrogen and progesterone therapy. The effect of parasympathetic agents on uterine muscle in vitro will be studied and the findings applied where possible to in vivo studies. Further in vivo and in vitro studies of the Fallopian tube will be done to examine the effect of the autonomic nervous system and related drugs on the activity of the tube and the possible importance of this in relation to infertility problems.
DEPARTMENT OF PATHOLOGY Professor R. C. Nairn, M.D., Ph.D., F.e.Path., M.C.P.A., F.R.S.E. Associate Professor W. G. R. M. de Boer, M.D .. D.T.M., M.e.Path. Dr T. Ghose, M.B., D.Phil., M.C.Path., Senior Lecturer in Pathology. Dr A. R. McGh'en, M.D., Lecturer in Pathology. Dr P. N. J. Ironside, M.B., B.S., D.Path., Lecturer in Pathology. Mr H. A. Ward, M.Sc., Senior Research Officer. Dr H. J. C. Ireton, M.D., Research Student. Mr E. Potworowski, M.Sc., Research Student. Projects Study of organ-specific antigens and autoantigens in man and experimental animals. Investigation of autoimmune diseases.
Report Expansion of the work is continuing and there is clear evidence of the importance of an understanding of organ-specificity in a number of clinical situations, particularly in the immunologically determined diseases. Here, investigations have been devoted in large part to the gastrointestinal tract and kidneys. In ulcerative colitis, two autoantibodies to gastrointestinal tract have been demonstrated in the sera of 15 per cent of a large series of cases studied. These autoantibodies show no specific cytot?xic act.ivity ag~nst colon mucosa in vitro and do not themselves appear to play a pathogellic role III the disease. On the other hand, they reflect underlying cellular autoimmunity, which may well be pathogenically important. In vitro, evidence has been 4275/67~
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obtained of specific auto aggression against colon mucosa by lymphocytes from patients with ulcerative colitis. Confirmation of the specificity of the reaction demands further experiments, which cannot be completed quickly because the relevant cultural techniques are unusually difficult. They require simultaneous growth In vitro of lymphoid tissue and colonic mucosa from fresh surgical specimens, and the colon, in particular, presents special problems af bacterial contamination of cultures. Cold storage preservation of fresh human tissues by new cryobiological techniques, to provide a bank for subsequent cultures, would do much to accelerate this type of work. Inter-related studies are proceeding in coeliac disease and pernicious anaemia. In the latter condition, further exploration of the role of the gastric parietal cell auto antigen has been facilitated by obtaining this material from subcellular fractions of gastric mucosa, for the first time in soluble form. This has been used to immunise rabbits to provide a specific heterologous antiserum against gastric parietal cells, providing a comparison with the activity of pernicious anaemia sera, most of which have similar activity. In a study of X-irradiation gastritis, the gastric parietal cell autoantigen and other gastrointestinal antigens have been shown to be selectively depleted and this response is being followed to gain some understanding of its relationship to c1 inical gastritis and neoplasia. Human kidney antigenicity has been studied by developing heterologous specific antisera in rabbits, in one series of experiments accompanied by an attempt at inducing tissue tolerance with a view to using any tolerant animals for the production of renal cancer-specific antibodies and for kidney homotransplantation investigations. Immunohistological studies now completed, on the development of the renal lesions in young New Zealand B/W mice, show that the glomerular localisation of immunoglobulins precedes inflammatory plasma exudation. This provides strong evidence that the lesions are of immunological origin. The several antisera obtained from patients with autoimmune diseases or produced experimentally in animals include those with activity specific for gastrointestinal tract, kidney. and lymphoid tissue and thymocytes. They have permitted the recognition of hitherto unknown macromolecular components of tissues and the investigation of their anatomical, developmental and species distribution. Their employment as selective labels in tissue culture has been of great value in permitting the precise identification of cell types which would otherwise be unrecognisable. Their capacity for specific binding to living cells has been extended to in vivo experiments, in which a specific immunoradioactive agent has been employed successfully against an experimental cancer. This opens up a promising field of application for tissue-specific antisera as possible 'homing carriers' of therapeutic or destructive agents. Developments in diagnostic immunology and immunological techniques are continuing, and demands by the Alfred Hospital and other hospitals in Victoria and other States are increasing as the undisputable need for them in modem medical practice is becoming more widely appreciated. Help and advice are given on the setting up of immunopathological diagnostic units in hospital laboratories in Australia and elsewhere, and several technical and medical personnel have received training in the relevant laboratory procedures. A Colombo Plan medical trainee has been able to develop an interesting new serological diagnostic test for amoebiasis soon to be published; it should prove to be of considerable diagnostic and epidemiological value. Publications
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de BOER, W. G. R. M. 'Byssinosis.' Med. 1. Aust., 1966, 2, 1040. GHOSE, T., CERINI, MILDRED, CARTER, MARALIS, and NAIRN, R. C. 'An immunoradioactive agent against cancer.' B.M.!. (In press.) IRONSIDE, P. N. J., de Boer, W. G. R. M., and NAIRN, R. C. 'Smooth-muscle antibody in lupoid hepatitis.' Lancet, 1966, i, 1210.
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MAXWELL, A, WARD, H. A, and NAIRN, R. C. 'Freezing in an isopentane-liquid nitrogen mixture and storage in 2-octanol: technical improvements for immunofluorescence.' Slain Technology. (In press.) McGIVEN, A R., DATTA, S. P., and NAIRN, R. C. 'Human serum antibodies against rat colon mucosa.' Nature. (In press.) McGlVEN, A. R., GHOSE, T., and NAIRN, R. C. 'Autoantibodies in ulcerative colitis.' B.M.1. (In press.) NAIRN, R. c., and de BOER, W. G. R. M. 'Species distribution of gastrointestinal antigens.' Nature, 1966, 210, 960. NAIRN, R. C., GHOSE, T., and TANNENBERG, A E. G. 'Kidney-specific antigen depletion in human renal carcinomas.' British Journal of Cancer. (In press.) NAIRN, R. C., McGIVEN, A. R., IRONSIDE, P. N. J., and NORINS, L. C. 'Plasma proteins in the glomerula lesions of NZB/NZW mice.' British Journal of Experimental Pathology, 1966, 47, 99. POTWOROWSKI, E. F., and NAIRN, R. C. 'Specific antigenicity of thymocytes.' Nature. (In press.) TANNEN BERG, A. E. G. 'Criteria of Immunological Tolerance to Tissue Antigens.' Clinical and Experimental Immunology. (In press.)
DEPARTMENT OF PHYSIOLOGY Professor A. K. McIntyre, M.B., B.S., D.Sc., F.AA. Dr M. E. Holman, M.Sc., D.Phil., Reader in Physiology. Dr R. F. Mark, M.med.Sci., M.B., Ch.B., Doctorat en Physiologie, Senior Lecturer in Physiology. Mr I. McCance, M.Sc., Senior Lecturer in Physiology. Dr J. W. Phillis, B.vet.Sc., Ph.D., Senior Lecturer in Physiology. Dr J. L. Veale, M.B., Ch.B., B.Sc., Senior Lecturer in Physiology (on leave from August 1965 to September 1966). Dr R. A. Westerman, M.B., B.S., Ph.D., Senior Lecturer in Physiology. Mr P. Vaughan, B.Pharm., M.Sc., Senior Teaching Fellow in Physiology. Mr J. B. Chapman, B.med.Sci., Research Student. Mrs P. Dorward, B.A., Research Student. Mr U. Proske, B.Sc. (Hons), Research Student. Mr A. Tebecis, B.Sc. (Hons), Research Student. Mr D. York, M.Sc., Research Student. Mr E. Gregory, B.Sc. (Hons), Research Student. Projects Sensory information-coding. Analysis of synaptic mechanisms. Factors influencing nerve growth and regeneration. Neural basis of learning.
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Report As noted in the 1965 report, these studies constitute a series of inter-related approaches to some outstanding problems of nerve and brain function. An understanding of sensory coding and synaptic transformations of afferent input is crucial to the further elucidation of the principles underlying central nervous function at various levels, including mechanisms of learning and memory. In attacking these complex problems, the advantages offered by the simpler neural arrangements in sub-mammalian species are being exploited, especially in the case of nerve regeneration and learning studies. Increasing use is being made of behavioural techniques in conjunction with electrophysiology and histology, including histochemistry and electron microscopy. Investigation of vertebrate mechanoreceptors and the central actions of their impulses has been continued, including further analysis of the relatively prolonged inhibitory action of single impulses from Pacinian corpuscles on cortical responses. Attention is now focused on the synaptic interruptions of the afferent pathways to the cortex, and the mechanisms underlying amplification of single impulse input and its inhibitory aftermath. It has been shown that impulses from Pacinian corpuscles excite spinal interneurones and depolarise primary afferent endings, findings consistent with the view that their central action includes presynaptic inhibition. Analysis of receptors in the duck's bill has been continued, and there appear to be two kinds of sensory response, the commonest being vibration-sensitive and rapidly adapting, corresponding to the Herbst corpuscle as studied elsewhere in bird skeletal tissues; the other giving little or no response to mechanical stimulation, but showing a background discharge and responding to temperature changes. It seems likely that this second type of response is that from Grandry corpuscles, the only other histologically defined receptor in the duck's bill. If further studies confirm this, the specific temperature-sensitivity of such an elaborate specialised ending is a finding of unusual interest. Responses of avian and reptilian stretch receptors have also been further investigated. Responses of tendon-organ pattern as well as those of muscle spindles have been found in bird skeletal muscles, and evidence has been obtained that the motor-innervation of the spindles' intrafusal fibres is a system of special small-fibre fusimotor neurones as in the mammal, and is not derived from branches of the ordinary large alpha motoneurones. By contrast, the motor supply of the single intrafusal muscle fibre in the simple muscle spindles of lizards is clearly derived from large alpha motoneurones. The functional significance of these differences in relation to central synaptic actions and behaviour in these different vertebrates remains to be elucidated. Electron miscoscope examination of the birds' pupillary constrictor muscle has confirmed the existence of multiple innervation as shown by electrophysiological technique and reported last year. The electron miscoscope shows a close spacing of motor nerve terminals characterised by synaptic vesicles and mitochondria. The receptive areas of the striated muscle fibres are rich in mitochondria and lack the infolding's characteristic of ordinary type striated nerve-muscle junctions, thus resembling the slow type of striated skeletal muscle. However, there are also resemblances to cardiac muscle in that fibre-branching is common and different fibres may terminate in close apposition to one another. Another problem concerning peripheral junctional transmission has also been the subject of experiments during 1966. A clinical state of muscular weakness has been produced by Dr G. Goldstein at the Walter and Eliza Hall Institute, as a result of implanting calf thymus into guinea-pigs and rats, with clinical features apparently resembling myaesthenia gravis. Careful tests have been carried out using microelectrodes on phrenic nerve-diaphragm preparations in vitro taken from affected and control animals; the results have not supported the view that the condition is akin to myasthenia gravis. The weakness seems more likely to
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be a result of general debility and possibly circulatory deficiency in the affected animals rather than the consequence of a specific defect in neuromuscular transmission. Experiments have been continued with the object of elucidating possible chemical transmitter actions at synapses of the thalamus, as reported last year, and these have been extended to the lateral geniculate body, the caudate nucleus and the deep cerebellar nuclei. Histochemical and related studies by various investigators have indicated possible roles for acetylcholine or monoamines as synaptic transmitter or modulator agents in various regions of the brain, including the thalamus and related nuclei, the caudate nucleus and the intracerebellar nuclei. Multibarrelled micropipette technique has been used in all these areas during the past year in order to stimulate and record from single nerve cells and to test their responses to possible transmitter substances or blocking agents ejected iontophoretically from different barrels of the pipette assembly. Acetylcholine-sensitive nerve cells have been found in all regions of the thalamus, especially in the ventral basal nuclear groups, in the lateral geniculate body, the caudate and deep cerebellar nuclei. However, synaptic activation of ventro-basal thalamic cells by peripheral nerve or tract stimulation was little affected by cholinergic blocking agents, so that it is unlikely that the synapses of these pathways are predominantly cholinergic in nature. Monoamines have an inhibitory action on some thalamic neurones, and excitatory action on others. Such agents also depress the excitability of cells in the lateral geniculate and caudate nuclei. Since fluorescence microscopy has revealed the presence of monoaminecontaining nerve terminals in the thalamus, it seems possible that catecholamines or serotonin may function as inhibitory or excitatory transmitters in this region. Iontophoretic application of dopamine to cells of the caudate nucleus depresses their excitability, as does stimulation of the pathway from the centro-median thalamic nucleus. Since both inhibitory effects can be blocked by the a-adrenergic blocking agent dibenzyline, these experiments support the view that this inhibitory pathway from the thalamus might operate by release of dopamine, as earlier suggested by McLellan's finding of an enhanced output of dopamine from the caudate upon stimulating the centro-median thalamic nucleus. These experiments give promise of providing a clearer understanding of synaptic transmission mechanisms in the basal ganglia, and consequently a more logical basis for developing effective treatment of Parkinsonism and related disorders. Studies on sensory coding in the fish visual system have been initiated, in which the firingpatterns of single nerve fibres running in the tectal commissure between the optic lobes are being examined in relation to the storage and transfer of learned responses to specific visual input. It has been shown that conditioned responses established by stimulating one eye are rapidly transferred via these commissural fibres to the opposite optic lobe, so that study of their discharge-patterns promises to give information about the information-coding involved in the highest levels of visuo-motor behaviour. The analysis of regeneration in fish olfactory pathways has been continued, using behavioural responses and histological, including electron microscope, studies. In most instances regenerating olfactory tract and nerve fibres make appropriate connections within the brain or olfactory bulb over a very slow time course of ten to twelve months. An investigation in the field of experimental neuropathology has also been carried out, namely, the effects of injecting concentrated extracts of eosinophils from various mammals into the !!uinea-pig brain, reported by other workers to produce cerebellar damage. This has been confirmed, animals receiving do~es of 2 X 100 eosinophils or more developing ataxia, with striking destruction of cerebellar Purkinje cells and proliferation of Bargmann glia. Control experiments indicate that the cerebellar damage is indeed effected by some component of eosinophil lencocytes common to various species.
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Further studies are to be made of sensory coding in somato-sensory pathways and the detailed synaptic processes involved in these signal-transactions. In particular, the interactions at various levels between impulses from different types of receptors will be studied, particularly in relation to inhibitory action, a topic of considerable relevance to mechanisms of pain production and suppression, and the effects of peripheral nerve damage by injury or disease. Experiments on the role of chemical transmitter agents at synaptic junctions will be continued and extended, together with the actions of pharmacological agents on synaptic transmission. The experiments which have been initiated on the coding, transfer and storage of signals in the brain as a result of visual input will be continued and extended. This project gives promise of helping to bring nearer the elucidation of that most puzzling of unsolved problems, the basis of learning and memory. Another unsolved problem of great interest is the manner in which growth and regeneration of nerve tissues is regulated. Two kinds of experiment relevant to this will be carried out: continuation of the study of olfactory tract regeneration, and investigation of the way in which an orderly re-establishment or nerve-muscle connections is brought about in lower vertebrates during regeneration after peripheral nerve sections. Another major field to be approached again during the coming year is the detailed analysis of factors determining synaptic excitation and inhibition of motoneurones by various inputs. The use of one-line computer technique should greatly extend the scope and speed of such studies. Publications HOLMAN, M. E., McINTYRE, A. K., and VEALE, J. L. 'Enhancement of small electrical responses in the central nervous system by averaging technique.' Symposium on Computers in Medicine and Biology, Melbourne. (In press.) KNIGHTS, ANN. 'The activity of single motor fibres in arthropods. II. The Australian Yabbie.' 1. expo Bioi. (In press.) McCANCE, I., PHILLIS, J. W., and WESTERMAN, R. A. 'Responses of thalamic neurones to iontophoretic ally applied drugs.' Nature (Lond.), 1966, 209, 715. McINTYRE, A. K., HOLMAN, M. E., and VEALE, J. L. 'Some central effects of single afferent impulses.' Proc. Aust. Physiol. Soc., 1966,9,22. MARK, R. F. 'Tectal commissure and interocular transfer of pattern discrimination in cichlid fish.' 1. expo Anal. Behaviour. (In press.) MARTIN, A. R., and VEALE, J. L. 'The nervous system at the cellular level.' Ann. Rev. Physiol. (In press.) PHILLIS, J. W. 'Innervation and control of a molluscan (Tapes) heart.' !. compo Biochem. Physiol., 1966, 17, 719. PHILLIS, J. W. 'Regulation of rectal movements in Tapes watlingi.' !. compo Biochem. Physiol., 1966, 17, 909. PHILLIS, J. W. 'Acetylcholine release from the cerebral cortex.' Proc. Aust. Physiol. Soc., 1966,9,10. PROSKE, U. 'Responses of muscle spindles in the lizard.' Nature (Lond.). (In press.) WESTERMAN, R. A., and SEILER, G. 'Cerebellar purkinje cell damage induced by intracerebral eosinophil injections.' Proc. Aust. Soc. Med. Res., 1966, 2, 46.
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Monash University Dr MoDie E. Holman, M.Sc., D.Phil., Reader in Physiology. Dr Y. Hashimoto, M.D., Visiting Post-doctoral Research Worker. Mr S. Goldner, M.Sc., Research Student. Miss K. E. Creed, B.A., Research Student. Miss A. Ostberg, B.Sc., Research Student. Dr Jane A. F. Wilson, M.B., Ch.B., part-time Research Student. Mr A. McLean, B.Med.Sc., part-time Research Student. Project Studies on autonomic effector mechanisms.
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Report The aim of this project is to clarify the physiological mechanisms involved in the control of smooth muscle and glands by their autonomic nerve supply. The approach which has been developed in this laboratory centres round the use of biophysical methods for analysis of the electrical activity of individual effector cells. For example, the membrane potentials of smooth muscles and glands have been recorded during electrical stimulation of their nerve supply. Interpretation of these records depends on a knowledge of the fine structure of the effector organ. This information is provided by concurrent studies with the electron microscope. Studies have continued this year on those aspects of the project which were discussed in the 1965 report. These include the problem of transmission from sympathetic nerves to smooth muscle and the relation between the structure and function of the autonomic ground plexus. The excitability of smooth muscle has been analysed and a tentative hypothesis put forward to explain the ionic basis of the action potential. This cellular approach to an understanding of the functioning of smooth muscle has been extended this year to include studies on the origin of the rhythmic mechanical activity of the small intestine and the relation between electrical and mechanical activity of the stomach.
Transmission of excitation from sympathetic nerves to smooth muscle The vas deferens of small laboratory animals continues to be used extensively by biochemists, pharmacologists and physiologists, as a model for the adrenergic nerve-smooth muscle junction. This is probably one of the most densely innervated smooth muscles in the body, and it has the highest nor-adrenaline content of any effector organ. Studies on biophysics of transmission in the mouse vas deferens have continued this year, as follows: An electron microscope study of the relations between sympathetic nerves and the smooth muscle cells has shown that" the smooth muscle of the mouse vas deferens has a somewhat different pattern of innervation from that of the gninea-pig. In the mouse, there are many more examples of close contacts (200A 0 to 1OOOA 0) between the naked axons of the sympathetic ground plexus and the smooth muscle membrane. Random sampling of transverse sections suggests that each smooth muscle cell may possess several such contacts. Most of the vesicles within the sympathetic axons contain the sharply defined electron dense granules which are probably storage sites for nor-adrenaline. These granules are not seen in preparations pretreated with reserpine. (Reserpine had no other effects on the fine structure of the mouse vas deferens.)
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These and other morphological studies (including fluorescent histochemical methodi for the localisation of catecholamines) have confirmed that this is an ideal preparation for in vitro studies. For example, the layers of smooth muscle are sufficiently thin to permit the rapid diffusion of ions and metabolites between the extracellular fluid and the individual smooth muscle cells. Further studies on the characteristics of the excitatory junction potentials in the mouse vas deferens It is generally accepted that the excitatory junction potentials (EIPs) in the vas deferens are generated by a change in membrane permeability for Na and K ions similar to that described for the skeletal neuro-muscular junction and excitatory synapses in the central nervous system. If this is so, it should be possible to change the amplitude of the EJP by altering the membrane potential of the smooth muscle cell. Early attempts to carry out this kind of experiment on the guinea-pig vas deferens suggested that the amplitude of the EJPs of many cells was independent of changes in membrane potential of up to + 10mV. This question has been reinvestigated this year for the mouse vas deferens, using improved techniques for intracellular polarisation. Sub-maximal EJPs were found to be independent of membrane .potential for hyperpolarisations of up to 20 mV and depolarisations of up to 10 mV. This suggests that they cannot be due to the action of the transmitter at a site close to the polarising electrode. It is more likely that they are due to the electrotonic spread of the depolarisation generated by the action of the transmitter in neighbouring cells. However, the possibility still exists that the EJPs may arise from a process that is different from that occurring at the skeletal neuro-muscular function. The action of cocaine on the EJPs ot mouse vas deferens It has been suggested that the most important factor which determines the inactivation of nor-adrenaline in sympathetically innervated tissues is its uptake by the axons of the ground plexus. When nor-adrenaline is added to the outside of the muscle (in the isolated organ bath) much of this is probably taken up by the sympathetic axons so that only a small proportion is available to react with the smooth muscle membrane. If the uptake of nor-adrenaline is partly or wholly prevented by denervation or by the action of drugs such as cocaine, the sensitivity of the muscle for added nor-adrenaline is greatly increased. Comparative studies on sympathetically innervated tissues including the vas deferens suggest that the degree of increase in sensitivity in the presence of cocaine is correlated with the density of innervation. In order to see whether the uptake mechanism is important in terminating the action of the nor-adrenaline which is released from the nerve terminals the effects of cocaine on the EJPs of the mouse vas deferens has been studied. Doses which were large enough to block the EJPs in response to nerve stimulation (due to the local anaesthetic action of cocaine) had no significant effects on the time course of the spontaneous EJPs. These results indicate that either the 'uptake' mechanism is not the most important 'factor which determines the time course of the junction potentials in this smooth muscle; or cocaine does not have access to those regions of the ground plexus which are responsible for the uptake of the noradrenaline which gives rise to the junction potentials. Ionic basis of the action potentials in visceral smooth muscle Intracellular stimulation has been used to initiate action potentials in the mouse vas deferens. Since these were unaffected by the drug tetrodotoxin, which blocks the action potentials in nerve and skeletal muscle, it was concluded that the action potentials of this
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smooth muscle must be due to a different mechanism. During the last twelve months, similar results have been obtained for many other mammalian smooth muscles. The lack of sensitivity of the action potential to low Na solutions and the blocking action of Mn ions on the excitability of smooth muscle suggest that Ca ions may be involved in excitation. Studies on the effects of Ca and other divalent cations, together with the effect of changes in membrane potential on the action potential mechanism, have suggested that excitability depends on a pool of Ca ions associated with the cell membrane. During depolarisation these ions move across the membrane discharging the membrane capacitance and giving rise to the upstroke of the action potential. Repolarisation is brought about by an increase in K permeability, similar to that occurring in nerve. It is possible that there may be a sufficiently large increase in the intracellular concentration of ionised Ca during the rising phase of the action potential which could act as a trigger for the contractile mechanism. Reflex inhibition of intestinal smooth muscle It has been demonstrated by pharmacological methods, that the transient relaxation in response to distension which occurs in the small bowel of most mammilian species is due to the reflex stimulation of intra-mural inhibitory neurones. This result was confirmed in a further series of experiments in which changes in the tension of the longitudinal muscle were recorded from one segment while the neighbouring segment was distended by an intraluminal balloon. This project has now been completed. The origin or spontaneous activity of the small intestine The problem of the nature of the pace-makers of the small intestine has interested electrophysiologists since the early days of this century. Electro grams from the small bowel of mammals (including man) show prominent slow waves whose frequency correlates with that of the spontaneous contractions of the segment. However, the slow waves can also be recorded in the absence of mechanical activity. There is evidence suggesting the more rapid spike-like deflections which arise from the slow waves are needed for contraction. Most of the work on the smooth muscle of the gastro-intestinal tract during the last ten years has been carried out on the guinea-pig. Unfortunately, the electrophysiological characteristics of the tract of this animal are very different from those of other species. It is not clear which, if any, of the components of the electrical activity of the guinea-pig bowel may be analogous with the slow waves of other species. A survey of the musculature of the small bowel of common laboratory animals has been carried out this year in order to find a suitable preparation for studies on the origin of the slow waves. It has been confirmed that these are myogenic in origin and are initiated in the longitudinal layer. Isolated strips from several species have been studied. In many instances, these preparations do not show the remarkable regularity of beat which is characteristic of whole segments, in vitro. However, isolated strips of longitudinal muscle from the rabbit appear to be very reliable and preliminary experiments on their electrical activity suggest that this will be an ideal preparation for studies on the ionic basis of the slow waves. Excitation-contraction coupling in smooth muscle The relation between membrane potential and tension has been studied during K contractures of the guinea-pig ureter. The increase in intracellular ionised Ca which brings about contraction during the maintained phase of depolarisation appears to be due to an influx of extracellular Ca. The Ca which enters the cell during the action potential, however, may be derived from a pool of Ca ions which is loosely bound to the cell membrane.
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This work has been completed. One of the characteristics of the smooth muscle of the stomach is the regularity of the electrogram recorded with external electrodes, in spite of great fluctuations in the force of its contractions. Some authors have suggested that there is no difference between the cycles of activity which are associated with contraction and those which are not. Others have found evidence that the duration of the cycle and its later components are increased if contraction occurs. It is clear that this problem can only be solved if the absolute magniture of the various components of the electrogram are known. Preliminary studies with intracellular electrodes were carried out during a brief visit to the Department of Surgery, Stanford University, in July this year. Further studies on the pharmacology of isolated venous smooth muscle have been carried out this year. A number of unexpected results remain to be clarified. For example, sympathetic nerve stimulation of preparations taken from animals pre-treated with reserpine respond with relaxation, rather than the contraction seen in normal preparations. This relaxation is not blocked by atropine or guanethidine but it is blocked by tetrodotoxin. The nature of the chemical transmitter which gives rise to this response is still obscure. Control of salivary secretion The innervation of the acini and ducts of the cat sub-maxillary gland have been studied by electron-microscopy and fluorescence microscopy. Evidence has been found for the presence of nerve fibres (probably parasympathetic) sandwiched between the membranes of neighbouring acinus cells. The separation between the axon membrane and that of the neighbouring secretory cells is very small (about 200A 0 ) . The distribution of the sympathetic axons is being studied by fluorescent histochemical methods for the localisation of catecholamines. Preliminary results suggest that these fibres run with the blood vessels round the outside of the acini but do not penetrate between the acinus cells. Electron microscope studies have demonstrated extensive coupling between neighbouring acinus cells. Intracellular recording has shown that the predominant cell type on the surface of the cat sub-maxillary gland to have a resting potential of 15-25 mY. Either sympathetic or parasympathetic stimulation causes hyperpolarisation which may be as much as 25 mY. Attempts have been made to alter membrane potential by passage of current, and to determine the effect of this on the secretory potential. Although up to IO-S amps was passed across the membrane, using a single intracellular microelectrode and Wheatstone bridge circuit, there was no significant change in the secretory potential. Current passed across the whole gland, from duct lumen to surface, also had no effect. Injection of isotonic KCI into the arterial supply caused reduction of the secretory potential when the venous plasma K conc. was 7 mequ./l; and abolition of 12.5 mequ./l. Gland blood flow and secretion were greatly reduced during KCl injection. This occurred immediately after the injection was begun, whereas the effect on a secretory potential was delayed by up to 60 minutes. Several aspects of this project will be developed next year, including adrenergic transmission and analysis of the factors affecting the EJPs in the mouse vas deferens. Emphasis will be on the effect of nor-adrenaline on the smooth muscle of the vas deferens. The possibility exists that regions of smooth muscle close to a site of release of transmitter from the axons of the ground plexus may have different physiological and pharmacological properties from regions elsewhere. This theory will be i~vestigat~d by furth~r studies on the iontophoretic application of nor-adrenaline. Also, the passive electncal propertIes of the smooth
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muscle of the mouse vas deferens and the nature of the electrical coupling between neighbouring cells, and the mechanism responsible for the release of nor-adrenaline during nerve stimulation. Other studies will cover the ionic basis of the action potentials in smooth muscle. Attempts will be made to give a quantitative account of the role of Ca ions in the generation of the action potentials of smooth muscle. On the origin and significance of the 'slow waves' of intestinal smooth muscle, isolated strips of rabbit longitudinal muscle will be used to analyse the properties of 'slow waves'. Attempts will be made to show whether or not their frequency can be altered by changes in membrane potential. Agents which affect the ionic pumps in smooth muscle (eg, ouabain) will also be studied. Investigation of the action potentials of the stomach and excitation-contraction coupling will be undertaken and attempts will be made to obtain reliable intracellular records from the stomach of various mammalian species (including man). Excitation-contraction coupling will be studied in 'in vivo' experiments. Further studies are anticipated on salivary secretion and on the role of catecholamines in ganglionic transmission in mammals. Publications BENNETT, M., BURNSTOCK, G., and HOLMAN, M. E. 'Transmission from perivascular inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.' !. Physiol., 1966, 182, 527. BENNETT, M., BURNSTOCK, G., and HOLMAN, M. E. 'Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli.' !. Physiol., 1966, 182,541. BURNSTOCK, G., and HOLMAN, M. E. Junction potentials at adrenergic synapses.' Pharmacol. Revs., 1966, 18, 481. BURNSTOCK, G., and HOLMAN, M. E. 'Effect of drugs on smooth muscle.' Ann. Rev. Pharmacol., 1966, 6, 129. CHAPMAN, J. B. 'Potassium contractures of ureteric smooth muscle.' Proc. Austral. Physiol. Soc., Feb. 1966. CREED, K. E. 'Secretory potentials in the cat sub-maxillary gland.' Proc. Austral. Physiol. Soc., Aug. 1966. HASHIMOTO, Y., and HOLMAN, M. E. 'Intracellular stimulation of single smooth muscle cells of the guinea-pig vas deferens.' Proc. Austral. Physioi. Soc., Feb. 1966. HASHIMOTO, Y., and HOLMAN, M. E. 'Effects of low Na and Mn on the smooth muscle of mouse vas deferens.' Proc. Austral. Physiol. Soc., Aug. 1966. HASHIMOTO, Y., HOLMAN, M. E., and TILLE, J. 'Electrical properties of the smooth muscle membrane of the guinea-pig vas deferens.' I. Physiol., 1966,186,27. HASHIMOTO, Y., HOLMAN, M. E., and McLEAN, A J. 'The effect of tetrodotoxin on the electrical activity of the smooth muscle of the vas deferens.' Nature. (In press.) HOLMAN, M. E. 'The electrophysiology of smooth muscle.' In 'The Handbook of Physiology', forthcoming volume on the 'Motility of the Gastro-intestinal Tract', to be published by the American Physiological Society.
McLEAN, A J., and HOLMAN, M. E. 'The innervation of sheep mesenteric veins.' I. Physiol. (In press.) McLEAN, A, and HOLMAN, M. E. 'Some properties of the longitudinal muscle of sheep mesenteric veins.' Proc. Austral. Physiol. Soc., Feb. 1966.
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DEPARTMENT OF SURGERY Professor H. A. F. Dudley, Ch.M., F.R.C.S., F.R.A.C.S. 1. P. MastertoD, M.B., F.R.C.S., Senior Lecturer. Project Measurement of non-esterified fatty acids in plasma of surgical patients. Report Studies this year have been directed towards perfecting thin layer chromatography to measure total circulating non-esterified fatty acids (NEFA) in plasma. These substances circulate in increased amounts in starvation and surgical stress. Satisfactory control results have been obtained and have now been extended to include normal values in standard surgical procedures. Patients under severe stress and on parenteral feeding regimens will then be assessed to ascertain if NEFA's levels can be used as an index of satisfactory nutritional replacement.
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DEPARTMENT OF MICROBIOLOGY Professor B. P. Marmion, M.D., D.Sc., F.e. Path. Mr G. F. Cross, B.Sc., Senior Teaching Fellow. Project Study of the biophysical and immunological properties and growth requirements of infectious hepatitis viruses. Report During 1966 the work has followed two main lines, the isolation of agents using the Parke Davis clone of Detroit-6 cells, and the characterisation of such isolates, and blind trials using hepatitis and control sera to relate isolations to clinical cases of hepatitis. A number of agents capable of producing cytopathic effect on Detroit-6 cells were isolated from acute-phase sera taken from infectious hepatitis patients. These agents could not be definitively characterised as viruses. All attempts to relate these agents to hepatitis using antigen-antibody reactions were negative. Blind trials were done to correlate the isolation of agents in Detroit-6 cells to the clinical state of the donor patient. No correlation between observed cytopathic effect and a clinical diagnosis of hepatitis could be made. Fibroblast cells of human origin were also used in an attempt to isolate agents from acute phase hepatitis sera. These cells included lines derived in this laboratory from embryonic material and the line of cells known as Wl-38. No isolations were made with these cells. The problems associated with the contamination of cells with mycoplasma (see 1965 report) have also been investigated. The presence of mycoplasma has no effect on the sensitivity of the cells to cytopathic agents in the serum of acute-phase hepatitis patients. The problems of detection and eradication of contaminating mycoplasma have also been studied. Publications CROSS, G. F., GOODMAN, M. R., and SHAW, E. S. 'Detection and treatment of contaminating mycoplasmas in tissue culture.' Aust. 1. Exp. BioI. Med. (In press.) CROSS, G. F., and MARMION, B. P. 'Cell culture and infectious hepatitis.' Med. 1. Aust. (In press.)
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UNIVERSITY OF NEW SOUTH WALES SCHOOL OF ANATOMY :; Professor Michael 1. Blunt, M.B., B.Sc., Ph.D. Assoc. Professor C. P. Wendell-Smith, M.B., B.S., D.R.C.O.O. Mr P. B. Paisley, B.Sc., Part-time Research Assistant. Projects The histochemistry of macroglia. The ultrastructure of developing glial elements. The ultrastructure and histochemistry of retinal glial elements. Report Nerve cell bodies and nerve fibres are surrounded by satellite cells which give them structural and metabolic support. In fibre tracts of the central nervous system there are two main types of satellite cell, the astrocyte and the oligodendrocyte. The aim of the present investigation is the determination of the nature of, and the method of effecting, the different roles of these two cell types. These considerations are relevant to an understanding of nervous function and basic to an understanding of disturbances of function in general and demyelinating diseases in particular. The cat optic nerve has been the prime model studied. The distribution and characteristics of astrocytes and oligodendrocytes have been determined by silver staining and light microscopy. and used as a frame of reference for the identification of these cell types in histochemical and electron microscope preparations. Histochemical studies have revealed a reciprocal relationship between mitochondrial enzyme activity in the nerve fibre on the one hand and the oligodendrocyte on the other. This relationship provides support for the concept of the oligodendrocyte as an energy donor. The astrocyte because of its enzyme activity has been thought to be concerned with phospholipid membrane production and turnover, and thus with the support of the myelin sheath. Studies on the distribution of hexosemonophosphate dehydrogenases have also given results which are consistent with these concepts. The findings from studies on immature cat optic nerve are also consistent. It has been found that there is initially a single undifferentiated glial cell present. This glioblast resembles an astrocyte in its histochemical profile and only later are cells with the histochemical profiles of oligodendrocyte found. Ultrastructural studies have not yet reached the same stage and correlation is incomplete. Analysis of the utrastructural characteristics of glial cells has led to the recognition of mutually exclusive features which typify astrocytes and oligodendrocytes and to the development of diagnostic criteria between them. It has also revealed that the cell type responsible for myelinisation is neither an astrocyte nor an oligodendrocyte but a bivalent cell with some of the characteristics of each. Finally it has cast doubt on the nature of the cell previously identified by electron microscopists as microglia and stimulated an inquiry into the nature and distribution of the latter. Studies on the nature and differentiation of the glioblast have also been initiated. To elucidate matters further it is proposed to study other enzyme systems (in particular those concerned with glycogen metabolism) in the adult cat optic nerve, to extend all histochemical studies to other sites to determine how far the concepts based on the optic nerve can be regarded as generalisations, to pursue the question of the nature and distribution of microglia and to study the maturation of glial cell types and their relation to myelinisation. Publications BLUNT, M. J., WENDELL-SMITH, C. P., and BALDWIN, F. 'An oxidative enzyme study during central myelination.' 1. Anal. Lond. (In press.)
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BLUNT, M. J., WENDELL-SMITH, C. P., PAISLEY, P. B., and BALDWIN, F. 'Histochemistry of glia-axonal relationships.' Proc. Roy. micro Soc., 1966, 1, 129. BLUNT, M. J., WENDELL-SMITH, C. P., PAISLEY, P. B., and BALDWIN, F. 'Oxidative enzymes in macroglia and axons of the optic nerve.' J. Anat. Land. (In press.) WENDELL-SMITH, C. P. 'Some aspects of the neuron-neuroglia relationship.' Proc. Aust. Assoc. Neural. (In press.) WENDELL-SMITH, C. P., BLUNT, M. J., and BALDWIN, F. 'The ultrastructural characterisation of macroglial cell types.' J. camp. Neural., 1966, 127, 219. WENDELL-SMITH, C. P., BLUNT, M. J., and BALDWIN, F. 'The ultrastructural characterisation of neuroglial cell types.' J. Anat. Land. (In press.)
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Dr G. S. Molyneux, B.D.S., F.D.S., R.C.S., Ph.D., Senior Lecturer.
Project The ultrastructure and histochemistry of epithelioid cells in the carotid body and in the walls of arterio-venous anastomoses. Report In mammals the carotid body is generally a compact encapsulated organ which lies in close proximity to the carotid arteries in the region of the carotid bifurcation. It acts as a chemoreceptor being stimulated by anoxia, hypercapnia and by acidosis and reflexly influences the rate and depth of respiration. It contains conspicuous cells which have been variously termed specific cells, epithelioid or glomic cells which are enveloped by supporting cells. It is the most vascular tissue in the body and blood flow is regulated by arterio-venous anastomoses. The carotid body receives its afferent innervation from the glossopharyngeal nerve and efferent sympathetic fibres from the superior cervical ganglion. Although the chemoreceptor function of the carotid body is well established, there is little evidence to suggest the mechanism of this function particularly in regard to the identity and innervation of the chemoreceptor ceIlular elements. In this project it was proposed to examine carotid body fine structure in animals breathing gas mixtures of varying oxygen tensions so that changes in cytology, with particular reference to the glomic and supporting cells, could be related to the physiological activity of the organ. Previous investigators using a similar approach were hampered by inadequate embedding and fixation technique, the carotid body being particularly sensitive to postmortem change. In this study optimal fixation was achieved by the perfusing the carotid body in situ with glutaraldehyde followed by post-fixation in osmium tetroxide. At normal oxygen tension, using 5% glutaraldehyde in McEwan's saline buffer, the glomic cells possessed marked cytoplasmic density besides containing numerous dense membrane bound granules (catecholamine-like) which tended to be grouped away from the plasma membrane. At reduced oxygen tension (the carotid bodies were fixed after animals had breathed 5% oxygen in nitrogen for 30 minutes), the background density of most granular cells was markedly diminished and the granules were dispersed throughout the cytoplasm and approximated the plasma membranes. These changes were most marked in cells immediately adjacent to blood vessels, the cytoplasm of such cells often being vacuolated. The cytoplasm density of supporting cells remained constant under normal and hypoxic condition. However, before the significance of these observations can be evaluated, the effect on cytoplasmic density of different perfusates must be considered. For example, following perfusion with a phosphate buffer the cytoplasmic density of glomic cells at normal oxygen
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tension was markedly diminished and a population of light and dark cells was observed. Work is in progress to determine if these appearances reflect changes in metabolic activity or signify the presence of different cell populations. Nerve endings characterisesd by pre- and post-synaptic membranes, numerous synaptic vesicles and concentrations of mitochondria were often observed in contact with glomic cells. Concentrations of vesicles were not observed in the glomic cytoplasm in proximity to the synaptic area and there is no evidence to suggest that these endings are related to the chemoreceptor afierent fibres. The nature of these endings, which structurally resemble efferent synapses are being investigated by section of the glossopharyngeal nerve and also by sympathetic ganglionectomy. Publications MOLYNEUX, G. S. 'The distribution, structure and histochemistry of arterio-venous anastomoses in sheep skin.' Ph.D. Thesis, University of New South Wales, 1965. MOLYNEUX, G. S., and SCOTI' , MARY J. 'The cytology of the carotid body in normal and hypoxic states.' J. Anat. Lond. (In press.) MOLYNEUX, G. S., and THORBURN, G. D. 'The distribution and ultrastructure of intercellular fluid pathways in the renal proximal tubules.' Proc. of the ninth meeting of the Australian Physiological Society, 1966. SCOTT, MARY J., and MOLYNEUX, G. S. 'Some observations on the presence of catecholamine-like granules in the carotid body.' Proc. of the eighth meeting of the Australian Physiological Society, 1966. THORBURN, G. D., CASEY, B. H., and MOLYNEUX, G. S. 'Distribution of blood flow within the skin of the rabbit with particular reference to hair growth.' Circulation Research, 1966, 18, 650. THORBURN, G. D., and MOLYNEUX, G. S. 'The role of intercellular space in fluid transport across epithelia.' Proc. of the ninth meeting of the Australian Physiological Society, 1966.
SCHOOL OF BIOLOGICAL SCIENCES AUSTRALIAN NATIONAL UNIVERSITY JOHN CURTIN SCHOOL OF MEDICAL RESEARCH Dr C. H. Doy, B.Sc., Ph.D., A.R.I.C., F.R.A.C.I., Senior Fellow, Department of Genetics. Dr E. H. Mercer, D.Sc., Ph.D., Professorial Fellow and Head, Electron Microscope Unit. Mr Y. K. Cho, B.Sc., Postgraduate Scholar, N.H. & M.R.C. Project The nature of the cell envelope of gram negative organisms. Report During the year Dr Doy transferred to the John Curtin School of Medical Research, where considerable time has been spent gaining further experience in the techniques of electron microscopy. Pictures of excellent quality are now obtained readily. Halobacterium halobium is an extreme halophile and the high salt concentration results in difficulties of technique. A new fixation method has been developed and this, coupled with
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a number of biochemical approaches, has enabled the cell envelope to be resolved into inner and outer structures. This is contrary to the earlier results of others who concluded that this cell is bounded by only a single triple layered unit membrane. This view is now untenable. At present it is not known whether the outer structure is more complex than the cytoplasmic (plasma) membrane and therefore more properly analogous to the wall of gram positive bacteria. The present findings with H. halobium indicate a closer similarity to the envelope of Escherichia coli than realised previously. This is of interest because both are gram negative. However, H. halobium was insensitive to penicillin and D-glutamic acid that convert E. coli into spheroplasts. Complex internal organelles, perhaps crystals (macromolecular aggregates) or stacks of membranes, have been demonstrated in H. halobium. Preliminary results with cells grown in the presence of potassium tellurite tentatively suggest a respiratory function analogous to that of the mitochondrion of other cells. Work has continued with E. coli. True protoplasts have been obtained, but only in poor yield. Electron micrographs of cells grown in a number of ways have shown suggestions of internal membranes. Following starvation of phosphate, internal membranes have been observed clearly, particularly at one pole. In the one experiment that has been done, the DNA and ribosomes failed to stain although the usual procedure was used. In a parallel experiment the addition of phosphate to the starved cells resulted in the resumption of rapid growth, indicating continuing viability. Spermine treated cells have shown increased contrast in micrographs. This compound was added because it was thought it might stabilise membranes. Diaminopimelic acid (DAP) starved DAP auxotrophs treated with spermine have been found to contain an unusual organelle at one pole. Spermine treatment results also in failure to stain DNA and has revealed the presence of membrane bounded vacuoles in otherwise normally grown E. coli, as well as in DAP starved cells. This work indicates that bacteria are highly organised cells. Excellent technique is often required for clear and unequivocal interpretations of electron micrographs. In this project this has been facilitated by the microbiological and biochemical approach. In 1967 work will continue supported by the award of an Australian National University Scholarship to Mr Cho. The N.H. & M.R.C. is thanked particularly for supporting Mr Cho during the transition from the University of New South Wales. Publication CHO, KY., and SALTON, M. R. J. 'Fatty acid composition of bacterial membrane and wall lipids.' Biochim. Biophys. Acta, 1966, 116, 73.
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DEPARTMENT OF BIOCHEMISTRY John F. Williams, M.Sc., A.S.T.C., F.R.A.C.I.
Dr Keith G. Rienits, Ph.D., M.Sc. Project Carbohydrate metabolism in vertebrate liver. Report The principal aim of this project is the kinetic investigation of the mechanism of the pentose phosphate cycle in adult female rabbit liver in both the starved and fed condition. The mechanism may be expressed by equations from which it can be shown that there are
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two features of the metabolism of 0 4 glucose which are believed to be uniquely related to the mode of operation of the pentose phosphate cycle in living tissues. The first of these features is the C t ICe ratio. If a tissue exhibits the property of having the ratio of the specific activity of C l i0 2 from glucose-I-Ct4 relative to the specific activity of 0 40 2 from g1ucose6-C14 greater than unity, then the alternative mechanism of glucose oxidation known as the pentose phosphate cycle or pathway is definitely present. In this study very high C t ICe ratio have been recorded with in vivo rabbit liver. The second feature and one which is believed to absolutely distinguish glucose metabolism by the pentose phosphate cycle from all other processes of glucose dissimulation is the distribution of C14 from glucose-2-0 4 into positions one and three of fructose-6-phosphate in a fixed 2,3,2 2,3,3 pattern. The immediate experimental aim was an investigation of the kinetics of the in vivo dissimulation of glucose-2-C14 into intermediates which are either exclusive or common to the pentose phosphate cycle and the Embden-Meyerhof pathway. These intermediates are ribose-5-phosphate (R-5-P), glucose-6-phosphate (0-6-P), fructose-6-phosphate (F-6-Pl and fructose-I, 6-diphosphate (F-l, 6-Dip) and glucose (0). The kinetic analysis was concerned with the rate and extent of the distribUtion of C14 from 0-2-C14 into specific carbon atoms of the above intermediates, in particular F-6-P. This information would thus provide evidence necessary to confirm the in vivo presence of the pentose phosphate cycle in a vertebrate animal liver and to allow a unique quantitative evaluation of the cycle. It is necessary to stress that the currently accepted mechanism of the cycle has yet to be demonstrated in vivo. The experimental work on which the mechanism of the cycle is based involved a long time (18 hours) in vitro incubation of ribose-I-C14 with a system of soluble dehydrogenase free enzymes extracted from rat liver (1). When an effort was made to demonstrate the mechanism of the cycle in the more organised liver slice, the investigators failed to evidence the characteristic 2,3,2---2,3,3 pattern in hexose-6-P (2). Other workers have also failed to demonstrate the above pattern in in vitro studies. The technique adopted was direct and simple. 0Iucose-2-C14 (10 uc) was injected at the rate of 4.0 ml/min. for 15 seconds into the portal vein of the anaesthetised female adult rabbit. The hepatic circulation was surgically controlled so that the isotope was metabolised by the whole liver for periods of time ranging from 1.0 through to 5.0 minutes. The whole liver was removed from the animal at the desired time into liquid nitrogen. The frozen tissue was extraced with percholic acid. Carbon dioxide was isolated and sugars and sugar phosphates were isolated as chemically and radiochemically pure compounds by ion-exchange chromatography of the borate complexes. The specific activity of the intermediates CO 2 , glucose, 0-6-P, F-6-P, F-I, 6 Di-P and R-5-P were determined at each time interval and at the specific activity of the individual carbon atoms of some of the sugars and sugar phosphates were also determined by specific chemical and microbiological degradation procedures. Results of a kinetic study of glucose-2-C14 metabolism in in vivo rabbit liver have shown the levels of the liver intermediates determined at one minute intervals during a five minute exposure to glucose-2-C". The specific activities are recorded together with the relative molar specific activity (R.M.S.A.) i.e. the specific activity of the intermediate relative to the specific activity of glucose (the precusor molecule) isolated from the tissue at the same time. The R.M.S.A. results clearly indicate that F-6-P accumulates C14 more consistently and extensively than any other intermediate during the time course of the reaction and that 0-2-C14 is only slowly metabolised to C140 2 during the initial three minute metabolic period. The high specific activity of F-6-P favours the demonstration of isotope distribution patterns into positions consistent with the operation of the pentose phosphate cycle i.e. the only known mechanism of transferring carbon two of glucose into position one of F-6-P is the 4275/67-6
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pentose cycle or pathway and C14 should be found in carbons 1 and 3 of F-6-P and in G-6-P (if recycling is significant) and also in glucose (as a consequence of 'recycling' and the action of g1ucose-6-phosphatase on G-6-P). The degree of labelling in carbons, I, 2 and 3 of intermediates for various values of the contribution of pentose cycle to overall glucose dissimulation can be calculated. It was the aim to determine the specific activity of carbons 1 and 3 of the intermediates glucose, G-6-P, F-6-P and thus calculate the percentage pentose cycle in liver. It is difficult to interpret the whole series or results in a report of this nature and the emohasis has been placed on those experiments which concern the extent of the pentose cycle.
SCHOOL OF MEDICINE Associate Professor A. W. Steinbeck, Associate Professor of Medicine. Miss Lorraine Smith, B.Sc. (Hons), Research Assistant, N.H. & M.R.C. Project Estimation of androgenic substances in human blood plasma. Report The continued investigation was a study of a possible method for estimation of testosterone and dehydroepiandosterone, with their conjugates, in blood plasma. The methods were based upon double isotope dilution derivative techniques for estimation of microquantities of substance and the manner of purification for extracted substances was chromatographic. The standard substance was added in the HC-labelled form and acetylation was carried out with 3H-acetic anhydride. Glucuronides and sulphates of the steroids were not available in high specific activity forms: for this reason, free steroids were used as markers in this aspect of the study, although unsatisfactory in terms of an equivalent. With the reservation that the free steroid might not constitute an exact internal standard, and might be lost differently from the conjugates during processing, the method should correct systematic losses. The manner of chromatographic purification was aimed at reducing blank substance to a minimum, as methods for free testosterone mostly have an appreciable blank value. Attainment of a constant l4Cj3R ratio has not ensured a minimum value for non-testosterone material. As conjugate standards are not available, the extent of blank contamination in these estimates remains uncertain. Glucuronides were enzymatically hydrolysed and sulphates chemically (solvolysis). Complete extraction of testosterone seemed consistent only with a dichloromethane : ethylacetate (l : 1) mixture. Chromatographic separations and purification prior to acetylation reduced contamination, although lengthening the procedure. Acetylation followed an accepted practice and was more likely to cause tritium contamination with testersterone than dehydroepiandrosterone, and also less likely to proceed to completion. A variety of paper chromatographic systems were used, all modifications of the Peterson type, to test purification. At all steps, identification of the test substance was possible by the radioactive tag and preliminary localisation by dyes and uItra-violet opaque steroids running with the unknown. Final purification followed conversion of acetates to benzhydrazones, a reaction that is ordinarily complete after 16 hours at 37° C, but not at room temperature. After 8 hours at 37° C the reaction is also incomplete which may explain some discrepancies in the technique.
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In chromatographic procedures a decalin system was associated with contamination of papers, requiring frequent reconstitution of the system. The recovery for micro-amounts of testosterone was constantly low. However, within anyone set of replicate estimations variability of results was not acceptable with the low final recoveries obtainable therefore study of the factors behind losses was undertaken, in association with investigation of losses in a method for aldosterone estimation. The tentative results for the method gave a free testosterone value on pooled male plasma of 1 mcg./ 100 m!., with a glucuronide value one third of the free level, and the sulphate loss. For dehydroepiandrosterone, the free value was 0.85 mcg./IOO m!. and the glucuronide value one half of the free level, and the sulphate 10 mcg.1 100 m!. Because of a need to purify the steroid by systematically reducing the steroid area of the chromatograms a 5% recovery has been accepted, although 20% is possible. With this low recovery contamination does not appear a factor although the magnitude of the non-steroidal blank is not defined. It is intended to continue study of the method along the above lines that the relationship between the free and conjugated steroids can be investigated.
SCHOOL OF PATHOLOGY Professor D. L. Wilhelm, M.D., Ph.D., M.C.P.A. Dr R. H. Steele, M.B., B.Ch. Project The inflammatory reaction to chemical injury. Report As more attention is paid to the individual components of the inflammatory reaction, the more apparent does it become that they may have no relation one to another. Erythema, increased vascular permeability, tissue leucocytosis and evidence of tissue damage may vary independently in inflammation evoked by various causes. In recent years, injury by trauma, heat, light, X-rays and bacterial toxins have all been used to provoke reactions which have been analysed in terms of erythema, vascular permeability and leucocytosis. Although chemical injury was a popular irritant with early investigators, it has lost favour in the last 40 years probably because irritant remains at the site and hence the lesion is difficult to standardise. Earlier work on chemical in jury has been confined to a few irritants such as turpentine, xylol and croton oil, but it seems that an advantage was being overlooked in the available variety of chemical irritants. If various chemicals provoke different types of reactions, their effects may throw more light on the basic mechanisms of the inflammatory reaction. The first chemically irritant substances which have been tested were effective on application to the surface of the skin-viz., xylol, benzene, chloroform, carbon tetrachloride, phenol, acetic acid, sodium and potassium hydroxide. Applied at the optimal concentration and for critical periods of time, each chemical provokes a diphasic permeability response. Increasing the concentration or period of application of the irritants tends to obliterate the second response and substitute a prolonged early phase alone. The usual pattern of the diphasic response was an early phase commencing in 2-3 minutes, maximal in 15-20 minutes and lasting 1-2 hours. The second phase begins about 10 hours after injury, becomes maximal in 12-24 hours and subsides in about 40 hours. The same irritants also induce a diphastic
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erythema, but the phases do not coincide with those of increased vascular permeability. The first phase of erythema appears 5 minutes after injury and has faded in 30 minutes. The second phase begins in about 2 hours; and by 4 hours the lesions are usually bright red, though vascular permeability at this time is typically minimal. The actual peak of the second phase of erythema occurs between 10 and 20 hours and does not subside completely until 70 to 100 hours after injury. The histological changes and particularly tissue leucocytosis induced by superficial irritants are currently being studied. To date, the tissue changes have been determined in injury by phenol 0/8-1/9) and carbon tetrachloride each applied for I minute. The amount of tissue damage varies considerably for the various irritants. Phenol and chloroform cause most damage, benzene and carbon tetrachloride the least, with xylol somewhat intermediate. The type of damage is similar for each irritant. There is an almost immediate loss of the normal basophilia of the cytoplasm of the epidermal cells which become brightly eosinophilic. This effect involves almost the entire epidermis injured with phenol or chloroform, but only small foci, particularly at the mouths of hair follicles, in carbon tetrachloride and benzene injury. The nuclei of the epidermal cells next exhibit vacuolation both within and around the nuclei, which may be reduced to narrow crescents, followed by nuclear disintegration. The nuclei of fibrocytes and histiocytes of the upper dermis may also become pyknotic. In 10-12 hours, the first evidence of repair can be seen as new epidermis grows from the hair follicles and spreads along the surface of the dermis and below the necrotic epidermis. In 24-48 hours, depending on the severity of the stimulus, the whole dead epidermis is lifted clear by regenerating cells and is eventually sloughed off. The vessel walls in the upper dermis show no recognisable changes during the whole reaction. With each irritant, tissue leucocytosis is proportional to the amount of tissue damage. The amount of leucocytosis is estimated firstly by counting the number of neutrophils per high power field (x480) in sections stained with haematoxylin and eosin, then by counting the number of P.AS. positive neutrophils in a cross section of the lesion, 1 cm. long, and finally by counting the number of eosinophils in a 1 cm. section of skin stained with carbol chromatrobe. The results to date indicate that although intravascular pavementing of leucocytes occurs within 30 minutes of injury, their accumulation in the tissues does not begin until the lesions are 3-4 hours old, but is then surprisingly rapid. This is particularly well shown by the counts of P.AS. positive neutrophils. Not only are these cells easy to identify in the tissues, but the cytoplasm of nearly all neutrophils contains material which is strongly P .AS. positive (glycogen) when the cells first escape into the tissues. However, after 2-3 hours in the tissues, this material fades away, and virtually none remains after 12 hours. Counts of these cells in conjunction with the total neutrophil count therefore indicates how many of these cells are new arrivals and permits the identification of more than one wave ot leucocytosis. In injury with l/9 phenol applied for 1 minute, there is a clear cut diphasic permeability response, but the Ieu~ocyte response is monophasic. The peak for P.A.S. positive neutrophils occurs in 4 hours with some 300-360 cells per cm. section. The peak for total neutrophils is broader and occurs between 4-6 hours, with an average of forty cells per high power field. The disappearance of the P .AS. positive cells is, as would be expected, much more rapid than that of the total neutro;Jhils. By 12 hours the P.AS. positive count is only slightly elevated and even at 48 hours there are still 4 or 5 neutrophils per high power field, though these do not stain with P.AS. When the concentration of phenol is raised to I in 8, the permeability response is still diphasic though the second phase occurs a little later and is rather less pronounced. Leucocytosis also seems to be a little delayed. When the concentration of phenol is raised to I in 7, the diphasic permeability response is abolished;
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leucocytosis on the other hand is more pronounced than ever. A sudden and pronounced rise in P.A.S. positive neutrophils, up to 500 in each section, occurs 3 hours after injury and a fairly high count is maintained until the lesions are at least 10 hours old. The result is an even broader peak in the total neutrophil count, which is still rising at 10 hours. The results for phenol I in 8 and I in 7 are not yet complete. Carbon tetrachloride applied for one minute causes much less visible damage than phenol and correspondingly less leucocytosis. The peak of both P.A.S. positive and total leucocyte counts occur at the sixth hour, but are only about half those with phenol, 1 in 9. By 24 hours there are only 4 to 5 leucocytes per high power field, despite the second permeability response being at its peak. Benzene applied for 1 minute causes even less leucocytosis than carbon tetrachloride, the peak response occurring at 6 hours. Benzene, it should be added, elicits a diphasic permeability response as strong as that with any other substances which were tested. Chloroform, applied for 30 seconds, causes as much histological damage as phenol, 1 in 9, applied for one minute. Like phenol, it also stimulates a brisk leucocyte response. A sharp rise in P .A.S. positive cells as early as 2t to 3 hours after in jury heralds a prolonged rise in total neutrophils with a broad peak between 4 and 10 hours. Application of chloroform for I minute results in the absence of the late permeability response, While the P.A.S. positive leucocytes emigrate an hour earlier-i.e., only H hours after injury. Eosinophil counts are complicated by the great variation in number of eosinophils in normal guinea-pig skin. In sections of skin 1 cm long, 50 to 60% of the animals exhibit only two to three eosinophils. These animals show no rise in the eosinophil count after injury. In 20 to 30% animals, there are ten to fifty eosinophils in a cm section of skin; of these, many show a marked rise in eosinophil count, coinCiding with the neutrophil infiltration in about 4 hours, although there may be a suggestion of an earlier peak in the first half hour after injury. Occasional animals, which in all other respects appear quite normal, exhibit large numbers of eosinophils in their skin (500 to 1,000 cells per cm to section), but there seem to be no significant changes provoked by injury. What is perhaps most important is that whether the eosinophil count is zero or 1,000, and whether there is a marked rise in the tissue eosinophil count after injury or not, the pattern of erythema or permeability is unaffected. Examination of sections stained with methylene blue failed to reveal a single mast cell in numerous animals, so that this investigation was abandoned. A diphasic pattern of vascular permeability having been demonstrated following the application of irritants to the surface of the epidermis, the effect of intradermal injections was next investigated. Phenol and acetic acid, which both gave diphasic patterns when applied to the skin surface, provoke only a monophasic response when injected intradermally, no matter what the concentration. A series of chemicals was then screened by intradermal injection to study their effects on both vascular permeability and tissue leucocytosis. They may conveniently be divided into three groups. Firstly, the chlorides of thirty-six elements; secondly, fifty-one salts of sodium; thirdly, various miscellaneous substances. The reactions can be grouped in four main categories. Firstly, substances evoking no significant reactions when injected in isotonic concentrations. Among the chlorides, this was the pattern obtained with all the alkaline metals of group one of the periodic table, viz., lithium, sodium, potassium, rubidium and caesium. These are all monovalent elements and aqueous solutions of their chlorides have pH concentrations between 4.8 and 6.5. Among the sodium salts a large number were ineffective, even at O.lM concentration. These include acetate, benzoate, bromide, bismuth ate, chloride, cinnamate, dithionate, glycerophosphate, fumurate, formate, gluconate, glycolate, hippurate, iodide, laevulate, malleate, malonate, meta phosphate, molybdate, nitrite, nitrate, oxylate, phthalate, proprionate, sulphate, tartrate and thiosulphate. These sodium salts are poorly dissociated salts of organic acids, or completely dissociated salts of strong mineral acids, or
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almost insoluble substances. They have a pH ranging between 5 and 9-except metaphosphate, which was ineffective even at a pH of 3.5, but has a relatively low solubility. Sodium hippurate and malonate each evoke similar patterns of permeability with moderately intense early phases, lasting 3 to 4 hours, followed by weak second phases maximal in 30 hours. Both solutions were mildly alkaline, with pH of 7.6 and 7.9 respectively. Although almost ineffective at O.IM, sodium molybdate causes a diphasic reaction at 0.2M. The second phase is very prolonged, with a peak between 16 and 30 hours, but still apparent in 70 hours. The second variety of response consists of marked increase in permeability with minimal macroscopic necrosis. Among the chlorides, this was shown by some metals of group two of the periodic table-magnesium, calcium and strontium. Of these, magnesium is only weakly effective even at 0.2 molar concentration and should possibly be classed with the ineffective elements of group one. The other two have a very powerful effect on vascular permeability, even at concentrations of O.OSM. The permeability changes are associated with no macroscopic necrosis in the case of strontium; and only a small central zone, appearing in about 10 hours in the case of calcium. The reaction to calcium is monophasic and disappears in 7 to 12 hours. With strontium however, the early phase disappears in 2 to 3 hours, being followed by a second phase of moderate intensity which is maximal between 16 and 20 hours. It seeems significant that the late phase with strontium chloride occurs at a time when necrosis without permeability is developing in calcium chloride lesions, which show only an 'early' monophasic response. In general, the pattern suggests that strontium chloride is a weaker irritant than calcium chloride. The pH of both solutions lies between 4.8 and 5. Among the sodium salts, only alginate (see below), arsenite, selenite and tellurite fall into this second category. The latter trio form a unique group. Selenite, and colloidal selenium itself, are much the most potent. Even at a concentration of 0.002M, selenite evokes a very marked increase in vascular permeability, with a time-course different from any other substance yet tested. An immediate phase appears to be subsiding for an hour, when a second phase of even greater intensity begins. Permeability becomes maximal in 10 hours, and then declines quite rapidly to return to normal in 24 hours. During the decline of the second permeability phase, necrosis begins to appear in many animals in lesions aged 16 to 24 hours. Sodium arsenite also has a very marked permeability effect, although somewhat less than that of selenium. Arsenite, 0.002M, elicits a simple monophasic reaction lasting 7 hours. There is no necrosis and no late response. At 0.01 M, the immediate response increases in intensity for the first 2 hours, but then fades almost completely in 7 hours. Necrosis begins to appear in 3 to 4 hours, but the lesion only averages 5 mm diameter. At O.OSM, a very intense early phase has subsided in 5 hours, at which stage there is marked necrosis. A late phase then occurs around the necrotic zone, being maximal in 7 to 10 hours and subsiding by 20 hours. Sodium tellurite resembles selenite in many respects. Even at concentrations as low as 0.002M, it provokes a considerable permeability response. This commences 10 to 15 minutes after injection and is maximal in 2 hours (c.f. Arsenite O.OlM). It then fades in 3 to 4 hours only to return as a moderate second phase between 6 and 24 hours. It never reaches the intensity of the selenite lesions, but this is not surprising since this element rapidly precipitated as inert metallic tellurium in the tissues. The third type of response consists of a marked increase of vascular permeability associated with considerable macroscopic necrosis. Such substances only cause permeability effects at concentrations which also cause necrosis. Among the chlorides, this pattern of response is obtained with some other elements of group two-viz., zinc, cadmium and barium; several
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elements of period four-viz., titanium, chromium, iron, manganese, cobalt and nickel; and to a lesser extent with indium which is in group three. These are mainly divalent ions, although titanium, indium, chromium and iron are trivabnt and are also the least effective in increasing permeability among the group. The divalent salts all have a pH close to 5. The four trivalent salts have pHs between 2 and 4. Zinc, at 0.02 molar gave an intense monophasic response which subsided in 4 hours and was followed by a static amount of necrosis. No late response was observed. Barium, 0.05M, causes an intense spasm of the vessels which lasts for 1 to 2 hours and is followed by a phase of increased permeability maximal at 3 hours. Necrosis appears in 6 to 7 hours and increases in amount until 24 hours. A second phase of increased permeability occurs between 12 and 16 hours, as a peripheral zone 4 to 8 mm wide round the central necrosis. It is maximal between 16 and 27 hours. Cadmium chloride, 0.02M, causes an intense early response which slowly fades for 4 hours, then again increases as a peripheral zon e round an area of necrosis, the increase being slowly progressive for at least 18 hours. By this time, the necrotic zone is 12 mm in diameter, surrounded by a faint 5 mm bands of leaking vessels. The chlorides of manganese, cobalt and nickel, 0.02M, all cause a marked increase in vascular permeability. With manganese, the single early phase of increased permeability does not begin to subside until the lesions are 5 hours old and then gradually disappears by 30 hours. Necrosis appears at 16 hours and gradually increases to a 7 or 8 mm lesion in 60 hours. The early response to cobalt chloride is even more intense, but soon begins to fade and continues to do so for about 5 hours. Then follows a prolonged reaction with a lesion only moderate in size, but with permeability markedly increased and lasting at least 80 hours. A little central necrosis appears in some of the cobalt lesions in 16 hours, but never reaches the dimensions of the manganese lesions. Nickel chloride causes a more clearly diphasic type of reaction, the intense early phase having almost faded in the first hour. It is followed by a moderate second phase in 16 to 40 hours with a peak between 20 to 27 hours. The amount of necrosis with nickel chloride is intermediate between that with manganese and cobalt. The pH of all three solutions is between 5 and 6, manganese at 5.75 being the least acid of the three. Chromic chloride, even at O.OIM, causes more prolonged necrosis than any other salt tested. The centre of the lesion becomes a chronic ulcer, sometimes remaining unhealed for 6 weeks. However, its effects on permeability are not spectacular, resembling ferric chloride more than manganese, cobalt or nickel. Ferric chloride at O.OIM closely resembles chromium chloride in its immediate effects. An immediate phase of increased permeability, moderate in intensity and of short duration (2 hours) is followed in 16 and 24 hours by a feeble second phase round a central necrotic area. Like the necrosis with chromium chloride, that with ferric chloride does not spread after the first 3 hours, but does not show the extreme chronicity of the chrome ulcers. Among the sodium salts, this third type of reaction-viz., increased permeability associated with necrosis, was shown by chromate, dichromate, bromate, iodate, tungstate, cobalti nitrite, nitro-prusside, carbonate, metaborate, persulphate, salicylate, hydrogen citrate, hydrogen malleate, hydrogen sulphate and hydrogen tartrate. The reason for the activity of some of these salts is their acidity. The hydrogen salts have a pH ranging from 2 for hydrogen sulphate to 6 for hydrogen citrate. Metaborate and carbonate are both alkaline, with pH's of 10.5 and 11.3 respectively. The remainder lie between pH 5 (bromate) and 8.5 (tungstate). As with the chlorides, different patterns of permeability change were found with each salt; but only two of the more striking will be detailed. Chromate and dichromate, 0.05M and 0.02M respectively, both evoke a marked diphasic type of response. The first phase fades in 3 to 4 hours, but is followed bv a strong second phase which begins 9 to 10 hours after injection, increases in intensity for up to 16 to 20 hours, and is then maintained for a further 40 to 50 hours.
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Both salts cause a moderate necrosis, which tends to increase after the late phase of permeability subsides 80 to 100 hours after injection. Chromate ulcers are chronic but last a shorter period than those produced with chromic chloride. Chromate ulcers usually heal in 2 weeks. Sodium tungstate is not an active inflammatory reagent; but at O.IM, it is one of the few substances which causes intense vascular spasm (cf. barium chloride). For about 30 minutes the injection site is dead white th~n, as the spasm relaxes, a phase of increased permeability supervenes, becoming maximal in 1 to 2 hours and subsiding in 5 hours. There is a feeble second phase at 16 hours accompanied by mild statis necrosis. The last type of response is necrosis, often appearing immediately after injection, not associated with more than a minimal increase in vascular permeability. Among the chlorides, copper, silver, gold (as sodium gold chloride), beryllium, mercury, aluminium, lanthanum, cerium, didymium, tin, thorium, antimony, rUbidium, palladium, germanium, gallium and scandium, each induces this reaction; cf. sulphates of vanadium and zirconium, vitrium nitrate and lead acetates. This group includes most of the heavy metals whose astringent action is well known; and those elements with chlorides that dissociate in solution-giving in effect, dilutions of hydrochloric acid. Many of these solutions have a pH round 2, and even that of the trivalent rare earth group is around 4. Among the sodium salts, antimonate, tetravanidate, trisodium morphophosphate and disodium-di-hydrogen-pyro-phosphate all cause much more necrosis than permeability changes; but the phosphates and tetravanidate represent extremes of pH. It is interesting that antimonates do not share the properties of increasing permeability shown by both arsenites and arsenates. The remaining test substances included distilled water and saline of molar concentration to test the effect of hypo- and hypertonicity respectively. Although both cause an immediate increase in permeability and a moderate amount of necrosis, distilled water produces a prolonged but moderate late phase of increased leaking round the necrosis, while molar saline evokes no late phase. Other substances with marked effects on vascular permeability are the colloids, sagiatum and alginate. These cause intense early phases lasting 6 to 7 hours with sagiatium, and 4 hours with alginate, followed in the case of sagiatum by a second phase of moderate intensity between 20 and 50 hours with 1 % preparation and 15 and 24 hours with 0.1 %. Alginate, 2.5 causes virtually no late response. Suspensions of kaolin 2 % and talc 2 %, cause a marked increase in permeability within a few moments of injection. This loses much of its intensity in the first half-hour, but a second phase occurs at about 12 hours, is maximal at about 16 hours, but does not completely subside until 55 hours after injection. N-ethyl-maleimide is a substance which is particularly toxic to mitochondria. It also has a very potent effect on vascular permeability. Even at a concentration of only 0.02 mg per ml, it causes quite an intense reaction. This is essentially monophasic, subsiding in 7 to 10 hours. At a concentration of 0.04 mg per ml, a feeble second phase appears between 7 to 24 hours and subsides in 48 hours, at which time a little necrosis appears. At a concentration of 0.02 mg per ml, a very intense monophasic response does not subside until 30 hours, but necrosis appears in an hour and increases to considerable dimensions in 40 to 50 hours. Other test substances included bromine, ascorbic acid, osmic acid, molybdenum trioxide, chloro-platinic acid, flowers of sulphur, carborundum, thiophenol, chloral hydrate, chromic sulphate, chromium oxide, croton oil and cantharides. At this stage of the work, different patterns of increased vascular permeability and necrosis have been established for a variety of chemical irritants. It now remains to relate these changes to the leucocytosis and cellular damage at a microscopic level. All lesions from every test animal have been blocked. Initally about one-third of the large number of lesions are being sectioned, but it is expected that further lesions will be examined as the work develops. The results for the work on increased vascular permeability and local necrosis will be submitted early in 1967. It is
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expected that the histology of the lesions for superficial irritants will be reported later in 1967. However, the considerable time required for microscopic assessment of the numerous sections makes it unlikely that the histology of the lesions injected intradermally will be completed before 1968. Publicatiou STEELE, R. H., and WILHELM, D. L. 'The inflammatory reaction in chemical injury.' Brit. 1. Exp. Path. (In press.)
DEPARTMENT OF PHYSIOLOGY Professor I. Darian-Smitb, M.D., Professor of Physiology. (On leave during 1966.) Mr B. J. Sessle, M.D.S., B.Sc., Teaching Fellow. Mr M. J. Rowe, M.Sc., Teaching Fellow. Project Neural mechanisms subserving facial sensation. Report The aim of this work over the past few years has been to define some of the neural mechanisms underlying the sensory appreciation of tactile stimulation of the skin of the face. It was anticipated that the organisation of the trigeminal and the spinal somatic afferent systems would have much in common but would differ in detail relevant to the midline nature of the face and the latter's specific sensory functions. An analysis of the static functional properties of single neurones isolated at successive levels within the ascending pathways from the face to the cerebral cortex was initially carried out. In addition, some of the feedback loops operating in this system were examined-attention being directed particularly to the topography of these loops, the inhibiting mechanisms subserving their actions, and the contribution these recurrent pathways make to the transmission of transient neural signals from the skin to the cerebral cortex. During 1966, investigations were begun on neural elements in the trigeminal complex responsive to thermal stimulation of the skin of the face. Individual primary neurones were first examined by recording from their cell bodies in the semilunar ganglion. All those units found to be thermally sensitive (sample of 300 units) also responded at low threshold to mechanical stimulation of the skin within a highly localised receptive field. No units specifically sensitive to changes in skin temperature were observed either in hairy skin of the cat's face, nor in the tongue. Estimates of conduction velocity revealed that in the neurone sample no unmyelinated fibres nor small myelinated fibres were included, possibly reflecting in part the relative infrequency of these fibres in trigeminal nerve branches, but also casting suspicion on the sampling characteristics of the technique of unitary recording used. The majority of the thermally sensitive units examined responded to cooling of the skin, but proved to be relatively insensitive, the maximal discharge rate rarely passing above lO/second, even with profound and rapid cooling. On the other hand, their responsiveness to mechanical stimulation within their receptive fields was exquisite and comparable to that of the popUlation of thermally insensitive mechanoreceptors. Investigations of the central projection pathways of these neurones by examining the levels within the trigeminal spinal tract from which they could be anti-dromically fired again revealed no differences between the thermally sensitive and in insensitive mechanoreceptors.
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Work in the immediate future will be directed to extending the neurone sampling to include small myelinated and unmyelinated fibres. In addition, a more quantitative definition of the responsiveness of the different cutaneous receptors to changes in skin temperature and to mechanical stimulation is to be undertaken. Only then can effective examination of second and higher order neurones which do respond to this stimulus be undertaken. This quantitative analysis will require more exact control of the thermal and mechanical stimulus, and considerably more elaborate techniques of data collection. Publications DARIAN-SMITH, I., and YOKOTA, T. 'Cortically evoked depolarisation of trigeminal cutaneous afferent fibres in the cat.' I. Neurophysiol., 1966,29, 170. DARIAN-SMITH, I., and YOKOTA, T. 'Corticofugal effects on different neuron types within the cat's brainstem activated by tactile stimulation of the face.' I. Neurophysiol., 1966, 29, 185. DARIAN-SMITH, I., ISBISTER, J., MOK, H., and YOKOTA, T. 'Somatosensory cortical projection areas excited by tactile stimulation of the face of the cat.' I. Physio/., 1966, 182, 67l. DARIAN-SMITH, I. 'Tactile sensory pathways from the face.' Trans. Ass. Austral. Neurol., 1966, 2, 27. DARIAN-SMITH, I. 'Neural mechanisms of facial sensation.' Internation. Review of Neurobiology, Vol. 9, 300. MOUNTCASTLE, V. B., and DARIAN-SMITH, I. Chapter 62 on 'Somatic sensation in "Medical Physiology" '-12th Edition, ed. by V. B. Mountcastle. In press, Mosby. (Previous editor: Bard.)
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UNIVERSITY OF QUEENSLAND DEPARTMENT OF BIOCHEMISTRY Professor E. C. Webb, M.A., Ph.D. Dr B. Zemer, M.Sc., Ph.D., Dip.Ed., F.R.A.C.I., Reader in Enzyme Biochemistry. Dr C. J. Masters, M.Sc., Ph.D., Senior Lecturer in Biochemistry. Dr M. D. Doherty, M.Sc., Ph.D., Lecturer in Biochemistry. Mr D. J. Horgan, B.Sc., Research Assistant, N.H.M.R.C. (to June 1966). Mr E. A. Bennett. B.Sc., Postgraduate Scholar,N.H.M.R.C. Dr R. L. Blakeley, N.I.H., Postdoctoral Fellow. Dr J. K. Stoops, Senior Demonstrator in Biochemistry. Miss E. M. Sampey, B.Sc., Senior Demonstrator in Biochemistry. Dr P. Duffy, M.B., B.S., B.Sc., Edwin Tooth S;holar (to October 1966). Mr R. S. Holmes, B.Sc., Commonwealth Postgraduate Scholar. Mrs M. T. C. Runnegar, B.Sc., Commonwealth Postgraduate Scholar. Mr J. de Jersey, B.Sc., General Motors Holden Scholar. Mr A. A. Kortt, B.Sc., Commonwealth Postgraduate Scholar. Miss F. P. Noonan, B.Sc., Commonwealth Postgraduate Scholar. Mrs J. Fitzsimmons, B.Sc., Demonstrator in Biochemistry. Miss A. I. Keto, B.Sc., Demonstrator in Biochemistry. Mr J. A. Hinds, B.Sc., Commonwealth Postgraduate Scholar. Mr P. A. Inkerman, Demonstrator in Biochemistry. Projects A study of the carboxylesterases of liver and related studies on other hydrolytic and proteolytic enzymes. The isoenzymes of animal tissues. Comparative enzymology of creatine kinase. Report A study of the carboxylesterases of liver and related studies on other hydrolytic and proteolytic enzymes The purification and titration of the pig liver carboxylesterase has been published. This work showed that the enzyme has two active sites per 163,000 molecular weight species. The enzymes from ox, horse, chicken and sheep have all been highly purified and the study of the homology of the active site peptides using [32P]DFP has been submitted for publication. All the enzymes have similar sequences very close to the active serine, viz., -glu-rer-ala-. However, the surprising observation was made that on peptic digestion, the major peptides from the ox and chicken enzymes are clearly different from one another and from the peptides from the horse, pig and sheep enzymes (which are identical). Orange skin acetylesterase, however, while apparently a serine enzyme is clearly differentiated from the mammalian enzymes. The ox liver enzyme has been fragmented by treating the urea-denatured enzyme with high concentrations of ,B-mercaptoethanol. The results are most readily explained as due to reduction of interchain disulphide bonds. Inhibition of the horse liver enzyme by alcohols and ketones leads to the conclusion that enzyme specificity can be explained in terms of enzyme-substrate affinity for a series of aliphatic esters. A comparative study of acetylcholinesterase, carboxylesterase and the proteinases, a-chymotrypsin and trypsin, shows that the esterases are enormously more efficient catalysts for the hydrolysis of esters.
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Proteolytic and hydrolytic enzymes A study of the alkaline hydrolysis of p-nitrophenyl hippurate revealed that the reaction proceeded via an oxazolinone intermediate. Further, oxazolinones (in particular, 2-phenyl-4, 4-dimenthyl oxazolin-5-one) are relatively non-specific and highly efficient acylating agents for a variety of proteolytic enzymes. Two further systems were studied to demonstrate the importance of labile derivatives in a study of specificity of these enzymes. Methyl a-benzamido-ciscinnamate and the corresponding oxazolinone, 2-phenyl-4-benzylidine-oxazolin-5-one were investigated as substrates of a-chymotrypsin. Deacylation was rate-limiting only for the oxazolinone. Of the six proteolytic enzymes (ficins) from fig latex, two have been obtained for the first time in a highly purified state. Further, two bromelains have been similarly purified for the first time from pineapple fruit. The native stem enzyme has been compared with the enzyme from 'bromelain powder' and found to be identical. Work on the chemistry of the active sites of these proteins has commenced. An extensive re-investigation of urease has been undertaken. A convenient, continuous rate assay, modified from our earlier report, has enabled us to study the chemistry of the active site. Iodoacetamide (3 x 1Q-3 M) caused complete irreversible inactivation of urease = 7 hr.). Benzhydroxamic acid, a known inhibitor of the enzyme, appreciably increased this rate of inactivation, while hydroxyurea, an 'inhibiting' substrate, decreased the rate of inhibition by iodoacetamide. Several possible interpretations of these results are being pursued using [14C]iodoacetamide and [l4C]iodoacetate. Attempts to trap a carbamoyl-enzyme intermediate using glycine, aniline, methylamine and benzylamine have so far failed to produce any result.
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The isoenzymes of animal tissues The pioneering investigations into the ontogenetic variformity of lactate dehydrogenase gave rise to the assumption that the early embryonic form of this enzyme was a parental type in all vertebrates. Furthermore, on the basis of this information, the type of lactate dehydrogenase synthesis (A- or B- subnnits) has been widely considered to be directed by the degree of oxygenation of the tissue source. During the past year, these postulates have been tested in the light of further studies of the developmental properties of this enzyme. These results have substantiated and extended previous findings by demonstrating that lactate dehydrogenase synthesis is initially monotypal in all vertebrates. Instead a relative expression of the genes is observed, which appears to be characteristic of the individual genera, and these values bear a limited phylogenetic inter-relationship. In addition, the experimental data illustrate the indirect nature of the epigenetic involvement of oxygen in the biosynthesis of lactate dehydrogenase. An alternative explanation of the subunit percentages of the embryonic enzyme has been suggested. In addition to this work, a number of previously unreported multiple forms of lactate dehydrogenase have been discovered. Since the present theories of isoenzyme structure do not account for these forms, it is hoped that further study of this multiplicity may provide information of basic significance in this field. With the aim of clarifying the isoenzyme status of esterases, also, the developmental and physicochemical properties of these enzymes have been studied in an extensive range of animal tissues. With the guinea-pig, a total of twenty-four multiple forms of esterolytic activity have been resolved, and the occurrence of individual forms in the different tissues inter-related. These forms have been divided into four main isoenzyme classes by means of substrate and inhibitor studies, with carboxylesterases existing as ten separate forms, arylesterases four, cholinesterase five, and acetylcholinesterase five. Each of these multiplicities appears to be more extensive than previously reported.
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Further subdivision of some of these major classes bas been acbieved on the basis of the physicochemical and developmental parameters utilized. This treatment would appear to implicate at least 12 structural genes, in tbe biosynthesis of tbe soluble cavian esterases; a multiplicity of control, wbicb is, again, considerably in excess of previous estimates for mammalian sources. This work bas considerably clarified the isoenzyme status of mammalian esterases. It is anticipated that tbe other esterase projects will complement thh information.
Comparative enzymology of creatine kinase Furtber purification of cbicken breast muscle creatine kinase (CPK) bas been acbieved. Despite the increase in specific activity of tbe protein used to prepare antibodies in rabbits, two cross reacting bands have been detected again by the Ouchterlony gel diffusion technique. The sedimentation constant of the purified protein has been shown to be dependent on the concentration of the protein and the pH. Evidence for the dissociation of the protein into sub-units in the presence of 1 M guanidine hydrochloride has been obtained in the ultracentrifuge. This dissociation may also be detected by following the increase in the number of -SH groups which react with 5,5'dithiobis-2-uitrobenzoic acid (Ellman's reagent). Recently CPK has been prepared from chicken leg muscle with a specific activity almost double that of the best preparation from breast muscle. The reason for this increase is not clear but the possibility of two isoenzymes which show no marked difference in their rate of migration on starch gel cannot be overlooked. Purification of CPK from an invertebrate source has progressed. This enzyme is to be studied because of its interesting evolutionary position. Marphysa sp. which can be obtained locally have proved a convenient source of the t nzyme. During the purification procedure, three isoenzymes were detected and these persisted in a preparation in which diisopropyl phosphorofluoridate (DFP) was included at all purification steps. It was subsequently possible to demonstrate the three enzymes in the origin a I starting material by increasing the levels of the ancillary enzymes used in the staining procedure which is linked to formazan formation. Thus it seems unlikely that the isoenzymes are artifacts of isolation. One of the enzymes has now been obtained free of the other two and the preliminary studies on the separation of these two enzymes using DEAE-cellulose and a pH gradient are quite encouraging. The metal activation studies will now have to be repeated on the individual isoenzymes. An experiment to compare the active sites of the three isoenzymes by labelling with ['4C]iodoacetate is planned. There are a number of reports in the literature based on electrophoretic evidence that the mitochondrial enzyme of rat heart is a distinct isoenzyme from the enzyme of the soluble fraction. Pig heart mitochondria are being investigated as a more convenient source of large quantities of mitochondrial enzyme with the aim of isolating and comparing the two enzymes. This will allow kinetic and active site studies on these proteins which previously have only been studied in crude extracts and identified on the basis of separation on starch gel electrophoresis. Publicatious BENNETT, E. A., WEBB, E. C., and ZERNER, B. 'A simple assay for urease.' Aust. I. Sci., 1966, 29, 85. DE JERSEY, J., KORTT, A. A., and ZERNER, B. 'On the mechanism of hydrolysis of Nacylamino acid nitrophenyl esters.' Biochem. biop/zys. res. Commun., 1966, 23, 745. DE JERSEY, J., RUNNEGAR, M. T. C., and ZERNER, B. 'Oxazolinones as enzyme acylating agents.' Biochem. biophys. res. Commun., 1966,25, 383. DOHERTY, M. D., and BHANUBHAND, B. 'Comparative studies of chicken muscle creatine kinase.' Aust. I. Sci., 1966, 29, 85.
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FIELDHOUSE, B., and MASTERS, C. J. 'Developmental redistributions of porcine lactate dehydrogenase.' Biochim. hiophys. Acta, 1966, 118, 538. FITZSIMMONS, J. A. E., and DOHERTY, M. D. 'Studies on ATP: creatine phosphotransferase.' Paper read to the Australian Biochemical Society, Brisbane Meeting, May 1966. HINKS, M., and MASTERS. C. J. 'The regulation of lactate biosynthesis during tissue differentiation.' Aust. J. Sci., 1966, 28, 382. HOLMES, R. S., and MASTERS, C. J. 'The developmental multiplicity of esterases.' Aust. J. Sci., 1966, 29, 83. HOLMES, R. S., and MASTERS, C. J. 'The developmental multiplicity and isoenzyme status of cavian esterases.' Biochim, biophys, Acta. 1967, 132, 379. HORGAN, D. J., WEBB, E. C., and ZERNER, B. 'Determinations of the normality of pig liver carboxylesterase solutions.' Biochem. biophys. res. Commun., 1966, 23, 23. HORGAN, D. J., WEBB, E. c., and ZERNER, B. 'A large scale purification of crystalline pig liver carboxylesterase.' Biochem. biophys. res. Commun., 196623, 18. MASTERS, C. J. 'Isoenzyme synthesis and ontogeny.' Aust. J. Sci., 1966,29, 83. MASTERS, C. J., and HINKS, M. 'The ontogenetic variformity of lactate dehydrogenase in feline and cavian tissues.' Biochim. biophys. Acta, 1966, 130, 458. WEBB, E. C., 'The use of inhibitors in specificity studies with carboxylesterases.' Aust. J. Sci., 1966, 29, 83.
Dr J. E. O'Hagan, M.Sc., Ph.D., F.R.A.C.I., Research Fellow, N. H. & M.R.C. Miss L. Power, B.Sc., Research Assistant, National Heart Foundation. Mr P. R. Bavinton, B.Sc., Demonstrator. Mr P. Willadsen, Student Research Assistant, National Heart Foundation. Project The relationship between structure and function of haemoglobins and myoglobins. Report The linkages between the haem and the apoprotein in haemoglobins and myoglobins are important not only because they undoubtedly are responsible for some of the functional properties of these haemoproteins but also because knowledge of their nature may be valuable in explaining somewhat similar binding of prosthetic groups and substrates of enzymes. The ability of the haem iron of haemoglobin to undergo reversible oxygenation without oxidation results from the linkage to the globin portion and by a reciprocal change carbon dioxide may be bound reversibly (Bohr effect). On the other hand, myoglobin has a much greater oxygen affinity, is more readily oxidised and has little, if any, carbon dioxide transporting ability. Any structural difference between the two types of proteins may be important in explaining their physiological function. In earlier studies it was reported that in horse haemoglobin and horse heart myoglobin the groups binding the haem propionate side-chains were likely to be imidazoles (in this haemoglobin) and much stronger basic groups (in this myoglobin). The work has been extended to a representative series of haemoglobins and myoglobins with comparable results-namely a weak binding in haemoglobins and a strong binding in myoglobins. The approach has been to substitute nickel meso porphyrin in place .of ferro~s protoporphyrin (haem) and to measure the'pH ra~ge of attachment to t~e pr?tem. I?, thiS way the specific mode of attachment of the Side-chams of the haem (espeCIally m relatIOn to
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the negatively charged propionate groups) can be deduced, since by replacing the iron by nickel, the linkage through the central metal atom to the protein is (as far as can be known) eliminated. Examination of the nickel mesoporphyrin attachment has been facilitated by the development of a new experimental method. A Radiometer Titrator/Titrigraph system has been coupled through a specially constructed titration cell to a Shimadzu recording photoelectric spectrophotometer so that continuous titration curves under automatically controlled conditions can be obtained. Another system has been built to enable the plotting of oxygen dissociation curves under conditions of temperature, pH and specific ionic concentration comparable with those of the titration experiments. Titration curves showing nickel mesoporphyrin attachment have been obtained for the following species: normal human adult, normal human foetal, horse, pig, ox, sheep and duck apohaemoglobins and human, sperm whale, horse, sheep, kangaroo, pig, buffalo, ox and duck apomyoglobins. Whilst only a limited series of oxygen dissociation curves have been obtained there does not seem to be (at least at this stage of the work) a simple direct relationship between the apparent pK of the dissociating groups of the proteins binding the haem propionates and the value of p! for the oxygen dissociation. In view of this, attention has been shifted to techniques which may give a more direct indication of the side-chain role. This will involve the synthesis of haems with modified propionate side-chains, their combination with apohaemoglobins and apomyoglobins and the determination of oxygen dissociation curves and Bohr effects of the new artificial haemoproteins. To investigate whether, on combination of the nickel mesoporphyrin and the altered haems with the apoproteins, a return to the original three-dimensional structure of the native haemoproteins occurs, the relative shapes of these complexes are being determined by viscosity, sedimentation in the ultracentrifuge and optical circular dichroism measurements. In a related study, the mode of attachment of haematin, nickel mesoporphyrin and bilirubin to human serum albumin has been examined further. In ferrihaemalbumin (methaemalbumin) the results to date are not inconsistent with earlier proposals that the linkage of the haematin is not through the metal atom but through one or both of the propionate side-chains. Publication O'HAGAN, M. E., and MOORE, P. J. 'A comparative study of haematin propionate linkages in certain haemoglobins and myoglobins as detected by a new titration system.' Proceedings of the International Symposium on Comparative Hemoglobin Structure, held at Thessalonika, April 1966. (In press.)
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DEPARTMENT OF DENTISTRY Dr W. A. McDougall, B.Sc., D.D.Sc., Reader in Oral Biology. Mr K. F. Adkins, M.D.Sc., Lecturer in Oral Biology. Project Studies of gingival epithelium. Irradiation effects on hard tissues of the jaws. __ Report The techniques developed in 1965 for demonstrating peroxidase and lysosome-like bodies in gingival tissues were applied to study the passage of the histochemically-identifiable foreign
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protein, horseradish peroxidase, through gingival epithelial and connective tissues. The method also permitted the study of the intracellular uptake of the foreign protein. Thin slices from gingivectomy specimens were incubated for two to twenty hours in Ringer phosphate with added horseradish peroxidase. Examination of cryotome sections showed that the plant enzyme spread rapidly throughout the gingival connective tissues but that its rate of spread in gingival epithelium was much slower. Spread in the epithelium took place primarily along the interfacial canals between cells. In crevicular and non-keratinised marginal gingivae entry occurred from both the free surface and the basement membrane. When a well keratinised stratum corneum was present no entry of the peroxidase into this layer was demonstrated. The marked differences of penetrability of these types of epithelia indicates that it is of clinical importance to establish and maintain well cornified marginal gingival tissues. An unspecific uptake of peroxidase occurred in most connective tissue cells. Active uptake was evident in macrophages in which the peroxidase accumulated in large cytoplasmic phago-Iysosomes. The influx into epithelial cells was slower. The first feature noticed was the accumulation of horseradish peroxidase on th~ plasma membranes and intercellular bridges. This was followed by its entry into the peripheral cytoplasm where it aggregated in small granules that also reacted for acid phosphatase. These were considered to be Iysosomes. Later the more centrally situated lysosome-like bodies showed an uptake of horseradish peroxidase and at about this stage disintegration of the granules began and continued until most or all of the acid phosphatase positive bodies had disappeared. Since the concentration of horseradish peroxidase used (2 mg. per m!.) was toxic, it was considered that the disintegration of lysosomes was a toxic effect. Both the amount of horseradish peroxidase taken up and the extent of lysosomal degranulation occurring in adjacent epithelial cells varied considerably. Studies of the effect of 1200R of x-radiation on the growth of bone, dentine and cartilage in the mandibles of rats have been continued. Undecalcified transverse sections through the incisor teeth of the rats used in this study were examined by micro-radiography. Injections of achromycin given immediately before and after the radiation period (day twenty-nine to day thirty-two) produced ealciotraumatic effects in the dentine which were apparent as radiolucent lines on the radiographs. These lines enabled recognition of pre-treatment, treatment and post-treatment zones in the images. The dentine formed during the treatment period when 300R were administered daily for four days was hypomineralized. Throughout the post-treatment period the dentine was again hypomineralized whether the radiation was administered in one, two or four doses. Evidence suggests that in these areas either there is a reduced availability of inorganic materials locally or the ability of the organic matrix to be mineralized is altered. Histological examinations of decalcified sections of the mandible showed early evidence of changes induced by irradiation. These changes included necrosis of cells, oedema at the apices of the incisor teeth, formation of osteodentine in the pulpal tissues in the incisors and molars, and aberrations in the endochondral ossification in the mandibular condyle with prolonged survival of some chondrocytes and impeded differentiation of osteoblasts. Within the short term observations of this study the effects produced both quantitatively and qualitatively were severe irrespective of the dose/time pattern of irradiation used. Publications ADKINS, K. F. 'The effect of single doses of x-radiation on mandibular growth.' Brit I. Radial. 1966,39,602. McDOUGALL, W. A. 'Histochemical observations on the penetration and uptake of horseradish peroxidase in gingival tissues.' Periodontics. (In press.)
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Dr A. M. Parfitt, M.B., B.Chir., M.R.C.P., M.R.A.C.P., Senior Lecturer. Mr T. French, B.Sc., Technical Assistant. Project The renal excretion and conservation of calcium and magnesium. Report Further studies on the effects of ethacrynic acid and furosemide in normal subjects have confirmed that the relationship between increased calcium and increased sodium excretion is similar to that found with the mercurial diuretics. It seems that all diuretics which have a major site of action in the proximal tubule (± loop of Henle) produce an acute increase in calcium excretion which parallels closely the increase in sodium excretion. It is considered that this can best be explained by postulating that at major sites of sodium reabsorption where the tubule wall is permeable to water, it is also permeable to calcium, and that the changes in calcium excretion are a passive consequence of the changes in sodium and water excretion. If this is so it is likely that most homeostatic regulation of calcium excretion occurs by changes in distal rather proximal reabsorption. For this reason it is considered that further analysis of the effects of diuretics with mainly proximal action (mercurials, furosemide, ethacrynic acid) would not be profitable. Further work with these drugs will be confined to exploring the different effects on phosphat excretion, to studying their effects on citrate excretion and to using the newer potent oral diuretics rather than mersalyl to produce acute diuresis, to study the calcium and sodium conservation which occurs in the post diuretic recovery phase. Calcium excretion has been studied during the accumulation and loss of odema in five patients with cardiac failure, nephrotic syndrome or chronic renal failure. In general, sodium retention is accompanied by calcium retention and sodium diuresis by calcium diuresis regardless of how this is achieved. Calcium and magnesium excretion have neen studied during the Stamey test of divided renal function in twelve hypertensive subjects. Changes in the tubular handling of sodium were accompanied by similar changes in calcium and magnesium, but the correlation was closer in patients with renal ischaemia than in patients with pyelonephritis. The acute effect of ammonium chloride acidosis has been studied in six subjects. The results do not support the view of Walser, based on experiments in dogs, that the hypercalciuria induced is due to increased sodium excretion. There was better correlation with chloride excretion than with sodium, but this also did not provide a satisfactory explanation of all the results. It has become clear that the hypocalciuric effect of the thiazide diuretics is a unique property of this group of drugs. In a patient -vith hypercalciuria due to Vitamin D therapy of osteoporosis, chlorothiazide produced a striking fall in urine calcium (600-350 mg per 24 hours), which was accompanied by hypercalcaemia (12.6 mg per 100 mI). On ceasing the drug, urine calcium rose and plasma calcium fell. This is the first unequivocal demonstration in man of hypercalcaemia resulting from a fall in calcium excretion. The experiment has been repeated in four subjects with hypercalciuria associated with osteoporosis or Vitamin D therapy, but only slight increases in serum calcium occurred. In one additional patient on long term thiazide therapy, an increase in sodium intake of 200rnEq. daily did not increase urine calcium to pretreatment levels, so that the hypocalciuric action is probably not due to continued sodium depletion. The mechanism of the hypocalciuric action of the thiazides is being explored further by studying the effects of citrate excretion, and by studying the effect of the non-diuretic thiazide diazoxide. 4275/67-7
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DEPARTMENT OF PARASITOLOGY Professor I. F. A. Sprent, Ph.D., D.Sc., F.R.C.V.S., FAA Mr E. G. Warren, B.Sc., Postgraduate Scholar, N.H. & M.R.C. Project
The pathogenic significance of ascaridoid nematodes of animals particularly in relation to human infection. Report
Particular attention has been given to the study of Toxocara canis, an established casual organism of human larva migrans, and to the closely related species Neoascaris vitulorum a parasite of ruminants and N eoascaris mackerrasae, a parasite of the allied bush rat. The programme of study described in the previous annual report has been continued. Due to the prevalence of the prenatal mode of infection of dogs by T. canis, studies have been carried out in an effort to simulate the larval migration from the maternal tissues into the foetus in an experimental host (the mouse). Groups of virgin and gravid female mice have been examined at various times after infection and the migration and distribution of the T. canis larvae were compared, no significant difference was found in the distribution of the larvae in the tissues and no migration to the foetus occurred. There have been many suggestions in published literature relating to the life cycle of T. canis to the effect that hormones may directly or indirectly effect the infection of the foetus by this organism. It was decided therefore to co mpare the migration and distribution of T. canis larvae in control groups of infected virgin female mice and groups of infected virgin female mice treated with hormone preparations. Under the present experimental conditions no major variations have been found following treatment with oestrogens, chorionic gonadotraphin, oxytocin and cortisone acetate. Further preparations remain to tbe tested and the effects of different experimental procedures remain to be examined. Experimental Neoascaris mackerrasae infections in mice have been repeated. It has been found that the treatment of mice with morphine sulphate prior to oral infection with eggs of N. mackerrasae markedly enhances the degree of infection. This enhancement appears to be due to the effect of morphine sulphate in reducing the intestinal emptying time, thus giving the eggs a greater chance to hatch. Further results on the distribution and development of this nematode in the mouse have been obtained. Several species of possible intermediate hosts, e.g. earthworms, tadpoles and small fresh water fish, have been fed with eggs, but no patent infection was established. Efforts have been made to infect laboratory-bred bush rats, the natural host, with N. mackerrasae. Various techniques have been employed, but on only one occasion has an adult infection been established. It is hoped that the experiments carried out on mice will eventually lead to the successful establishment of this species in rats. This would provide a unique opportunity for the study of an ascaridoid nematode in a small laboratory animal. Trapping for the allied bush rat in rain forest areas of S.E. Queensland has continued and further results regarding the incidence of N. mackerrasae have been compiled. Experimental infections of mice with Neoascaris vitulorum, a species which also utilises prenatal infection, have proved successful, and results concerning the distribution, growth and fate of the larvae in this host have now been obtained. These results have corrected and added to earlier published descriptions of this particuluar host-parasite system. Pregnant cows have been infected with N. vitulorum and mature infections have been established in newly born calves. Attempts are now being made t~ establish this species in she~p with the object of describing the migration and development III the foetal an neonatal rumlllant.
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Studies related to the development of the ova of these three species have shown that, under identical conditions, there is significant species variation in the rate of development to the infective stage. All three species migrate and grow, in mice, to highly characteristic degrees. The degree to which they are infective is also highly variable depending on the species concerned. In addition to the life cycle experiments described above, a study has been made of the mutual affinities of the genera Toxocara and Neoascaris. Morphological studies have been made on the adult specimens, including type material, of ten of the twelve member species of these genera. The results obtained appear to confirm the fact that no satisfactory differentiation can be made between the two genera and that they should in fact be regarded as one. Future studies will continue the investigations outlined above. The information being sought is regarded as fundamental for accurate determination of the hazard to public health caused by larva migrans and for the diagnosis and prevention of this condition.
DEPARTMENT OF PHYSIOLOGY
Professor R. W. Hawker, M.D., Ph.D., F.R.A.C.P. Mr G. H. Klemm, M.Sc., Senior Lecturer in Physiology. Mr W. G. North, B.Sc. (Hons.), Research Officer. Projects Effect of increased circulation on venous oxytocic activity in human subjects. Oxytocic blood levels in a case of diabetes insipidus during pregnancy and labour. Studies on gel filtration of oxytocic activities of human blood extracts. A progress report on separation of hypothalamic oxytocic activities as a means of obtaining large amounts of an unidentified second oxytocic principle for chemical analysis. Report Further studies were made on the effect of increased circulation on venous oxytocic activity in human subjects. As venous blood may be dormant for long periods, especially during winter, and as it is venous blood oxytocic potency generally measured in humans, an experiment was carried out on increasing circulation prior to sampling as a means of obtaining a closer approximation to circulating levels of blood oxytocic activity. Increased circulation was effected by having the subject place his forearm in a water bath at 40-45 0 C. for five minutes before sampling blood from the antecubital vein. Blood taken beforehand from the other arm served as a control. This experiment was carried out in June. In all four subjects (three males and one female) increasing the circulation resulted in an almost two-fold increase in total oxytocic activity. For the three male subjects the oxytocin activity increased from a negligible quantity to almost 30% of the total activity. This result demonstrates the necessity for workers in the field to guard against indiscriminate sampling of blood for oxytocic activity when attempting to relate variations in levels with psysiological condition. Work on the oxytocic blood levels in a patient suffering from post-traumatic diabetes insipidus were determined prior to pregnancy, during pregnancy and during and after labour. The pregnancy was the patient's second successful one. The investigation was carried out to obtain a better understanding of the lesion underlying the condition and to examine the controversial question of the interdependency of oxytocin and vasopressin production release mechanisms.
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The results showed that in all samples the levels of oxytocin and the second oxytocic substance were substantial ones, and fall within the limits of those values published by workers in this laboratory (1963) for a number of cases of normal primiparous and multiparous labours. This suggests that oxytocin and vasopressin are independently synthesised and/or released into the blood and that the lesion preventing vasopressin production/release most probably involved the supraoptic region of the hypothalamus. Studies on gel filtration of the oxytocic activities of human blood extracts were continued. Acid-alcohol extracts of whole blood have been passed through three grades of sephadex columns. It had been thought that small peptides travelled ideally through these grades of sephadex as exemplified by oxytocin, and that gel filtration would serve as a means of determining the molecular weight of the unidentified oxytocic principle in blood. This has proved not to be the case. Synthetic oxytocin has been shown to suffer an adsorption onto the gel particles which gives it a distribution coefficient for sephadex G25 very little different to that of salt (which can interfere with assay). Indeed, the peptide bradykinin has been found to be irreversibly adsorbed to sephadex G25 particles under the conditions used, as is 5-hydroxytryptamine. This adsorption is further demonstrated by runs on sephadex G (15) and G (10). Sephadex G (10) excludes substances of molecular weight greater than 800, and this should apply to oxytocin (M.W. ea 1,000). However, oxytocin has been shown to have a coefficient of distribution again in excess of 1.0 on this grade. Gel filtration does however afford a means of partially segrating oxytocin from the second principle. As O.S. is held-up to a greater degree than oxytocin, the study would suggest that the second substance is more likely to be more aromatic or basic, rather than it possessing a smaller molecular weight. It can be concluded that these grades of sephadex are not desirable for molecular weight studies of small peptides or aromatics. Studies continued on the separation of hypothalamic oxytocic activities as a means of obtaining large amounts of an unidentified second oxytocic principle for chemical analysis. Attempts are under way to obtain the second oxytocic principle of mammalian blood and hypothalamus in sufficient quantities for chemical analysis and physiological evaluation. As the quantity of this principle in the blood is very small and difficult to separate from interfering salt, extraction of oxytocic activities from acetone-dried ox hypothalami has been carried out. This source affords much greater quantities of oxytocic substance. Quantities obtained vary between 200 and 400 mU (oxytocin equivalents per hypothalamus). In the hypothalamus-neurohypophyseal tract, oxytocin is associated with the protein neurophysin by ionic bonding (Hope, 1964). Maximal association is at pH 5.2 and pH 5.8, with little or no binding at pH 3.2 and pH 7.4 (Girsburg, 1964). Acetic acid extracts of ox hypothalamus have been passed through sephadex G (25) (fine) columns at two pH's to make use of this binding action to segregate oxytocin from other uterotonic activities, and hence remove its interference to bioassay. In two runs at pH 2.9 about half of the total oxytocic activity was found in the exclusion volume (M.W. > 5,000). This contained no oxytocin activity. Another optical density peak (280 mIL) contained the remaining oxytocic activity of the gland, comprising almost equal quantities of oxytocin and thioglycollate resistant activity. It appears that hypothalamic thioglycollate resistant activity is due to two or more substances. From four runs at pH 5.3, it has been demonstrated that all the oxytocin activity of the gland is eluted in the exclusion volume. In these runs separation of oxytocin from the activity it is associated with at pH 2.9 was affected. These results illustrate that by the use of pH, investigations into the nature of the two thioglycollate resistant uterotonic substances in the absence of oxytocin can be carried out. Bioassay would indicate that the smaller molecule of these two activities is most likely to be that found in blood, and present research is concentrating on this substance. At present
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extraction of 100 ox hypothalami is being carried out. The extract will be passed through sephadex 025 at pH 5.3, and is expected to yield sufficient of the crude activity to allow chemical analysis to commence on further purification. Ion exchange chromatography will be used as a second stage of purification. Successful runs for oxytocin, 5-hydroxytryptamine and bradykinin have been made on CM-cellulose columns using an acetate salt gradient, with percentage recoveries in excess of 90% for all three substances. The oxytocic substance is eluted in this system between oxytocin and bradykinin, suggesting an ionic charge intermediate between these two peptides.
Dr A. Lipton, B.Sc.(Hons.), Ph.D., Senior Lecturer in Physiology. Dr G. J. Huxham, M.B., B.S., Lecturer in Physiology. Dr D. Hamilton, M.B., Ch.B., Lecturer in Physiology. Mr D. N. Barry, B.sc., Research Assistant. Projects Ionic changes in myometrium and cardiac muscle in non-pregnant state and in pregnancy and labour. Effects of steroid hormones on the fundamental properties of muscle. Report With the long term aim of clarification of endocrine effects on muscle activity, e.g. the production of the quiescent uterus of pregnancy and the resolution of this quiescence at the approach of labour, investigation has continued into the changes in the ionic content of uterus and heart muscle when subjected to incubation in various media and changes in temperature, supply of oxygen and nutrients. Detailed ion exchange measurements from uterine studies have been made using improved incubation apparatus and techniques. The four major cations-calcium, magnesium, sodium and potassium have been measured in myometrial and endometrial strips from rat uteri. It is now clear that the rapid ion exchanges which occur on first immersion of the dissected tissues in nutrient media are caused primarily by membrane damage associated with the dissection, however rapid and delicate this is, which swiftly produces irreversible effects on the total cell chelating activity for the cations-resulting in a sustained high level of calcium and sodium and low level of potassium in the tissue. Magnesium content changes very little, however. The hypothesis that these persistent changes in ionic content are due to alteration in cell site availability for these ions under investigation. By contrast, when the tissues are incubated in low temperature media, the ion movements although greater, are reversible on return to normal temperatures, suggesting that active mechanisms, e.g.; membrane pumps, are involved in this case. Studies of the effect of changing the calcium concentration of the medium have led to the conclusion that it is advantageous to use approximately half the usual concentration of this ion to approximate the tissue interstitial concentration rather than the plasma calcium content, of which only half is in free ionic form. Other workers in this field have recently come to the same conclusion. Quite marked changes in the ionic concentrations occur subsequent to depletion of the tissues of calcium in media free of this ion, and studies are in progress to relate these changes to previously measured effects on tension developed in myometrial strips from pregnant and non-pregnant animals.
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Similar incubation techniques have been used combined with depletion and exchange procedures to study the uptake and loss of Ca 45 from myometrial strips. The rate of attainment of equilibrium under various conditions has been determined, and it is clear that at least three processes occur in these tissue calcium exchanges, each with its own characteristic rate. More elaborate experiments on these lines are being made to obtain data capable of analysis by analogue computer, which it is hoped will clarify these processes. The effect of changes in the ionic content of the media, the temperature and the availability of energy (by removal of oxygen or glucose, or by use of metabolic inhibitors) have been observed in parallel studies of cardiac muscle, with measurement of the four cations, together with nitrogen and water content. C14-labelled mannitol has been obtained for estimation of the tissue water compartments. Isolated heart strips were found to be excessively prone to the rapid ionic movements due to dissection, referred to above, so a perfusion technique was adopted, and after suitable modification now gives good survival with well maintained rate and force of beat, normal electrical rhythms and steady perfusion rate through the coronary circulation. Determination of the ionic content of subcellular fractions of rat heart have been started, but this technique will require considerable further work to establish criteria for purity of the fractions. Studies of Ca45 uptake and loss by heart muscle strips have been made, and this work is now being extended to the perfused hearts, in which it is intended simultaneously to study Na22 movements. Heart and myometrial strips have been incubated with very high activity Ca4 " and after fixation and embedding, sections were cut, coated with nuclear emulsion and mounted for electron microscope autoradiography. Exposures of several months are necessary even with the high activity used, and one of the major problems at present is retaining the activity and the silver grains it produces, while treating the tissues to obtain adequate contrast for the electron microscope viewing. Alternative tissue contrast media and calcium fixing procedures are being evaluated. Publications BARRY, D. N., HUXHAM, G. J., and LIPTON, A. 'Calcium exchange in isolated rat heart.' Proc. Aus. Physiol. Soc. 1966,2, 18 (Abst.). HAMILTON, D., GUBAR, Y., STREET, W., LIPTON, A., and HUXHAM, G. J. 'Effects of changes in incubating medium in the uptake and loss of Na, Ca, K and Mg in rat uterine muscle.' Proc. Aust. Physiol. Soc. 1966, 2, 18 (Abst.). HUXHAM, G. J., and LIPTON, A. 'Resolution and efficiency in electronmicroscope autoradiography.' Proc. Aust. Physiol. Soc. 1966, 1,45 (Abst.). LIPTON, A., and HUXHAM, G. J. 'Calcium content of rat heart and uterus muscle.' Proc. Aust. Physiol. Soc. 1966, 1, 45 (Abst.).
UNIVERSITY OF SYDNEY DEPARTMENT OF BACTERIOLOGY Dr D. S. Nelson, B.Sc.(Med.), M.B., B.S., Ph.D., Reader. Dr A. E. Cronin, B.A., M.B., B.S., Ph.D., D.D.M., Lecturer; Honorary Assistant Dermatologist, Royal Prince Alfred Hospital. Miss Prudence E. Cox, B.Sc., Research Assistant, N.H. & M.R.C. Projects The reactions of macrophages to antigens. The mechanism and significance of immune adherence. Immunological aspects of dermatological conditions. Report The immunological phenomena surrounding macrophages was studied. The role of macrophages in manifestations of the delayed type of hypersensitivity (as exemplified by tuberculin sensitivity) is of special interest since this type of hypersensitivity appears to be related to the rejection of grafts of foreign tissues and some diseases believed to be due to autoimmunity. All these immunological reactions are believed to be due to antibodies carried by cells rather than by conventional circulating antibodies. There exist antibodies which, although found in serum, are capable of becoming attached to macrophages. The work in progress in the laboratory is concerned with the effects of antigen on peritoneal macrophages of guinea pigs with delayed-type hypersensitivity and the properties of macrophage cytophilic antibodies, with particular reference to their possible role in delayed-type hypersensitivity in guinea pigs, mice and rabbits. Earlier studies have shown that when antigen is injected into guinea pigs with delayed-type hypersensitivity free-floating macrophages clump and disappear from the peritoneal fluid, adhering to the lining of the peritoneal cavity. It has also been shown that the injection into normal animals of antigen together with peritoneal cells from a hypersensitive donor is followed by the partial disappearance of the recipient's macrophages. The injection of normal cells treated with serum from a hypersensitive donor, then washed and mixed with antigen, is also followed by a partial disappearance of peritoneal macro?hages. The latter finding suggests that a cytophilic antibody is involved in this reaction. As the peritoneal cell population is a heterogeneous one, further studies have been carried out to identify the type of cell responsible for the transfer of reactivity. Transfers have been effected with cells of different provenance containing predominantly macrophages, mixed macrophages and lymphocytes or peritoneal lymphocytes contaminated with blast cells, but not with virtually pure lymphocytes obtained from lymph nodes. No single simple explanation fits these findings and it is postulated that two mechanisms of transfer exist by means of macrophages carrying cytophilic antibody and by means of cells (? blast cells) synthesising cytophilic antibody. The production and properties of antibodies cytophilic for macrophages have also been investigated. Earlier experiments by Boyden and by Jonas, Gurner, Nelson and Coombs showed that guinea pigs produced cytophilic antibodies only when the immunising antigen was injected with Freund's complete adjuvant (mineral oil, emulsifying agent and killed Mycobacteria); such immunisation also resulted in the development of delayed-type hypersensitivity. In the present experiments sheep red blood cells have been used as the antigen. Guinea pigs have been immunised with antigen injected, together with adjuvant, by various routes and their immunological responses (degree and type of hypersensitivity, production of cytophilic and other antibodies) have been measured at different times. In general there is a correlation between the occurrence of delayed-type hypersensitivity and the production of
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University of Sydney
cytophilic antibody, but there is little or no correlation between the intensity of delayed-type hypersensitivity and the titre of cytophilic antibody in serum. In contrast, similar experiments with mice have revealed a correlation between the intensity of delayed reactions and the titre of cytophilic antibodies after primary immunisation. In neither species is there a correlation between the titres of cytophilic and other antibodies this suggests that cytophilic antibodies are produced independently. The differences observed between the two species prompted an examination of the chemical and functional properties of macrophage cytophilic antibodies. Some factors affecting the uptake of cytophilic antibodies by macrophages have been investigated. The most notable finding has been that the cytophilic antibodies produced by guinea pigs are almost entirely to be found in the 7 S Y2-globuIin fraction of serum, where other antibodies are found, whereas those produced by mice occur both in this fraction and in an albumin-alglobulin fraction. Antibodies in the former class, in both species, are avidly taken up by macrophages treated with proteolytic enzymes, but those in the latter class are not taken up by macrophages so treated. This finding indicates the existence of a hitherto unsuspected class of antibody which is of considerable interest as a possible mediator of delayed-type hypersensitivity. The term 'immune adherence' describes the attachment to human and some other red blood cells of complexes formed by antigen, antibody and complement (non-specific cofactors in normal serum). The biological significance of this reaction is not certain but its usefulness in detecting and measuring antibodies is undoubted. In some circumstances the reaction causes visible agglutination of the red blood cells. The immune adherence haemagglutination assay has been adapted to a microtitration system in which very small quantities of the reagents are used (0.025 ml) and titrations can be carried out very rapidly. This system has been utilised for the measurement of a particular type of antibody (complementfixing antibody) in the sera of immunised mice and guinea pigs. When an animal receives a graft of tissue from a genetically different animal, the graft is treated as 'foreign' and rejected. Such rejection is generally believed to be due, like delayed-type hypersensitivity, to some form of cell-bound antibody. Other antibodies are, however, also found. It has been found possible to measure some of these antibodies, rapidly and easily, by means of immune adherence; this technique has been applied to the investigation of the phenomenon of immunological enhancement. In normal circumstances mice of one inbred strain immunised with tissue of another inbred strain subsequently reject a tissue graft from that strain very rapidly. In different circumstances pre-immunisation can result instead in prolonged survival of the graft, especially when the tissue grafted is that of a malignant tumour. The tumour is said to be enhanced and considerable evidence suggests that humoral antibodies cause enhancement. An investigation has been made of the antibody response during enhancement of tumour grafts, using immune adherence to detect complement-fiixing antibodies and another technique to measure the overall humoral antibody response. The results indicate that enhanced growth of the tumour graft is accompanied by depressed production of complement-fixing antibodies and normal or increased production of other antibodies. The latter may thus be considered as harmless or actually beneficial to the graft. If the phenomenon of enhancement is a general one, it may be possible to immunise human recipients of organ (e.g., kidney) grafts in such a way that they produce only enhancing antibody and thus to induce survival of the graft without recourse to intensive drug treatment. Further experiments are in progress on these projects with a view to elucidating the mechanism of the macrophage disappearance reaction, characterising further the functional and chemical properties of cytophilic antibodies especially in relation to delayed-type hypersensitivity; and determining the mechanism of enhancement of tissue grafts.
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Paraphenylene diamine (PPD) is co=only used in hair dyes and fabrics and in the it c:m produce contact dermatitis in man. It has been postu. reacts WIth p.roteID by first forming a quinone or quinone imine. The for;~on _of ~ commo~ m,:tabolIte has ~een suggest.ed to explain the cross reactivity between • : ~ amIDob~nzOlc aCId, sulphonaulldes and ammo-azo dyes, which is sometimes observed In C~IDICa1 practice. As the cross reactivity in some human cases may have been due to preVIous exposure to the various compounds, experiments were performed to sensitise groups of guinea pigs to PPD, p-benzoquinone and hydroquinone in order to determine whether reactions could be elicited with sulphanilamide, ortho-and metaphenylene diamine and p-amino azobenzene. Despite repeated applications of the compounds, none of the guinea pigs developed contact sensitivity, so the question remains, for the present, unanswered. Auto-antibodies to skin in patients with pemphigus and dermatitis herpetiformis have been demonstrated by Witebsky and co-workers using fluorescent antibody techniques. The mixed antiglobulin reaction appeared to be an alternative method for detecting antibodies to epidermal cells and attempts have been made to adapt it for this purpose. As the A and B blood group antigens are present on epidermal cells, this system has been used as a model. Epidermal cells are obtained from split-skin grafts. treated with trypsin according to the method of Medawar. Dermatologists have been requested to forward samples of serum from cases of pemphigus or dermatitis herpetiformis, but, so far, none have been received. The observation that the prognosis for human meIamona is uniformity short after the appearance of secondaries, however long they may take to appear, and the occasional spontaneous regression of these tumours, suggest the possibility of a mechanism analogous to immunological enhancement and resistance which occur with some animal tumours. A number of experiments have been carried out using the mouse melanoma B16, which grows readily in the inbred C57B1 strain. The main object was to determine whether the tumour possessed antigens which were not shared by other C57BI tissues. One group of C57B1 mice was injected with 2.5 mg B16 emulsified in Freund's complete adjuvant, and a control group was injected with saline in adjuvant. One month later, no tumour was visible or palpable, and both groups were injected with 5 mg of the tumour in saline. If there were any significant difference in the rate of growth of the tumour in the two groups of mice, this could be interpreted as either resistance or enhancement in the animals previously exposed to the tumour; this could be consistent with presence of tumour antigens distinct from those of normal tissues. However, no difference in the size or rate of growth of the tumour was observed in the two groups of mice. Attempts to enhance the growth of B16 inbred in A/J mice by active and passive immunisation were unsuccessful. Work is in progress to develop an ascites form of the B16 tumour. This will enable more sensitive immunological techniques, such as immune adherence, to be used for the detection of antibodies to the tumour. Fl hybrid (C57Bl X A/J) mice were injected intraperitoneally with the ascites form of Sarcoma I (which grows in A/J, but not C57B1 mice), mixed with B16. Ascites fluid mixed with fresh B16 was injected into C57Bl mice. This resulted in a solid form of B 16 and blood-stained ascites fluid. This fluid has been transferred to other B57Bl mice, and it is hoped that the tumour can be kept indefinitely in this form, by regular passive transfer. The question whether tumours possess antigens different from those present in normal tissues is being studied with the Sarcoma I tumour in A/J mice. Groups of mice have been immunised with the tumour emulsified in Freund's complete adjuvant and later challenged with tumour cells to determine whether resistance or enhancement has occurred. It is proposed to continue work on the above subjects and to expand the melanoma investigation to include the S91 tumour which grows in inbred mice of the DBA strain.
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Experiments to determine whether this tumour has 'melanoma' antigens will be carried out.
in common with B16
Publications CRONIN, A. E. 'The production and detection of antibodies to streptomycin in rabbits and man. A study of the chemical basis for the antigenic potential of this compound and related substances.' Aust. I. Derm., 1965, 8, 78. CRONIN, A. E. 'Haem agglutinating antibodies to PAS and phenacetin.' Proc. XI Congr. Haemat%gy, Sydney, 1966 (Abstract). CRONIN, A. E. 'Mycosis fungo ides.' Cutis. (In press.) CRONIN, A. E. 'An experimental study of penicillin anaphylaxis.' Aust. I. Derm. (In press.) HAFERLAND, W., KIM, Z., UHLENBRUCK, G., and NELSON, D. S. 'Zur Frage der Einheitlichkeit des Agglutinis Anti-Ahel.' Z. Immunitatsforsch. (In press.) NELSON, D. S. 'Local passive transfer of reactivity of peritoneal macrophages to antigen: possible role of cytophilic antibody in one manifestation of delayed-type hypersensitivity.' Nature, 1966,212,259. NELSON, D. S., and BOYDEN, S. V. 'Macrophage cytophilic antibodies and delayed hypersensitivity.' Brit. Med. Bull. (In press NELSON, D. S., and KOSSARD, S. 'The peritoneal macrophage disappearance reaction in guinea pigs with delayed-type hypersensitivity.' Proc. XI Congr. Int. Soc. Blood Transfusion, Sydney, 1966, Basel, Karger. (In press.) NELSON, D. S., and MILDENHALL, P. 'Studies on cytophilic antibodies I. The production by mice of macrophage cytophilic antibodies to sheep erythrocytes: relationship to the production of other antibodies and the development of delayed-type hypersensitivity.' Aust. !. Exp. Bioi. Med. Sci. (In press.) NELSON, D. S., and UHLENBRUCK, G. 'Studies on the nature of the immune adherence receptor I. The inhibition of immune adherence by soluble mucoids and mucopeptides and by human erythrocyte ghosts.' Vox Sanguinis, 1967, 12, 43.
DEPARTMENT OF BIOCHEMISTRY Dr A. L. Hunt, B.Sc. (Hons.), Ph.D., Senior Lecturer. Project Induced synthesis of nicotinic acid hydroxylase complex in Ps. fluorescens. Report Research has continued on the nature of the changes occurring in the membrane complex lipid components during the induced synthesis of the particulate nicotinate hydroxylase respiratory complex in this organism. Considerably more refined methods for the separation and analysis of the membrane lipid components have been developed. This involves preliminary separation of the total lipids into six major c1a'ses of ion exchange cellulose followed by thin layer chromatography. Preparative scale separations have been achieved for a number of previously unidentified components and detailed analysis of these is in progress. Using the new methods it is now possible to study in greater detail the turnover of membrane unit components during induction of the nicotinate ETP complex. Preliminary experiments have sho"",
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greatly varied labelling patterns of individual fatty acid members of many of the isolated lipid components during induction confirming previous data with p32 labelling and further suggesting cosynthesis of ETP components during respiratory induction. Similarly cells grown under conditions of low oxygen tension where respiratory induction is maximal, show a particularly high level of 17-cyclopropane fatty acid in the membrane lipids. The synthesis of the latter component has been shown to be strikingly inhibited by glucose which also inhibits respiratory induction. Cells grown under conditions of low oxygen tension in the presence of glucose have fatty acid components little different from cells grown under optimal conditions of aeration. There is also a large increase in the short chain acids in low oxygen cells and this is similarly reversed by glucose. These results lead to the conclusion that a significant proportion of the membrane lipids may be associated with respiratory sub-units and that the composition of the lipids is greatly modulated by the number and nature of such sub-units according to conditions of respiratory induction. A large number of mutant strains of the organism characterised as nicotinate minus have been successfully prepared. A number have been shown to be blocked at the nicotinate hydroxylase site and are phenotypically incapable of synthesising hydroxylase activity. Preliminary studies with one of these deficient mutants has shown nicotinate is still capable of inducing the previously observed changes in membrane lipid components suggesting a possible independent control of synthesis of structural ETP components. Large scale continuous culture of the wild type organism is in progress with view to preparation of isolated membrane fractions for extraction and analysis of structural protein components. The latter are considered to play an important role in the induction process and may provide a possible point of action of glucose control.
Dr G. T. Stevenson, M.D., D.Phil., Senior Research Officer, N.H. & M.R.e.
Dr F. K. Stevenson, M.Sc., D.Phil., Lecturer in Biochemistry. Dr C. BeB, Ph.D., Research Fellow, Phyllis Anderson Fund, University of Sydney.
Mr D. Strauss, B.A., Demonstrator in Biochemistry. Project Properties of the peptide chains of immunoglobulin G. Report Research has been conducted on immunoglobulins, those proteins among which antibody activities reside. The present project is concerned with physicochemical properties of the proteins, with the ultimate aim of gaining information relevant to the ways in which antibody activity is acquired and exerted. The predominant class of immunoglobulin is called immunoglobulin G. This is a heterogeneous protein, each molecule of which consists of four peptide chains, two y chains and two light chains. Properties of whole molecules and of both the y and light chains have been investigated. The study of activity of immunoglobulin G antibodies exposed to unfolding agents arose from the wish to obtain immunoglobulin G antibodies freed completely of contaminating antigens. Removal of the last traces of antigen is a well known problem in the purification of antibodies. Among the methods employed is exposure of the antibody-antigen complexes to an
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unfolding agent such as urea: the antibody-antigen union is thereby weakened, removal of the antigen is facilitated, and upon removing the unfolding agent the antibody molecules regain their native conformations. Anti-hapten antibodies obtained from the secondary response in rabbits were notably refractory to this procedure. The amounts of antibody activity retained in the presence of 8M urea were much higher than reported by other workers. This retention of activity was manifested in two ways. Firstly, some antibody-hapten complexes simply failed to dissociate during prolonged exposure to the unfolding agent. Secondly, the antibodies were actually able to bind free hapten during the exposure. These findings demonstrate an unusual degree of conformational stability inherent in antibody combining sites. Previous work has shown that isolated y chains from whole immunoglobulin G are capable of binding tightly small amounts of dyes of various configurations and net charges. This suggests that free y chains possess a conformational plasticity which is not apparent when they are incorporated with light chains in whole immunoglobulin molecules. During 1966 this phenomenon was studied further, and perturbations due to aggregation of both the peptide chains and dyes were defined. Binding of the dyes is slow but becomes eventually very firm and accompanied by a molecular relaxation effect. Similar kinetics of binding were seen when the dye was actually a hapten (the sulphanilate ion), exposed to y chains from the homologous antibody. The only difference observed here between the behaviour of antibody and nonantibody y chains was the that valency of the former was higher. Dissociation of the y and light peptide chains in an intact immunoglobulin G molecule involves exposure to a dissociating solution, such as 1M acetic acid, capable of breaking the non-covalent bonds between the chains. A slow removal of the dissociating solute has been reported by several laboratories to be accompanied by a recombination of the y and light chains, yielding four-chain units which resemble the original molecules. However this observation does not reveal the reaction path involved: several paths are possible, such as y + L~y L, followed by 2 y ~Y2 L 2. Evidence has been obtained that the path (2 y~Y2' 2 ~L2' and Y2 L~Y2 L 2 ) can operate in the reconstitution of immunoglobulin G molecules. The experiment consisted of diSSOciating immunoglobulin G molecules, separating the y and light chains by column chromatography, transferring the chains separately into a dilute acetate buffer in which they both form dimers, and then mixing them in this buffer. Rapid recombination occurred, to give molecules which resembled the original immunoglobulin G by chromatographic, ultracentrifugal and immunochemical criteria. Currently the rate of the reaction Y2 + L2~Y2 L2 is being studied in more detail.
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The transfer of light chains from acetic acid to acetate buffer pH 5, as described above, is accompanied by dimerisation of the chains. The light chains are heterogeneous by several criteria, and the question arises as to whether any specificity is involved in the dimerisation. The most extreme specificity would entail the union of chains of identical amino acid sequences. The problem was answered partially by demonstrating that the dimerisation is specific by at least one criterion, electrophoresis. Both the monomers and dimers exhibit mUltiple electrophoretic components. The chains were allowed to dimerise, single electrophoretic components of the dimers were prepared, and these were shown by a second electrophoresis to have a specific monomeric constitution.
Publications STEVENSON, F. K., and STEVENSON, G. T. 'Antibody activity in the presence of urea or guanidine.' Biochim. Biophys. Acta. (In press.) STEVENSON, G. T. 'Recombination of the peptide chains of inununoglobulin G.' Proc. Xlth Congress Internat. Soc. Blood Transfusion. (In press.)
University of Sydney Dr R. G. Wake, M.Sc., Ph.D., Senior Lecturer in Biochemistry. !- ~ ~
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Project DNA replication in synchronously germinating Bacillus subtilis spores. Report Studies by other workers on the incorporation of 3H-thymidine into the DNA of germinating, thymine-requiring spores have suggested that a significant amount of repair-like DNA synthesis takes place prior to the onset of an actual round of DNA replication. The existence of such a synthesis to the extent of 1 % or more would cause considerable difficulties in the present attempts to fractionate the chromosome, particularly the initiation region, on the basis of its replication. A study of the extent and possible nature of this repair-like synthesis has been commenced using the thymine requiring SB566 strain of B. subtilis. Essentially, two types of experiment have been carried out. The kinetics of incorporation of 3H-thymine and thymidine and 32p into alkali-resistant and acid insoluble material has been followed. The nature of the incorporation (repair-like or normal replicative type) has been studied by looking at the distribution of radioactivity between non-density labelled and hybrid DNA when germination is allowed to proceed in the presence of bromuracil. The kinetics of uptake of 3H-thymine and thymidine has been found to depend upon the spore preparation used. Some preparations show no detectable incorporation prior to the rapid uptake as rounds of replication commence. Others show a small incorporation which could easily be explained on the basis of a slight asynchrony in the time of commencement of replication. The addition of chloramphenicol to prevent the initiation of replication at various times suggests that this is so. 32p appears to be incorporated into DNA prior to the onset of a round of replication. It goes in fairly quickly, reaching a constant level well before replication commences. However, it has the unusual property of exchanging out again when chased with 31P. The possible extent of repair synthesis in terms of the percentage of the total genome has been studied for both the 3H-thymine and 32p incorporations. No 3H-thymine «0.2%) nor 32p «0.1 %) is incorporated into non-density-Iabelled DNA when germination is allowed to proceed in the presence of bromuracil. The value of 0.2% for 3H-thymine incorporation could be an underestimate due to the presence of a pool of cold thymine in the spore. However, this does not apply in the case of the 32p which is incorporated immediately and at its maximal ratc into RNA at the onset of germination. The nature of the small amount of 30p which goes into acid-insoluble material prior to DNA replication and which apparently turns over is not known. It is concluded that there is no repair-like synthesis «0.1 % of the genome) prior to the onset of a round of replication in germinating B. subtilis spores. When thymine-requiring E. coli are stan-!'d for thymine over a certain interval of time and then allowed to grow normally, a new roum; of DNA replication is specifically initiated. This is in addition to the round proceeding at the time of starvation. Thymine-requiring B. subtilis have been starved and then allowed to continue growth in the presence of bromuracil. The hybrid and non-labelled DNA have been separated after various times of growth and assayed for genetic marker activity using markers near the initiation point and other end of the genome. The expected preferential increase in activity of the Ade marker over that of Met in the newly replicated material has not been observed. This does not agree with the results of investigations summarised in this ~eport last year. The experiments are being repeated. As reported in 1965, knowledge of the size and structure of the B. subtilis genome is incomplete.
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Synchronously germinating B. subtilis SB566 spores have been labelled with 3H-thyrnine for just part of the first round of replication. After diluting and spreading on an .ag~r m.ediurn microcolonies derived from single spores have been allowed to develop. The distributIOn of radioactive material within these microcolonies has been examined by autoradiography using Kodak ARlO stripping film. So far, over 50% of the colonies have shown two 'hot-spots' in contrast to a minimum of four which would have been more likely had two genomes been initially labelled. These results strongly favour the presence of only a single genome in the B. subtilis spore. Publication DENNIS, E. S., and WAKE, R. G. 'Autoradiography of the Bacillus subtilis chromosome.' I. Mol. Bioi. 1966, 15, 435.
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'. , DEPARTMENT OF HISTOLOGY AND EMBRYOLOGY Dr J. K. Pollak, B.Sc., Ph.D., Senior Lecturer. Miss Helen Oates, B.Sc., Honours Student. Miss Maria Woog, B.Sc., Research Assistant. Project The enzymic activities of reticulosomes isolated from cells at various physiological states. Report On investigating the enzymic activities of reticulosomes it became apparent that they possessed glucose-6-phosphatase and adenosine triphosphatase activities. During the past year the glucose-6-phosphatase activities of reticulosomes, smooth microsomal vesicles, rough microsomal vesicles and reconstituted membranes were investigated in some detail. Recent work has indicated that the enzyme glucose-6-phosphatase has also pyrophosphatase and pyrophosphate-glucose-phosphotransferase activities. A great number of experiments were carried out, measuring the glucose-6-phosphatase and pyrophosphatase activities of rough and smooth microsomal vesicles and reticulosomes or normal and starving rats, as well as alloxan diabetic and alloxan diabetic-insulin treated rats. The specific activities of all the three reactions catalysed by glucose-6-phosphatase of reticulosomes are 2-4 times greater than those of the microsomal vesicles, which are the most active of the membrane fractions. After the reticulosomes have given rise to membranous vesicles the specific activities of these newly formed membranes are comparable to those of microsomal vesicles. More recent experiments, using rat hepatomas which had been induced with azo-dyes, yielded rather unexpected results. The rough microsomal fractions showed slightly lower activities for all the three reactions of glucose-6-phophatase, while in the smooth microsomal fraction the pyrophosphate-glucose-phosphotransferase activity was considerably reduced. The reticulosome preparations from such hepatoma possessed the usual activities of glucose-6-phosphatase and pyrophosphatase, but were either completely devoid of pyrophosphate-glucose-phosphotransferase activity or had only marginal activity (less than 5 per cent of the activity of glucose-6-phosphatase). Thus the three reactions which were only recently demonstrated to be catalysed by the one enzyme, are dissociated in reticulosomes of chemically induced hepatoma.
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Publications POLLAK, J. K., WARD, K., and SHOREY, C. D. 'The formation of a membranous reticulum by the interaction of reticulosomes and micellar phospholipids.' J. Mol. Bioi., 1966, 16,564. POLLAK, J. K., WARD, DENISE B., and SHOREY, C. D. 'The correlation of morphological and biochemical changes during the development of embryonic liver.' J. Anal. (In press. ) POLLAK, J. K., and WARD, DENISE B. 'Changes in chemical composition and the enzymic activities of hepatic microsomes of the chick embryo during development.' Biochem. J. (In press.)
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DEPARTMENT OF MEDICINE Professor C. R. B. Blackburn, M.D., F.RC.P., F.RAC.P. Associate Professor J. McRae, M.B., B.S., Ph.D., M.RAC.P. Dr Marcus Ma, M.B., B.S., Research Fellow. Miss G. Mitchell, Laboratory Technician. Dr G. Stathers, M.B., B.S., M.RA.C.P., Temporary Lecturer. Dr P. Wakeford, M.B., B.S .. M.RAC.P., Research Fellow. Dr J. G. Morris, M.B., B.S., M.RA.C.P., Temporary Lecturer. Project Studies in liver disease. Report A therapeutic trial of 6-mercaptopurine and its analogue imuran in patients with chronic active hepatitis was continued as a follow-up study. A prima facie case was made out that 6-mercaptopurine and imuran exerted beneficial effects and could be substituted for prednisone in a selected series of cases. Some patients studied by other workers do not do well on these agents. A paper incorporating these data was presented by Dr S. Mistilis at the International Gastroenterology Meeting in Tokyo in September, 1966. A study of the cytological changes was made in an attempt to detect earliest changes of malignancy following the induction of carcinoma of the liver and cirrhosis in rats. No further progress has been made in attempts to isolate and identify the virus-like particles seen in a human hepatoma. Cultures from a second biopsy were negative but no hepatoma cells were obtained. Epidemiological, histological and biochemical studies of natives in New Guinea have continued. Some 16,000 natives have now been examined and 340 biopsies studied. One hepatoma has been found on biopsy. The initial object of this study has been attained; a studied population has provided some knowledge of liver histology, liver function tests and some ideas of prevalence of hepatomegaly. On future visits to New Guinea etiological factors will be sought, and, in Sydney, correlations between clinical, biochemical and histological changes will be made. Most of the data is now on magnetic tape for the KDF9 computer, but considerable delays occur due to shortage of stafl to care for the records which now number over 21,000. It is possible that current correspondence may lead to a joint approach on some immunological aspects related to infestation with helminths.
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A study has been set up at the Repatriation General Hospital, Concord, in which patients with alcoholism but without cirrhosis are being studied and followed on a long-term basis in an attempt to determine the genetic basis of the liability to develop cirrhosis of the liver when exposed to a given harmful agent. In association with the Department of Pharmacy, University of Sydney, pharmacological agents, whose metabolism is known, are to be used to determine enzymatic differences. Publications ARTER, W. J., PERKINS, K. W., and BLACKBURN, C. R. B. 'Experience with the use of y-mercaptopurine and imuran in the treatment of progressive hepatitis-(active chronic hepatitis),' Aust. Ann. Med., 1966, 15, No.3. BLACKBURN, C. R. B., ARTER, W. J., BURCHETT, P., MURRELL, T., RADFORD, A., MEEHAN, K., MA, M., and McGOVERN, V. J. 'Hepatomegaly: an epidemiological study in the Eastern and Western Highlands districts of New Guinea.' Papua and New Guinea Medical Journal, 1966, 9, No. 1. MA, M. H. 'Virus-like particles in a human primary hepatocarcinoma.' Nature, 1966, n, 212. MA, M. H., and WEBBER, A. J. 'Fine structure of liver tumours induced in the rate by 3 ' _ methYI-4-dimethylaminoazobenzene.' Cancer Research, 1966, 26, 935.
Professor B. G. Firkin, M.B., B.S., B.Sc.(Med.), M.R.A.C.P., Associate Professor in Medicine (Biochemistry). Dr Laurel Harvey, M.B., B.S., Part-time Research Fellow. Dr Sandra Silink, M.B., B.S., Research Fellow. Mr I. Gan, B.Sc., Research Assistant. Miss Elisabeth Kilburn, B.Sc., Research Assistant. Projects Mechanisms of anaemia. Platelet physiology and function. Report Mechanisms of anaemia Further work has been carried out on paroxysmal nocturnal haemoglobinuria (p.N.H.), a rare anaemia which is generally recognised as a probable key to the recognition of the fundamental mechanisms of haemolysis and of the interaction of erythrocyte membrane and various plasma components important in an antibody's attack on the cell. Evaluation of glucocorticoid therapy in this condition has continued and sustained improvement has occurred in a number of patients. Red cell life span studies have shown no alteration in the red cell life span, and presumably steroids act either by prevention of the acute episodes of haemolysis, or by an increase of the effective erythropoietic mass of the bone marrow. Investigation of the red cell membrane defect of this disorder is also continuing. The recent hypothesis that the abnormality may be the result of lipid peroxidation has been examined. It has been confirmed that exposure of normal red cell membrane to peroxidatioD results in a reduction of the cells' acetylcholinesterase level; however, it was also shown that
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another esterase (tributyrinase) was also inhibited by this treatment. Examination of P.N.H. red cells by two different techniques has shown that there is no reduction in esterases other than that of acetylcholinesterase in these cells. It may be concluded from these studies that if peroxidation is the cause of the defect in paroxysmal nocturnal haemoglobinuria it must be specifically associated with that portion of the membrane concerned with acetylcholinesterase activity and not with other esterase activity. So far, efforts to separate the protein moiety of the red cell membrane in order to compare P.N.H. stroma with normal using a starch gel technique have been disappointing technically, although with some modification this approach may still prove worthwhile. Cholesterol and fatty acid incorporation into normal red cell membrane is at present being measured, and this will be compared with the findings in P.N.H. and hereditary spherocytosis, as well as other forms of haemolytic anaemia. Next year it is planned to perform ferrokinetic and chromium life-span studies on patients who have had aortic valve replacements, in an attempt to define more clearly the haemolytic anaemia which has been reported in these circumstances and which may be related to a membrane defect. Aplastic anaemia
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An apparently successful bone marrow transplant has been performed in a patient with aplastic anaemia by intravenous injection of bone marrow particles obtained from an identical twin. Study of this patient has partially answered some of the questions raised by earlier studies. An increase in deoxynucleic acid (DNA) synthesising cells has been observed in approximately 50% of patients with aplastic anaemia. The DNA synthesising cells present in this patient's peripheral blood were normal in numbers before and after the transplant, and more specifically during the period when iron clearance studies and bone marrow aspirate examination revealed bone marrow re-population. A previous suggestion that the DNA synthesising cells represents cells attempting to re-populate the bone marrow therefore appears unlikely. The results of this study also suggest that in this patient at least, there was no inhibition of the part of the bone marrow ('soil') on the growth of cells implanted, and that in this instance, the abnormality must have arisen from effect on the 'seed'. It is also suggested that in the human, as in the animal, a specific number of cells must be transplanted if there is to be a successful 'take', and that also as in animal studies, there is a delay in the onset of erythroid and myeloid proliferation for some two weeks after the transplantation attempt has been made. Chromosome analysis of bone marrow cells from patients with aplasia has proven to be difficult, but in those patients with sufficient samples for study the only abnormality has been that of occasional polyploidy. Counts of mitotic indices in patients with hypoplastic anaemia have revealed normal to low/normal levels, and the cell type involved has been difficult to classify, but appears to be morphologically like a plasma cell or lymphocyte. At a clinical level, an evaluation of the use of a testosterone derivative, oxymethylone ('Adroyd' Parke Davis) is being undertaken in the treatment of primary or secondary hypoplastic anaemias. The patient's haematological status is thoroughly investigated by the more classical techniques and also by iron clearance studies. Eleven patients have so far been included in this study. There have been three instances where the introduction of oxymethylone has resulted in a complete remission of the patient's anaemia, and indeed in one instance induced a polycythaemia. In one patient a partial success appears to have been obtained and in five others death occurred before the agent had been administered for adequate time to assess the result. Oxymethvlone appears to have a definite place in the therapy of hypoplastic anaemia, and it is proposed to continue its evaluation. 4275/67-8
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Platelet physiology and function Electron microscopic studies of the human platelet have led to the suggestion that this cell may contain far more internal membranous structure than had previously been appreciated. The role of this internal membrane an d of the platelet granules is still uncertain, although the latter are being regarded as lysosomes by increasing numbers of investigators in the area. At present, investigations have centred on the thrombocytes of the Port Jackson shark (Heterodontus portus jacksoni). The thrombocytes in this animal are extremely interesting, since, although nucleated, they contain no granules visible to phase microscopy. These cells are, however, rich in acid phosphatase which in the mammalian platelet is mainly localised in the granule. Preliminary work shows that these cells can cause clot retraction, are rapidly aggregated on contact with foreign surfaces and have a remarkable property to spread on glass surfaces. A thorough survey of the properties of the shark's thrombocyte is at present being undertaken and will be extended to other species next year, and this should give some interesting information on the evolution of the platelets' structure and function. The enzymatic breakdown of C14ADP by human plasma and its possible relationship to platelet aggregation as well as the role of platelet esterase activity in this phenomenon have been examined in detail and have yielded informative results, but the basic question of the precise mechanism of platelet aggregation remains unanswered. Publications PENNY, R., ROZENBERG, M. C., FIRKIN, B. G. 'The splenic platelet pool.' Blood. 1966. 27, No. 1. ROZENBERG, M. C., 'The place of angicoagulant therapy in cardiovascular disease and its methods of control.' Inl of Indian Medical Profession, 1965. ROZENBERG, M. C., DINTENFASS, L. 'Platelet aggregation in Waldenstrom's macroglobulinaemia.' Thrombosis et Diathesis Haemorrhagica, 1965. ROZENBERG, M. C., DINTENFASS, L. 'Platelet aggregation in the variable-frequency thromboviscometer.' Nature, 1966. 211, 525. ROZENBERG, M. C., FIRKIN, B. G. 'The rate of platelet aggregation in haemorrhagic disease and thrombosis.' Scand. I. Haemat., 1966, 3, 5. TURTLE, J. R., FIRKIN, B. G., 'Changes in nucleotides following the addition of adenosine diphosphate to platelet suspensions.' Aust. Ann. Med., 1965, 14, No.4. WEBBER, A. J., FIRKIN, B. G., DRUMMOND, D. G. 'Morphology of human thrombocytes.' Vlth Inter. Congress for E.M., Kyoto, 1966. W!LKINSON, T., FIRKIN, B. G. 'Idiopathic cyclical acute thrombocytopenic purpura.' Med. 1. Aust .• 1966,1,217.
DEPARTMENT OF OPHTHALMOLOGY AND EYE HEALTH Dr .Joffre B. Cowie, B.Sc.(Med.), M.B., B.S. Miss Elizabeth Ham, B.Sc., Research Assistant, N.H. & M.R.C.
Project The pharmacology of enediols in aqueous drainage.
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Report A number of groups of chemical substances are known to have a similar type of spreading activity to that of hyaluronidase. Among these are ascorbic acid and related compounds which compnse the enediols. These substances produce a marked acceleration of the rate of infused fluid in subcutaneous tissue of rabbits. This action is also known to be potentiated by accelerating agents such as hydrogen peroxide, cupric salts, iron salts and some redox dyes differing for the mdividual enediols. These spreading agents have also been shown to be depolymerizes of hyaluronic acid measured by viscometry. A hyaluronidase sensitive material is known to be bound to the trabecular drainage mechanism in the eyes of humans, sheep, cattle and rabbits, and perfusions on the enucleated eyes of rabbits and cattle have shown that the outflow resistance can be reduced to about half after the injection of hyaluronidase. On account of these observations the present investigations are to detennine if spreading agents may be of value in increasing the drainage of aqueous humour and reducing intraocular pressure. It was also considered that such investigations would lead to a better knowledge of the biochemistry and pharmacology of the angle and be of some significance in the understanding and in the treatment of glaucoma. In the present investigations experiments have been conducted using constant pressure infusions in subcutaneous tissue of rabbits and with perfused isolated rabbit eye preparations. Spreading activity in skin and reduction in outflow resistance in the eyes is measured by the increased rate of infused fluid. Viscosity studies have been carried out with capillary viscometers using reconstituted freeze dried vitreous preparations from cattle eyes. The viscosity of these preparations is due to the high content of hyaluronic acid which is probably identical to the hyaluronidase-sensitive material coating the trabecular area. The spreading action to injections of hydrogen peroxide an accelerator of ascorbic acid has been confinned by subcutaneous infusions and produced a pronounced increase in outflow facility in the isolated eye preparations. Responses obtained by the addition of ascorbic acid may not be specific as these investigations have shown that similar responses can be obtained by the reduction of pH from the injection of non-specific acid. Reduction of viscosity is produced by the mixture of ascorbic acid and the accelerator hydrogen peroxide but not by either alone or by a change in pH. The isolated rabbit eyes in the experim~nts contain aqueous humour at the commencement of the perfusions and sufficient ascorbic acid would be present prior to the injections to produce a response with the accelerator. Ascorbic acid would also be present in the subcutaneous tissue but would have been removed from the freeze dried vitreous preparations by dialysis. The outflow facility response to hydrogen peroxide an ascorbic acid accelerator suggests that ascorbic acid which is secreted into the aqueous humour in higher concentrations than is present in blood plasma may playa part in the physiological regulation of aqueous drainage. These preliminary findings have been reported. During the course of these investigations periodicity of responsiveness was found in both the iolated eye preparations and in the subcutaneous infusions, to injections of hydrogen peroxide. This periodicity may not be strictly seasonal in character. In the phase of nonresponsiveness the isolated eye preparations are non-hyaluronidase sensitive and there is a reduced outflow resistance to the infusions. The sclera in this phase tends to become transparent between the insertions of the recti muscles. It appears that the periodicity insensitivity of response is due to alterations in the degree of polymerisation of hyaluronic acid in the angle. Alterations in hyaluronidase spreading activity in skin produced by environmental conditions has been observed bv other workers. Also variations in pressure infusion relationships have recentl v been reported. This work has now been extended using anaesthetised animals by studving the effects of intra-ocular micro-injections of enediols on the steady state pressure infusion curves. This procedure enables their effects to be determined both on intra-ocular pressure and on outflow facility. Much time has been spent on establishing this refined technique which is now satisfactory. These injections are made by micro-syringe and infusions carried out by a motor driven
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micro-syringe. The steady state pressures are measured electronically using an intra-ocular canula, a pressure transducer, and a polygraph recorder. Also a cone-in-cone viscometer has been built to extend the viscosity studies on intact vitreous. On account of the periodicity of response in rabbits, sheep will also be used in extending these experiments. These animals have the appropriate biochemical structure in the drainage mechanism. Dihydroxy-maleic acid, an enediol which is non toxic, is now being tested for its action on intra-ocular pressure and outflow facility response. Publication COWLE, J. B., and DANCE, V. L. 'Recent studies on the mode of action of glaucoma drugs.' Transactions of the Ophthalmological Society of Australia, 1965,24, 69.
DEPARTMENT OF PATHOLOGY Associate Professor D. A. Cameron, M.D.S., Ph.D. Dr H. Tyer, M.B., B.S., F.R.A.C.S., Senior Research Officer. Project The origin and function of osteoclasts. Report Further studies have been made on bone remodelling, an important phenomena in establishing skeletal form in the growing animal and in maintaining it in the adult. Changes in the skeleton as a result of trauma or metabolic disturbance are very much the result of remodelling and the way in which the process is carried out is still only vaguely understood. This study is concerned with increasing knowledge of the mechanism of remodelling and in particular of the origin and function of the cells that are responsible. Further studies have been carried out on the relationShip between parathyroid hormone and bone cells. Rats have been given small (in comparison with previous work) doses of parathyroid extract by infusion over periods from 6 to 70 hours. This has produced changes in cells that do not seem to be due to a toxic effect of the extract but are more likely to be related to the physioloical activity of the parathyroid gland. These small doses have produced increases in the osteoclast population in the treated animals along with change in shape of osteoblasts but, despite careful treatment of the tissues, there is still no evidence of fusion of spindle shaped osteoblasts to form multinucleated osteoclasts. However, evidence has been obtained that one of the proposed mechanisms of osteoclast formation, namely by fusion of macrophages does not occur in these animals. Many of the osteoclasts contained macrophages within their cytoplasm but these were incorporated into vacuoles and did not fuse with the osteoclast cytoplasm. By looking at a number of cells it is possible to build up a picture of macrophages being phagocytosed by osteoclasts and subsequently undergoing digestion. Refinements in the technique of tissue preservation have provided new information of the structure of osteoclasts, particuluarly in relation to the formation of secretory granules that may be concerned in the breakdown of organic matrix. Further studies of this project will be concerned with other ways of promoting bone remodelling in an effort to follow the formation of osteoclasts. Publication CAMERON, D. A., PASCALL, H. A., and ROBINSON, R. A. 'Changes in the fine structure of bone cells after the administration of parathyroid extract.' I. Cell Bioi. (In press.)
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DEPARTMENTS OF MEDICINE AND PAmOLOGY . ~_ Dr Peter M. Ronai, M.B., B.S., B.Sc.(Med.).
Projects Assessment of transplantation immunity in vivo using grafts labelled with radioisotopes. Transplacental induction of lymphoid differentiation by maternal thymus hormone. Report The purpose of the first project is to find an alternative to skin grafting as a means of assessing immune responses against transplantation antigens. Skin grafting is a tedious, traumatic and subjective way of measuring transplantation immunity. Experiments have involved the use of both dispersed cell and solid tissue grafts labelled with radioisotopes. The work on solid tissue grafts is in an early stage and will be detailed in the next report . Dispersed cell grafts comprised peritoneal cells derived by washing out the peritoneal cavities of normal donor strain mice. Peritoneal cells were used because they were readily available as a single cell suspension without red cell contamination and without the need for traumatic separation procedures. Recipients were syngeneic (same strain), allogeneic (different strain) and presensitised allogeneic, in relation to the donor strain. The donor peritoneal cells were labelled in vitro with chromium-51 and injected intravenously after repeated washing, into recipient mice. The fate of labelled grafts was assessed on the basis of changes in whole body activity, blood disappearance of labelled cells and organ uptake of labelled cells. Whole body activity remained identical in all three groups, indicating retention of label in a nonexcretable form after death of the labelled donor cells. Rates of disappearance of labelled cells from the circulation were also the same in the three groups. This was confirmed by identical rates of lung uptake and release. (Intravenously infused cells are temporarily arrested in the lungs). Uptake of labelled cells by the lymphoid organs, however, was significantly reduced in the sensitised allogeneic recipients compared with that in the other two groups. This reduction was most marked in the spleen. Third party (indifferent strain) labelled donor cells were handled by sensitised recipients as though the latter were unsensitised. The effect is thus immunologically specific in that it occurs only when the labelled cells are of the s arne strain as the cells used in the sensitisation. The effect is due to a serum antibody, not a cellbound antibody. This was shown by injecting serum or lymphoid cells from sensitised animals into unsensitised animals and then repeating the labelIed cell studies. Recipients of sensitised serum showed spleen uptake curves of the sensitised recipient type. Recipients of sensitised lymphoid cells showed spleen uptake curves of the unsensitised recipient type. The sensitised type of response could therefore be transferred to unsensitised recipients only by sensitised serum and not by sensitised lymphoid cells. Since peritoneal cells are a mixture of lymphoid cells and macrophages, it was of interest to see which of the two populations was susceptible to the effects of the serum antibody. Chromium-51 was first demonstrated by radio autography to label both cell types. Colloidal gold-l98 was shown by radioautography to label only macrophages. When the labelled cell distribution studies were repeated with gold-198 labelled peritoneal cells the sensitised recipients exhibited an un sensitised type curve. The effects of the serum antibody therefore seem largely confined to the lymphoid population of the peritoneal cell mixture. The second project is aimed at showing that maternal thymus hormone is partially responsible for foetal lymphoid tissue differentiation and maturation. Mice were neonatally thymectomised or sham-thymectomised. At weaning, the females were selected and each given
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two spleen equivalents of adult syngeneic spleen cells by intraperitoneal injection. Despite these injections about 90 per cent of the thymectomised animals died from the postthymectomy wasting syndrome. The I<!mainder were mated with normal males and the offspring tested at 6 weeks of age with a variety of standard antigens including allogeneic skin grafts, sheep red blood cells and. Salmonella typhimurium. Preliminary results indicate that skin graft survival can be prolonged by up to three times in offspring of thymectomised compared with offspring of sham-thymectomised mothers. The results of further skin grafts, and of the serum antibody titrations will shortly be available. Publications RONAl, P. M. 'The use of sodium sulphide to facilitate tail vein injections in mice and rats.' Transplantation, 1966, 4, 208. RONAl, P. M. 'Assessment of transplantation immunity using grafts labelled with radioisotopes.' Proc. Aust. Soc. Med. Res., 1966, 2, 42.
DEPARTMENT OF PHARMACY The late Professor S. E. Wright, D.Sc., Ph.D., Dip.Pharm., F.R.A.C.l. Dr A. J. Ryan, M.Sc., Ph.D., Senior Lecturer in Pharmaceutical Chemistry. Miss Jeannette Doel, Research Assistant, N.H. & M.R.C. Project The enzymology of food additive and foreign molecule metabolism. 1{eport Previous studies on azo dyes have continued. The excretion of 2-methyl-4-dimethylamino-azo-benzene is being re-examined. Using a sample doubly labelled with tritium and carbon-14 it has been shown that the biliary excretion of both isotopes is identical. This indicates that no fission products of the dye are excreted in rat bile but only complete dye metabolites. These are excreted as glucuronides and sulphates. Further work is being carried out on the fractionation of these conjugates. The metabolism of tartrazine in the rat has been further investigated. The dye has been synthesised with the 1-(p-sulphophenyl)-group labelled with sulphur-35. Oral dosage leads to the urinary excretion of 20 per cent of the radioactivity. The remaining activity is excreted in faeces. Of the urinary activity, 80 per cent is sulphanilic acid and 10 per cent is 4-sulphophenylhydrazine. It is interesting to note that sulphanilic acid arises both from reduction of tartrazine and degradation of the pyrazolone fragment. Both reactions may be due to the action of the gut flora. The reduction of tartrazine by a Proteus vulgaris species isolated from rats has been studied in detail. The reaction requires riboflavine and reduced pyridine nucleotides. It is inhibited by oxygen. In whole cells aged preparation reduce the dye best and this has been correlated with cell wall permeability. A cell free soluble enzyme has been partially purified. The cofactor requirements are as previously noted but magnesium is also required. The metabolism of some bisazo dyes has been examined. It has been shown that previous work by others on Sudan III is erroneous. Pure Sudan III is poorly absorbed from the gut and mainly excreted unchanged in facces. Parenteral doses are not readily excreted.
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Using tritiated Sudan III it has been found that the dye is taken up in the body fat after parenteral injection. Small amounts of radioactivity appear in the urine most of which is p-aminophenol. Studies of the biliary metabolites of butylated hydroxytoluene (BHT) have identified and quantitated the compounds identified by others. However, at least three additional metabolites have been detected, one in large quantity. The biliary metabolites are present mainly as glucuronides and sulphates. Incubation of the bile with gut contents causes changes which are probably due to hydrolysis. The relationship between this and the enterohepatic circulation of BHT metabolites is being investigated. Further work on the metabolism of amines has begun, including study of 2,6-dichloro4-nitroaniline which is used as a fungicide on fresh fruits and vegetables. This compound is readily absorbed and excreted by rats. The major metabolite is 2,6-dichloro-4-hydroxyaniline, with small amounts of 2,6-dichloro-p-phenylenediamine. 2,6-dibromo-4-nitroaniIine gives similar metabolic results but 2,6-dimethyl-4-nitroaniline is largely excreted unchanged and no aminophenol has been detected. The replacement of the nitro group by hydroxyl is a novel biological reaction. The mechanism is under study. Carbaryl (N-methyl-I-naphthyl carbamate) is oxidised to the 4 and 5-hydroxy derivative in rats. Some naphthalene-l,4 and -1,4-diols are also excreted, together with conjugates of I-naphthol. This metabolic pattern also appears in the cattle tick Boophilus microplus though there are quantitative differences. Studies on the inhibition of drug metabolising enzymes are in progress and a number of ketones which occur in Australian flora have been found to act as pyrethrin synergists in the house fly. These have now been examined as inhibitors of the reduction of prontosil and the demethylation of aminopyrine in vitro by rat liver preparations. The degree of inhibition ranged from 20-90 per cent of that found with SKF-525A. It paralleled synergistic properties. There appear to be correlations between structure and inhibitory activity. Electron micrographs of liver cells show that the most active compound in this series, conglomerone, causes changes in the endoplasmic reticulum, depletes glycogen, enlarges the Golgi apparatus and produce other changes, indicating cellular damage. There is some evidence that these compounds inhibit the transport of molecules across cell membranes.
Publications BARRETT, J. F., PITT, PATRICIA A., RYAN, A. J., and WRIGHT, S. E. 'The demethylation of m-methyl orange and methyl orange in vivo and in vitro.' Biochem. Pharmac., 1966, 15, 675. JONES, R., RYAN, A. J., and WRIGHT, S. E. 'The metabolism of some fat soluble phenylazopyrazolones in the rat.' Fd. Cosmet. Toxico/. 1966,4. LADOMERY, L. G. 'The metabolism, excretion and metabolic effects of butylated hydroxytoluene in the rat.' Ph.D. Thesis, University of Sydney, 1966. ROXON, J. J., RYAN, A. J., and WRIGHT, S. E. 'Reduction of tartrazine by Proteus sp. isolated from rats.' Fd Cosmet. Toxieol. 1966, 4. RYAN, A. J. 'The enterohepatic circulation of butylated hydroxytoluene.' Proceedings of The Australian Physiological Society, Aug., 1966. ~'--,
WRIGHT, S. E. 'Drug metabolism and the duration of drug action.' Aust. 1. Pharm. Sci. Supp., 1966, No. 47, S40-43. WRIGHT, S. E. 'The metabolism of 2,6-dichloro-4-nitroaniline.' Proceedings of The Australian Physiological Society, August, 1966.
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Dr. J. Thomas, Ph.D., M.Sc., F.P.S., Senior Lecturer in Pharmaceutical Chemistry. B. D. Roufogalis, M.Pharm., Teaching Fellow. Project Studies of the mechanism of the potentiation of acetylcholinesterase by certain quaternary ammonium compounds Report The work carried out during the year concerned chemical synthesis and enzyme studies. In the chemical studies, twelve more spiran quaternary ammonium compounds and related compounds have been synthesised for examination as potentiators of acetylcholinesterase. The structures of the compounds have been selected on the basis of results previously obtained with other similar compounds. The object of this approach is to produce a series of structurally closely related compounds and examine them for their ability to cause potentiation of acetylcholinesterase and from these results it is hoped that the structural features required for potentiation will be defined. There have been two objects in the enzymic work. One has been to examine the compounds synthesised, under a number of different conditions, to determine their ability to potentiate acetylcholinesterase. The second object has been to examine a few selected compounds in depth in an attempt to elucidate the mechanism of potentiation. From this work a clearer understanding of the mechanism of the potentiation phenomenon is emerging. Potentiation of acetylcholinesterase occurs only at substrate concentrations higher than optimum. Since this enzyme shows substrate inhibition, which is generally considered to be due to the binding of a second substrate molecule on the enzyme, then it appears that some quaternary compounds are able to protect the enzyme against inhibition by excess substrate. The shift in optimum substrate concentration to higher values in the presence of potentiators which is observed supports this concept. If such a situation was the mechanism for all the cases of potentiation which have been observed then it would be expected that the activity of the enzyme in the presence of a potentiator would never rise above its activity when optimum substrate concentration was used in the absence of a potentiator. This is the case when the medium in which the enzyme reactions are carried out contains sodium chloride and magnesium chloride. However, when the reaction medium does not contain added inorganic ions, the activity of the enzyme, in the presence of potentiators, rises above that of control activity. It is clear that as well as protecting the enzyme against the actions of excess substrate some of the quaternary ammonium compounds can accelerate the enzyme by another mechanism. By using phenyl acetate and other esters as the substrate it has been possible to show that the mechanism by which absolute potentiation occurs is related to the deacetylation step of the overall hydrolysis reaction. The steps involved in the hydrolysis of esters by acetylcholinesterase are considered to be the formation of a Michaelis complex, the transfer of the acetyl group from the ester to the enzyme, desorption of the alcohol from the enzyme and deacetylation of the acetylated enzyme to generate the free enzyme and liberate acetic acid. Phenyl acetate has been used as a substrate in this work because it does not show substrate inhibition and also it has been demonstrated that the rate determining step in the hydrolysis of this ester with acetylcholinesterase is the deacetylation step. Some quaternary ammonium compounds and inorganic ions have now been shown to potentiate the hydrolysis of phenyl acetate. It is considered that the potentiators form a ternary complex with the acetylated enzyme and that this ternary complex can be hydrolysed faster than the normal acetylated enzyme.
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The reason why some compounds are more effective than others in this regard remains an outstanding problem. One line of thought which is being followed is that the effect of the compounds on the structure of water is connected with their ability to accelerate the deacetylation process of acetylated acetylcholinesterase and hence act as potentiators. Publication TIIOMAS, J., and ROUFOGALIS, B. D. 'Structural specificity of substrates of acetylcholinesterase.' Molecular Pharmacology. (In press.)
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DEPARTMENT OF PHYSIOLOGY Professor P. O. Bishop, M.B., B.S. Dr W. R. Hayhow, M.B., B.S., Senior Lecturer. Dr R. W. Rodieck, M.Sc., P.R.D., Senior Lecturer. Dr J. Stone, Temporary Lecturer. Dr J. Leicester, Medical Postgraduate Scholar, N.H. & M.R.e. Mr T. Nikara, B.Sc., Selby Fellow. Mr J. D. Pettigrew, M.Sc., Postgraduate Student. Miss M. Fabian, B.Sc. (Hons), Postgraduate Student, Teaching Fellow, 1966. Mr W. Kinston, B.Sc. (Med.), Postgraduate Student. Mr M. Vadas, B.Sc. (Med.), Postgraduate Student. Miss G. Burrows, B.Sc. (Hons), Postgraduate Student. Project Neurophysiology of vision and neurohistological studies. Report The aim of the studies on the visual system is to determine the way in which information concerning the various features of the visual world (contours, shapes, distance from the eye, etc.) are coded by the eye as patterns of nerve impulses in the optic nerve and the way in which this coded information is analysed by the nerve cells at the successive levels in the visual parts of the brain. The various research projects are being carried out using both histological and electrophysiological techniques and work is being done at the various levels in the visual system from the retina at the back of the eye through the lateral geniculate nucleus up to the visual parts of the cerebral cortex. R. W. Rodieck and P. O. Bishop have been attempting to provide as complete a description as possible of the coding of visual information by the eye in terms of single-unit discharge patterns in the optic nerve. A major difficulty in the understanding of these coding patterns arises from the fact that even without any pattern in the visual field the ganglion cells maintain a high discharge rate of impulses up the optic nerves. Rodieck has completed a detailed study of this spontaneous activity on the part of the ganglion cells. Under certain conditions this maintained activity may show remarkably regular, though complex, oscillations in discharge rate. These slow rhythms have been particularly studied by Rodieck and Smith. In earlier studies of the projection of the visual field on the lateral geniculate nucleus we had evidence which indicated that the visual fi eld had a double representation in each nucleus. Kinston, Vadas and Bishop have shown that there is, in fact, a triple representation of the
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visual field onto the thalamus and that this representation has many points of resemblance to the multiple representations in the visual cortex. Pettigrew, Nikara and Bishop have completed a detailed study of binocular interaction on visual neurones in the cerebral cortex. They gave particular attention to the neurology of corresponding retinal points by studying single units in the visual cordex. The control of residual eye movements in the paralysed animal was a vital component in this study (Rodieck, Pettigrew, Bishop and Nikara). Leicester has studied various aspects of the retinal division into nasal and temporal components with particular reference to the naso-temporal overlap shown by Stone by means of histological methods. Leicester is investigating this overlap by studying the receptive field positions of single neurones in the right and left visual cortices. He is also attempting to determine whether a naso-temporal overlap occurs in the monkey retina. A number of purely histological problems are being investigated. Leicester and Stone are studying the various cell types in the eat's retina. Hayhow is studying the comparative ultrastructure of invertebrate nerve fibres and synapses. He is also studying the ultrastructure of the synaptic connections in the lateral geniculate nucleus of the rat and cat. Hayhow and Burrows are studying the projections to the cerebral cortex from the various visual parts of the thalamus. Hayhow is continuing his detailed .itudy of the accessory optic system in a variety of representative animal types. Publications BISHOP, P. O. 'The nature of the representation of the visual fields in the lateral geniculate nucleus.' Proc. Aust. Assoc. Neurologists, 1965, 3, 15. BISHOP, P. O. 'Central nervous system: afferent mechanisms and perception.' Ann. Rev. Physiol. (In press.) BISHOP, P. O. and RODIECK, R. W. 'Discharge patterns of cat retinal ganglion cells.' Proceedings of Symposium on Sight Sensory Systems, California Institute of Technology, November, 1965, p. 116. BISHOP, P. O. and TAUB, A. 'The spinocervical tract; dorsal column linkage, conduction velocity, primary afferent spectrum.' Exp. Neurol., 1965, 13, 1. HA YHOW, W. R. 'The accessory optic system in the marsupial phalanger, Trichosurus vulpecula. An experimental degeneration study.' I. compo Neurol., 1966,126, 653. OGAWA, T., BISHOP, P. O. and LEVICK, W. R. 'Temporal characteristics of responses to photic stimulation by single ganglion cells in the unopened eye of the cat.' I. Neurophysiol., 1966, 29, 1. RODIECK, R. W. 'Quantitative analysis of cat retinal ganglion cell response to visual stimuli.' Vision Res., 1965, 5, 583. RODIECK, R. W., PETTIGREW, J. D., BISHOP, P.O., and NIKARA, T. 'Residual eye movements in receptive field studies of paralysed cats.' Vision Res. (In press.) RODIECK, R. W. and SMITH, P. S. 'Slow dark discharge rhythms of cat retinal ganglion cells.' I. Neurophysiol., 1966, 29, 942. RODIECK, R. W. and STONE, J. 'Analysis of receptive fields of cat retinal ganglion cells.' I. Neurophysiol., 1965, 28, 833. RODIECK, R. W. and STONE, J. 'Response of cat retinal ganglion cells to moving visual patterns.' I. Neurophysiol., 1965, 28, 819. STONE, J. 'The naso-temporal division of the cat's retina.' I. compo Neurol., 1966, 126, 585.
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STONE, J. and FABIAN, M. 'Specialised receptive fields of the eat's retina.' Science, 1966, 152,1277. STONE, J. and HANSEN, S. M. 'The projection of the cat's retina on the lateral geniculate nucleus.' I. Compo Neurol., 1966, 126, 601.
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Assoc. Professor W. Burke, Ph.D. Dr Ann Jervie Sefton, Ph.D., M.B., B.S., B.Sc.(Med.), Lecturer. Miss Ann Donovan, M.Sc., Teaching Fellow. Miss M. I. Fabian, B.Sc. (Hans), Teaching Fellow. Mr I. S. C. Bruce, B.Sc. (Hans), Postgraduate Student. Miss L. Malcolm, B.Sc. (Hons), Postgraduate Student. Project Electrophysiological studies of vision. Report In previous years the existence of a system of recurrent inhibition in the lateral geniculate nucleus (LGN) of the rat has been described. Principal cells (P cells) projecting to visual cortex receive an inhibitory innervation from interneurones (I cells) in the LGN which in turn are innervated by P cell axon collaterals. This work made use of electrical stimulation of the optic nerve. In order to study the functioning of this inhibitory system under more natural conditions, the work is being continued using photic stimulation. Receptive fields of both P and I cells are being mapped using small flashing spots of light. P cells have receptive fields resembling those of the retinal ganglion cells. Some possess a centre-surround organisation; in others it has not been possible to detect a surround. In all cases the centre is either ONcentre or OFF-centre. The smallest centre found subtended about 50. I cells have receptive fields uniformly ON-OFF and their response ;s more prolonged than that of the P cells. The number of cells studied is small as yet and hence the above conclusions are tentative. There has been a tendency to regard the LON simply as a station on the way to the visual cortex. Our studies on the sleeping cat using implanted electrodes have shown that quite large changes in synaptic transmission in the LGN can occur under physiological conditions. The phase of sleep has been monitored by re.::ording from sensori-motor cortex, hippocamus, neck muscles and LGN and by observing the animal's behaviour. There is a decrease in presynaptic inhibitition of the optic tract endings when the cat goes to sleep. There is also an increase in postsynaptic inhibition during slow wave sleep but this decreases during activated (paradoxical) sleep and synaptic transmission may even be improved with respect to the alert state. The study of the late receptor potential (LRP), a component of the electroretinogram, has continued using the technique of close-arterial injection of barbiturate and other substances. The effect of barbiturate in increasing the LRP amplitude seems to be partly due to its vasoconstrictor action. This possibility is being examined by measurement of the blood flow through the retina. The retinal ganglion cells of the cat under nitrous oxide discharge with a very slow rhythm. This rhythm is similar in the two eyes but the two rhythms are not synchronised. This phenomenon is being studied by means of chronically implanted electrodes to see whether under any conditions there is any synchrony between the two eyes, whether there is a characteristic rhythm from day to day and whether different cats exhibit different rhythms.
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Publications BURKE, W. 'Neuronal models for conditioned reflexes.' Nature, 1966, 210, 269 BURKE, W., and SEFTON, ANN J. 'Discharge patterns of principal cells and interneuron!:s in lateral geniculate nucleus of rat.' I. Physiol., 1966, 187, 201. BURKE, W., and SEFTON, ANN J. 'Recovery of responsiveness of cells of lateral geniculate nucleus of rat.' I. Physio/., 1966, 187, 213 BURKE, W., and SEFTON, ANN J. 'Inhibitory mechanisms in lateral geniculate nucleus of rat.' J. Physiol., 1966,187,231. DONOVAN, ANN M. 'The postnatal development of the cat retina.' Exp. Eye Res., 1966, 5, 2, 149. SEFTON, ANN J., and BURKE, W. 'Mechanism of recurrent inhibition in the lateral geniculate nucleus of the rat.' Nature, 1966, 211, 1276.
Dr C. W. Dunlop, M.Sc., Ph.D., Senior Lecturer. Mr L. M. Aitkin, M.Sc., Research Student. Miss Miriam Waks, B.Sc. (Hons), Student. Project Electrophysiological correlates of hearing in cats. Report During the presentation of a monotonous (regular) stimulus the response of an organism to that stimulus declines over time (behavioural habituation). Similar response decrements occur in the brain (electrophysiological habituation.) Studies in this laboratory have shown that the degree of habituation in the auditory system has some dependance on the stimulus intensity and the rate at which the stimulus is given. However, these investigations have failed to show a precise relationship between habituation trends (response decline) and stimulus rate and intensity. As the animals are unanaesthetised and unrestrained the auditory responses are recorded during varying period of alertness, relaxed wakefulness, drowsiness and sleep throughout the habituation tests. Studies in progress show that when the state of consciousness of the animal is strictly monitored by observing its overt behaviour and studying its brain wave activity the duration and amplitude of the auditory responses undergo changes during the different conscious states. Since changes in the amplitude of the response is the measure commonly used for estimating electrophysiological habituation trends it is likely that the failure to find a precise relationship between stimulus rate and intensity and the degree of habituation has been due to these response fluctuations. Following a comprehensive analysis of the auditory response changes during the different conscious states it is proposed to re-investigate the dependance of acoustic habituation on stimulus rate and intensity. Publications AITKIN, L. M., DUNLOP, C. W., and WEBSTER, W. R 'Click-evoked response patterns of single units in the medial geniculate body of the cat.' I. Neurophysiol., 1966, 29, 109. DUNLOP, C. W., WEBSTER, W. R, and RODGER, R S. 'Amplitude changes of evoked potentials in the auditory system of unanaesthetised cats during acoustic habituation.' I. Auditory Research, 1966, 6,47.
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SIM0N.S, ~. ~., DUNLOP, C. W., WEBSTER, W. R., and AITKIN, L. M. 'Acoustic habltu~tlOn In cats as a function of stimulus rate and the role of temporal conditioning of the middle ear muscles.' Electroenceph. c/in. Neurophysiol., 1966, 20, 485.
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Dr W. R. Hayhow, M.B., B.S., Senior Lecturer in Physiology. Mr S. Ooi, B.Sc., Research Assistant, N.H. & M.R.C. Miss G. Burrows, B.Sc. (Hons.), Postgraduate Student. Projects An experimental degeneration study of the cortical projection of the medical interlaminar nucleus of the lateral geniculate body in the cat. The effects of disuse upon synaptic transmission in the lateral geniculate body in the cat. Comparative ultrastructural studies of neurones and synapses. Report It has been shown that a primary visual centre of the cat's brain, the lateral geniculate nucleus, receives a double projection from the two eyes. In addition to the major connection with the main nucleus a smaller second projection has been recently demonstrated between the eyes and a specialised inner region of the former nucleus termed the medial interIaminar nucleus. At the present time the cortical projection field of the latter nucleus is unknown. The present investigation is principally concerned with the identification and delineation of this projection field. Using a three dimensional co-ordinate system, fine electrodes have been guided into the medial interlaminar nucleus of anaesthestised cats. Small regions of the nucleus have then been destroyed by electric currents passed through the tips of the electrodes. Subsequently the cerebral cortices are stained and examined microscopically for evidence of degenerating nerve fibres. The distribution of these fibres is plotted on maps of the cat's brain. The experiments carried out to date .how that the medial interlaminar nucleus ;s connected not with the classical visual area of the cerebral cortex (area 17) but with adjacent cortical regions of distinctive structural organisation, termed areas 18 and 19. The initial lesions, whilst definitely implicating the medial interlaminar nucleus have also implicated adjacent nuclear structures to a varying extent. Future endeavours will be directed toward~ placing smaller, more discrete lesions, entirely within the medial interlaminar nucleus, that is, with the production of lesions as pure as possible. In this way it is hoped to show that area 18 is the principal cortical terminus of the medial interIaminar nucleus, and that area 19 is connected principally with an adjacent nucleus inadvertently implicated by the larger lesions, the nucleus posterior of the thalamus. Earlier work has suggested that when connections between nerve cells (synapses) are subjected to prolonged disuse the transmission mechanism is adversely affected. In the present series of long term experiments disuse of the connections between nerve fibres from the eyes and the lateral geniculate nerve cells within the cat's brain has been produced by keeping animals in total darkness for prolonged periods and by the administration of a drug, M & B 968A, which specifically damages the light receptive cells of the retina. Subsequent electrical testing of the synapses in the dark room cats has shown no change in synaptic efficacy, that is the synapses appear to behave in a normal manner, whereas in the 'drug treated' cats there has been some enhancement of synaptic efficacy. In the dark room cats synaptic function would appear to be maintained by spontaneous retinal activity so that
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the synapses in these animals had not actually been subjected to disuse. In the drug treated cat spontaneous activity is either considerably reduced or completely absent and the lateral geniculate synapses have been subjected to actual disuse. During 1966 additional quantitative data relating to the altered excitability of the synapses in drug treated cats has been sought. Future studies may include an electron microscope examination of the disused synapses with a view to correlating any changes in fine structure that may be observed with the electrophysiological findings. The aim of this investigation has been to study and compare the structural organisation of synapses in selected invertebrates and vertebrates, using principally the techniques of electron microscopy. Earlier work on the central nervous system of the earthworm, Pheretima difJringens has shown that a majority of the junctions between nerve cells are very similar in structure to the typical vertebrate synapse. These earthworm synapses show a striking structural polarity (sy=etrical synapses) suggesting a unidirectional, chemical type transmission mechanism. During the present year this work has been continued principally in relation to the special transmitting synapses between adjacent segments of the giant nerve fibres in Pheretima. In material fixed with osmium tetroxide prior to examination in the electron microscope these synapses appear structurally unpolarised (symmetrical synapses) with the apposed cell membranes separated by a narrow interval of about 100A. This structural symmetry is in agreement with earlier electrophysiological findings which indicate that these synapses transmit excitation with equal facility in either direction, quite unlike the strictly unidirectional transmission of ordinary asymmetrical junctions. In known electrically transmitting synapses in other animals electron microscopy following fixation with potassium permanganate has always shown the occurrence of partial fusion between the apposed cell membranes (tight junctions). During the present year considerable effort has been expended in fixing earthworm tissue with potassium permanganate in an endeavour to ascertain whether or not the giant synapses of this animal show the tight junction type of structure. To the present time these endeavours have been unsuccessful principally due to the well known difficulties of producing good fixation with potassium permanganate and to difficulties in actually finding these synapses in thin sections. Should material become available, this study will be continued in the Victorian giant earthworm-Megascolex. Similar difficulties have been experienced in obtaining satisfactory fixation of the synapses in the lateral geniculate nucleus of the cat and rat. The electron microscope images obtained to date have indicated incomplete fixation. Currently, newer fixatives consisting of aldehydes and mixtures of aldehydes are being applied by intra-arterial perfusion in an endeavour to improve the quality of the electron images. The primary objective of this study is to establish ultrastructural norms for future studies in experimentally modified lateral geniculate synapses. Publication
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HAYHOW, W. R. 'The accessory optic system in the marsupial phalanger, Trichosuru.t vulpecula.' I. Camp. Neur., 1966, 126, 653-672.
Mr B. S. Gow, M.D.S., Senior Research Officer, N. H. & M.R.C.
Project Measurements of visco-elastic constants of arteries in living normotensive and hypertensive dogs.
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Report In the previous report it was noted that the use of conventional techniques applied to the analysis of pressure and diameter pulse waves produced results which were difficult to interpret. In order to observe the frequency behaviour of these constants, methods have been developed which take account of elastic non-linearity. (The presence of this property was shown to restrict the use of a more simple analytical procedure such as Fourier analysis). Despite the limitations to the use of the Fourier technique it has, however, been possible to provide values of these constants at frequencies at the lower end of the physiological range in the normal dog. Contrary to the findings of some other investigations, it has been concluded that the aorta in the dog has essentially the same visco-elastic properties whether in or out of the animal. Although higher values were obtained here in the living femoral artery than had been previously reported for excised vessels, this finding can be readily explained in terms of both differences in experimental technique and the probable contribution of living smooth muscle to elastic properties. The problem of how prolonged arterial hypertension affects the elastic properties of arteries has in the past received little attention. Experimental hypertension has thus been induced in a number of dogs by bilateral renal artery constriction. Control measurements of one superficial femor~l artery in each animal prior to the development of the elevated blood pressure have been made. It is intended to make measurements of visco-elasticity at a number of different sites in the arterial tree in these hypertensive animals at the end of this year.
Publication GOW, B. S. 'An electrical caliper for measurement of pulsatile arterial diameter changes in vivo.' I. appl. Physiol., 1966, 21, 1122.
DEPARTMENT OF SURGERY Mr J. A. Myhill, M.Sc., Research Fellow.
Project Experimental tracer dynamics. Report This project concerns the theory and use of tracers. A tracer is a substance which can be readily measured and which behaves the same as another substance which cannot be readily measured. Radioactive substances are used extensively as tracers. By introducing a radioactive element into a biological system, notably in man, it is possible to obtain information about the behaviour of the corresponding non-radioactive element in the system. Useful information can be obtained if there is available some means of mathematically analysing the observations. This analysis must afford a method of converting the observations on the radioactive element into a useful description of the behaviour of the ordinary nonradioactive element. Accurate mathematical formulae for studying chemical systems in a reaction vessel are available and widely used. The same formulae have been used in biological systems because t~ey ,,:,ere the best available for such purposes. However, it has been realised that their use in bIOlogICal systems is only an approximation. This is because biological systems, unlike chemical systems, cannot really be thought of as homogeneous. Therefore, a mathematical formalism is.
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needed for treating inhomogeneous systems. In recent years some attempts along these lines have been made and it has become necessary to test by experiment some of the theoretical conclusions. This project will allow a comparison of two ways of measuring the amount of iodine in the thyroid gland, which is the organ which primarily concentrates iodine. Tracer measurements by radioactive iodine are being performed, and by using some mathematical formulae the amount of non-radioactive iodine is being calculated. Other measurements of the nonradioactive iodine in the thyroid will be made using an X-ray technique. The two types of measurement will be compared in an assessment of the validity of the tracer theory. Some preliminary X-ray measurements have been satisfactorily completed and system design modifications carried out. The X-ray technique involves measuring the absorption of selected X-ray wave lengths and thereby deducing the amount of iodine in the transmission path. The measurement is complicated by the presence of water and other substances in the transmission path of the X-rays, and considerable further technical development is needed to obtain useful results by this method. The construction of special equipment for the extensive isotope measurements has been very successful. The establishment of good methodology is proceeding satisfactorily and several patients have been studied. More work is required to establish all the techniques and to proceed into a series of comparisons between radioisotope tracer measurements of various quantities and the corresponding non-tracer measurements. As an additional benefit from the project it is expected that useful information about iodine dynamics and thyroid physiology will be obtained.
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Publications MYHILL, J. 'The calibration of thyroidal uptakes in Australia.' Brit. J. Radiol., 1965, 38, 465. MYHILL, J., HALES, I. B., and REEVE, T. S. 'Thyroid radiosensitivity in hyperthyroid and euthyroid subjects treated with 1-131.' 'Current topics in thyroid research.' Proceedings of the Fifth International Thyroid Conference, 1965, 1143. MYHILL, J., REEVE, T. S., and HALES, I. B. 'Thyroid function in breast cancer.' Acta Endocrinologica, 1966, 51, 290. MYHILL, J., and HALES, I. B. 'Comparison of thyroid suppressibility by triiodothyronine and calcium acetyl salicylate.' Brit. Med. J., 1966, 1, 137.
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UNIVERSITY OF TASMANIA DEPARTMENT OF ANATOMY l
Professor C. H. Barnett, M.B., F.R.e.S. Project Studies of normal human joints and osteoarthritic tissue. Report The grant was expended in buying an ultramicrotome for sectioning diseased tendons and articular cartilage removed at biopsy. Some specimens have been obtained, but the work has been held u!l due to the delay in receiving the diamond knives ordered from a separate research grant. When these are in use it is believed that these refractory human tissues will be cut with greater success.
DEPARTMENT OF BIOCHEMISTRY Professor E. S. Holdsworth, D.Sc., F.R.I.e. Dr M. E. S. Neville, Ph.D., B.Sc. Project The study of calcium and phosphorus metabolism as affected by vitamin D. r
Report The study of calcium and phosphorus metabolism as affected by vitamin D has been undertaken in several different ways. Several reports have suggested that vitamin D affects the synthesis of phospholipids. To see whether the turnover of PO. in phospholipid was related to the movement of calcium across membranes, everted sacs or in vivo loops of chick small intestine were studied under conditions where calcium was being transported, and with the aid of 32PO, the specific activities of the different phospholipids were observed. Vitamin D increased calcium transport across the gut membrane and, in many experiments, the incorporation of 32PO. into phospholipid was also increased. In the absence of calcium in the gut lumen vitamin D has no effect on the incorporation of 32PO. into phospholipid and therefore it is unlikely that vitamin D directly affects phospholipid synthesis. When incorporation into phospholipid was increased by vitamin D this could usually be correlated with an increase in the specific activity of the acid-soluble32p compounds of the mucosal cells. Attempts are being made to decide whether this is entirely due to increased specific activity of the inorganic phosphate or whether nucleotide phosphate specific activity is also increased. The possibility that vitamin D, by increasing the concentration of calcium in mucosal cells, is affecting phospholipid synthesis appears to be ruled out because more total calcium was found in vitamin D deficient mucosal cells. rCa is a known cofactor in the synthesis of some phospholipids]. Thus it is when calcium is being accumulated that some process is increased that causes increased movement of PO. or increased synthesis of some phosphate-containing intermediate. Experiments with HC labelled ethanolamine or serine showed that these components of phospholipids were incorporated to the same extent in vitamin deficient or repleted mucosal tissue. Since vitamin D is alleged to have some local effect on bone causing ossification, attempts have been made to see whether the vitamin affects the formation of protein and chondroitin sulphate in bone. 35S0. and tritiated proline were injected into chicks and the specific activity of protein and chondroitin sulphate in mucosal cellS" of the intestine and epiphyseal plate of 4275/67...JJ
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vitamin D deficient and replete chicken compared. No differences were found in the total specific activities. The question remains as ~o whether there is an effect of the vitamin on the location of chondroitm sulphate in tissues and this should become evident when autoradiographs are developed and evaluated (February, 1967). When tendon is recovering from damage, it may mineralise and this phenomenom has been studied in rats. The research is a joint project with Dr R. Heddle of the Department of Anatomy. The achilles tendon of one hind leg of a rat was severed and the process of repair followed, the other hind leg serving as a control tissue. At weekly intervals after the cutting of the tendon, 45Ca was injected into the rat and the deposition of calcium in the tendon followed. It was found that between 3 and 4 weeks after cutting the tendon, there was a sudden increase in accumulation of calcium and this was several weeks before obvious mineralisation of the tendon took place. Similar experiments using 35S0. showed that there was an incorporation of 35S into those sites that were eventually mineralised. It is intended to study this process in vitamin D deficient rats but, so far, satisfactory deficiencies have not been produced. It is for this reason that the projected experiments to study the influence of vitamin D on calcium and phosphorus excretion by the kidney have not been attempted. The work reported above has required the use of radioactive isotopes and often, in one experiment, three isotopes would be present c.g. in transport studies-tritiated inulin, 32PO. and .5Ca would be used. To count these isotopes in the same extract, the three channel liquid scintillation counter provided by a grant from the N.H. & M.R.C. has been indispensable.
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UNIVERSITY OF WESTERN AUSTRALIA DEPARTMENT OF BIOCHEMISTRY Dr R. Logan, B.Sc., Ph.D., Senior Research Fellow. Project A study of the biochemical changes which occur in mouse fibroblast strain-L cells during the mitotic cycle. Report Further modifications to the growth medium (Waymouth's MB 752/1) have been made. Additions of foetal calf serum, a-ketoglutarate and insulin to the MB 752/1 medium have reduced the mean generation time of the cells by approximately 10 per cent (from 32 hours to 28.5 hours). The oxygen uptake of the cells has been investigated manometrically and with an oxygen electrode. Using the oxygen electrode, it was found that more reproducible results could be obtained and that the uptake of oxygen could be followed for periods up to 40 hours. Using the oxygen electrode procedure, it has been observed that there is a low uptake of of oxygen immediately following scynchronisation, but this returns to the normal value of approximately 81-'0 02/cell/hours, after approximately 2 hours. Whether this is due to the cells having completed mitosis, or whether it is due to the handling of the cells at this point, is being investigated. Using logarithmically dividing cultures, the effect of glucose on the oxygen uptake has been studied. In the absence of glucose from the medium, the oxygen uptake fell to approximately half the normal value. Autoradiography, using Kodak Nuclear Emulsion (NTBs), has been used to determine the uptake of radioactive precursors by synchronised cells. Pulse labelling with Hs-thymidinc has been carried out and the various phases of the interphase of cell division have been determined. The'S' period, i.e. the period during which the DNA of the cell is synthesised, falls 8 hours after mitosis is completed. The'S' period lasts for 2 hours. In these experiments, the mitotic time (Tm) was found to be much shorter than had been found in previous experiments (15 minutes as compared with 45 minutes). This is being investigated further. From this work it would appear that under the conditions used in these experiments, the mitotic cycle could be divided into various phases Tm (15 minutes), interphase (28.25 hours); interphase could further be divided into 'G' period (8 hours), oS' period (2 hours) and 'Go period (17.25 hours). Pulse labelling of synchronised cells with C14 uridine for a very brief period of 3 minutes, has shown that RNA synthesis is very active throughout interphase. There is, however, a small but significant, fall in the rate of uptake of uridine during the'S' period. Further investigations of micro-assay techniques for enzymes have been made.
Dr Ivan T. OUver, M.Sc., Ph.D., Reader in Biochemistry. Mr William F. C. Blumer, M.A., B.M., B.Ch., Senior Lecturer in Anatomy. Mr D. Robertson, B.Sc., Research Assistant. Mr R. W. Wise, B.Sc., Research Student. Mr D. Yenng, B.Sc., Research Student. Project Biochemical aspects of development in neonatal rat liver.
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Report The problem of tissue differentiation in embryonic development has been investigated ;n biochemical terms by a study of the synthesis of proteins and enzymes which are specific to particular cells and organs. Elucidation of the mechanisms whereby such processes are initiated is essential for understanding of embryogenesis and differentiation. In rat liver, phases of differentiation as defined in the above terms occur both early and late in foetal development and several of the p rocesses have been studied. Early in foetal life the rat liver produces a specific foetal albumin which is gradually replaced by the adult type albumin. The foetal albumin has been purified and studied by physicochemical and immunological techniques. Although it has the same molecular weight, sedimentation coefficient and diffusion coefficient as adult albumin, it is unrelated to albumin in serological reactions and would thus appear to be under the control of a separate gene whose activity it repressed during development while the albumin gene is activated. Further work is necessary to establish the function of the protein, its cellular, as distinct from tissue origin and the possibility of its synthesis in non-hepatic tissue. Late-phase differentiation of rat liver has been studied by the production of specific enzyme systems which are concerned with the control of blood glucose concentration, carbohydrate interconversions and glucose synthesis. These systems all appear postnatally or at the time of birth in the liver. The activities of enzymes concerned with glucose synthesis have been shown by others to increase in adult liver following glucocorticoid administration, but the hormones are without effect on the postnatal appearance of the systems in recent experiments. However, it has beer. shown that premature delivery of foetal animals results in the dramatic appearance of phosphopyruvate carboxykinase activity, one of the obligatory quartet of the enzymes in glucose synthesis. Further work is planned to elucidate the mechanism of this effect, and initially the use of inhibitors of protein synthesis should decide whether the process represents de novo synthesis or activation of enzyme precursor. In tissues such as the central nervous system and red blood cells, differentiation and growth seem to be mutually exclusive and it is of interest to investigate the overall occurrence of such phenomena. Accordingly, growth processes in the rat liver are being investigated by measurements of DNA and RNA synthesis. In adult liver, parenchymal cell nucleii are largely tetraploid and recent techniques of density equilibrium centrifugation in suitable media enable separation of cell nucleii according to their content of DNA. These techniques are being applied to neonatal rat liver cell nucleii and together with labelling studies of the nucleic acids in vivo with suitable precursors should give information about some aspects of growth. The distribution of parenchymal nucleii among different density (DNA) classes alters markedly during neonatal development and the rates of synthesis of DNA and RNA within such nucleii are currently under investigation. Publications KIRSCH, J. W., WISE, R. W., and OLIVER, I. T. 'Post-albumin, a foetal-specific rat plasma protein. Purification, physicochemical and immunological studies.' Biochem. ]. (In press.) WISE, R. W., and OLIVER, r. T. 'Sites of synthesis of plasma proteins in the foetal rat.' Biochem. ]., 1966,100,330. WISE, R. W., and OLIVER, I. T. 'Plasma albumin synthesis during neo-natal development of the rat.' Biochem. I. (In press). YEUNG, D., and OLIVER, r. T. 'Gluconeogenesis from amino-acids in neo-natal rat liver.' Biochem. I. (In press.)
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University of Western Australia DEPARTMENTS OF MICROBIOLOGY, PATHOLOGY AND MEDICINE Professor N. F. Stanley, D.Sc. Dr R. A. Joske, M.D., F.R.A.C.P., Reader in Experimental Medicine. Dr M. N. I. Walters, M.D., M.R.A.C.P., M.C.Path., Reader in Pathology. Dr J. M. Papadimitriou, M.B., B.S., Research Fellow. Mr D. Keast, B.Sc., Senior Demonstrator, Department of Microbiology.
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Project The biological spectrum of reovirus. Report Since the first isolation and description 'lf reoviruses, it has been shown that this group of viruses is very widespread in nature and is unique among animal viruses due to the double-stranded RNA core and the cytoplasmic replication in close association with the mitotic apparatus of the cell. It has been shown that reovirus 3 may be transmitted by mosquitoes. These properties are shared by wound-tumour virus and rice-dwarf virus, which are plant viruses that mUltiply in insect vectors. These properties of reovirus are vitally important, because it has been implicated in the aetiology of Burkitt', lymphoma, which is believed to be insect transmitted. The epidemiology studies of the Perth group, with those of Dr Bell in Entebbe, Uganda, are now most convincing in implicating reovirus 3 as a possible cause of a solid human tumour. In studying the mechanism whereby a virus can transform a cell so that it becomes malignant, it has been shown with the reovirus 3 murine system that autoimmune type processes are almost certainly invoked. The study of the chronic autoimmune disease caused by reovirus 3 in mice has been continued in detail and is throwing considerable light on the relationship between auto-immune disease and neoplasia. Cellfree extracts of the reovirus 3 induced murine lymphoma have been shown to cause both autoimmune disease and cancer. The processes by which this is accomplished are being elucidated. The control and the regression of tumours by chemotherapeutic agents has been investigated. It has been shown that the murine lymphomas respond similarly to the human Burkitt lymphoma. This experimental investigation has enabled the research workers to study more closely the relationship between the activity of the chemotherapeutic agent and the immunological activity of the host. This is vital for any further progress in the understanding and control of cancer by these methods. Karyotype studies of developing tumours have shown an interesting relationship between the chromosome pattern, autoimmune disease and cancer. In addition, an examination is being made of the part played by leucocytes and macrophages in experimental autoimmune processes and neoplasia. This brief summary does not really reflect the rapid progress that has been made, nor the exciting nature of the work and the international interest which it is stimulating.
Publicatious DALES, S., GOMATOS, P. J., and HSU, K. C. Virology, 1965,25, 193. JOSKE, R. A., LEAK, P. J., PAPADIMITRIOU, J. M., STANLEY, N. F., and WALTERS, M. N.-I. 'Murine infection with reovirus. IV. Late chronic disease and the induction of lymphoma after reovirus type 3 infection: Brit. I. expo Path., 1966, 47 (4), 337. KEAST, D. 'Karyotype studies on a lymphoma (2731jL) resulting from reovirus type 3 infection of neonatal mice.' Exp. Cell Research, 1966. (In press.)
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KEAST, D., and STANLEY, N. F. 'Studies on a murine lymphoma induced by reovirus type 3: Some general aspects of the lymphoma 2731/L. Proc. Soc. expo Bioi. Med., 1966, 122, 1091. Leading Article. 'The lymphoblastic lymphoma of childhood.' Lancet, 1966, ii, 1225. MILES, J. A. R., AUSTIN, F. J., MacNAMARA, F. N., and MAGUIRE, T. Proc. Univ. Otago Med. School, 1965, 43, 23. PAPADIMITRIOU, J. M. (introduced by N. F. Stanley). 'Electron microscopic findings of a murine lymphoma associated with reovirus type 3 infection.' Proc. Soc. expo Bioi. Med., 199, 121, 93. PARKER, L., BAKER, E., and STANLEY, N. F. 'The isolation of reovirus type 3 from mosquitoes and a sentinel infant mouse.' Aust. I. expo Bioi. med. Sci., 1965,43, 167. SHIKATA, E., and MARAMOROSCH, K. Virology, 1965, 27, 461. SHIKATA, E., and MARAMOROSCH, K. I. nat. Cancer [nst., 1966, 36,97. STANLEY, N. F. 'The aetiology and pathogenesis of Burkitt's African lymphoma.' Lancet, 1966, i, 961. STANLEY, N. F. 'Reoviruses. Recent research on Burkitt'S tumour: Conference at Kampala, Uganda.' Brit. Med. I., 1966, 1, 1043. STANLEY, N. F. 'Virus induction of autoimmune disease and neoplasia.' Lancet, 1966, ii, 589. STANLEY, N. F., and KEAST, D. 'Murine infection with reovirus 3 as a model for the virus induction of autoimmune disease and neoplasia.' Perspectives in Virology V., 1966. (In ~a) ~
STANLEY, N. F., PAPADIMITRIOU, J. M., and EPSTEIN, M. A. 'Burkitt's lymphoma.' Brit. Med. I., 1966, ii, 767. STANLEY, N. F., WALTERS, M. N. I., LEAK, P. J., and KEAST, D. 'The association of murine lymphoma with reovirus type 3 infection. Proc. Soc. expo Bioi. Med., 1966, 121, 90. STANLEY, N. F., and WALTERS, M. N. I. 'Virus induction of autoimmune disease and neoplasia.' Lancet, 1966, i, 962.
DEPARTMENT OF PATHOLOGY Dr 1. M. Papadimitriou, M.B., B.S., Seuior Research Officer.
Project Transport of reovirus to target organs. Report This project is concerned with reovirus type 3 which produces in neonatal mice a syndrome characterised by hepatitis, encephalitis and pancreatitis. In a previous report it has been indicated that virus is transported within polymorphonuclear leucocytes, monocytes and even lymphocytes. Many of these cells degenerate and eventually are destroyed, liberating virus which can then enter various target organs. The aim of the following experiments was to elucidate the means by which virus eventually reaches the host cell and the processes surrounding virus invasion, mUltiplication and cellular degeneration.
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During pathogenesis of reovirus encephalitis in neonatal mice, it has been observed that following release from destroyed carrier cells, virus enters and actively replicates in the cytoplasm of capillary endothelial within four days of inoculation. In the twenty-four hours following this phenomenon reovirus is seen within perivascular astrocytes and the presumption is that virus passes from infected endothelium into the astrocytic cytoplasm. However, the virions although present in astrocytes are found within lysosomal dense bodies and never in the para-crystalline form, suggesting that reovirus multiplication does not occur in astrocytes. By the sixth day of infection virus replicates actively within neurones. Again the process of neuronal invasion by virus is not clear. Either the virus passes from perivascular infected astrocytes into neurones or enters directly from infected endothelium in vessels where the astrocytic perivascular barrier is incomplete. An incomplete astrocytic barrier has been demonstrated in some 30 per cent of blood vessels from foetal and neonatal brains. Neuronal degeneration and destruction becomes evident by the seventh day after inoculation. In comparing the cell type in which reovirus was actively replicating with cells in which virus multiplication did not occur, it was noticed that one striking difference was the relative larger content of dense bodies or lysosomes in the cytoplasm of cells not showing virus replication. On re-examining electron micrographs of the acute murine reovirus type 3 hepatitis it was noted that reovirus did not replicate in KupfIer cells which are rich in lysosomes but crystals of progeny virus were present in hepatocytes in which the dense bodies were few or absent. To verify this observation in some other organs the pancreas which shows signs of active disease but which is rich in dense granules was investigated during the first few days of the acute phase of infection. These dense granules are known to contain zymogen but probably contain other proteolytic enzymes, some of which may be related to the lysosomal group. Surprisingly enough despite the evidence of cellular damage in pancreatic acini, no evidence of replicating virus could be found. To exclude any peculiarity of zymogen granules which may interfere with reovirus replication, the kidney during the phase of high virus titres was examined. Again, virus multiplication as judged by the appearance of para-crystalline arrays, occurred only in the distal and collecting tubules of the kidney but not in the proximal tubules which are rich in lysosomal dense bodies. From these observations it would thus appear that cells rich in dense bodies (or lysosomes) do not support reovirus replication. In a particular cell type it is those cells with a relatively small content of dense bodies which display the presence of active virus replication. Thus a quantitative relationship is involved the nature of which is not at present clear. It has been established that reovirus is fatal only to newborn mice whilst animals three or more days old show little tendency to develop the classical murine syndrome induced by reoviruses. To try and evaluate the importance of lysosomal enzymes with respect to viral susceptibility during the first three days of life, a series of histochemical studies on the livers of foetal and neonatal mice were performed. Acid phosphatase was chosen as a lysosomal marker since this enzyme has consistently been found in biochemical studies on Iysosomes. In foetal livers there is little or no acid phosphatase activity in hepatocytes and the activity is confine~ to some but not all KupfIer cells. In the first day of life phosphatase activity markedly mcreases in KupfIer cells but remains minimal in hepatocytes. During the second and third day of life acid phosphatase increases and by the first week of life there is a moderate degree of activity in all hepatocytes. Thus in the liver at least, the results seem to indicate that many hepatocytes in the first d~y ?r t~o of li.fe have not synthesised their full complement of lysosomal enzymes. During thIS mterun penod when lysosomal enzymes are at a low concentration, virus can enter the cell not be destroyed and initiate the process of replication. ' ~is, however, fails to explain the cause of injury to the pancreatic acinar cells. It is pOSSIble that virus invasion interfers with zymogen production in the exocrine pancreatic cells
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resulting in abortive or deformed forms which may in turn prove adverse to cell viabili~y. However, the dilatation frequently observed in pancreatic acini suggested an obstructtve element in the production of the pancreatitis. As a result of this obs~rvation the common bile duct and its ampullary region in the duodenum were closely examined in reovirus infected neonatal mice for any evidence of obstruction. It was found that macroscopically the lower end of the common bile duct and also its ampullary region were oedematous and increased in size when compared with those of normal controls. Under the electron microscope, virus was seen to have invaded both the lining mucosal cells and also cells composing the wall of the common bile duct. Thus virus invasion proved to be the cause of the obstruction which by interfering with the flow of bile and pancreatic fluids has induced some degree of pancreatic damage. In a few cases the early oedematous obstruction progresses to organisation and fibrosis. This fibrosis and resultant obstruction initially triggered by reovirus infection eventually produces obstruction and subsequent dilation of the biliary system above with evidence of hepatic and pancreatic damage. In the future it is intended to extend and enlarge on the present observations and to study in detail the histochemical changes which occu r during early neonatal life as well as the deviations produced by reovirus infection. It is intended that not only the liver, but other organs should be investigated. Secondly, the production of albuminuria during the viraemic phase of reovirus infection needs to be further investigated. Some early observations indicate glomerular changes in affected kidneys. This may be a useful experimental model for virus induced nephrotic syndrome. So far the results are only preliminary. The detailed examination of the pattern of involvement in the ampullary region of the duodenum in the production of pancreatitis and obstructive jaundice needs to be further studied. Again such an experimental model may explain some of the aetiological factors and pathogenetic mechanisms in human disease. It is interesting in this context that reovirus has been isolated from some patients with steatorrhoea. Lastly, the investigation of the lymphomata produced in mice which are somehow associated with reovirus infection. These may be primarily reovirus induced or possibly result by activation of the inherent leukaemic virus present in all mise. Apart from elucidating pathogenic mechanisms in neoplasia a direct application to the Burkitt lymphoma from which reovirus has been isolated is possible. Publications KEAST, D., and PAPADIMITRIOU, J. M. 'Virus induction of autoimmune diseases and neoplasia.' Lancet, 1966,2,589. PAPADIMITRIOU, J. M. 'Ultrastructural features of chronic murine hepatitis after reovirus type 3 infection.' Brit. J. Exp. Path. (In press.) PAPADIMITRIOU, J. M. 'Reovirus encephalitis.' Amer. J. Path. (In press.) PAPADIMITRIOU, J. M. 'An electron microscopic study of reovirus haemagglutination.' Aust. J. Exp. Bioi. Med. Sci. (In press.) PAPADIMITRIOU, J. M. 'Cell membrane changes during contact with some microorganisms.' Nature, 1966, 212. PAPADIMITRIOU, J. M., KAKULAS, B. A., and MERCY SADKA. 'Virus-like particles in proximity to myelin in progressive multifocal leukoencephalopathy.' Awt. J. Science. (In press.)
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PAPADIMITRIOU, J. M., KAKULAS, B. A., and MERCY SADKA. 'The presence of virus-like particles in proximity to myelin in a case of progressive multifocalleukoencephalopathy.' Proceedings of the Australian Association of Neurologists, 1966. (In press.) PAPADlMITRIOU, J. M., SHILKIN, K. B., ARCHER, J. M., and WALTERS, M. N-1. 'Inflammation induced by dimethylsulfoxide II.' Exp. and Molec. Path. (In press.) SHILKIN, K. B., PAPADlMITRIOU, J. M., WALTERS, M. N. I. 'The effect of dimethyl sulphoxide on hepatic cells of rats.' Aust. I. Exp. Bioi. Med. Sci., 1966, 44, 581. STANLEY, N. F., PAPADlMITRIOU, J. M., and EPSTEIN, M. A. 'Burkitt's lymphoma and reovirus.' Brit. Med. J., 1966, 2, 767.
DEPARTMENT OF PHARMACOLOGY Professor M. F. Lockett, M.D., M.R.C.P., Ph.D. Dr H. H. Siddiqui, B.Sc., B.Sc. Tech. (Pharm.), Ph.D. Mr B. Nail, B.Sc., Research Assistant. Project Sodium retaining protein hormones of blood. Report The object of the research has been to develop a method for the biological assay of the protein hormones of blood which can be used in parallel with immunoassays for the study of the genesis and treatment of oedema in patients. Therefore, a method has been found by which the sodium retaining hormones of human plasma can be precipitated in one fraction for assay purposes and for identification. Since the maximum quantity of blood on which hormone balance is to be determined should not exceed 20 ml, it has been necessary to develop a series of new assays of the requisite high sensitivity and of good specificity. Two assays have been developed. The growth and lactogenic hormones can be treated with a-chymotrypsin at controlled pH and yield large stable peptides with oxytocic activity. These active peptides can be separated from other products of the reaction for assay by dialysis. Hence a first method for the quantitative biological assay of growth and lactogenic hormones in plasma has been prepared. The superfused rat's uterus is the assay organ. A second method of assay suitable for the quantitation of total sodium retaining power of a plasma before and after sub-fractionation of the first plasma precipitate has also been developed. Rats are prepared aseptically and are then used during controlled saline diuresis in assays statistically designed to quantitate the sodium retaining power of hormones or plasma fractions over a period of forty-eight hours. The method has good sensitivity and reproducibility. Finally, a method has been developed which enables proteins precipitated at pH 3.4 to be separted into three main fractions, Bh B2, and Bg • Bl is inert in all tests. The B2 fraction binds oxytocin and vasopressin, probably non-~pecifically but has no sodium retaining activity. The Ba fraction which is sodium retaining, growth promoting (tibial growth test) and oxytocic after treatment with a-chymotrypsin has been separated into two fractions by ion exchange. These fractions are under study. It is proposed to make use of these methods of biological assay, clinically, in 1967.
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Publications LOCKETI', M. F. 'The formation of peptides with uterine activity from human, ovine and bovine growth hormone and from bovine and ovine lactogenic hormones.' I. Physiol., 1966, 183, 167. OGLE, C. W., and LOCKETT, M. F. 'The release of neurohypophyseal hormone by sound.' I. Endocrin., 1966,36,281.
DEPARTMENT OF PHYSIOLOGY Professor W. J. Simmonds, B.Sc., M.B., B.S., D.Phil. (Oxon.). Dr B. M. Johnstone, B.Sc., Ph.D., Senior Lecturer. Mr J. R. Johnstone, B.Sc. Hans., Graduate Assistant. Miss S. M. Jordan, B.Sc., Graduate Assistant. Dr I. Kaldor, M.D., Senior Lecturer. Mrs J. Laszlo, B.Sc. Hans, Temporary Lecturer in Psychology. Mr A. Leslie, B.Sc., Graduate Assistant. Dr J. Masarei, M.B., B.S., Senior Research Officer, N.H. & M.R.C. Dr E. H. Morgan, M.B., B.S., Ph.D., Senior Lecturer. Dr T. Morizono, M.D., D. Med. Sci., Postdoctoral Fellow. Mr L. Muller, B.Sc., Research Assistant. Dr T. G. Redgrave, M.B., B.S., Research Fellow. Dr B. K. Shrivastava, B.S., M.D., Ph.D., Research Fellow. Mr Lob, Tart Tuck, B.Sc., Research Assistant. Projects Gastrointestinal physiology. Iron and protein metabolism. Biophysics of the cochlea. Report Role of pancreatic juice in fat absorption (I. Masarei) Work done during early 1966 showed that in the absence of both bile and pancreatic juice, rats absorbed no triglyceride even if it is finely emulsified. If bile is returned, some triglyceride is absorbed following lipolysis by a non-pancreatic lipase. Further, there is no impairment in capacity to absorb long chain unsaturated fatty acids and to convert them into chylomicron triglyceride, provided that the fatty acid is finely emulsified and that the animal is in good clinical condition. The short term aim of the project was achieved since it seems clear that pancreatic juice in the rat plays no significant part in fat absorption other than splitting triglyceride to monoglyceride and fatty acids, which can then be solubilised by bile salts for absorption by the epithelium. Points which will be taken up in future work are, the physical state in which fatty acid is absorbed in the absence of the natural detergents of bile, and the source of lipolytic activity in children who have severe fibrocystic disease and who can absorb a large proportion of ingested fat.
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The origin oj lipid in fasting lymph (B. K. Shrivastava and W. I. Simmonds) In fasting animals there is still an appreciable amount of triglyceride in the thoracic duct lymph, equivalent in rats to 10-20 per cent of the fat ingested in the animal diet. The possible sources of this lipid are-lipid content in digestive secretions, particularly bile, which has been reabsorbed; lipid synthesised in intestinal epithe lium from the metabolic pool of fatty acids; and lipoproteins which have escaped from blood capillaries into the tissue fluids especially in the liver and have been reabsorbed into the lymph. The short term aim of this project was to evaluate the contribution by lipids reabsorbed from bile. It has been shown in 1966 that absorption of fatty acids from the phospholipids in bile could account for a major proportion, perhaps 80 per cent, of the glycerides in fasting thoracic duct lymph. Using a re-entrant biliary cannula, operation and interruption of the enterohepatic re-circulation of bile sal Is were both shown to depress the output of hiliary lipid. These factors would lead to an underestimate of lipid entering the intestine in bile if only bile from a chronic external fistula were analysed. Work is now being done to show that biliary fistula causes a decrease in fasting lymph of those fatty acids in which biliary phospholipid is known to be rich. A long term problem opened up by the work is the mechanism of the rapid decrease in biliary lipid when bile is lost from the intestine. Mitotic inhibitors and fat absorption (T. G. Redgrave) The aim of this project is to determine the relation between the maturity of the epithelial cells of the intestine and their ability to absorb fat. Mitosis in the crypts is inhibited by a dose of aminopterin and lymphatic absorption is measured at intervals thereafter when the villi are covered with cells at varying stages of maturation. Further work on fat absorption following mitotic inhibition in rats has supported the idea that epithelial cells either do not take up fat digestion products or do not incorporate them into chylomicron triglyceride until they have moved a considerable way up the villus. To distinguish between these two alternative, cells in the crypts are being labelled with thymidineH3 when mitosis recommences after previous inhibition with aminopterin has left the villi covered with old cells which are virtually unable to absorb fat. At various times thereafter, C14 oleic acid is given intraduodenalIy, the mucosa is sectioned serially working down from tips of villi to depths of crypts and isotopes measured at the various levels. The results suggest that uptake of fatty acid occurs in both young and mature cells but that only mature cells can form and extrude chylomicrons. An attempt will be made to define the stages in chylomicron formation which are critical in the maturation process. Preliminary results suggest that fatty acid which is taken up is resynthetised to triglyceride in both young and mature cells. It may be that the nature of the surface coating of the chylomicrons determines their extrusion from the cell and that the coating process is the last to mature. Absorption from micellar solutions (W. I. SImmonds and T. G. Redgrave) There is fairly strong evidence that lipid is absorbed mainly in chemical forms such 'is fatty acid and monoglyceride, which can loosely combine into soluble molecular aggregates (micelles) with conjugated bile salts. It has been shown in this laboratory in vivo and by others in vitro that histological appearances which are often regarded as evidence for particulate absorption of fat can be demonstrated equally well when only micellar solution is being absorbed. It was found, in association with a group at the Rockefeller Institute that the restricted micellar solubility of cholesterol might be an important limiting factor in its absorption in man. Experiments are now in progress to test in rats whether difference in absorption rate of saturated and unsaturated long chain fatty acids are related to differences in micellar solubilisation or in partition and exchange between oily and micellar phases of the intestinal contents.
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Iron storage in suckling rats (A. Leslie and I. Kaldor) It was reported previously that in the suckling rat the iron-haem iron and water soluble non-haem iron content of the liver, representing total storage iron and ferritin iron respectively, are both high immediately post partum but become drastically reduced after the first week of life. These changes, particularly in respect of ferritin, the chief reserve iron compound of the body, were further investigated using an immunochemical method developed during the past year. Ferritin from rat livers was isolated and crystallised and anti-ferritin immune serum was produced in rabbits. The use of (he immune serum in a quantitative precipitation reaction provides a sensitive and specific technique for measuring the ferritin protein as well as the ferritin iron content of tissues. It was found that ferritin protein was reduced much less severely than was ferritin iron after the first week of life. During this phase the apparent iron content of the ferritin molecule was diminished from its normal (immediate post partum and/or adult) values, 20 to 25 per cent, to less than 5 per cent. This finding is at variance with current concepts developed from experiments on adult animal tissues on the formation and breakdown of ferritin. Towards the end of the suckling period hepatic iron stores become gradually replenished. This phase was characterised by a preponderance of non-ferritin over ferritin iron. This represents yet another metaoolic pattern unlike that found in adult animals, where at physiological storage iron concentrations the bulk of the iron is in the form of ferritin. Distribution and chemical form of iron in iron-rich milk (Loh, T. T. and I. KaZdor) This project was commenced in 1966 and represents resumption of a line of investigation pursued earlier under a grant with Dr Ezekiel. The marsupial quokka and the rat both produce milk rich in iron. In both species the whey fraction of milk has a relatively constant iron content but the iron content of whole milk is high only during the earlier stages of lactation. The immediate aim of this project is to identify the constituents of milk which carry iron during this stage. A micro-modification of the standard method used in this laboratory was developed and this now enables measurements to be made on replicate aliquots from a single milking and treated in different ways. A combination of centrifugal and isotopic techniques has shown that a large fraction of iron is associated with the easily sedimenting portion of milk, probably representing casein. This contrasts with the earlier assumption, based on indirect evidence, that the fat globule membrane protein carries a significant portion of the iron in iron-rich milk. Secretion of iron into milk (I. KaZdor) It was reported last year that suppression of erythropoiesis by hypertransfusion of lactating rats with donor red cells leads to a significant rise in milk iron concentration. This finding contrasts with other results which indicate that erythropoiesis is considerably accelerated during the early phase of normal lactation coinciding with high milk iron concentrations. Experiments are now in progress on the direct effects of exogenous erythropoietin on milk iron concentration. Plasma protein metabolism in pregnancy and lactation (S. Jordan and E. H. Morgan) During pregnancy and lactation marked changes occur in the concentrations of the proteiolS of the blood plasma in the maternal animal and in the foetus and suckling young. These changes depend largely on the hormonal alterations which occur in the mother, on the passage of proteins from mother to young by the placenta or milk and on the development of the mechanisms of protein synthesis in the developing organs of the young animal. There are large gaps in knowledge in all of these three processes. For instance, although it is known that antibodies can be transferred from mother ~o young in many animals, and other proteins cannot pass, the mechanism whereby antibody proteins are selected for this transfer is not known, and in many animals the actual pathway of transfer is also uncertain.
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The aim of the present work is to investigate the above aspects of protein metabolism in pregnancy and lactation. Initially the project will consist of a comparative study in the rat, rabbit and a marsupial, the Rottnest Island quokka, but later it is hoped to extend pertinent aspects where possible to humans. The three animals were chosen because of differences in the relative duration of pregnancy and lactation, in the structure of the placenta and mammary gland, and in the degree of maturity of the young at birth. First the changes in plasma proteins in mother and young which occur in pregnancy and lactation will be established. Then the rates of synthesis and destruction of the proteins in the maternal animals, and the rate of transfer from mother to the young will be measured, followed by investigations into the pathways of transfer and mechanism of selection of certain proteins for transfer. Finally the effects of maternal hormones on the plasma proteins of mother and young, and other factors affecting the development of plasma protein synthesis in the young will be studied. During the past year work has been mainly concerned with lactation. The concentrations of the proteins in the blood serum of the mother and young and in the milk whey have been measured at various stages of lactation in the rabbit, rat and quokka. It was found that about 50 per cent of the milk whey proteins in the rabbit and quokka and 30 per cent in the rat were of types very similar to the proteins present in the blood serum, while the other SO or 70 per cent were quite different and were therefore formed in the mammary glands themselves. Of the blood serum-type proteins almost alI'lppeared to be derived directly from the blood in the quokka and rat, while most were sythesised in the mammary gland in the rabbit where only small amounts of two proteins, albumin and gamma globulin passed from blood to milk. The other major blood-type protein in rabbit milk was an iron-binding protein very similar to the transferrin of blood plasma which was present in the milk in very much higher concentrations than ever described for other animals, and which was synthesised in the mammary gland. The concentrations of the serum proteins of the rat and rabbit young changed only a little during the suckling period. In the quokka, however, in which the young is very mature at birth, the serum proteins changed progressively during suckling in a manner similar to th:lt described for the foetus of higher mammals during development within the uterus. In the case of the rabbit and quokka the suckling young were found to be unable to absorb intact significant amounts of the proteins of milk. In the rat however proteins were absorbed intact from the intestine into the blood plasma. In the first few days after birth all serum and milk whey proteins were absorbed, then there was a progressive loss of absorption first of proteins with the greatest electric charge and then of proteins with less and less electric charge until by the 21 st day after birth no proteins were absorbed. Work is now in progress on the measurement of the rates of formation and destruction of proteins of the blood plasma during lactation and the rate of their transfer to the milk. Then it is proposed to study the mechanism of the selection of certain proteins for transfer across the placenta to the foetus, and across the mammary gland to the milk, and to investigate the exact pathway that this transfer takes.
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Cochlear blood flow (T. Morizono and B. M. lohnstone) A system for perfusing the guinea pig cochlea from an external source of oxygenated resuspended red blood cells has been developed. The cochlea remains responsive for up to 2 hours and the dependence of the cochlea microphonics on haematocrit (responses start to fall at 12% Hbt) and blood flow rate has oeen measured. The interaction of these two parameters is being studied. The variations of blood flow through the cochlea are being measured by a special impedance plethysmograph, originally developed in Japan for the study of cerebral blood flow, and adapted to the cochlea by Dr Morizono.
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Peripheral inhibition (L. Muller and B. M. lohnstone) Peripheral inhibition has been investigated using two closely spaced tone pips. The~_ response of the auditory nerve to the 2nd tone pip is a function of the lst tone pip's intensity and frequency. It is thus possible to construct a frequency curve of peripheral inhibition. This curve is very similar to the Bekesy travelling wave envelope thus showing that the inhibition has very small spread and is confined to closely adjacent nerve fibres. The dependence of this phenomenon on intensity and duration and its recovery time have been elucidated. Psychoacoustic experiments using essentially the same experimental form were planned in an endeavour to find the psychological correlate. Electrical properties of the cochlea (1. D. Pugsley and B. M.lohnstone) Measurements of the voltage response to square pulses of current passed into the scala media of the cochlea of guinea pigs show a series of time constants. There is a fast time constant of 20 MS associated with the passive capacities of the membraneous labryinth, in addition there is a long time constant of at least several minutes duration which appears to have some relationship to the ionic pumps present in the stria vascularis. One of the responses to sound, the summating potential, follows this long time constant for several seconds. It is possible that this time constant is an explanation of some aspects of temporary threshold shift (temporary deafness) after loud sounds. Comparative neurophysiology (I. R. lohnstone and B. M.lohnstone) The phenomenon of peripheral inhibition and excitation has been investigated in lizards. The presentation of sound, immediately prior to a test sound, causes an enhancement of the response to the test sound. This is in opposition to the effect in monotremes and mammals where the same regime cause the response to the test tone to be inhibited (see Muller and Johnstone). Intensity functions of these enhancements have been obtained and the effect is shown to be frequency independent, again in contrast to the mammalian ear. A study of the interaction of intensity functions at various tempeI atures has established that the effect is some active process and not a change in the mechanical properties of the lizard ear. The problem is being studied further by recording from primary and auditory nerve fibres. Human peripheral auditory responses (I. Laszlo and B. M.lohnstone) The response of the auditory pathway to click stimuli is being recorded in humans, using external surface electrodes and an average response computer. One of the purposes is to see if central activity can modify peripheral responses via the efferent pathway. Responses recorded while the subject counts the clicks are compared with those recorded when the subject is asleep or performing a distracting task. Peripheral responses have been recorded from some subjects but not in others, probably due to anatomical difference of the temporal bone. A response, possibly from the medial geniculate, with a latency of 6 ms is markedly effected by central activity such as counting clicks but the peripheral response is modified only slightly. Normal cortical responses are also being recorded for later comparison with responses in people with disorders of hearing.
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Publications BAKER, E., and SIMMONDS, W. J. 'Membrane ATPase and electrolyte levels in marsupial erythrocytes.' Biochim. Biophys. Acta. (In press.)
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JOHNSTONE, B. M., JOHNSTONE, J. R., and PUGSLEY, I. D. 'Membrane resistance in endolymphatic walls of the first tum of the guinea-pig cochlea.' I. Acoustical Soc. America. (In press.) JOHNSTONE, J. R., and JOHNSTONE, B. M. ' On the origin of summating potential.' I. Acoustical Soc. America. (In press.) MIGNON, M., RUSSELL, M. C., SEMB, L. S., MORGAN, E. H., FINCH, C. A., and NYHUS, L. M. 'Effect of gastric juice on the absorption of iron.' Surgical Forum, 1965, 14, 319. MORGAN, E. H., HUEHNS, E. R., and FINCH, C. A. 'Iron reflux from reticulocytes and bone marrow cells in vitro.' Amer. I. Physiol., 1966, 210, 579. MORGAN, E. H., and FINCH, C. A. 'Iron and transferrin distribution and turnover in iron overloaded rabbits.' Proc. Soc. Exp. Bioi. Sci., 1966, 122, 92. MORGAN, E. H. Transferrin and albumin distribution and turnover in rats with altered iron stores, erythropoiesis and reticulo-endothelial function.' Amer. I. Physiol. (In press.) REDGRAVE, T. G., and SIMMONDS, W. J. 'The effect of aminopterin on the absorption of fat into the lymph of unanaesthetised rats.' Gastroenterology. (In press.)
NEW SOUTII WALES INSTITUTES AND HOSPITALS INSTITUTE OF DENTAL RESEARCH. SYDNEY Dr K. W. Knox, M.Sc., Ph.D., Assistant Director Miss KIara Bogsanyi, B.Sc., Research Assistant, N.H. & M.R.C. Project Studies on the structure of the cell wall of L. Casei and other Gram-positive bacteria. Report Previous work has provided evidence that the polysaccharide and mucopeptide components of the cell wall of Lactobacillus casei are joined through a phosphate grouping. Evidence is being sought that this linkage also occurs in organisms. L. ferment; has been chosen because of its incidence in the mouth and because it is a heterofennenter, whereas L. case; is a homofermenter. Cell wall preparations have beef! obtained from several strains of L. ferment;, including NCTC6991 and two strains isolated at the Institute. In addition to the expected components of the mucopeptide the wall contained glucose and galactose in approximately equimolar amounts. Heating cell wall under the same conditions as those previously employed for L. casei, viz. 60° in O.IN H 2S04 , has shown that an indiffusible polysaccharide component is readily released from the insoluble mucopeptide, 50 per cent release being obtained in one hour. These results are consistent with the presence of a phosphate linkage between the polysaccharide and mucopeptide and supporting evidence has been sought. Soluble products have been obtained from cell wall by the action of both lysozyme and a Streptomyces enzyme preparation. The soluble products were fractionated with (NH.)2S0. and further purified by column chromatography on DEAE Sephadex or Sephadex G75. The final preparation contained 0.2 per cent phosphorus and was free from contaminating nucleic acid or teichoic acid (both of which contain phosphorus). Complete analyses showed that the preparations contained a polysaccharide made up of glucose and galactose, and a mucopeptide; that obtained with the Streptomyces enzyme had less mucopeptide and a correspondingly lower molecular weight as determined by chromatography on Sephadex G75. Samples of both preparations were heated at 60° in O.IN H 2 S0 4 for two hours and the action of phosphatase on the products examined. The enzyme released 80 per cent of the phosphorus from the product obtained by Streptomyces action but none from that obtained with lysozyme. The preparation obtained with lysozyme contained a greater amount of mucopeptide and the lack of phosphate action may be related to the difference in molecular weil(hts of the substrates. The results are consistent with the presence of a phosphodiester linkage which is hvdrolysed by acid to a phosphomonoester, the latter then being susceptible to phosphatase. The presence of hexosamine phosphate in the mucopeptide has been indicated from an examination of the products of acid hydrolysis and experiments are now in progress to obtain sufficient of this material for identification. Dr Gwen J. Walker, B.Sc., Ph.D., Senior Biochemist. Miss Janet E. Builder, B.Sc., Research Assistant, N.H. & M.R.e. Project The enzymic mechanisms for the synthesis and degradation of polysaccharides in oral streptococci. Report The aims of the study are to determine the nature of all the enzymes of Streptococcus mitis that are concerned in the metabolism of the reserve polysaccharide. Previous work has
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shown a direct correlation between dental caries and the number of streptococci in the mouth ~at are capable of storing iodine-staining polysaccharide. Gibbons has suggested that one dIfference between a cariogenic and a non-cariogenic flora may be a difference in the stability of iodophilic pOlysaccharide production by the collective organisms. Further work with branching enzyme (a-I,4-glucan: a-I,4-glucan 6-glycosyltransferase) has indicated that this enzyme converted amylose into a glycogen that was indistinguishable from the storage polysaccharide of S. mitis. The exterior and interior chain lengths were similar to those of animal glycogens. The branching enzyme could introduce a-l,6-glucosidic branch linkages into substrates having degree of polymerization as low as twenty-four glucose units, but the activity towards natural amylose was greater. Glycogen synthetase activity has been detected in all strains of S. mitis examined, including those that do not store polysaccharide. The enzyme was also present in high concentration in extracts of bacteria that had grown in a medium unsuitable for carbohydrate storage. The glucose donor in the enzymic reaction was adenosine diphosphate glucose, and no evidence was obtained for transfer of glucosyl units from uridine diphosphate glucose. Glycogen was the best primer (acceptor) for the glucosyl units, but maltotriose and maltotetraose were also effective. Glucose, maltose, maltopentaose, maltohexaoseand maltoheptaose did not prime the reaction. Future work will be aimed at the synthesis of glycogen in the presence of glycogen synthetase, branching enzyme and primer. A pullulanase of S. mitis has been investigated in detail. Pullulanase has previously been found only in Aerobacter aerogenes, and since this is a most valuable enzyme for the study of the fine structure of glycogen, it is of interest that the S. mitis enzyme has a different specificity. Whereas the original pullulanase will act rapidly on a a-I,6- bonds only when each of the components joined through the linkage is maltose or a higher maItodextrin, the S. mitis enzyme requires that at least one, and preferably both of the components be maItotriose or higher maltodextrin. The pullulanase has been isolated free from the other carbohydrases of S. mitis. and its mode of action is such that it can hydrolyse most of the branched dextrins previously found to be resistant to the attack of the a-I,6-glucosidase of S. mitis. These two debranching enzymes can account for the hydrolysis of all the a-I,6- branch linkages of glycogen, glvcogen phosphorylase limit dextrin and the dextrins produced during further stages in the breakdown of the glycogen molecule. Further work needs to be directed towards the factors that determine ability of oral streptococci to store glycogen, and also towards knowledge of the causes of variability in glycogen storage. Publicatiou WALKER, G. J. 'Metabolism of the reserve polysaccharide of Streptococcus mitis. Properties of a transglucosylase.' Biochem. I. (In press.)
INSTITUTE OF MEDICAL RESEARCH, THE ROYAL NORTII SHORE HOSPITAL OF SYDNEY Dr D. Frey, D.Sc., Research Fellow, N.H. & M.R.e. Projects Maintenance of type cultures. Antifungal activity of eucalyptus oils against dermatophytes. Superficial mycoses in Sydney. 4275(67-10
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Report The Mycology Reference Laboratory has built up and maintains a collection of fungi. The collection consists of 267 strains (belonging to 51 genera and 115 species of fungi pathogenic to man and animals, keratinophilic fungi and common laboratory contaminants. Since the primary aim of the laboratory is to provide information on cultures of medical interests, a list and a catalogue of these fungi is being prepared. The latter incorporates needs for epidemiological or taxonomic studies and for diagnostic work. Cultures have been supplied (50) on request to various hospitals, research institutes, Departments of Health and Universities in Queensland, South Australia, New South Wales, Western Australia, Italy and the United States of America. Cultures for identification have been received (322) from public hospitals, pathologists, dermatologists, research institutes, Departments of Health, in New South Wales, Western Australia, Queensland, Victoria, Japan, United States of America. Advice and culture identification (46) was given to the Asthma Foundation of South Australia and the University of 'N.S.W. The in vitro antifungal activity of twenty-seven eucalyptus oils was investigated. The oils were tested in 1 per cent, 0.1 per cent, 0.01 per cent, 0.001 per cent and 0.0001 per cent concentrations incorporated into Sabouraud's agar against five pathogenic fungi (Microsporum canis, Microsporum gypseum, Epidermophyton floccosum, Trichophyton mentagrophytes and Candida albicans) isolated from lesions of skin and nails. It was found that these oils possess antigungal activity against the dermatophytes tested. The surveys of superficial mycoses in Sydney is based on the mycological investigation of 6,045 specimens during the years 1954-1966. It has been done to provide information about the incidence of mycotic infections and offend ing pathogens. 755 dermatophytes were isolated from 2,047 skin specimens. It was found that M. canis, T. mentagrophytes and T. tonsurans were the most frequent pathogens.
Dr I. B. Hales, M.B., B.S., M.R.C.P., M.R.C.P.E., Physician and Officer in Charge, Thyroid Investigation Clinic. Project Study of endemic goitre in New South Wales. Report The presence of goitre had been known to exist in various areas of the world, and associated with areas of high goitre incidence there have been reported increased incidence of deaf mutism, cretinism, hyperthyroidism and thyroid cancer. Earlier work in the Thyroid Investigation Clinic has illustrated a definite relationship of goitre to various general symptoms. For these reasons any region with high goitre incidence is one with a public health problem. The cause of goitre has been investigated in many areas and although iodine deficiency appears to be a major cause it is obviously not the only cause and assessment of causes of goitres is very important particularly if preventive treatment is to be undertaken. Various areas in New South Wales are known to have high incidence of goitre as shown by a School survey in 1957. This survey however, is far from complete but it did show some of the major endemic areas. It was suggested by Dr Manzie that seasonal variation in goitre occurred in the West Wya!ong area and it was for this reason that this area was selected as the centre for investigation. The presence of seasonal fluctuations in goitre incidence was highlighted in Tasmania by Clements and others who concluded on an apparently logical reasoning that milk carried a goitrogen. Later investigations have failed to demonstrate more than mild
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goitrogen activity in milk and this would be readily overcome by the amount of iodide being ingested by the children reported. The cause of seasonal changes may therefore need reassessing and the following possibilities can be considered: goitrogens, infective processes, changes in amount of iodine available (in Italy Corta has shown that iodide content of milk falls at the peak of goitre incidence), specific physiological response to temperature and climatic conditions. Preliminary studies were undertaken to confirm that the West Wyalong area was in fact an endemic goitre area. In high school children there was an incidence of goitre of SS per cent compared with 17 per cent in Sydney in the same age group. Iodide excretion levels in a pilot group was undertaken and this showed about 100 micrograms per day compared with 120 micrograms for a Sydney group. Studies were undertaken to assess the overall incidence in goitre in children at school and fluctuation in goitre incidence at various times over a two-year period. From the age of 5 (6.7% incidence) up to 16 (66.7 %) significant incidence of goitre was present in February. The relative incidence with sex was higher for girls than boys, approximately 2 to 1, while in Sydney this figure is approximately 4 to 1. The incidence in goitre fell to a minimum in June and rose again to a maximum in February to fall again in June. These variations were approximately at the same rate irrespective of age or sex. To study the relationship of temperature changes alone on goitre incidence the seasonal incidence was investigated in a Sydney High School group as control and a high goitre incidence group on the Coast (Wyong with 34% incidence). In both these groups there was no fluctuation in goitre incidence. The possibility of changes in iodide intake were investigated using estimates of random iodide excre-tion per gram of creatinine. At the goitre peak in West Wyalong the level was S2p.g and this rose to 80 at the time of the lowest incidence (P<.OOOl). In Sydney a level 13Sp.g was maintained while in Wyong a rise from 95 to 120 occurred. It was not possible to confirm any change in iodide levels in milk. In West Wyalong further details relating to infection was undertaken particularly those which might be associated with iodide mixtures. Although as expected there was an increased incidence of colds and 'flu' in winter the incidence of this was the same for those who had a change in goitre size as for those in whom there was no goitre change. The alternative of the maximal incidence being the result of viral infection was not confirmed as there was no evidence of an increased incidence of upper respiratory or other viral infections at the time of maximal incidence. The use of iodized salt was investigated in the community and the results analyzed in those, adults and children, who had been examined and in whom there had been answers to questionnaire. No significant difference in goitre incidence occurred between those taking iodized salt and those not using it. The source of water supply was also investigated; two sources are available, one from Burrenjuck dam and the other individual tank water. If anything the incidence was slightly higher in those using the Burrenjuck water supply but statistically this as not quite significant. In assessing the symptoms resulting from the goitre previous data obtained in the clinic was used as a guide. In the clinic symptoms for patients with diffuse goitre varied from those with multinodular goitre, the occurrence was 7 diffuse for each 2 multinodular. In the adult population studied in West Wyalong only 2 multinodular goitres were found among 35 subjects over 40 years of age. So no comparison could be made. Of those with diffuse goitre, weight change, heat intolerance, perspiration and nervousness were twice as common as in those with no goitre and this is consistent with the data from these two groups attending the thyroid clinic. A true seasonal fluctuation of goitre incidence has been demonstrated in the West Wyalong area-this change is related to a fluctuation in the urinary iodide excretion; probablv due to environmental factors, as the change is not sufficient to be accounted for by injection of
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therapeutic doses of iodiae and also the change doesn't occur differentially between those who have and who have not had conditions for which iodide may have been given. Further proof of the environmental factor in aetiology is the fact that similar temperature fluctuations in Wyong and Sydney have not been associated with goitre incidence changes. The role of iodide in causing the change has to be further considered, it may be that a certain number of subjects are at a critical level of iodide repletion for their thyroid and a small rise in iodide removes them from this critical range and reduces goitre incidencehowever, it could equally be explained that some other factor is no longer reducing thyroid activity and consequently its avidity for iodide reduces and more is thus excreted. This latter is the parameter measured. Further considering the use of iodide in goitre prophylaxis it is clearly shown that in this area the use of iodized salt is of no value in protecting people against the development of goitre. Analysis of the effect of goitre on the subject confirms previous work in which it was shown that diffuse goitres tend to be associated with symptoms suggestive of thyrotoxicosis. At least 3 cretins reside in the area. Family history effect is difficult to assess but to date no definite hereditary features have been described. Further work required in West Wyalong includes more detailed studies to assess environmental seasonal factors, analysis of food stuffs, water supplies including impurities, correlation between sewered and unsewered areas for incidence, biochemical studies on groups of individuals to assess possible hereditary defects. Also the extent of the areas of seasonal goitre changes should be established so that various common denominators can be studied, and in the whole state a complete survey of goitre incidence together with study to assess the presence of other seasonal areas is required. It should then be possible to assess the different aetiological factors likely to exist and to develop and determine useful preventive methods and their effect on general health.
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Dr M. R. Lemberg, Ph.D., F.A.A., F.RS. Principal Research Fellow, N.H. & M.R.C. Dr D. B. Morell, M.Sc., Ph.D., Senior Research FelIow, N.H. & M.Re. Mr W. H. Lockwood, B.Sc., Research Fellow, N.H. & M.RC. Mr 1. Barrett, M.Sc., Research Fellow, N.H. & M.RC. Miss Y. Chang, B.Sc., Research Assistant, N.H. & M.RC. Miss 1. Davies, M.Sc., Research Assistant, N.H. & M.RC. Mr P. Sinclair, M.Sc., Research Assistant, N.H. & M.Re. Miss 1. Thomson, B.Sc., Research Assistant, N.H. & M.Re.
Project Haemoproteins and tetrapyrolle chemistry. Report Work on cytochrome c oxidase, the principal respiratory enzyme of all aerobic organisms has continued at the Institute of Medical Research, the Royal North Shore Hospital, Sydney until January 31, and from February to August during sabbatical leave at the Johnson Research Foundation, Department of Biophysics and Physical Biochemistry at the School of Medicine, University of Pennsylvania, Philadelphia. In Sydney, the reaction of ferrous cytochrome oxidase with molecular oxygen and hydrogen peroxide was studied in an attempt to elucidate the stoichiometry of the reactions, while preparations of porphyrin a, haem a and its acetylation product continued.
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Work (with Dr Gilmour) at Philadelphia had the main aim of using the unique rapidreaction apparatus available at that institution to gain further insight into the reaction mechanism, in particular the role of the oxygenated compound formed by the autoxidation of the ferrous enzyme, Double-beam spectrophotometers with stop-flow attachment and continuous flow scanning split-beam spectrophotometers were used. The results show that the oxygenated oxidase rather than the ferric is formed in the rapid (half time abt. 30 milliseconds) autoxidation of the ferrous enzyme, that it is formed without preceding formation of hydrogen peroxide and that its reaction with cytochrome c is also rapid enough to make it a suitable intermediate. A study of the kinetics of the reduction of the ferric enzyme by dithionite showed it to be biphasic, the rapid reduction of ferricytocbrome a being followed by a much slower reduction of ferric)'tochrome a3; in contrast, the reduction of the oxygenated compound was fast and monophasic. Another aim was to gain further information on the nature of the oxygenated compound. That it is not a reversible oxygen compound comparable to oxyhaemoglobin, had been previously demonstrated. Meanwhile, other workers (Yamanaki, Wittenberg) have obtained a compound by autoxidation of ferrous horse-radish peroxidase which closely resembles the oxygenated oxidase. Studies of the reaction of the latter with hydrogel! donors able to react with peroxidase-peroxide complexes, have shown that it has a high specificity for reaction with cytochrome c, but that a reasonably fast rate is also found with other hydrogen donors, notably pyrogallol. This strengthens the evidence for a peroxidic nature of the oxidase compound. The absorption band at 830 ml' was studied in order to gain insight in the role of the copper. The band was found equally strong in oxygenated and ferric oxidase. If this band is, in fact, due to ferric copper alone, this raises problems with regard to the stoichiometry of the reaction. The results strongly support the importance of copper in the enzymic reaction mechanism. Low temperature absorption studies failed to show a splitting of bands of the oxygenated oxidase, whereas it could be confirmed by studies with partial reduction that the y-maximum of cytochrome a is double at liquid nitrogen temperature. In another study it was shown that pigeon breast muscle contains the same type a porphyrins as ox heart muscle, in contrast to earlier claims of Negelein. Dr Lemberg has been awarded the 1965 Britannica Australia Award for Science. In the Symposium on Haem and Haemoproteins to which he contributed three lectures, far-reaching agreement on the structure of porphyrin a was reached. In the United States 16 lectures were given, at Philadelphia, Buffalo, Baltimore, Washington, D.C., Lexington (Kentucky), Cincinnati, and at the Gordon Research Conference on Tetrapyrrole Biosynthesis at Crystal Inn (Washington State), at which the Institute was represented by Dr Lemberg, Dr Gilmour, Mr Barrett and Mr Sinclair. At the Atlantic City meeting of the American Society of Experimental Biology, Dr Lemberg received the Honorary Membership of the American Society of Biological Chemists; he was also invited to read a paper at the meeting of the American Philosophical Society. In Israel, he lectured at the Weizman Institute, Rehovot.
Animal peroxidases (D. B. Morell and graduate assistants) Previous work has shown that the porphyrins of sulphhaemoglobin, sulphcatalase, sulphmvoglobin and probably of myelo-neutrophil peroxidase have chlorin-type conjugations. In this respect these haemoproteins form a class in which are also included cytochrome d (a,) of some bacteria and some of the chlorophylls of plants and some micro-organisms. The preparation and chemistry of a number of chlorins and derivatives has therefore been studied as well as the spectroscopic properties of the compounds of their iron complexes with globin.
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In addition to deutero- and meso-chlorins, monoacetyldeuterochlorin has been prepared together 1¥ith a major byproduct which app~ars to be a diacetyldeuterochlorin presumably acetylated at one of the meso-positions. The chemistry and spectroscopic properties of these compounds and some derivatives has been studied. The conversion of chlorins to porphyrins by a zinc- or copper-catalysed oxidation involving an oxidant present in analytical i reagent-grade acetic acid has been investigated. This conversion has been found to be significant when the chlorin has been formed by saturation of a double bond in an 'A' or 'B' ring of the porphyrin. Chlorophylls saturated in the 'D' ring are much more resistant to oxidation probably due to stereochemical hindrance in the region of the j3-pyrrole I position 7. This property of chlorophylls appears to be important in resisting photo-oxidation in the plant cell. Other aspects of chlorin chemistry and properties are being studied in relation to the relevant haemoproteins in animal cells. It is now known from work in this and other laboratories that the same peroxidase is found in active mammary gland, some salivary glands, lachrymal glands and in eosinophils. There is increasing evidence to suggest that one role of the enzyme may be due to its production from thiocyanate and hydrogen peroxide of an anti-bacterial compound. For the above glands this role <!ould constitute a defence against invasion by bacteria and would be exerted by the constant secretion of thiocyanate plus enzyme into ducts where peroxide formed by an aerobic bacteria would cause the production of the anti-bacterial agent. In order to examine this possible role the thiocyanate levels of blood and of various tissues, including eosinophils, are being measured by a sensitive method. The first analyses confirm some existing data which indicate that an adequate amount of thiocyanate exists in blood plasma for secretion by the relevant glands. Studies on salivary glands from guinea pigs show that the enzyme is probably not associated with any particulate subcellular fractions such as lysosomes. This location is consistent with continuous secretion into the gland ducts. The eosinophil enzyme, on the other hand, is know to be located in subcellular or~anelles and its role, if similar, must be exerted under different circumstances. The location of the peroxidase in the cells of the mammary and lachrymal glands is not known.
Porphyrin metabolism (W. H. Lockwood) The porphyrias form a group of diseases which have in common the excretion of increased quantities of porphyrins. The term covers at least three distinct metabolic disorders: erythropoietic porphyria; erythropoietic protoporphyria; hepatic porphyria. The first of these arises from the partial failure of an enzyme 'isomerase' in the erythropoietic centres; porphyrins of the'!' isomeric series instead of those of the 'III' series are formed, accumulate and are excreted; the accumulation in the circulating blood of porphyrin causes the photosensitivity characteristic of this type of porphyria. Erythropoietic protoporphyria appears to be due to an impaired ability of the erythropoietic centres to insert iron into porphyrin; accumulation of protoporphyrin occurs, which is largely confined to the erythrocytes causing the photosensitivity of this type of porphyria; protoporphyrin is excreted via the liver in the faeces on the breakdown of the erythrocytes. In hepatic porphyria there is an increased excretion (mainly or partly from the liver) of the precursors of porphyrin formation; much porphobilinogen and 8-aminolaevulic acid appear in the blood and are excreted in the urine; in experimental hepatic porphyria it has been shown that there is an increase in the amount of 8-aminolaevulic acid synthetase in the liver mitochondria. Subjects suffering from hepatic porphyria accumulate and excrete a range of metabolic products; in some 8-aminolaevulic acid and porphobilinogen duminate in others uroporohyrin, coproporphyrin (and porphyrins intermediate between these) and protoporphyrin. The first show a group of symptoms unrelated to porphyrin accumulation-abdominal pains and colic, paralysis and psychotic svrnptoms; the second group, those accumulating large quantities of porphyrin, often show light-sensitivity.
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The diagnosis and classification of porphyria depends on analysis of porphyrin accumulation in the blood and of porphyrin excretion in the urine and faeces; several satisfactory methods are available for the isolation and analysis of the ether-soluble porphyrins, protoporphyrin and coproporphyrin, but methods of analysis for the ether-insoluble porphyrins found in urine, faeces, blood and other biological material have been very unsatisfactory. These porphyrins include uroporphyrin and three porphyrins arising from decarboxylation of uroporphyrin containing seven, six and five carboxylic groups. To these must be added a further porphyrin recently demonstrated by work with Rimington at London University College Hospital Medical School in two porphyria patients and in many relatives of both 0f these patients, this porphyrin appears to be a dicarboxylic porphyrin conjugated, possibly through a thio-ether bridge, to an amino acid or to a peptide. Not only are methods of isolation and detection of these porphyrins inadequate but the quantitative optical characterIstics of all the above porphyrins except uroporphyrin are unknown. The methods developed in this laboratory for studying these porphyrins depend on esterification and electrophoresis. Special precaUl;ons are necessary in the handling of small quantities of porphyrins particularly to avoid the formation of copper complexes. Using these methods it has been possible to demonstrate the presence of the three derivatives of uroporphyrin and of uroporphyrin in all normal and porphyric faeces. In order to measure the quantitative optical characteristics of the intermediate porphyrins these have been prepared in pure state both from biological material (urine and faeces) and by decarboxylation of uroporphyrin. In collaboration with Mrs Latter of London University College Hospital Medical School a series of copper titrations have been carried out to establish values for the optical absorption of the main extinction peaks both of the free porphyrins and of their copper derivatives. A further su pply of the porphyrins is being prepared to repeat some of the titrations. The porphyrin mentioned above, the dicarooxylic porphyrin, conjugated with a peptide or an amino-acid was detected in a subject in London. It was found in the urine, in the faeces and in the serum. It was subsequenlly shown to occur in considerable quantities in faeces of mony of the relatives of the subject.. As well as the relatives in England other~ have been investigated by colleagues }n America and Israel and relatives in Australia are currently being investigated. This has geneuc interest; it also offers supplies of material for further investigation of the conjugated porphyrin. There are some porphyrins which do not fit into the above classification. A patient under Dr Gunther of Newcastle has been investi/!ated here and shows some puzzling features. She was first referred as a possible erythropoietic porphyria, based on the early age of onset of symptoms. This diagnosis was excluded by the presence of mixed I and III isomers in the urine and faeces and by the absence of uroporphyrin in the erythrocytes. There was, in fact, protopophyrin in large amounts in the erythror:ytes which could not be explained by hepatic porphyria and is characteristic of erythroietic protoporphyria. However, this fails to explain the present of uroporphyrin in the serum and urine. The porphyrin levels in urine, faeces, red cells and serum were all completely normal in both parents. Both erythropoietic protoporphyria and hepatic porphyria are known to be inherited as Mendelian dominants.
Porphyrin synthesis (with Miss I. L. Davies) During the year Miss Davies successfully completed the synthesis of 2,6-diacetyldeuteroporphvrin II with the production of useful amounts of the porphyrin as the crystalline dimethyl ester. She submitted this work in a thesis to the University of Sydney and was granted the degree of M.Sc. This porphyrin promises to be very valuable in the study of the effect of the position of certain substituent groups on the properties of porphyrins and their derivatives,
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particularly the haematin derivatives. The work required the complete synthesis of porphyrin from simple pyrroles in many single steps. Mi>s Davies has since resigned in order to accept a position with Professor J. H. Caughey at Baltimore. United States of America. Structure oj phycochromoproteins (I. Barrett) Studies on the photochemistry of porphyrins and their metal complexes (see earlier reports) led to the formation of the hypothesis that magnesium protoporphyrin was a precursor in the biogenesis of biliviolin, the supposed chromophore of phycocyanin. Some uncertainty has arisen in recent years whether this open chain is actually the native chromophore or is an artifact. This is partly because of the considerable differences in the spectra of of biliviolin and phycocyanin and partly because of other pigments have been obtained under different conditions of hydrolysis. Advantage therefore has been taken of facilities in Professor Calvin's laboratory to explore this problem with a different experimental approach. The chromophore has been studied whilst still attached to the peptide chain with special emphasis on the interaction of the chromophore with its protein environment, using ultraviolet spectroscopy, spectropolarimetry and fluorescence spectroscopy. Optical rotatory dispersion studies show that the chromophore of phycocyanin has marked optical asymmetry and this is considered to be due to a twisting and extension of the chromophore, stabilised by the protein. Iodination studies show that tyrosine plays an important role in the maintenance of the optical configuration of the chromophore. The tyrosyls are buried, since they do not react with acetyl imidazole. An important function of these tyrosines is to maintain the protein conformation though it cannot be excluded that these tyrosines directly interact with the chromophore through the phenolic hydroxyls. Studies on the formation of a zinc complex with the chromophore, in situ, provide additional evidence that the tetrapyrrole has a nonplanar configuration, and that the chromophore is a biliviolin probably having one free vinyl group covalently bound to the peptide chain. By controlled enzymic hydrolysis of the chromophore a series of chromopeptides, of molecular weight of 1,000-10,000 have been obtained and the effect of the chain length and the aromatic-amino acid content of the peptides have on modifying the biliviolin spectra has been studied. As the smaller peptides contain only a few amino acids the way is open to identifying the specific amino acids covalently bound to the chromophore and the nature of the linkage. Knowledge of this structure will permit the preparation of magnesium-protoporphyrin pep tides to investigate the photochemical stage of the formation of phycocyanin and other related chromoproteins. These studies can also be expected to provide insight into the nature of the light-induced transitions in phytochrome-a growth-regulatory pigment, the chromophore which has characteristics of both the biliviolins and the oxophlorins. Cytochrome c, of E. coli (I. Barrett and P. Sinclair) In the absence of Mr Barrett overseas this project, reported previously, was not continued. Mr P. Sinclair submitted a thesis for the degree of M.Sc. on this topic which has been accepted, and is at present investigating electron transport in Haemophilis sp. at the University of Kentucky. Whilst resident at the Laboratory of Chemical Biodynamics, Berkeley, Mr J. Barrett was invited discussant to the Symposium on Haemoproteins at the Johnson Foundation and to the Gordon Conference on Tetrapyrrole Biochemistry. Several laboratories whose interest centred on tetrapyrrole biochemistry or protein chemistry were visited in the United States of America and seminars were given at a number of these. A short visit was made to the United Kingdom at the end of the fellowship year and visits were made to several laboratories there.
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Publications . -->-- DAVIES, J. 'Synthesis of porphyrins with electrophilic substituents.' M.Sc. thesis, Sydney University. LEMBERG, R. 'Chemische Struktur und Reaktionsmechanismus des Atmungs-ferments.' Stizungsber. der Heidelberg Akademie d. Wissenschaften, Mathematisch-naturwiss. Klasse, 1966,2, Abhandlung, 121. LEMBERG, R. 'Haemoproteins.' Proc. American Philosophical Society. (In press.) LEMBERG, R. 'Chemical structure and reaction mechanism of cytochrome c oxidase.' Revs. Pure and Applied Chern., 1966, 15, 125. LEMBERG, R., GILMOUR, M., and STANBURY, J. T. 'Effect of cytochrome c on the compound formed from ferro-cytochrome oxidase by autoxidation or hydrogen peroxide.' Federation Proceedings, 1966,25, 2582. LEMBERG, R., and MANSLEY, G. E. 'Cytochrome oxidase and its derivatives. The reaction of ferrous cytochrome c oxidase with oxygen and hydrogen peroxide in the presence of sodium dithionite.' Biochirn. Biophys. Acta., 1966, 118, 19. MORELL, D. B., CHANG, Y, and CLEZY, P. S. 'The structure of the chromophore of sulphhaemoglobin.' Biochirn. Biophys. Acta. (In press.) P. 'A study of some bacterial oxidase systems.' M.Sc. thesis, Sydney University. . ; SINCLAIR, i.A
KANEMATSU MEMORIAL INSTITUTE, SYDNEY HOSPITAL Dr H. M. Whyte, B.Sc., M.B., B.S., D.Phil., M.R.C.P., F.RA.C.P. Director of Medical Research Department (until August 1966). Dr A. A. Palmer, M.B., B.S., Dip.Path., M.C.P.A., Assistant Director (until August 1966); Acting Director (from August 1966). Dr K. D. G. Edwards, M.D., M.RA.C.P., Associate Director. Dr R. B. Goldrick, M.D., M.RA.C.P., Cardiologist. Dr J. H. Stewart, M.B., Ch.B., M.RC.P., M.R.A.C.P., Physician in Renal Diseases. Dr Nancy W. Alcock, B.Sc., Ph.D., Research Fellow, N.H. & M.RC. Dr J. A. Young, B.Sc., M.B., B.S., M.D., C. J. Martin Fellow, N.H. & M.RC. (until October 1966). Miss Coralie Armstrong, B.Sc. Hons, Research Assistant, N.H. & M.RC. Dr A. Z. Gyory, M.B., B.S., M.RA.C.P., Renal Research Fellow, Postgraduate Medical Foundation. Dr C. S. Grace, B.Sc., M.B., B.S., Fellow in Cardio Renal Diseases. Dr P. F. Sinnett, M.B., B.S., Research Assistant, National Heart Foundation. Miss Margaret lloyd, B.Sc. Hons, Graduate Assistant, National Heart Foundation. Projects Metabolic studies of obesity and coronary heart disease. Cellular transport studies, particularly in the kidney. Studies of the renal acidification mechanism, and the role of citrate in hydrogen ion transport.
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Calcium, magnesium, fluoride and citrate metabolism in bone and cartilage. Studies in drug binding to proteins and resins. Organisation of the tri-ennial Kanematsu Conference on the Kidney and Australasian Society of Nephrology Combined Meeting. Report
Detailed studies have been made on the relationship of obesity to the various factors involved in the blood fibrinolytic mechanism, and the effect of starvation. Fibrinolytic activity was found to be inversely related to the degree of obesity. Other factors (fibrinogen, insulin, glucose and lipid levels) did not account for the depression of fibrinolytic activity in obese individuals. Employing the isolated fat cell preparation, differences between human and rat adipose tissue have been found, both in rates of metabolism of glucose and in the metabolic pathways used. A comprehensive survey of factors which may be related to the low incidence of atherosclerosis and coronary occlusion in Papua and New Guinea has been commenced. Methods for urinary acid-base measurements including pH, bicarbonate, titratable acid, ammonium ion, total acid, and phosphate were developed so that all parameters could be measured titrimetrically with a single instrument (the Radiometer automatic titrator). Further studies were made with a large number of patients found to have a defect in the ability of the kidneys to excrete acid. Family studies clarified one mode of inheritance of the disorder. Abnormalities in citrate metabolism were a ttributed to the general body acidity that develops. It is proposed that an extramitochondrial metabolic glutamate pathway exists in the collecting duct cells and utilises citrate and glutamate to provide ammonia, carbon dioxide and energy for the process of acid excretion. Studies on the assessment of diuretics have continued, and three methods have been devised. A multifactorial design was devised to test the renal tubular effects of four diuretics concurrently, offering information on the effects of individual drugs, and on interactions between combinations of drugs. The mineralisation of rat rib cartilage was i IlVestigated further. Progressive deposition of calcium in cartilage was found to commence in the first two weeks of life and continued until the rat was fully grown. The percentage of ash in adult cartilage was comparable with that of bone. The citrate content of cartilage increased with calcification. Total phosphate content altered in parallel with calcium. Variations in the concentration of magnesium in rat cartilage followed a different pattern from that of calcium, and are being further investigated. Rat rib cartilage was also studied for the influence of fluoride feeding on mineralisation and intermediary metabolism. Incorporation of fluoride in the diet led to deposition of this element with mineral, and caused changes in citrate metabolism during the early stages of growth. Investigations of the binding of drugs to ion exchange resins and charcoal have continued. Forces involved in binding appear to include electrostatic or ionic bonds, hydrogen bonding, dipole-dipole interactions, and lipophilic bonds, and are thus closely analogous to those present in protein-binding. Multifactorial partially confounded designs in rats have shown that cholestyramine (an anion exchange resin) is a valuable antidote in poisoning by acidic drugs (aspirin, secobarbital or phenobarbital); a mixture of Resonium A and Katonium (cation exchange resins) is valuable in poisoning by basic drugs (mecamylamine); and activated charcoal is the only effective antidote for poisoning by the non-ionic drug, glutehimide. - The Keith Kirkland Renal Unit, which is largely supported by N.H. & M.R.C., organised a successful meeting of Australasian nephrologists from 29 November to 2 December 1966, at Sydney Hospital.
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Other projects which are indirectly aided by N.H. & M.R.e. support given to the department include blood flow through capillary-sized channels, other studies of blood rheology, and the effects of treatment by dialysis on the survival and function of blood platelets in patients with kidney failure.
Publications ALCOCK, NANCY W. 'A simple method for the extraction and esterification of some organic acids.' Analytical Biochemistry, 1965, 11, 335. ALCOCK, NANCY W. 'The relation of fluoride to other inorganic substances III the rat.' Proc. Soc. expo BioI. Med., 1965, 120, 150. ALCOCK, NANCY W. 'Magnesium in biological materials-An evaluation of methods of determination.' Proc. Aust. Ass. cZin. Biochemists, 1965, 1, 195. ALCOCK, NANCY W., MAcINTYRE, 1., and RADDE, INGEBORG. 'Concentration of magnesium in human plasma or serum.' Nature (Lond.), 1965, 206, 89. ALCOCK, NANCY W., and MACINTYRE, 1. 'Methods for estimating magnesium in biological materials.' Methods of Biochem. Anal. (Edited by D. Glick), 1966, 14, 1. ARMSTRONG, CORALIE, and EDWARDS, K. D. G. 'Multifactorial design for testing oral ion exchange resins, charcoal and other factors in the treatment of aspirin poisoning in the rat. Efficacy of cholestryamine.' Bull post-grad. Comm. Med. Univ. Sydney. (In press.) EDWARDS, K. D. G., and McCREDIE, MARGARET. 'Studies on the binding properties of acidic, basic and neutral drugs to anion and cation exchange resins and charcoal in vitro.' Med. 1. Aust. (In press.) EDWARDS, K. D. G., STEWART, J. H., ASHLEY, B. e. E., and WHYTE, H. M. 'Oneday renal function tests.' Proc. Aust. Ass. cZin. Biochemists, 1964,1, 101. EDWARDS, K. D. G., STEWART, J. H., and SINNETT, P. F. 'Ethacrynic acid: effective saluretic and diuretic agent in chronic renal failure.' Third Internat. Congr. Nephrology, Washington, D.C., 1966, 2, 186. EDWARDS, K. D. G., LE QUESNE, D., SINNETT, P. F., and STEWART, J. H. 'Some studies on the clinical assessment of diuretics.' Bull. Post-grad. Comm. Med. Univ. Sydney. (In press.) EDWARDS, K. D. G., SINNETT, P. F., and STEWART, J. H. 'Ethacrynic acid: assessment of saluretic and diuretic potency in patients with severe chronic renal failure.' M ed. 1. Aust. (In press.) FAIRBAIRN, A. L., and WHYTE, H. M. 'The composition of dietary fat and the possible effects of dietary changes on serum cholesterol and coronary disease.' Med. 1. Aust., 1965, 1,459. GY6RY, A. Z., and EDWARDS, K. D. G. 'Simultaneous titimetric determination of bicarbonate and titratable acid of urine.' Aust. 1. expo Bioi. med. Sci. (In press.) GY6RY, A. Z., ALCOCK, NANCY W., ARMSTRONG, CORALIE and EDWARDS, K. D. G. 'Abnormal citrate metabolism in patients with renal tubular defects.' Bull. postgrad. Comm. Med. Univ. Sydney. (In press.) HERRIOTT, B. A., and PALMER, A. A. 'Rupture of small ducts and acini in the pancreas of the rat and guinea pig following major duct obstruction.' Aust. I. Exp. Bioi. med. Sci., 1966, 44, 143. PALMER, A. A. 'Platelet and leucocyte skimming.' Fourth European Conference on Microcirculation, Cambridge, 1966, 75. PALMER, A. A. 'Some aspects of plasma skimming.' First International Conference on Haemorheology, Reykjavik, 1966.
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SCHOEGEL, E., and YOUNG, J. A. 'Micropuncture and perfusion investigation of sodium and potassium transport in the rat submaxillary gland.' 1. Physiol., 1966, 183, 73. STEWART, J. H., TUCKWELL, L. A., SINNETT, P. F., EDWARDS, K. D. G., a n d , WHYTE, H. M. 'Peritoneal and haemodia!ysis: a comparison of their morbidity, and of ~ the mortality suffered by dialysed patients.' Quart. 1. Med., N.S., 1966, 35, 407. • WHYTE, H. M. 'Behind the adipose curtain. Studies in Australia and New Guinea relating to obesity and coronary heart disease.' Amer. 1. Cardiol., 1965, IS, 66. YOUNG, J. A. 'Stop-flow studies and amino acid transport in the rat.' M.D. Thesis, University of Queensland, 1965. YOUNG, J. A., and EDWARDS, K. D. G. 'Clearance and stop-flow studies on histidine and methyldopa transport by rat kidney.' Amer. 1. Physiol., 1966, 210, 667. YOUNG, J. A., and EDWARDS, K. D. G. 'Competition for transport between methyldopa and other amino acids in rat gut loops.' Amer. 1. Physiol., 1966,210, 1130. YOUNG, J. A., FROEMTER, E., and SCHOEGEL, E. 'Electrolyte fluxes and potential differences in the main excretory duct of the rat sub-maxillary gland.' Pfluegers Archiv. ges. Physiol., 1966, 289, RBI.
NEW SOUTH WALES RED CROSS BLOOD TRANSFUSION SERVICE, SYDNEY Dr Gordon T. Archer, M.B., B.S., D.C.P., Assistant Director. Miss Annette Angyal, B.Sc., Research Assistant, N.H. & M.R.e. Projects The function of the eosinophil leucocyte. Zinc contents of eosinophils. Chemotactic substances responsible for eosinophilia in rats infected with Amplicaecum roberlsi. Eosinophil changes in the blood and tissues of cows infected with the cattle tick Boophilus microphus. Report Previous studies have established the prese nee in human eosinophils and basophils of a protein which on crystallisation had the characteristic appearance of Charcot Leyden crystals. This protein was shown to contain zinc and in view of previous reports of a high zinc content in eosinophils and basophils it was decided to study the uptake and distribution of zinc in eosinophils, using atomic absorption spectrophotometry. It was first necessary to devise a suitable method for the extraction of zinc from biological material. The first part of this report deals with the methods tried and the method finally adopted for the extraction of zinc. The second part of the report gives the results of zinc assays performed on preparations of human and rat white cells. The third part of this report deals with studies on blood and tissue eosinophilia in cows infected with the tick Boophilus microphus. Human serum was used as the starting material and the following methods of extraction of zinc were tried. Firstly, by acid digestion, using concentrated sulphuric acid and perchloric acid. This method was time consuming and it was found difficult to obtain a sufficient concentration of zinc in the final preparation owing to the amount of dilution necessary before
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passing the acid solution through the spectrophotometer. Strongly acid solutions were found to corrode the burner. Secondly, the formation of a soluble complex of zinc and ammonium pyrollidine dithiocarbamate and extraction of this complex into butyl acetate. Only some 6070% of the zinc present in serum was extracted into butyl acetate and the amounts extracted were not reproducible. Teepol was added before ammonium pyrollidine dithiocarbamate in an attempt to release zinc bound to protein but the teepol was found to interfere with the separation into layers of butyl acetate and the aqueous phase. A third method used tri-chloracetic acid precipitation of protein and assay 0 f zinc in the supernatant solution. This method proved unsatisfactory because significant quantities of zinc were lost in the precipitate. In a further method undiluted serum was passed directly into the machine but owing to the viscosity of the serum inconsistent resnlts were obtained. Dilution of the serum one in three with distilled water overcame this problem but the zinc concentration was at the lower limit of sensitivity of the spectrophotometer. Further this method was not applicable to white cells. The final method of extraction used was by dry ashing. This method was found to give reproducible results and was the method adopted in the subsequent experiments. It was found that porcelain crucibles were satisfactory at the temperature used (500 C.). There was a loss of zinc by sublimation when serum or cell preparations were heated alone but the addition of small amounts of concentrated sulphuric acid prior to ashing prevented this loss of zinc. The amount of sulphuric acid to be added was controlled because excessive amounts caused loss of the sample by frothing. One hundred per cent recovery of zinc was obtained when standard solutions were treated by this method. Studies were undertaken of the zinc content of human eosinophils and rat eosinophils. Contrary to previous reports in the literature the eosinophil was not found to contain more zinc than other white cells. Human eosinophils, obtained from patients with well marked eosinophilia, were found to contain approximately l20,...gm zinc/l09 eosinophils and the zinc content of rat eosinophils was found to be less than 120 ,...gm/109 eosinophils. While undertaking the studies on eosinophils obtained from the peritoneal cavity of the rat it was found that the zinc content of rat mast cells was some twenty times greater than the other white cells present in the peritoneal washings. Further experiments were performed using preparations of peritoneal cavity cells separated by differential centrifugation in albumin. The results of these experiments suggest that large mature mast cells have a much greater zinc content (approximately 2.5 ,...gm zinc/l06 cells) than small immature cells « 0.5 ,...gm zinc/l0 6 cells). It is planned to investigate further the zinc content of mast cells using radioactive zinc 65. The isotope will be injected into rats and the mast cells will be harvested from the peritoneal cavity at various time intervals to determine the uptake and turnover of zinc 65 by these cells. Extracts of the nematode Amplicaecum robertsi and various fractions of wool protein were injected into rats but no eosinophilia was obtained. It has been possible to release viable larvae of Amplicaecum from infective ova by means of a squeegee and injections of the larvae have resUlted in local eosinophilia. Preliminary experiments suggest the eosinophils are attracted to the secretory pores of the parasite rather than the worm sheath. Further experiments are being undertaken in which the larvae are being injected into the peritoneal cavity of rats. Omental spreads obtained from these animals will be examined at various time intervals after the injection to determine when the local eosinophilia occurs and what portion of the worm provides the chemotactic stimulus. A new population of mast cells has been shown to arise in the rats within two weeks of infection with Amplicaecum larvae. The mature mast cells undergo disruption and degranulation in this time. Evidence to date suggests that eosinophilia precedes the mast cell changes. Zinc 65 will be injected into these animals in order to establish when the isotope is 0
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taken up by the young mast cells. The fate of the zinc present in the mature mast cells and particularly any uptake by eosinophils will also be determined. The isotope will be detected by scintillation counting and autoradiography. In conjunction with the CSIRO Division of Animal Genetics a study has been undertaken of the eosinophil changes in the blood and skin of cows infected with the cattle tick Boophilus microphus. The main purpose of this study is to determine if there is any relationship between eosinophilia and resistance to infection. In the first series of experiments at the CSIRO Agricultural Research Station at Wollongbah daily blood counts were performed on animals infected for the first time with the cattle tick. The results of these experiments showed a transient blood eosinophilia at 1-2 days after infection with a return to normal levels at 4-5 days. The animals were reinfected eight weeks later and samples of blood were sent daily to the Blood Transfusion Service, Sydney for counting. A more pronounced eosinophilia lasting for a longer time period, is apparent on the second occasion. This experiment is in progress at present and the histological sections have yet to be studied, to determine whether the presence of local eosinophilia is related either to the tick burden or the resistance to infection. It is planned to reinfect these animals on several more occasions to study further the eosinophilia and its relationship to immunity to tick infection. Publications AIR, G., ARCHER, G. T., BARKER, ANGELA, and McGOVERN, V. J. 'Eosinophilia in rats infected with Amplicaecum robertsi.' Aust J. expo bioi. med. Sci., 1966, 44. ARCHER, G. T.: 'The function of the eosinophil.' Book of Plenary Sessions of the Xl International Congresses oj Haematology and Blood Transfusion, 1966, p. 304.
A. W. MORROW DEPARTMENT OF GASTROENTEROLOGY, ROYAL PRINCE ALFRED HOSPITAL Dr A. P. Skyring, M.B., B.S., M.R.A.C.P., Director. Miss D Harrison, B.sc., Senior Research Officer, N.H. & M.R.C. Project Studies of the crypt cell zone of the mucosa of the small intestine of rats. Report The aim of the first part of this study was to develop a method for the isolation of crypt cells from the intact small intestine of the rat. It was essential that the final collection of crypt cells be free of columnar cells from the mucosal villi. The enzyme content of the crypt cells could then be assayed and compared with that of columnar villus cells. The method used to remove cells from the mucosa involved mechanical vibration of the supported gut. This has been used to prepare isolated brush borders as previously reported from this laboratory. It appeared that an extension or modification of this method might prove suitable for the isolation of the crypt cells and other intestinal celltypes. Each step of this vibrational procedure and subsequent modifications were SUbjected to critical assessment. Experiments were designed to investigate the effects of variation of the mechanical support for the everted intestine and of altering the tonicity of the extracting medium. (The use of 150mM NaCl with and without varying concentrations of EDTA was evaluated.) Also
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investigated were the effects of altering the amplitude of vibration to which the gut was subjected. (This was varied from 0.3 to 3 mm. The degree of vibration was found to be critical.) The effects of altering the time of vibration to which the gut was subjected were also studied. Once the optimum conditions wt:re established, altering the time of vibration was found to be important in the final harvest of crypt cells. Attempts were made to identify the cell types and the state of the mucosa at intervals between 5 and 90 minutes. Various modifications, such as presoaking the tissue in 5mM EDTA/150 mM NaCl before vibration, or altering the extracting medium to ImM EDTA/150 mM NaCl during the procedure were investigated but these did not improve the ultimate yield. Several methods were used to identify and assess the efficacy of varying the above conditions for the release of columnar villus cells and crypt cells. The technique of examination of the tissue with the dissecting microscope permits an immediate inspection of the surface of the bowel without prior fixation. Since this technique has not been previously used for this purpose, correlation with other methods was undertaken. The next method used was the examination of the material dislodged by phase microscopy. Fixed and stained sections were examined by light microscopy and correlation of the stage of mucosal shedding found with the above methods. In addition, protein assay was used as an index of the rate of mucosal release of the mucosal cells. Strict control of the site of sampling of the small intestine was introduced to standardise the experiments and compare the information derived from the above methods. It was found that considerable differences in the relative rapidity of release of mucosa from the jejunum and the ileum exist. Also, within the one section of bowel differences in release of cells along the mesenteric and antimesenteric borders were observed. A satisfactory method for preparing crypt cells separated from the mucosal villus cells has been developed. Briefly, the procedure is as follows. The entire length of rat small intestine is everted over four parallel straight rods. The supported tissue is then suspended in 100 ml 5mM EDTA in 150mM NaCl, attached to the Vibromix motor and vibrated at 2mm amplitude for thirty minutes in the cold. At the end of this time all cellular material from the small intestine is released with the exception of crypt cells in the proximal small intestine. The tissue at this stage is transferred to vibration in hypnotic 2.5 mM EDTA/ water, and the crypt cells are released following hypotonic rupture. The cellular fractions are then assayed for invertase and alkaline phosphatase activities. When suspensions of whole cells (prepared at the EDTA/saline stage) are assayed prior homogenisation in a Waring-blendor is necessary. Work by dissection microscope and light microscope has shown that the final fractions are obtained from the crypt cell regions of the proximal gut. Phase microscopic investigations did not prove helpful in separating columnar villus and columnar crypt cells. Most crypt cells were not intact and thus differentiation of those cells from columnar villus cells was not possible. The observations on enzyme distributions showed that after fifteen minutes vibration at 2mm when all villus cells had been removed from the tissue as well as some distal crypt cells, 51 per cent of the total mucosal protein had been released together with 86 per cent of the total alkaline phosphatase activity and 76 per cent of the total invertase activity. In the period from fifteen to thirty minutes an additional 22 per cent of the total protein, 17 per cent of the total invertase and 10 per cent of the alkaline phosphatase was released. This fifteen-thirty minute fraction consisted predominately of distal crypt cells. The morphology of the proximal gut made it difficult to remove proximal crypt cells by prolonged vibration. These were collected by changing to vibration in hypotonic EDTA, after which a further 27 per cent of the total protein, 7 per cent of the total invertase and 4 per cent of the mucosal phosphatase was released.
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Previous investigations in this department had suggested that disacchari~ ilctivity is not exclusively localised in the brush border of the mature villus cell. The crypt cell preparation described above contained 7-24 per cent of the total invertase activity 4-14 per cent total phosphatase activity. The mean specific activities of invertase (expressed as plIloles substrate split per minute per gram protein) were as follows: villus cells sixty-five units and proximal crypts fifteen units. Thus it has been shown that a crypt cell preparation has invertase and alkaline phosphatase activity. It is not suggested that such activity has any digestive function. These observations are more important when considering the problem of the sites of synthesis of the digestive enzymes. The site of action is known to be primarily localised in the microvillus membrane. Studies of the subcellular distribution of these enzymes in crypt cells and villus cells are in progress to test the possibility that these enzymes are translocated from an intracellular site of synthesis to their site of action at the microvillus membrane. It is clear from the work described above that experiments have to be designed to identify unequivocally the crypt cells and establish their release in anyone fraction of cells after vibrational treatment. Experiments have been designed to take advantage of the observations of Leblond who labelled nuclei of dividing crypt cells uniquely with H3-thymidine and with autoradiographic techniques followed the subsequent turnover rate of intestinal mucosal cells in the rat. The experimental approach would be in two parts, using 3H-thymidine as a positive marker for crypt cells, and, 3H-thymidine as a negative marker. In the first approach, which has already been carried out the interval after injection of the marker was restricted to eight hours so that only the crypt cells could have been labelled. In the second approach, the time interval was extended to thirty hours by which time all labelled cells have migrated out of the crypt area and now serve as markers for mature cells at the tips of the villi. In both experiments the intestinal cells are removed as described previously and each fraction of cells is assayed for enzyme activity, the total DNA is extracted and assayed by the method of Schmidt and Tannhauser, the labelled DNA is determined in each fraction and the specific activity of labelled DNA to total DNA established. Control examination of the tissues is made by autoradiography at eight and thirty hours. PubUcations HARRISON, D. D. 'Studies on intestinal crypt cells.' Proceedings Aust. Soc. Med. Res., 1966, 2, 1,24. HARRISON, D. D., and WIE-POH FUNG. 'Disaccharidase activities of human small bowel biopsy samples.' Proceedings Aust. Soc. Med. Res., 1966, 12, 1, 24. WALKER-SMITIi, J. A., and HARRISON, D. D. 'Small bowel biopsy in children.' Proceedings Aust. Soc. Med. Res., 1966, 12, 1, 27.
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I FAIRFAX INSTITUTE OF PATHOLOGY, ROYAL PRINCE ALFRED HOSPITAL Dr Phyllis M. Rountree, D.Sc., Dip. Bact., Microbiologist. Miss M. A. Beard, M.Sc., Senior Research Officer, N.H. & M.R.e. Projects Study of an intensive care unit. Genetics of antibiotic-resistance in staphylococci.
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The effect of ultra-violet irradiation on total bacterial counts in the air and on cross-mfection in patients requmng intensive care was studied in a two-bedded unit. Basic data was obtamed on infection and on air-borne bacteria in the absence of irradiation. The numbers of bacteria-carrying particles settling in one hour on Petri dishes were enumerated. In the absence of patients or nurses, the mean basIc count was two per plate. When the room was occupied but the ultra-violet lights were not turned on, the mean count was 23.3 (119 observations). With ultra-violet irradiatIOn the mean count was 19.9 (145 observations). Since there was great variation between individual counts, depending on the degree of activity in the unit, this reduction cannot be regarded as significant. With regard to infection of the patients, of 13 patients with tracheostomies, nursed without irradiation, 9 were infected. Of eighteen patients nursed under ultra-violet light, 13 had tracheostomies all of which were infected. The infecting organisms were Staph. aureus, Pseudomonas aeruginosa, or both. Swabs were taken from equipment, bedding and curtains. From 585 swabs, Staph. aureus was isolated on 193 occasions (32 per cent). However, at times when a patient was a heavy disperser of these organisms, they were found on 80 per cent of all swabs. Observations implicated humidifier connections, respirator tubing and sphygmanometer cuffs as a possible source of cross-infecting organisms. It was concluded that under the conditions in this unit. no beneficial effect of ultra-violet irradiation could be observed. Methicillin-resistant staphylococci have been isolated from eleven patients. After incubation with pencilJin to induce enzyme production, all inactivated completely fifty mcg/ml of methicillin. This is greater inactivation than reported by other workers but in all other respects the strains were similar to those described in other countries. Attempts were made to transduce methicillin-resistance using two different phages and three distinct receptor strains. All were unsuccesful although penicillinase-production could be transduced. Transduction of neomycin and kanamycin resistance was obtained with preparations of phage S3 grown in one particular donor; preparations made in other donors were inactive, indicating that the genetic constitution of the donor cells may influence the production by them of transducing particles. The neomycin and kanamycin resistance factors were always tran~duced together. The frequency of transduction appears to depend on the genetic constitution of the acceptor strain. This has been observed for both neomycin and tetracycline resistance. Strains of Group II are reported not to be transducible and this has been confirmed. However, alteration of the genetic constitution of staphylococci by lysogenisation is accompanied by alterations in the frequencv of transduction. Preliminary observations indicate that the frequency of transduction varies with differences in the kinds of prophage inserted into the cell. These observations require further amplification.
Publication ROUNTREE, P. M., BEARD, M. A., LOEWENTHAL, J., MAY, J., and RENWICK, S. D. 'Staphylococcal sepsis in a new surgical ward.' Brit. med. !. (In press.)
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QUEENSLAND INSTITUTES AND HOSPITALS DEPARTMENT OF NEUROLOGY AND NEUROSURGERY, ROYAL BRISBANE HOSPITAL Dr K. G. Jamieson, M.S., Neurosurgeon. Dr A. W. Duggan, B.Sc., M.B., B.S., Medical Research Fellow. Mrs Judith A. TweddeH, B.Soc.Sc., Sociological Research Fellow. Project Traffic injury in Brisbane. Report Work has continued on analysis of an on-the-spot survey by flying squad technique of a sample of accidents to which an ambulance had been summoned. This project, which had also engineering aspects supported by a grant from the Australian Road Research Board, started in 1964 and work on the road ended during 1965. Most of the data analysis is now complete and the results are being written up for publication jointly by the National Health and Medical Research Council and the Australian Road Research Board. It is anticipated that this will be completed early in the new year. The report will have two major sections, the first concerning injuries sustained in relation to the vehicle structures which were struck by car occupants or which injured pedestrians and cyclists. The mechanisms of the accidents have been studied in detail together with engineering data concerning accident causation. The second section of the report discusses sociological data concerning the characteristicof the drivers involved in accidents as compartd with matching data for a control sample of Brisbane drivers. Factors studied include educational, social and economic backgrounds; driving experience; employment; marital and criminal records; and attitudes to leisure activity and alcohol. Further analysis is also being undertaken of various items in the data collected in both the 1962-63 and 1964-65 studies, which will fonn the basis of separate papers on particular topics. Publication JAMIESON, K. G. and TAIT, I. A. 'Traffic injury in Brisbane-Report of a general survey.' National Health and Medical Research Council Special Report, 1966.
CAIRNS Dr J. H. Barnes, M.B., B.S., Medical Practitioner. Mrs M. Hayes, B.Agr.Sci., Research Assistant, N.H. & M.R.C. Mrs R. G. Yarrow, B.Sc., Research Assistant, N.H. & M.R.C. Projects Ecology of Chironex fleckeri and Chiropsalmus quadrig~tus. Correlation between marine stings and causative orgamsms. Prophylaxis and treatment of marine stings.
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The consequences of contact between man and jellyfish are extremely varied, ranging from no detectable effect to excruciating pain, full-thickness skin necrosis, severe illness and, occasionally, death. The causative agent of such injuries is seldom seen and quite exceptionally recognised, but methods recently developed now allow recovery and examination of diganostic material from the sting itself, in the form of nematocysts or stinging capsules. Like fingerprints, these distinctive structures can be matched against suspected organisms, usually resulting in reliable identification. Thus it has become possible to define the characteristics of injuries from all major stingers and to reassess the stinging capabilities of many other medusae prevalent in Australian tropical waters. Some unsuspected medusae have in consequence been elevated to potent stinger status, while others once regarded as dangerous have been downgraded to nuisance level only. Pre-eminent amongst the highly noxious jellyfish are three Cubomedusae (Seawasps)Chironex fleckeri, the lrukandji carybdeid (soon to receive its specific name as a new species) and Chiropsalmus quadrigatus. Unfortunately, C. fleckeri and C. quadrigatus have the same general appearance and seasonal incidence, often occurring together in mixed swarms and inflicting injuries of superficially similar nature. Failure to distinguish adequately between these two species has in the past seriously hampered the investigation of fatal injuries, and jeopardised the accuracy of stinger warnings. Confusion has also occurred between the lrukandji carybdeid and at least two other closely related species, all remarkably alike in outward form but having quite different toxicities to man. Because of the necessity for accurate identification, and the inadequacy of formal descriptions of the three most important stingers, little progress could be made until certain zoological problems had been solved and the species studied as separate entities in their natural environment. Morphological studies completed in 1966 have corrected errors in earlier descriptions of C. fleckeri and C. quadrigatus and provided new criteria for rapid recognition. Both species can now be identified on sight, in or out of the water, without handling. Differences in behaviour and distribution have been noted, but final assessment of practical significance awaits accumulation of additional data. For lrukandji and its counterparts distinctive physical characteristics have also been established, eliminating the need for experimental stinging of volunteers. The number of lrukandji specimens captured are still not adequate for the work proposed, due to difficulties in capture, but apparatus designed to take advantage of the phototropism of carybdeids has been tested with success against closely related species. Through the co-operation and assistance of the Queensland Department of Harbours and Marine, observation stations are now maintained at strategic points both north and south of Cairns, supplying specimens and data for the compilation of weekly reports on the presence or absence of stingers. Press and radio warnings give wide publicity to dangerous conditions and have achieved a marked reduction in casualties. One fatality occurred in the serviced area, despite a warning of maximal risk just two days previously. Educational pamphlets, wall charts and a short television programme have been prepared for distribution within the tropical area. Punch card analysis of medical and field records indicates that Chiropsalmus is a far less dangerous jellyfish than Chironex, and unlik~ly to inflict a fatal sting under normal circumstances. This conclusion is supported by microscopy of the tentacles of both species, showing fewer and smaller capsules per unit area on the tentacles of Chiropsalmus. Also, a survey of the Cairns reference collection of more than 1000 specimens show that from Australian habitats Chiropsalumus is consistently the smaller species, and at comparable sizes possesses
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shorter and much less robust tentacular equipment than Chironex. The composition and potency of capsular fluid appears to be simila{ tor both species. These findings in respect to Chiropsalmus are in conflict with published reports from other areas, notably the Philippines, where Chiropsalmus is regarded as a lethal stinger. On the invitation of the International Society on Toxinology, and with the financial assistance and fares provided by that body and the u.s. Office of Naval Research, a paper on cnidarian venom was presented and discussed at the First International Symposium on Animal Toxins (Atlantic City, April 1966). While in America opportunity was taken to visit marine aquaria, research institutes and commercial laboratories working on venomous animals and their toxins. At the U.S. National Museum an invitation was accepted to work on the cubomedusan collection, including many specimens of chirodropids from the Philippines, Malaya and the South China Sea. Thirty-one specimens previously identified as C. quadrigatus were examined in detail. Of ,hese, according to the revised criteria previously mentioned, only two were acceptable at C. quadrigatus, while the remainder all exhibited features characteristic of C. f/eckeri. This represents the first direct evidence that Chironex occurs in other than Australian waters, and may in fact be the true cause of fatalities els..:where attributed to Chiropsalmus. Arrangements have been made to check further materials from the tropical Indo-Pacific area. In experimental studies on tentacle mechanisms and the operation of nematocysts, animal membranes have been stung by Chironex, Chiropsalmus, Cyanea and other cnidarians, under natural conditions and also in response to a variety of physical, chemical and electrical stimuli. This approach has demonstrated that classical beliefs on tentacular functions are largely erroneous, at least in relation to Cubomedusae, and that the processes of injector penetration and transfer of venom are influenced by factors not hitherto appreciated. Findings from this work have dictated important changes in first-aid treatment, and form the basis for new concepts in extraction of medusan venom, utilising the natural responses of the living animal. Two complementary techniques have been developed, one having a low yield of very high quality and the other an excellent yield, but allowing the inclusion of some extraneous material. It is intended that the first should serve as a reference standard for fractionation of the second, thus ensuring that spurious toxicities are eliminated. The venom content of both products is unmodified, stable at room temperatures, and readily determined by bioassay. Laboratory animals injected with these extracts die in the same manner as do human victims of massive accidental envenomation, with pulmonary oedema as the outstanding and consistent post-mortem finding. Work is proceeding on the isolation of large quantities of venom suitable for physical, chemical and pharmacological investigations, and for use in the preparation of vaccines and anti-venines should the molecular structure ~end itself to these applications. Publications BARNES, J. H. 'Studies on three venomous Cubomedusae.' Symposia of the Zoological Society of London, No. 16 (The Cnidaria and their Evolution). BARNES, J. H., and Queensland Health Edu~ation Council. 'Marine stingers, recognition and first aid treatment.' Health Education Publication No. 114, 1966, Government Printer, Brisbane. BARNES, J. H., revised issue of 'Major stin~ing jellyfish-tropical Australian coast,' iIlu~ trated wall chart of the North Queensland Branch of the Surf Lifesaving Association of Australia, 1966. BARNES, J. H. 'Extraction of cnidarian venom from living tentacle.' Proceedings of the International Symposium on Animal Toxins, Atlantic City, April 1966. (In press.)
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QUEENSLAND INSTITUTE OF MEDICAL RESEARCH, BRISBANE Dr R. L. Doherty, M.B., B.S., M.P.H., M.R.A.C.P., M.C.P.A., Director. Mr J. G. Carley, B.A., Virologist. Mr R Domrow, B.A., B.Sc., Entomologist. Mr H. A. Standfast, B.Sc., Entomologist. Dr E. G. Westaway, B.Sc., Ph.D., Virologist. Mr B. M. Gorman, B.Sc., Research Officer, Virology. Mr R. H. Whitehead, B.Sc., Research Officer, Virology. Miss P. A. Grait, B.S., M.S., Visiting Scientist (Australian American Educational Foundation). Project The epidemiology of arbovirus disease in Queensland with particular reference to Murray Valley encephalitis and epidemic polyarthritis. Report This study aims to elucidate the epidemiology of three diseases of man caused by arthropod-borne viruses (arboviruses) in Australia-Murray Valley encephalitis (MVE), epidemic polyarthritis and dengue-and to assess the importance to medicine of other viruses isolated from mosquitoes in North Queensland. The approach chosen involves isolation of viruses from arthropods and vertebrates at two sites in Queensland (Mitchell River Mission and Innisfail), serological surveys of vertebrates in these and other areas, and investigation of epidemics and sporadic cases of human disease. Previous reports have recorded arbovirus infections each wet season studied at Mitchell River Mission; much less virus activity was found there in the dry season; arbovirus transmission occurred at a low level in rain-forest in the Innisfail area; several arboviruses were shown to have caused infections in dry areas of south-west Queensla nd in recent years. In the present year mosquitoes, birds, reptiles and amphibians were collected at Mitchell River Mission in the wet (March-April) and dry (October-November) seasons, reptiles and amphibians were collected at Innisfail, and s~ntinel fowl studies continued at Charleville. Strains of a group B virus (prototype strain MRM3929) related to but recognizably distinct from MVE were isolated from a swamp pheasant (Centropus phasianinus) and from the mosquito Aedeomyia catasticta, both collected at Mitchell River in the wet season of early 1966. A virus strain (MRM3630) isolated from anopheline mosquitoes collected there in late 1965 also appears to be previously undescribed; it is distantly related to Mapputta virus. Kunjin virus was again isolated from mosquitoes collected in the wet season. Three closely related virus strains (prototype strain MRM4059) were isolated from blood or organs of lizards of the species (A blepharus boutonii virga/us collected at Mitchell River. The prototype strain multiplies in experimentally-infected mosquitoes and the virus can therefore be accepted tentatively as an arbovirus. It has not been found related to any other known Australian arbovirus. Sentinel fowl studies gave evidence of infection by group B arboviruses at Mitchell River, and by group A and Koongol group viruses at Charleville, in the summer of 19651966. Children at Mitchell River were found to have developed antibody to group A or group B viruses in the year before April, 1966. Sera from over 300 reptiles and amphib'ans were tested for antibody to the known Australian arboviruses. A number inhibited haemagglutination by group A viruses, and a few (all amphibians) by group B viruses. However the reacting sera did not neutralize the viruses concerned, and the results may be due to some inhibitor other than antibody.
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Other antibody studies showed significant changes in antibody titre to Ross River virus in 22 patients with epidemic polyarthritis in early 1966, including cases from Brisbane, Townsville, Dirranbandi and Bollon. Eight of 276 patients with undiagnosed pyrexia studied at Innisfail in 1953-1955 were found to have serological evidence of arbovirus infection, and their sera will be studied further. Evidence of infection with Edge Hill virus was found in rats and bandicoots from the Innisfail and Atherton Tableland areas. Neutralizing antibody to three ungrouped viruses (Corriparta, Kowanyama and MRM3630) was found in sera from adult aborigines at Aurukun Mission. This is the first evidence that these viruses may be able to infect man. Mosquito collections at Mitchell River provided further information about seasonal variations in population. Laboratory studies of mosquito behaviour were continued, concerned in this year with the effects of light, blood feeding and metamorphosis on the circadian activity rhythm. Attempts to colonize Culex annulirostris and Aedes vigilax continued to be unsuccessful, but Aedes notoscriptus has been maintained in the laboratory through several generations and may now be established. Other studies were concerned with more basic aspects of the arboviruses and their reaction with antibodies. It was shown that rabbit antisera to group B viruses contain both 7S and 19S immunoglobulins, and that the 19S antibody reacted in higher titre to the infecting virus than to related viruses in haemagglutination-inhibition tests, in contrast to the expected group-specific response given in this study by 7S antibody. Electron microphotographs of Corriparta virus suggested that it had a subunit structure similar to that described for the reoviruses; this is of some interest as another arbovirus, causing bluetongue of sheep, has also been shown recently to have the structure of a reovirus, and further studies of Corriparta virus are in progress. Studies of the chemical basis of arbovirus haemagglutination were concerned with the effects of lipids as inhibitors; various experiments were designed to determine whether lipids play any essential part as receptors for arboviruses on red cells, but results have to date been equivocal. Ectoparasites other than mosquitoes might well be concerned in the survival of arboviruses; a study is continuing of mites parasitic on native birds, especially those which suck blood and whose habitat is the nasal cavities. This study is still at the descriptive stage but when the taxonomy and host-parasite association of these mites are understood it will be possible to plan further studies on their possible importance in arbovirus epidemiology. The discovery in this year of three previously unknown viruses underlines both the complexity of the arbovirus picture in North Queensland and the amount of information that must still remain to be found. It is planned to continue field and laboratory studies in the study areas for several more years.
Publications ALLAN, B. C., DOHERTY, R. L., and WHITEHEAD, R. H. 'Laboratory infections with arboviruses, including reports of two infections with Kunjin virus.' Med. I. Aust., 1966, 2, 844. DOHERTY, R. L., GORMAN, B. M., WHITEHEAD, R. H., and CARLEY, J. G. 'Studies of arthropod-borne virus infections in Queensland. V. Survey of antibodies to group A arboviruses in man and other animals.' Aust. I. expo BioI. med. Sci., 1966, 44, 365. DOHERTY, R. L., WHITEHEAD, R. H., ALLAN, B. C., NOLAN, K., and McADAM, E. 'Investigations of enteroviruses in the aetiology of aseptic meningitis, poliomyelitis, encephalitis and other syndromes in Queensland, 1958-1962.' Med. I. Aust., 1966, 2, 535.
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DOMROW, R. 'Some mite parasites of Australian birds.' Proc. Linn. Soc. N.S.W., 1966, 90, 190. DOMROW, R. 'The seasonal distribution of birds and their rhinonyssine nasal mites at Mitchell River Mission.' Proc. Linn. Soc. N.S.W. (In press.) STANDFAST, H. A. 'Biting times of nine species of New Guinea Culicidae (Diptera).' I. med. Ent. (In press.) WESTA WAY, E. G. 'Assessment and application of a cell line from pig kidney for plaque assay and neutralization tests with twelve group B arboviruses.' Am. I. Epidemiol. (In press.)
SOUTH AUSTRALIA INSTITUTES AND HOSPITALS THE QUEEN ELiZABEm HOSPITAL Dr Maurice L. Wellby, M.Sc., M.D., M.C.P.A., Clinical Biochemist. Mr Michael W. O'HaIlorau, M.Sc., Biochemist. Project Investigations of the chemical nature of the circulating thyroid hormones. Report The aim of the investigation is to define the conditions which are associated with the presence of monoiodotyrosine (MIT) and di-iodotyrosine (DIT) in human plasma. Earlier work in this Hospital had demonstrated that, when using paper chromatographic techniques, MIT and DIT are not present in normal human plasma and can be detected there in significant amounts only in states of thyroid stimulation, such as in the condition of thyrotoxicosis and in normal subjects during thyrotrophic hormone stimulation. Since those observations, however, there have been two reports from elsewhere claiming that DIT and MIT together account for at least 50% of the organic iodine compounds in normal human plasma. Other reports have denied this claim and hence there has arisen a controversy about whether or not the iodotyrosines are a constituent of normal plasma. That is why it was considered important to investigate more fully, and with alternative techniques, the conditions associated with the presence of MIT and DIT in the plasma. The work completed to date on this project has again shown the absence of MIT and DIT in normal human plasma. By contrast, quite definite amounts of both are found in the plasma of untreated patients with thyrotoxicosis. Furthermore, the alternative technique used, namely 'isotopic dilution,' is allowing a precise quantitation of the iodotyrosine in the plasma. The method being used is dependent on the isotopic dilution of 131I-labelled DIT and MIT of known specific activity by the DIT and MIT content of the plasma specimen being assayed. It is necessary to isolate the labelled DIT and MIT, after the addition of the plasma, in a highly purified form. This is achieved by the absorption of all organic iodine components of the mixture on to a Dowex anion exchange resin and the subsequent elution of MIT and DIT separately and free from any ~ignificant amount of iodinated protein, throxine or triiodothyronine contained in the plasma. The specific activity of the DIT and MIT derived from the resin column is measured, the degree of dilution in the specific activity of the DIT and MIT calculated and from this is derived the level of DIT and MIT causing this dilution, namely. the D1T and MIT content of the plasma. From the results it can be seen that the investigation is showing clearly that DIT and MIT do not occur to any significant extent in normal human plasma. DIT was measured as zero in 18 of the 22 normal subjects studied and was never in an amount in excess of the trace amount of 0.08 ug/lOO ml. MIT was always measured as zero. It is also showing that, in the example of thyroid stimulation studied, namelv the condition of thvrotoxicosis, very definite amounts of both DIT and MIT .lre consistently found in the 25 subjects. DIT and MIT are normally deiodinated within the thyroid gland and the inorganic iodine released is reutilised for further thyroid hormone synthesis. The appearance of iodotyrosine in the plasma is thus associated with a loss of iodine from the gland and, as the half life of the idotyrosines in the blood is quite short, the loss is probably considerable. This loss has an important bearing on the biosynthesis of thvr lid hormone in the thyrotoxic subject and may well lead to a change in the ratio of triiodo~hvronine to thyroxine secreted by the gland. Before this part of the project is completed it is necessary to precisely quantitate the amount of DIT and MIT in the plasma during other types of thvroid stimulation. The first situation of interest will be the normal subject following thyrotrophic hormone stimulation as earli;!T
UNIVERSITY OF MELBOURNE Department of Dental Prosthetics
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Injectio n of lympho cytes into tbe tail vein of a mouse. Mr G. Mitchell, Researc h Assistant
Mr G. Mitchell, Researc h Assistant and Dr J. F. A. P. Miller (I. to r.), Princip al Researc h Fellow (N.H. & M.R.C. ), perform ing microscopic surgery to remove the thymus from a new born mouse
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work in this Hospital had demonstrated quatitatively the appearance of DIT in the plasma in such subjects. The second situation will be in subjects undergoing acute stress; any demonstration of iodotyrosine in the plasma of these patients may be related to a modified biosynthesis of thyroid hormone occurring during stress.
RED CROSS BLOOD TRANSFUSION SERVICE, ADELAIDE Dr R. W. BeaI, M.B., B.S. Projects Plasma protein binding of radioactive vitamin B12 • Neutrophil alkaline phosphatase in pregnancy. Report Research has shown that vitamin B12 metabolism is altered in certain myeloproliferative states, notably myeloid leukaemia; serum levels are elevated, there is increased in vivo and in vitro binding of vitamin B12 to plasma proteins, and the distribution of the bound vitamin B12 differs from normal. Column chromatography of dialysed labelled plasma (or serum) has revealed six major protein peaks, wi th peaks of radioactivity similar in pattern in association with four of these. In myeloid leukaemia, a marked increase of radioactivity above normal has been observed in peak V; this increased binding is probably associated with the al acid glycoprotein (orosomucoid) fraction. Detailed study of serum from a patient in whom myeloid leukaemia was associated with a post-gastrectomy vitamin B12 deficiency, has shown that all detectable radioactivity was in peak V. This pattern differs from that found in uncomplicated vitamin B12 deficiency, and suggests that abnormal binding of vitamin B12 in myeloid leukaemia occurs preferentially, and not as an overflow phenomenon following upon saturation of other vitamin B12 binding proteins. Binding and chromatographic studies are in progress on a large number of sera from patients with vitamin B12 deficiency, in order to elucidate the pattern of binding in this disease. A technique which allows almost complete separation of granulocytes and lymphocytes from whole blood has been set up and utilised in an attempt to determine the relationship of normal and abnormal granulocytes to the B12 binding phenomenon. Increased binding has been demonstrated in more than half the experiments using granulocyte-rich plasma, while no differences in binding have been observed "ith lymphocyte-rich plasma and the controls used. A marked variation in peak V has also been observed in the early chromatographic studies of dialysed granulocyte-rich plasma, which does not appear with lymphocyte-rich plasma and controls. The apparent relationship demonstrated between normal granulocytes and vitamin BI2 binding is being further investigated in disease states, including the leukaemias and infective neutrophilia. Neutrophil alkaline phosphatase levels have been studied in a series of over 200 pregnant women. A refinement of the generally used technique has been developed, in which a white cell concentrate is made. This enables the requisite number of cells to be counted and scored in a shorter time than is possible using blood films prepared in the conventional manner. An evaluation of this concentrate tecnnique has been done, and the results from an unselected series, on which both the' standard method and the revised method were used, reveal no discrepancy between the two methods.
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This study has confirmed the previously described elevations of neutrophil alkaline phosphatase in pregnancy, but in contrast with the results of other workers, no relationship has been found between the stage of the pregnancy, and the neutrophil alkaline phosphatase score. There is also no correlation between the neutrophil alkaline phosphatase score and the age, parity, or white cell count of the pregnant women. Isozyme studies are being set up to investigate the possible hormonal or placental influences on the elevation of the neutrophil alkaline phosphatase levels in pregnancy. Publicatious BEAL, R. W. 'Serum binding of C0 5s-vitamin 8 ,2 : further studies of abnormal binding in disease states.' (Abstract) Med. Res., 1961-65,1,151. BEAL, R. W., and TURVEY, P. A. 'Neutrophil alkaline phosphatase in pregnancy.' (Abstract) Med Res., 1961-65, 1, 152. BEAL, R. W., and READ, W. M. F. 'Serum protein binding of C0 5s-vitamin B,2 : relationship of granulocytes to increased binding.' (Abstract), Proc. Aust. Soc. Med. Res., 1966,2,30. BEAL, R. W. 'Preferential in vitro binding of radioactive vitamin BI2 by an abnormal serum protein in chronic myeloid leukaemia.' Nature. (In press.) BEAL, R. W. 'An age survey of South Australian blood donors.' Med. I. Aust., 1965, 2, 519. BEAL, R. W. 'A prospective survey of South Australian blood donors.' Proc. Xlth Congress. Int. Soc. Blood Transfusion. (In press.)
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SOUTH AUSTRALIAN MUSEUM Dr R. V. Southcott, D.Sc., M.D., B.S., D.T.M. & H., Honorary Zoologist. Project Medlcal effects of marine invertebrates and other marine and terrestrial animals harmful to man, also of plants of clinical significance. Report Studies upon marine and terrestrial harmful animals have continued, the major part of the effort being directed to continuing investigations upon the marine invertebrates of the seas around Australia. Professor P. L. Kramp of Copenhagen has now published his review of the larger jellyfishes in the collections of A ustralian material forwarded to him, and this has clarified the identifications of a number of stinging or potentially stinging medusae, as these collections included a good deal of material which had originated in medical studies, or had been centred around them. The study of the 'Irukandji medusa' has been completed, and the description of species responsible for the 'Irukandji syndrome or Type A stinging will be published in 1966. More comprehensive data of this and other stingings have been collected. Other clinical histories of harmful animals continue to be accumulated for analysis. One notable item among these is a number of histories of stingings from the South Australian stinging sponge (first recorded in the monograph on marine invertebrate injuries published by the N.H. & M.R.C.) The monograph by Cleland and Southcott has stimulated the gathering of additional clinical data in this and other groups. Among these is an account of various
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sponge stingings in South Australia in 1890, which had been stored in the Museum's collections for 75 years, as well as dried pieces of the sponge responsible. Further experimental stingings on the sponge have been undertaken with fresh material collected during 1966. Attention is being directed also to injuries from Australian fish, both from traumatic lesions as well as the effects of toxins and venoms. During October 1966, prominence was given to injuries to man from animals in the Australian region at the Third Convention of the Australian College of General Practitioners, with the cooperation of the Commonwealth Serum Laboratories. The Laboratories' scientific exhibits included venomous insects, spiders, snakes and fish, and have acted as a useful stimulus in this field. The Botanic Gardens, Adelaide, also arranged a display of harmful plants, and follow-up data-gathering and analysis planned in this field is proceeding. The writer has also made various further studies upon the clinical effects of various terrestrial arthropods, among them the caterpillars Roeselia, Doratifera and Euproctis, and studies on the clinical effects and ecology of these and other arthropods, such as insects, spiders and scorpions, are continuing as opportunity permits. PublicatioDs FRANCIS, D. F., and SOUTHCOTT, R. V. 'Plant injuries to man in Australia. (Botanic Gardens, Adelaide),' 1966. (Mimeographed.) KRAMP, P. L. 'Some medusae (mainly Scyphomedusae) from Australian coastal waters.' Trans. Roy. Soc. S. Aust., 1965, 89, 257-78. SOUTHCOTT, R. V. 'The bristle-worm.' Med. I. Aust., 1, 92. SOUTHCOTI, R. V. 'Revision of some Carybdeidae (Scyphozoa: Cubomedusae) , including a description of the jellyfish responsible for the lrukandji syndrome.' Aust. I. Zool. (In press.)
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VICTORIA INSTITUTES AND HOSPITALS FAIRFIELD HOSPITAL, EPIDEMIOLOGICAL RESEARCH UNIT Mrs Ruth A. Cole, B.Sc., Senior Research Officer, N.H. & M.R.C. Miss Elizabeth E. Kicld, M.Sc., Research Assistant, N.H. & M.R.C.
Project Tissue culture studies with hepatitis viruses.
Report Previous work has shown that cytopathic changes in Detroit-6 cells are readily obtainable with serum specimens from the majonty of patients with acute hepatitis, with almost all convalescent hepatitis sera, with many sera from patients with chronic and lupoid hepatitis, with neonatal hepatitis sera and with a number of non-hepatitis sera. It was presumed that these cytopathic changes denoted the presence of hepatitis virus but there was no proof that the agent (or agents) responsible were viral in nature. In co-operation with Dr Ian Holmes (Microbiology Department, Melbourne University), attempts were made by means of electron microscopy to visualise virus in Detroit-6 cells inoculated with appropriate positive sera. These studies failed to confirm those of Taylor et a!. (Parke DavIs laboratories) but Dr Holmes' work is continuing. Attempts were made to concentrate the agent by means of the ultracentrifuge, but viruslike particles could not be visualised electron microscopically in any of the fractions obtained. Since there was a low degree of cytopathic act! vity in sera and tissue culture passage material (not beyond 102 per 0.5 m!.) it was assumed that titres of viru& were too low for purification studies to be practicable. When additional sera from a variety of clinical conditions were tested a greater proportion than would have been expected were found to produce cytopathic changes. These results seemed to be meaningful in terms of hepatitis virus only if it was assumed that the virus was quite ubiquitous. A blind trial, similar in nature to the blind trial of serum specimens previously reported, was carried out simultaneously and independently by Mrs Cole and Miss Kidd. The results obtained by both workers differed from those expected and those obtained previously, and there were inconsistencies with duplicate specimens. This work was repeated by Dr Ferris working independently in another laboratory and it was found that the majority of sera, obtained from both hepatitis and control patients, produced cytopathic changes. Difficulty was also experienced with cell and passage controls on several occasions. The Detroit-6 cloned cell line was supplied to Professor Marmion and Mr Cross of Monash University m order to facilitate further independent checking of our findings. Finally a further blind trial was conducted jointly by Mrs Cole and Dr Ferris. A similar blind trial was also conducted at Monash University by Mr Cross and Professor Marmion. The results of both trials have been reported and indicate that no correlation was observed between the cytopathic effect in Detroit-6 cells and the clinical state of the donors of sera used as inocula. Inconsistencies in the results from duplicate specimens were again observed. At the present time it appears that there is no good evidence to suggest that the changes observed in the Detroit-6 cell system indicate the presence of hepatitis virus. Further work seems indicated however and it is considered possible that the agent or agents responsible for cytopathic changes may be pharmacological ra ther than viral in nature. Publication FERRIS, A. A., and COLE, RUTH A. 'Detroit-6 cells and infective hepatitis.' Med. 1. Aust., 1966, 1, 1213.
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MEDICAL RESEARCH CENTRE, PRINCE HENRY'S HOSPITAL, MELBOURNE Professor Bryan Hudson, M.D., Ph.D., F.R.A.C.P., Director. Mrs Ausma Mirovics (nee DuImanis), B.Sc., Research Assistant, N.H. & M.R.C. Dr J. P. Coghlan, Ph.D., Howard Florey Laboratories of Experimental Physiology. Mrs M. Coghlan, M.Sc., Howard Florey Laboratories of Experimental Physiology. Dr Paula Pitt, M.B., B.S., Research Fellow. Miss G. Madsen, B.Sc., Technical Officer. Project The secretion and metabolism of androgens. Report Physiological studies have been directed to measuring the interconversion between the two principal androgens, testosterone and androstenedione. This has been done by infusing trace amounts of each steroid labelled wi th tri tium, and after a constant level of radioactivity has been achieved comparing the ratios of radioactivity in the two compounds. This technique has enabled the calculation of the contributions of androstenedione to testosterone production and of testosterone to androstenedione prodll :tion. In the normal female at least 60 % of testosterone in blood is derived from androstenedione whereas less than 5% of blood androstenedione is derived from blood testosterone. In the normal male the situation is reversed: at least 40 % of blood androstenedione is derived from blood testos terone and virtually none of the blood testosterone is derived from blood androstenedione. In making these calculations it has been necessary to assume values for blood androstenedione because of current difficulties with measuring this steroid. During the year more than 100 patients with apparent abnormalities of androgen production have been studied. They have induded males with deficiencies of androgen production in whom testicular function has been evaluated by the measurement of blood testosterone with and without stimulation by human chorionic gonadotropin. In this way differentiation can be made between those patients with primary testicular disease, and those with androgen deficiency secondary to a low or absent secretion of pituitary gonadrotropin. Measurements of plasma androgens have been of material assistance in a number of patients in evaluating those children and adolescents in whom puberty is apparently delayed. Serial measurements of plasma testosterone have been used to follow the course of puberty in several of these patients. Studies of plasma androgens have been of great value in the diagnosis of three young boys with precocious sexual development, and the changes in these levels with different hormone treatment has made it possible to devise an appropriate scheme of treatment for this condition. The problem of hirsutism in the female is now becoming better understood by the study of plasma androgens. In a substantial number (in excess of 60%) of patients the level of plasma testosterone is elevated. The problem in these patients has been to determine the origin of this hormone. Manipulation of the hormonal environment by sequential adrenocortical and ovarian suppression has been of value in determining the origin of this compound and thus assisting with a rational form of therapy. In addition to these studies measurements are also being made in these patients in order to determine whether abnormalities of metabolism as opposed to secretin are present. This has been done bv applying the physiological studies referred to earlier in this report. At this stage it is not possible to state to what extent such abnormalities may be present in these patients. These studies will continue. The difficultv of measuring androstenedione in b'ood has already been referred to. The method that had been devised and found to be unsatisfactory was based on the method used for the measurement of testosterone in plasma. Over the past eight months attempts have
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been made to measure this hormone by using 3"S-thiosemicarbazine, employing methods suggested by Horton and by Lim & Brooks. A number of difficulties have been encountered with the yield and stability of the dithiosemicarbazone of androstenedione. New compounds appear to form after chromatography, the nature of which is uncertain. Publications COGHLAN, J. P .• KANE, M .• DULMANIS, A., HUDSON, B., and SCOGGINS, B. 'The measurement of concentration and metabolism of steroids in body fluids by application of double labelling procedures.' Acepta Medica Foundation. Int. Congress Series 111. Abstract 52. HUDSON, B., and COGHLAN, J. P. 'Testicular function in man.' Ciba Colloquia of Endocrinology.' (In press.) HUDSON, B., and COGHLAN, J. P. 'Testosterone secretion'. Clinical Endocrinology 2. Edited by E. B. Astwood. (In press.) HUDSON, B., DULMANIS, A., COGHLAN, J. P., and WINTOUR, M. 'The measurement of androgen production in normal SUbjects.' Aust. Ann. Med., 1966, 15, 236.
GASTROENTEROLOGICAL RESEARCH UNIT, ROYAL CHILDREN'S HOSPITAL Dr Charlotte M. Anderson, M.D., M.Sc., M.R.A.C.P., Director. Mr K. R. Kerry, B.Ag.Sc., Research. Assistant, N.H. & M.R.C. Projects Clinical investigations into the nature of secondary absorption of monosaccharides from the intestine and into the occurrence of sugar malabsorption in neonates following small bowel surgery. Determination of intestinal enzymes involved in the digestion of maltotriose in man. Comparative study of the intestinal disa::C'haridase enzymes of mammals. Report
Intestinal malabsorption of monosaccharides Five young babies in whom severe diarrhoea, commencing in the first week of life, was found to be the result of inability to absorb any monosaccharides, were studied clinically. Disaccharidase levels of duodenal mucosa were normal as was the histo~ogy. Test feeding with different sugars demonstrated the inability of these babies to tolerate disaccharides or monosaccharides. Cessation of symptoms only occurred after all sugar was removed from the diet. The disorder was temporary and there was no evidence of a genetic cause; it is possible, however, that the disorder is due to cnteric infection. Studies to elucidate the nature of the absorption defect are in progress. Sugar intolerance in the neonate following small bowel surgery It was observed that in many infants, diarrhoea commonly follows small intestinal surgery performed to overcome various forms of obs truction. In all of the eighteen such patients referred over the last two years diarrhoea was found to be associated with the intake of one or more of the normal dietary sugars. Those with lesions in the upper part of the alimentary tract tended to become intolerant of all sugars, whereas those patients with disorders of
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the large bowel requiring colostomy were intolerant of disaccharides only, usually lactose alone but occasionally sucrose as well. The nature of the disorder is not known but in some cas~s is possibly related to the finding of an overgrowth of the small bowel flora above the anastomosis.
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Intestinal digestion of maltotriose in man Patients with congenital sucrase-isomalbse deficiency have often been reported to be intolerant to starch, since maltotriose is produ:ed by the action of pancreatic amylase and represents approximately 25 % of the end products it was considered that this trisaccharide may be partially responsible. It was found tha t the intestinal disaccharidase enzymes maltase la, Ib and III all exerted some maltotriase activity. Over 80% of the maltotriase activity however was due to the maltase 1a, and 1b, whi:h are both absent in the above disorder. This finding is consistent with the maltotriase deficiency observed in sucrase-isomaltase deficient patients. Comparative study on the intestinal disaccharidases in mammals Preliminary investigations on representatives of the monotremes, the marsupials and rwo orders of placental mammals (Pinnipedie and Carnivora) have revealed marked variations in the patterns of intestinal disaccharidases. The most notable results obtained so far are the finding of the absence of sucrase in the Echid na, the Grey Kangaroo and the seals; deficiency of lactase in the seals and absence of trehalase in the domestic cat, lion, Koala Bear and the seals. Publications
BURKE, V., and ANDERSON, C. M. 'Sugar intolerance as a cause of protracted diarrhoea following surgery of the gastrointestinal tract in neonates.' Aust. Paediat. J., December 1966. MESSER, M., and KERRY, K. R. 'Intestinal digestion of maltotriose in man.' Biochim. Biophys. Acta. (In press.)
ST VINCENT'S SCHOOL OF MEDICAL RESEARCH, MELBOURNE Dr Pebr Edman, M.D., Director. Project
Microheterogeneity in protein structure. Report
~;,o..
This work is a continuation of an earlier project. Its purpose is to search for microheterogeneity in the structure, i.e. the amino acid sequence of an individual protein. Such changes could be envisaged as being caused by somatic mutations, and would then probably involve only a small fraction of the total population of a particular protein species. Changes of this kind have so far not been detected, but it is <-Iso unlikely that they would have been detected with the available techniques for structure determination. The new technique for sequence determination recently developed in the department is in principle much more suitable for the detection of microheterogeneity. However, it does require a high degree of refinement in the automated degradation technique. This stage has now been reached and it is possible to proceed with the main project.
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WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH, MELBOURNE Professor G. J. V. Nossal, M.B., B.S., D.Sc.Med., Ph.D., M.RAC.P., Director. Dr G. L. Ada, D.Sc., F.AA, Principal Research Fellow, N.H. & M.Re. Miss Pamela Giltinan, B.Sc., Research Assistant, N.H. & M.RC. Dr G. Goldstein, M.D., M.RA.C.P., Senior Research Officer, N.H. & M.R.C. Mr N. Kraft, B.Agr.Sci., Postgraduate Scholar, N.H. & M.RC. Miss Gillian Lang, B.Sc. Hans., Research Assistant, N.H. & M.RC. Dr Patricia Lind, M.Sc., Ph.D., Senior Research Officer, N.H. & M.RC. Dr I. R. Mackay, M.D., M.RC.P., F.R.A.e.P., Principal Research Fellow, N.H. & M.R.e. Dr W. H. Marshall, B.A, M.B., B.Chir., M.RC.P., Senior Research Officer, N.H. & M.R.C. Dr J. F. A. P. Miller, M.B., B.S., B.Sc.Med., D.Sc., Principal Research Fellow, N.H. & M.R.e. Mrs Judith Mitchell, M.Sc., Research Assistant, N.H. & M.RC. Mr J. Pye, B.Sc., Research Fellow, N.H. & M.Re. Dr K. Shorlman, B.Sc., Ph.D., Research Fellow, N.H. & M.R.C. Miss Lorraine Sibthorpe, B.Sc., Research Assistant, N.H. & M.RC. Miss Merrill J. Smalley, B.Sc., Postgraduate Research, N.H. & M.RC. Dr A. Szenberg, M.D., Docent, Research Fellow, N.H. & M.R.C. Dr Senga Whittingbam, M.B., Ch.B., D.e.P., Senior Research Officer, N.H. & M.Re. Mrs J Williams, B.Sc., Research Assistant, N.H. & M.RC. Project Experimental immunology and oncology. Report Following the retirement of Sir Macfarlane Burnet as Director, and the completion of building extensions known as the Nuffield-Burnet Laboratories, some re-organisation of the work of the Walter and Eliza Hall Institute has taken place. Firstly, the existing scientific staff of the Institute was divided into four main Units (Cellular Immunology, Cancer Research, Clinical Research, and Biochemistry & Biophysics) under individual Unit Heads of professorial status (Professor O. J. V. Nossal, Dr D. Metcalf, Dr I. R Mackay and Dr O. L. Ada, F.A.A., respectively). Further, a new Unit of Experimental Pathology was created, under Dr J. F. A. P. Miller, formerly of the Chester Beatty Research Institute, and Reader in the University of London. Dr Miller, a Sydney graduate in medicine who has been working in England for ten years prior to joining the Institute staff, is widely known for his pioneering work on the thymus gland and its relation to immunity and cancer. While the work of the Institute continues to centre around the body's immune defence system, there is now a considerably intensified interest in research into cancer, particularly leukaemia, and the whole of the 6th floor of the Institute has been converted to this purpose. The new 5th floor is occupied by the Cellular Immunology Unit under Professor Nossal where research into autoimmune diseases, problems of transplantation and basic immunological problems is being carried out. These two floors together constitute the NuffiedBurnet Laboratories, and were opened in August 1966, by Sir Henry Bolte. The Cellular Immunology Unit has spent much effort in working out how vaccine (antigen) m~lecules really w~rk. It is known that antigen can turn on the process of antibody formatIOn under s~me cIrcumstances and can. turn .it off, temporarily or permanently, under others. More detaIled knowledge of the way III whIch antigen can carry out these two
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apparently contradictory functions could illuminate our understanding of all human diseases with immunological implications, and particularly our understanding of the way in which the body destroys grafts such as kidney transplants, and also foreign cancer cells. Workers in the Cellular Immunology Unit have devised a new method of attacking this problem. An obvious first step is to find out exactly where antigen goes in the body. They have combined two powertools to determine this-the electron microscope which can enlarge cells 100,000 times; and radioactive atomic disintegrations which can signal the presence of single vaccine molecules. It turns out that these molecules do not go to antibody-forming cells but rather to two radically different types of scavenger cells. In one type, the antigen is placed into tiny, submicroscopic stomachs or digestive vacuoles and is broken down. In the other, it is held bound to the outer lining of the cell and makes contact with surrounding white blood cells called lymphocytes, some of which are probably triggered into growth, division and antibody production by cell surface reactions. Another approach to the kidney graft problem is to try to induce a state of non-reactivity or tolerance against the antigen concerned. Using a highly purified bacterial product, Salmonella flagella, it has been established that there are two ways of rendering animals tolerant to this antigen. In both cases, material must be given repeatedly during the first weeks of life, but the difference comes in the dosages concerned. In the so-called high dose tolerance, microgram quantities of the material are involved-still remarkably little, but much more than would be needed to immunize an adult animal. In the so-called low zone tolerance, less than one-millionth of a microgram given repeatedly can be effective. These truly minute doses are such as would not immunize an adult animal. It may, one day, be possible to use similar low do. age schedules in attempts to induce immunological tolerance to constituents of kidney grafts in man. Another facet of the Cellular Immunology Unit's interests is autoimmune di5ease of NZ mice. In particular, a study has been made of the kidney condition of female 'B/W' hybrid mice. This closely resembles certain severe forms of human nephritis and is 100 per cent fatal. It has been found that prolonged treatment with the drug cyclophosphamide will arrest kidney damage, and will prevent it if it has not yet occurred. Established renal damage, however will heal by scarring and, though the life-span of a treated mouse is greatly prolonged, the kidneys will not return to complete normalcy. Significantly, even a brief course of treatment at the early stages will reduce the progress of renal trouble. This is an encouraging finding, because in the human situation, the adverse side-reactions of lymphocyte-destroying drugs may make prolonged, high dose treatment undesirable. The Cancer Research Unit under Dr Metcalf has been actively engaged in two areas of cancer research: firstly the immune responses in old age and in animals developing leukaemia and secondly cultivation of bone marrow cells in vitro. The question of the competence of the immune system in old age and cancer is an important one. It is now apparent that immune responses are employed by the body as a highly effective defence system against cancer development. Abnormal cells arising in the body and containing foreign substances on a surface which the body can recognise as being forei~n, are held in check or killed by immune lymphocytes. If this defence system fails, these cells may be allowed to grow and lead to the formation of cancer. It has been suggested that with increasing age there may be a gradual breakdown of this normal defence mechanism and that this may be responsible in large part tor the high incidence of cancer in the elderly. Investigations in mice have now revealed that deficiencies do develop in immune responses in old age and some of the factors responsible for this fall off in immune competence have been identified. An active study is now in progress on the ability of various procedures, e.g. lymphoid organ grafting and lymphoid cell injections to restore or improve the immune responses with ageing. Contrary to what is now helieved by some, abnormal immune responses do not however seem to be a necessary prerequisite for leukaemia development. 4275/67-12
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One of the major drawbacks in leukaemia research in the past has been the inability to grow bone marrow cells responsible for this disease outside of the body. A new technique has been developed which for the first time allows the cultivation of these cells in a solid agar media replacing the old method of liquid culture, which in the past has proved unsuitable for main taining these cells in their natural state and with specialised functions. Bone marrow cells in this culture system form large colonies which can be counted and statistically evaluated. Colony forming cells have been found in the bone marrow and in other areas, particularly the spleen and the blood, but in no other organs. This new technique has already greatly increased our understanding of normal bone marrow cells and the reasons for their abnormal behaviour in leukaemia development, and the technique should have many future applications in haematology, immunology and cancer research. Of special interest has been the finding that very small doses of serum from mice with virus-induced leukaemia and some humans with lymphoid leukaemia are capable of stimulating colony formation from normal bone marrow cells when grown in this system. The nature of this serum factor is under intense investigation. The Clinical Research Unit of the Institute is continuing investigations into the causation and treatment of diseases related to immune disorders, particularly autoimmune diseases. Such diseases are believed to occur as a result of an interaction between an individual's immune system and one or another of the tissues of the body. Pernicious anaemia, chronic hepatitis, myasthenia gravis and multiple sclerosis are being investigated in the Clinical Research Unit from the autoimmune standpoint. Pernicious anaemia has been shown to be associated wir.h a familial tendency to form autoantibodies which may damage the stomach resulting in a failure to absorb a food factor essential for the formation of blood. An autoimmune reaction has been shown to be operative in chronic hepatitis and appears to cause the transition .)f this disease to cirrhosis of the liver; a new form of drug treatment for hepatitis, azathioprine, is being used to arrest or prevent this transition. Myasthenia gravis, a disease of muscle, is believed to have its origin in an autoimmune reaction in the thymus gland; strong evidence for this was obtained from work within the Unit wherein animals immunised with thymus developed the features of human myasthenia gravis. Another promising animal model of human disease, multiple sclerosis, is being investigated in the Clinical Research Unit in collaboration with the Department of Biochemistry of the University of Melbourne. A small highly active polypeptide extracted from brain tissue was used to immunise animals and brain disease resulted even with doses smaller than one millionth part of a gram. An immune reaction to a similar material in human brain could be concerned in the development of multiple sclerosis. A strong effort is being made in the Clinical Research Unit to apply electronic processing techniques by computers to the storage and analysis of medical records. Although initial difficulties were encountered, a system is now operative whereby a synopsis of entire records can be transferred from typed records through collection forms, punch cards, and onto magnetic tape. The pathology section of the Clinical Research Unit developed a method for producing cancer of antibody-forming cells in the hybrids of two special inbred strains of mice, one strain being susceptible to cancer and the other to autoimmune disease. The tumour cells ;n these hybrids produced unique antibody molecules, the analysis of which is proving extremely valuable in understanding control mechanisms over the manufacture of blood proteins in health and disease. Work studied in the Biochemical and Biophysical Unit has been concerned with reactions which take place at the cellular level and have involved techniques which allow separation .,f classes of cells from mixed cell populations and classes of sub-cellular components of cells. One of two problems of immediate interest has been the separation of different categories of cells from mixtures of lymphoid cells obtained from spleen or lymph nodes of experimental animals. These cells were subjected to centrifugation in density gradients of
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bovine serum albumin solution. In such gradients it was found that large, medium and small lymphocytes were largely separated from each other as had been expected to happen; in addition, however, it was found that each of these major classes of lymphocytes was heterogeneous, and were separated into two or three further categories according to their density. The technique has had immediate application in two problems in the Institute. The first case was the isolation of those cells from fowl blood which were responsible for initiating graft versus host reactions when injected into chick embryos. It was shown that the cells concerned belonged to a small lymphocyte category. In the second case, cells removed from an animal previously injected with an antigen were studied. If these cells were taken at an appropriate time after antigen injection, antibody-forming cells were recovered from the density gradient. They were found to be located in a part of the gradient free from most other cells so that a great enrichment of these cells was obtained. This was a first step towards future biochemical studies on antibody producing cells. The other problem has been the study of factors present in leukaemic serum which allow growth of bone marrow cells in tissue culture. This was carried out in association with colleagues in the Cancer Research Unit. The factor(s) is present in serum from leukaemic mice and some headway has been made in characterising it. Of particular interest was the finding that under appropriate conditions the factor will sediment in a centrifugal field and this raises the possibility that the active agent may be a virus. The techniques used to study the factor in mouse leukaemic sera are also being used to study factors in human leukaemic sera which have a similar activity. The lymphocyte population of neonatally thymectomised CBA mice has been studied in the Experimental Pathology Unit in order to obtain a more precise definition of the immunological defects that exist in such mice. Using the technique of thoracic duct cannulation we have found that the output of lymphocytes over a period of three days at the age of five weeks in neonatally thymectomised mice is 95 to 99 per cent below that of normal or sham-operated controls of the same age. There are indications that qualitative defects also exist in the reduced population of circulating lymphocytes in the thymectomised mice. Tests have revealed the existence of only very few normal antigen-reactive cells in the population of lymphocytes in thymectomised mice (6 to 12 such cells per five week-old thymectomised mouse in contrast to about 6000 per control, using sheep erythrocytes as antigen). The tests have also revealed a dilution of these few rea:tive cells by other cell types, which are insensitive to the antigen. Normal responsiveness to sheep erythrocytes can be conferred upon neonatally thymectomised mice by introducing pure populations of lymphocytes, presumably free of macrophages. In addition antigen-reactive cells are capable of proliferating and differentiating to antibody-producing progeny as efficiently in thymectomised hosts as in sham-operated controls. This suggests strongly that the thymus must exert its influence on the development of the precursors of antigen-reactive cells. Once these cells have matured, their subsequent behaviour no longer depends upon the thymus but upon antigen. An assay for the precursors of antigen-reactive cells is being developed in vivo and in vitro. Such an assay will give us a more powerful means of studying the biological activity of various extracts of thymus tissue. Publications ADA, G. L. 'Specialized cell function in the lymphoid and reticulo-endothelial cell series.' Immunity, Cancer and Chemotherapy, An International Symposium. AUSTIN, C. M. 'Studies on the migration of lymphoid cells in the presence of antigen.' Proc. Aust. Soc. Med. Res. (Abstract), 1966 2, 38. AUSTIN, C. M., and NOSSAL, G. J. V. 'Mechanism of induction of immunological tolerance. III. Cross-tolerance amongst flagellar antigens.' Aust. I. expo Bioi. med. Sci., 1966, 44, 341.
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BRADLEY, T. R., and METCALF, D. 'Colony growth of bone marrow cells in vitro.' Proc. XIth Congo Inst. Sco. Haematol. (Abstract), 1966, 156. BURNET, F. M. 'Studies on autoimmune disease in NZB mice. I. Autoimmune haemolytic anaemia.' Journal of the Royal Institute of Hygiene, 1966. BURNET, F. M. 'Studies on autoimmune disease in NZB mice. II. Renal and thymic disease.' Journal of the Royal Institute of Hygiene, 1966. BURNET, F. M. 'Studies on autoimmune disease in NZB mice. III. Genetics and pathogenesis of autoimmune disease.' Journal oj the Royal Institute of Hygiene, 1966. BURNET, F. M. 'The concept of autoimmunity.' Proc. 11th Congress of the International Society for Blood Transfusion. Plenary s ?ssions, 1966, p. 202. CARNEGIE, P. R., LAMOUREUX, G., and BENCINA, B. 'A technique for classifying and identifying encephalitogens.' Nature. DIENER,"E. 'The immune response in NZB and NZB X C3H Fl-hybrid mice as measured by the haemolysin plaque technique.' Int. Arch. Allergy, 1966, 30, 120. DIENER, E., and EALEY, E. H. M. 'Phylogenetical development of the immune system with special reference to the primitive mammals, Echidna and Platypus.' Proc. oj the Xlth International Congress oj Haematology (Plenary Sessions), 1966, p. 37. GOLDSTEIN, G. 'Host resistance to cancer,' ANZJ Surgery, 1967, 39, 238. GOLDSTEIN, G. 'Plasma cells in the human thymus.' Aust. J. expo Bioi. med. Sci, 1966,44, 695. GOLDSTEIN, G. 'Mast cells in the human thymus.' Aust. J. expo Bio. med. Sci., 1966, 44. 593. GOLDSTEIN, G., and MACKAY, I. R. 'Lupoid hepatitis. Computer analysis defining "Hepatitis" and "Cirrhosis" phases and relationships between hepatocellular damage and immune reactions in the liver.' Aust. Ann. Med. GOLDSTEIN, G., and WHITTINGHAM, S. 'Myasthenia gravis due to experimental thymitis in guinea pigs.' Lancet, 1966, 2, 315. HOLMES, M. C. 'Autoimmune haemolytic anaemia.' Proc. 11th Congress 0/ the International Society for Blood Transfusions, Plenary Sessions, 1966, p. 226. HOLMES, M. C., and BURNET, F. M. 'The characteristics of Fl and backcross hybrids between "high leukaemia" (AKR) and "autoimmune" (NZB) mouse strains.' Aust. J. expo Bioi. med. sci., 1966, 44, 235. JAROSLOW, B. N. J., and NOSSAL, G. J. V. 'Antigen localization in lymph nodes of Xirradiated rats.' Federation Proceedings (Abstract), 1966,25,612. JAROSLOW, B. N. J., and NOSSAL, G. J. V. 'Effects of X-irradiation on antigen localization in lymphoid follicles.' Aust. J. expo Bioi. med. Sci., 1966, 44, 609. JAROSLOW, B. N., and SHORTMAN, K. 'Restoration of Actinomycin D-inhibited antibody synthesis by RNA digests.' Journal of Infectious Diseases. LEGGE, J. S. 'Decline of immunological competence with age, Its relation to antigen localization.' Proc. Aust. Soc. Med. Res. (Abstract), 1966, 2, 39. LEGGE, D. G., and SHORTMAN, K. 'Analysis and purification of antibody-forming lymphocytes using density gradient centrafugation.' Proc. Aust. Soc. Med. Res. (Abstract), 1966, 2, 39. MACKAY, I. R. 'Autoimmune disease in humans.' Proc. 11 th Congress 0/ the International Society for Blood Transfusion Plenary Sessions, 1966, p. 233.
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MACKAY, I. R. 'The effects of alcohol on the gastrointestiual tract.' Med. J. Aust., 1966,2, 372. MARSHALL, W. H., RIGO, S. J., and MELMAN, S. 'Lymphocyte transformation and mitosis in vitro initiated by homologous macrophages. An improved method for histocompatability testing.' Lancet, 1966, I, 730. METCALF, D. 'The thumus, Its role in immune responses, leukaemia development and carcinogenesis.' Recent Results in Cancer Research, 1966, S, Berlin, Springer-Verlag. METCALF, D. 'Histological and transplantation &tudies on the preleukemic AKR mouse thymus.' Journal oj the National Cancer Institute, 1966, 37, 425. METCALF, D. 'Biology of the immune system.' W.H.O. Scientific Report Series: 'Immunotherapy oJ Cancer.' METCALF D. 'The role of the thymus in autoimmunity.' Proc. 11th Congress of the International Society jor Blood Transfusion. (Plenary Sessions), 1966, p. 220. METCALF, D. 'The kinetics of lymphocyte production in the normal and neoplastic thymus.' Proc. Xlth Congress International Society of Haematology (Abstracts), 1966, 31. METCALF, D., and BRUMBY, M. 'Migration of cells to the thymus demonstrated by parabiosis.' Proc. Soc. expo Bioi. med. Sci, 1967, 124, 99. METCALF, D., and BRUMBY, M. 'The role of the thymus in the ontogeny of the immune system.' J. Cell. Compo Physiol. Suppl. Gatlinburg Symposium Oak Ridge National Laboratory, 1966. Suppl. 1 to 67, 149. MILLER, J. F. A. P. 'Biology of the immune system.' 'Clinical aspects of immunology,' ed. by P. G. H. Cell and R. R. A. Coombs, 2nd ed., Oxford, Blackwell. MILLER, J. F. A. P. 'The function of the thymus in immunity: Evidence from experiments in rodents.' Hospital Medicine, 1966, 1, 199. MILLER, J. F. A. P. 'Lymphoid cells and the thymus.' Proceedings of the XIth International Congress in Haematology (Plenary Sessions), 1966, p. 19. MITCHELL, J., and NOSSAL, G. J. V. 'Mechanism of induction of immunological tolerance, I, localization of tolerance-inducing antigen.' Aust. J. expo BioI. med. Sci., 1966, 44, 211.
MITCHELL, G., WEISS, N. S., and MILLER, J. F. A. P. 'The influence of the thymus on the pool of immunologically competent cells.' Proc. Aust. Soc. Med. Res. (Abstract), 1966,2,40. MOULDS, R. 'The effects of cortisone on the primary immune response of mice to sheep red blood cells.' Proc. Aust. Soc. Med. Res. (Abstract), 1966, 2, 40. NOSSAL, G. J. V. 'The biology of the immune response.' Conference Monograph of the Intensive Study Programme of the Neurosciences Research Programme of the Massachusetts Institute of Technology, Boulder, Colorado, 1966, ed. by F. O. Schmitt. NOSSAL, G. J. V. 'Single cell studies on the antigen-content of plasmablasts during the inductive phase of antibody formation.' Symposia oj the Tissue Culture Association, 2, ed. by M. N. Goldstein. NOSSAL, G. J. V., and ABBOT, A. 'Antigen-induced proliferation amongst lymphoid cells.' Proceedings of the 7th Canadian Cancer Conference, held at Honey Harbour, June 1966. NOSSAL, G. J. V. 'The future of medical research in Australia.' Proceedings of a Symposium organised by the Australia Association of Ethical Pharmaceutical Industry, Svdney, Nov 1966. NOSSAL, G. J. V. 'Contributions to Symposium on Rh immunization.' Proceedings of the Xlth International Congress on Haematology (Abstract), 1966, p. 74. ~.'
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NOSSAL, G. J. Y. 'Principles of antibody production.' Froc. 11th Congress of the International Society for Blood Transfusion. (Plenary Sessions), 1966, p. 212. NOSSAL, G. J. Y., and ABBOT, A. 'Lymphoid cells and antibody formation.' Proceedings of the XIth International Congress on Haematology (Plenary Sessions), 1966, p. 5. NOSSAL, G. J. Y., and AUSTIN, C. M. 'Mechanism of induction of immunological tolerance. II. Simultaneous development of priming and tolerance.' Aust. I. expo Bioi. med. Sci., 1966, 44, 327. ROBINSON, W., BRADLEY, T. R., and METCALF, D. 'In vitro colony production from bone marrow cells by leukemic serum.' Proc. XIth Congress of the International Society of Haematology, 1966, p. 313. RUSSELL, P. J. 'Autoi=une renal disease, Antigen-antibody complex of nephrotic serum nephritis.' Proc. Aust. Soc. Med. Research (Abstract), 1966,2,42. RUSSELL, P. J., HICKS, J. D., and BURNET, F. M. 'Cyclophosphamide treatment of kidney disease in (NZB X NZW) Fl mice.' Lancet, 1966, I, 1279. SHELLAM, G. 'A model system for the induction of immunological tolerance in adult rats. Proc. Aust. Soc. Med. Res. (Abstract), 1966, 2, 43. SZENBERG, A., and SHORTMAN, K. 'Fractionation of fowl blood lymphocytes by their buoyant density, Localization of cells active in graft versus host reactions. Annals of the New York Academy of Sciences. SZENBERG, A., and WARNER, N. L. 'The role of antibody in delayed hypersensitivity.' British Medical Bulletin, 1961, 23, 30 WHITTINGHAM, S., IRWIN, J., MACKAY, 1. R., and SMALLEY, M. 'Smooth muscle autoantibody (SMA) in autoimmune hepatitis.' Gastroenterology, 1966, 51, 499. WHITTINGHAM, S., and MACKAY, I. R. 'Autoimmune aspects of Myasthenia Gravis.' (Presented at the Annual Meeting of the Association of Neurologists, Adelaide, May 1966). Proceedings of the Australian Association of Neurologists. WHITTINGHAM, S., MACKAY, I. R., and IRWIN, J. 'Autoimmune hepatitis, immunofluorescence reactions with cytoplasm of smooth muscle and renal glomerular cells.' Lancet, 1966, I, 1333. WILLIAMS, G. M., and NOSSAL, G. J. Y. 'Ontogeny of the immune response. I. The development of the follicular antigen-trapping mechanism.' lournal of experimental Medicine, 966, 124, 47. WILLIAMS, G. M. 'Ontogeny of the immune response. II. The development of antibodyforming capacity and immunological memory.' Journal of experimental Medicine, 1966, 124, 57. WILLIAMS, G. M. 'Antigen localization in lymphopenic states. 1. Localization pattern following chronic thoracic duct drainage.' Immunology, 1966, 11, 467. WILLIAMS, G. M. 'Antigen localization in lymphooenic states. II. Further studies on whole body X-irradiation.' Immunology, 1966, 11,475.
c.
J. MARTIN OVERSEAS TRAVELLING FELLOWSHIP
Dr J. A. Young, M.D., B.S., B.Sc. C. J. MARTIN FELLOWSHIP The Fellowship was awarded to enable work to be undertaken with Professor K. J. Ullrich, in the Physiology Institute of the Free University of Berlin, on problems involving micropuncture analysis of molecular transport across renal tubular and other biological membranes. Work commenced in Berlin on 15 February 1965 and ceased there on 29 July 1966. With the approval of the Council a number of weeks was spent in the United States of America visiting various laboratories and presenting work at two international symposia. Dr Young returned to Australia on Thursday, 6 October 1966. Report The project originally proposed by Professor Ullrich, a micropuncture investigation of urca transport in the medullary structures of the rat kidney, was almost completed prior to Dr Young's arrival in Berlin. Alternative investigations were suggested and, in consultation with Professor H. M. Whyte, it was decided that sodium, potassium and fluid transport across the duct epithelium of the rat submaxillary gland should be studied. In 1964, Professor Ullrich and his co-workers had studied the osmolality and sodium chloride concentrations from fluid collected from different levels of the submaxillary duct system at rest; the present project was intended to extend this investigation in two directions; firstly, by analysis of the composition of precursor saliva not only in the unstimulated gland but also in the gland following parasympathomimetic stimulation, and secondly by extension of the investigation to include a study of potassium transport since it was known that submaxillary saliva is rich in this cation. An initial period of five weeks was devoted to the acquisition of the special techniques associated with micropuncture and microanalytical work. These included the construction and sharpening of glass microcapillaries and polyethylene microcatheters, and various operative procedures for the preparation of organs such as kidney and submaxillary gland for micropuncture also studied were the procedures for performing micropuncture including the use of micromanipulators, the construction and calibration of glass micropipettes and the manipulation under oil of minute samples of biological fluid preparatory to microanalysis. The techniques of the analysis of the composition of volumes of fluid of the order of one micro litre by means of cryoscopy, flame photometry and spectrophotometry as adapted for ultra-micra work were also acquired. Techniques for the analysis of osmolality and sodium and chloride concentrations were already in use in the laboratory. It was necessary, however, to develop a procedure for the ultramicro determination of potassium. The necessary apparatus was designed and built in the institute workshop and put into operation. A procedure was devised whereby sodium and potassium could be determined simultaneously in volumes of biological fluid as small as 0.1 manolitres. The apparatus gave accurate reproducible results to within 1.0-1.5 mEq/l. Free-flow studies: Precursor saliva was sampled from four levels of the salivary duct system: the acinarintercalated duct region, lobar ducts, upper main duct, and lower main duct. In the unstimulated gland the acinar-intercalated duct fluid was found to be plasma-like with respect not only to sodium chloride and osmolality, but also to potassium concentrations. During passage along the salivary duct system there was a progressive rise in the potassium concentration and a fall in the sodium concentration and in the osmolality so that final saliva was slightly hypotonic, with sodium concentration less than 5 mEq/1, and potassium concentrations greater than 100 mEq/l. Following stimulation of the gland with parasympathomimetic drugs, the composition of the acinar-intercalated duct fluid was not altered but the composition of saliva collected from
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C. J. Martin Overseas Travelling Fellowship
other levels of the gland duct system were profoundly hypotonic with low sodium concentrations and only moderately increased potassium concentrations. Final saliva had an osmolality of 100 mOsm/kg or less, with sodium concentration less than 5 mEq/l, and potassium of about 32 mEq/1.
Perfusion studies: In order to characterise the electrolyte transport processes more closely, a segment of the main duct was cannulated at either end with polyethylene microcatheters and perfused at various rates with solutions containing inulin as a marker of water shifts. Perfusion with Ringers solution revealed a nett outward movement of sodium (from lumen to interstitium) until the intraluminal sodium concentration fell to a steady-state value of 2.5 mEq/ I. Concomitantly there was a small nett inward movement of potassium until a steady-state concentration of 135 mEq/ I. was present. The imbalance between sodium efflux and potassium influx resulted in the development of a slight degree of hypotonicity. Perfusion of the duct with sodium-free solutions of choline chloride (isotonic) or mannitol (isotonic and hypotonic) reversed the direction of sodium flux but this nett inward sodium flux ceased when the steady-state concentration of 2.5 mEq/1. had developed within the lumen. In these experiments there was a 50 per cent reduction in the magnitude of potassium influx and, although nett influx decreased as the intraluminal potassium concentration rose, It did not cease altogether since the steady state concentration was not attained even after a contact time of twenty minutes. Potential studies: Trans-epithelial potential differences were measured during perfusion of the duct with Ringers solution, choline chloride solution, potassium chloride solution, and various mixtures of these. When the duct was filled with Ringers solution there was a stable transmural potential difference of -70 mY (lumen negative). When the duct was filled with a high potassium, low sodium fluid this potential fell to a stable value of -11 mY. When perfused with a series of solutions with sodium concentrations ranging between 150 mEq/1. and zero an approximately logarithmic function between potential d ilIerence and intraluminal sodium concentration was revealed. General conclusions relating to the sodium, potassium and fluid transport were derived from the overseas study. The rat submaxillary gland elaborates an isotonic primary secretion with a plasma-like sodium, chloride, and potassium composition in the acinar-intercalated duct region of the gland. Stimulation can cause an increase in the rate of formation of this secretion without change in its electrolyte composition. The primary salivary secretion passes from the site of its formation to a region of the sublobular ducts with low water permeabilitv, where sodium is reabwrbed in excess of water, to produce a hvpotonic low-sodium fluid. This results in the development of a steady-state sodium concentration of about 2 mEq/ I. Only at a maximal flow rate does the contact time necessary for the development of this steady-state become insufficient with a consequent rise in the concentration of saliva leaving the duct segment. In the sublobular ducts, in a region thought to be co-extensive with the reg;on of sodium reabsorption, is a mechanism capable of secreting potassium to produce a steadystate concentration of about 135 mEq/1. The contact time necessary for this to develop is very great so that all except the lowest flow rates potassium concentrations in fluid leaving the duct segment are less than the steady-state value. After leaving the sublobular duct electrolyte transport segments the saliva passes to a region of the duct system probably in the upper parts of the lobar duct tree where re-equilibration with plasma tends to occur. The contact time required for this to occur is great and the effect is therefore only evident at very low rates of salivary flow. Finally, the saliva passes along the main excretory duct where further sodium reabsorption in excess of water and potassium secretion takes place. This
C. I. Martin Overseas Travelling Fellowship
177
results in the re-establishment of high potassium low sodium steady-state concentrations at very low rates of salivary flow. At higher flow rates, however, contact time becomes insufficient and main duct function becomes inconspicuous. The processes for sodium and potassium transport in the sublobular ducts and in the main duct are both considered to be active. Potassium secretion, however, is enhanced by favourable transmural electrical driving forces which are believed to be associated with the process of active sodium transport. Publications FR6MTER, E., YOUNG, J. A., SCH6GEL, E., and HAMANN, K. F. 'Reabsorption of sodium and secretion of potassium by the main excretory duct of the rat submaxillary gland.' Proc. Int. Cysticfibrosis Congress, Grindelwald, Switzerland, 1966. eds K. J. Ullrich and H. Wirz. SCH6GEL, E., and YOUNG, J. A. 'Micropuncture and perfusion investigation of sodium and potassium transport in the rat submaxillary gland.' I. Physiol. (Lond.), 1966, 183, 73. YOUNG, J. A., FR6MTER, E., and SCH6GEL, E. 'Electrolyte fluxes and potential differences in the main excretory duct of the rat submaxillary gland.' Pfiugers Arch. ges. Physiol., 1966, 289, SR 81. (Abstract.) YOUNG, J. A., and SCHOGEL, E. 'Micropuncture investigation of sodium and potassium excretion in rat submaxillary saliva.' P{liigers Arch. ges. Physiol., 1966, 291, 85. YOUNG, J. A., FR6MTER, E., SCH6GEL, E., and HAMANN, K. F. 'Micropuncture and perfusion investigation of electrolyte transp)rt in the ducts of the rat submaxillary gland.' Proc. 3rd Int. Congr. Nephrology, Washington, 1966,2,299. (Abstract.) YOUNG, J. A., FR6MTER, E., SCH6GEL, E., and HAMANN, K. F. 'Micropuncture and perfusion studies of fluid and electrolvte transport in the rat submaxillarv gland. in " MECHANISMS OF SALIVARY SECRETION AND THEIR REGULATION'" eds L. Schneyer and C. Schneyer, Academic Press, New York, 1966.
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NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL MEDICAL AND DENTAL RESEARCH SCHOLARSHIPS These Scholarships are provided to assist medical and dental students to extend their undergraduate courses to study for the B.Med.Sc. or equivalent degrees. The universities receiving these Scholarships determine the individual students to receive the N.H. & M.R.C. stipends appropriate to the Scholarship. The stipends have been set out at a range of $260$400 per annum so that universities can select the appropriate amount to be awarded to individual students taking into account the amount permitted without affecting the Commonwealth Scholarship living allowance. There has been a continuing demand for these Scholarships. thirty-four of which were awarded to the universities during the year.
NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL POSTGRADUATE MEDICAL AND DENTAL RESEARCH SCHOLARSHIPS At the 59th Session in May 1965 the Council recommended the award of a number of N. H. & M.Re. Medical and Dental Postgraduate Research Scholarships for graduates undertaking full time studies in research. Each university having a Medical or Dental School was invited to make application for the number of Scholarships required and the appointments to these scholarships were to be made by the universities. During 1966 the first of these Scholarships were taken up by the following graduates: University University of Adelaide Dr C. G. LUKE, M.B., B.S. Dr V. R MARSHALL, M.B., B.S. Projects
Mr J. M. McINTYRE, B.D.Sc. University of Melbourne Dr G. S. HARRIS, M.B., B.S.
Chelation in the absorption of metals in man. The effect of homograft rejection on the function of the reticulo endothelial system. The discrimination of phagocytosis by invertebrate cells.
Dr F. R TRINKER, M.B., B.S. Monash University Dr M. D. JONES, M.B., B.Chir. University of Queensland Dr J. R. BOURKE, M.B., B.S. University of Sydney Dr J. W. DONOVAN, M.B., B.S.
A study of physiological and biochemical aspects of hyaluronic acid. Pharmacology of antidepressant drugs.
Aspects of the control of bone growth in organ culture.
Studies in measurement of thyroid stimulating hormone in blood.
An inquiry into the decline of mortality in New Zealand over the last hundred years, relating the findings of the official statistics to recent researches into the theory of epidemics.
N.H. & M.R.C. Scholarships
179
Dr A. H. GOODMAN, M.B., B.S.
Dr J. LEICESTER, M.B., B.S.
Dr A. SINGER, M.B., B.S ... Miss Sophia JACUBOWSKI, B.D.S. University of Western Australia Dr P. L. THOMPSON, M.B., B.S.
The application of genetic theory to the large scale incidence of disease and to specific medical problems. An inquiry into the accuracy of clinical pathological procedures. An investigation of blood flow and blood flow measurement in health and disease. Includes an investigation of normal and more particularly abnormal cardiovascular physiology, chiefly with respect to atherosclerotic vascular disease. Study of pattern of degeneration of the retinal ganglion cells in the monkey following lesions in the central nervous system and particularly the optic tract. A quantitation of certain environmental factors within the cervical canal. Electronmycroscopic studies of bone pathology.
Investigation into rabbit car window techniques, using various toxins, on developing capillaries and established blood vessels.
DIABETES SURVEY IN GOULBURN AND TOOWOOMBA Dr D. C. WALLACE, M.B., B.S., M.R.C.P., M.R.A.C.P. Dr D. 1. McCRACKEN, M.B., B.S. Report
Large scale pilot diabetes surveys were conducted successfully in Goulburn, New South Wales, and Toowoomba, Queensland, in May and June 1966. The surveys were carried out by local committees of citizens and medical practitioners of the two cities in co-operation with the Australian College of General Practitioners and the State Departments of Health and under the supervision of the ad hoc Diabetes Survey Sub-Committee of The Public Health Advisory Committee, N.H. & M.R.C. The surveys were based upon the self-testing of urine samples using a glucose oxidase strip and entering the results together with other information (age, sex, history of diabetes, etc.) on a card which was then returned in a sealed envelope to a medical sub-committee for evaluation. Those respondents with a positive test for glycosuria were then invited to have a glucose tolerance test. Those whose glucose tolerance tests were regarded as significant were then referred to their private medical practi tioner for follow-up, advice or treatment. The principal aim of the surveys was to determine the incidence of unrecognised diabetes mellitus in these communities as accurately as possible and hence concerted efforts were made to obtain the maximum response in terms of test-strips used and cards completed and returni:d to the medical sub-committees.
180
N.H. & M.R.C. Scholarships
In Toowoomba, 33,000 adults were invited to participate, 23,546 responded (71 per cent), 840 (3.5 per cent) reported glycosuria "tnd on further testing, 124 (0.52 per cent) were found to have previously unrecognised diabetes. In Goulburn, the whole population over the age of five years was included in the survey. Respondents totalled 15,783 (88 per cent), 414 (2.6 per cent) reported glycosuria and on further testing 37 (0.23 per cent) were found to have previously unrecognised diabetes. Each card in the survey contained information on age, sex, colour changes of the test-strip and relevant history of glycosuria or diabetes. In addition, the full details of the glucose tolerance tests on those with glycosuria at the surveys and of various control population samples are available. This epidemiological information has been entered on IBM cards and will be processed and reported on in 1967. A preliminary report on the surveys was presented to the Public Health Committee at the 63rd Session of Council (October 1966). Adviso~y
THE AUSTRALIAN JOURNAL OF EXPERIMENTAL BIOLOGY AND MEDICAL SCIENCE Report Continued support was provided by the Council and during the year seventy papers were published in the Journal from a total of 112 submitted. The total number of pages printed was 718, compared to 680 pages in 1965. The published papers can be divided into the following categories: 14 (of which 10 needed some modification) Physiology 11 (of which 4 needed some modification) Pathology .. Microbiology 6 (of which 5 needed some modification) Biochemistry 7 (of which 5 needed some modification) Immunology 16 (of which 8 needed some modification) 3 (of which 3 needed some modification) Virology 13 (of which 9 needed some modification) Biology
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Circulation figures have increased over recent years and in 1966 1,300 copies were distributed. No special issues were printed during the year. The Editorial Board was enlarged during 1966 to include Professor R. F. Whelan, and at the end of 1966 Dr C. R. Jenkin and Professor R. C. N aim retired by rotation. The following scientists have accepted an invitation to join the Editorial Board in 1967, onwards: Dr Donald Metcalf of the Walter and Eliza Hall Institute. Dr Bruce Holloway, Microbiology Department, University of Melbourne. Dr I. S. de la Lande, Department of Human Physiology and Pharmacology, University of Adelaide. Dr A. B. Roy, Department of Physical Biochemistry, Australian National University.
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GRANTS FOR ROAD SAFETY RESEARCH The Council has set up a Traffic Injury Committee to inquire into the factors of medical significance in the causation, prevention and treatment of injuries in traffic accidents. During the year a grant from the Medical Research Endowment Fund was recommended to mt'et lIalf of the publication expenses for 1,500 copies of the report of the joint National Health and Medical Research Council-Australian Road Research Board 'on the spot' project in Brisbane. A grant of $2,000 was also made for the publication of 1,000 copies of the report 'Traffic Injury in Brisbane' by Drs Jamieson and Tait for free distribution.
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WOLFSON FOUNDATION OF THE UNITED KINGDOM
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During the year the Council assisted the Australian Postgraduate Federation in Medicine and its affiliated committees in the States in tlIe final distribution of a grant from the Wolfson Foundation of the United Kingdom. This grant, totalling $100,000 has been used to improve the facilities available for education, at a postgraduate level, for general practitioners and specialists throughout Australia. It has also been used to assist in meeting the travelling expenses of overseas lectures, to increase libr3ry facilities, to hold a medical conference via international cable between doctors at an Australian hospital and at a hospital in the United States of America, and to begin a survey of 'he postgraduate educational needs of the country general practitioners.
MRS PRECILA MAY BOWLING BEQUEST The late Mrs Precila May Bowling stated in her Will that the residue of her Estate should be applied for the assistance and support of medical or scientific research. The trustees have previously taken the advice of the Council in making distributions of the Estate and during the year the Council recommended that the Trustees be advised to distribute the final residue of the Estate as a grant of $574 to Professor R. F. Whelan, Department of Human Physiology ani Pharmacology, University of Adelaide, for his investigation into the nervous and humoral control of blood vessels in man. Since 1963 grants totalling $45,000 have been distributed from the Estate. The Council recommended that a letter of appreciation be $ent to the Trustees on behalf of the Council and the recipients of grants for the considerable mpport given to medical research in Australia from the Bowling Estate.
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RENEWALS AND NEW GRANTS FOR THE YEAR 1967 On the advice of the Medical Research Advisory Committee, the membership of which is given in Appendix V, on page 202, The National Health and Medical Research Council recommended that the grants be made for the projects listed hereunder:
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UNIVERSITY OF ADELAIDE Department of Biochemistry Professor W. H. Elliott (Renewal) Isolation of aminolevulinic acid synth::tase. Department of Child Health Professor G. M. Maxwell-Dr R. B. Elliott (New Grant) Investigation of nutritional and microbiological factors as causes of diarrhoea in Australian Aboriginal children. Department of Dental Science Professor J. C. Thonard (New Grant) Metabolism of human gingival epithelium. Department of Human Physiology and Pharmacology Professor R. F. Whelan (Renewal) Nervous and humoral control of blood vessels in man. Dr I. S. de la Lande (Renewal) Analysis of venom of Myrmecia pyriformis, the sandlly (family ceratopogenidae). Dr S. L. Skinner (Renewal) Physiology of the renin-angiotension system. Department of Medicine Professor D. J. Deller (New Grant) Studies of mucoviscidosis and gall stone formation. Professor B. S. Hetzel (Renewal) Thyroid function in health and disease. Dr I. J. Forbes (Renewal) Studies of human lymphocyte function. Department of Microbiology Professor D. Rowley (Renewal) Mechanism of acquired resistance to intracellular parasites. Dr C. R. Jenkin (Renewal) Synthesis of artificial antigens. Department of Obstetrics and Gynaecology Dr R. I. Cox (Renewal) Studies on the control or gonadal adrenocortical and pituitary function. Dr E. M. Symonds (New Grant) The correlation of foetal heart action and acid-base status. Department of Surgery Dr J. S. Charnock (Renewal) Mechanism of cation transport.
Renewals and New Grants for the year 1967
183
Dr P. R. Knight (New Grant) Effect of homograft rejection on the reticulo-endothelial system. Dr J. D. Sallis (Renewal) Mechanism of action of parathyroid hormone. Australian Journal of Experimental Biology and Medical Science Publication expenses.
FLINDERS UNIVERSITY School of Biological Sciences Professor M. R. Atkinson (New Grant) Nucleotide metabolism and control of growth.
UNIVERSITY OF MELBOURNE Department of Anatomy Professor K. C. Bradley (New Grant) Cerebrospinal fluid circulation. Dr A. F. Roche (Renewal) Physical aspects of child growth. - "*'..
Department oj Biochemistry Professor V. M. Trikojus (Renewal) Studies on thyroid enzymes and thyroglobulin. Professor P. F. Hall (New Grant) The action of hormones on melanogenesis. Professor F. D. Collins (Renewal) Studies on phospholipids. Department of Dental Prosthetics Professor H. F. Atkinson (Renewal) Mandibular movements in speech and mastication. Department of Conservative Dentistry Professor E. Storey-Dr W. A. McDougall(Renewal) Factors effecting the development and m~tabolism of hard tissues. The role of lysozomes in normal and inflamed tissues. Dr H. 1. Orams (New Grant) A study of enamel structure and the cuticles attached to the enamel surface with particular reference to the initial carious process. Department of Medicine (Austin Hospital) Professor A. E. Doyle (New Grant) The pathogenesis of malignant hypertension. Department of Medicine (Royal Melbourne Hospital) Dr J. K. Dawborn (New Grant) Potassium! aldosterone relationships. Dr J. R. E. Fraser Physiological and chemical studies of hyaluronic acid.
184
Renewals and New Grants for the year 1967
Dr P. Kincaid-Smith (Renewal) The aetiology and treatment of renal infection. Correlation of structure and function in renal disease. The treatment of chronic uraemia by diet, dialysis and renal transplantation. Analgesic abuse and renal disease. Hyptertension in pregnancy. Electron microscopy of the kidney with special reference to vascular and glomerular changes in homograft rejection. Dr F. I. R. Martin (New Grant) To determine the effect of insulin on peripheral glucose uptake and hepatic glucose output in patients with juvenile onset diabetes mellitus. To investigate the relation between the immunological and biological activity of injected insulin in the plasma of juvenile onset diabetics. Department of Medicine (St. Vincent's Hospital) Professor G. C. De Gruchy-Dr J. Hirsh (Renewal) The metabolism and turnover of platelets in relation to their function. Red cell metabolism in relationship to cell age and in haemolytic anaemia. Dr J. G. D. Rankin (New Grant) Natural history, treatment and prognosis of alcobolism. Department of Microbiology l'rofessor S. D. Rubbo Prophylaxis against tetanus. Professor F. W. E. Gibson (Renewal) The biosynthesis of vitamin K and ubiquinone in bacterial cells. Other aspects of aromatic metabolism. Dr. B. W. Holloway (Renewal) Conjugation and the study of gene distribution in Pseudomonas aeruginosa. Dr 1. H. Holmes (Renewal) Electron· microscopy of hepatitis viruses. Dr D. O. White (Renewal) Expression of the viral genome in cells infected with oncogenic and non-ecogenic adenoviruses. Dr. A. J. Pittard (Renewal) A genetic and biochemical investigation of aromatic biosynthesis in Escherichia coli. Department of Obstetrics and Gynaecology Dr J. B. Brown (Renewal) Development of oestrogen, pregnanediol and gonadotrophin assays and study of ovarian and placental function in gynaecological and obstetrical disorders. Dr I. J. Hopkins (New Grant) Neonatal convulsions. Department of Pathology Dr I. K. Buckley (Renewal) A microscopic study of the meachanisms of progressive damage following focal heat injury. Department of Pharmacology Professor M. J. Rand (New Grant) Drugs affecting activity and release of catecholamines.
Renewals and New Grants for the year 1967
185
Depart'nent of Physiology Professor R. D. Wright (Renewalj Histological studies of salivary glands and other histological projects. Dr D. A. Denton (Renewal) Continuation of studies on ablation of kidneys in hypophysectomised animals in relation to site or origin of ASH. Study of hypophysectomised sheep with adrenal transplant. Effect of large or discrete ablations in the central nervous system on aldosterone secretion. Effect of induction of emotional states in trained animals on the corticosteroid secretion. Effect of local haemodynamic changes in splanchnic and renal circulation on corticosteroid secretion. Effect of changes of plasma and extracellular volume on corticosteroid secretion and renal haemodynamics. Effects of N a+deficiency and physiological response of secretory tissues. Continuation of studies on the biosynthesis of aldosterone. Study of aldosterone of sheep immunised to give high titre anti-renin in the circulation. Investigation of neural mechanisms involved in selective appetite for Na+ shown by Na+ deficient sheep--the influence of hypertension on this mechanism. Dr D. J. Dewhurst (Renewal) The precise control of human muscular movement. Dr A. Shulman (Renewal) The use of metal chelates in the investigation of biological mechanisms. The mode of action of central nervous system stimulant and depressant drugs in the intact animal. Department of Zoology Professor G. Burnstock (Renewal) Autonomic nerve-smooth muscle transmission. MONASH UNIVERSITY
Department of Anatomy Professor G. C. Schofield (Renewal) Experimental studies on biologically active substances in the alementary canal. Department oj Biochemistry Professor J. Bornstein (Renewal) The structure and mechanisms of action of insulin and its antagonists. Dr A. W. Linnane (Renewal) The origin of mitochondria and the synthesis and organisation of mitochondrial enzymes. Dr D. A. Lowther (Renewal) The macromolecular structure of cartilage and of invertebral disc tissue. Department of Microbiology Dr J. H. Marshall (New Grant) Physiology of pigment formation by staphylococci and lipid metabolism in mycoplasma. Department oj Obstetrics and Gynaecology Professor E. C. Wood (Renewal) Influence of the autonomic nervous system upon the human uterus. 4275/67-13
186
Renewals and New Grants for the year 1967
Department of Pathology Professor R. C. Nairn (Renewal) Study of organ-specific antigens and autoantigens in man and experimental animals. Investigation of antoimmune diseases. Department of Physiology Professor A. K. McIntyre (Renewal) Quantitative analysis of synaptic actions on central neurones. Dr M. E. Holman (Renewal) The electro-physiology of autonomic effector mechanisms, cardiac muscle, excitation-contraction coupling of mammalian smooth muscle. Department of Psychology Dr R. H. Day (New Grant) Electrophysiological correlates of attentional mechanisms. Department of Surgery Dr J. M. Watts (New Grant) A study of the physiology of bile secretion and tests of hepatic function in the isolated perfused porcine liver. UNIVERSITY OF NEW SOUTH WALES School of Anatomy Professor M. J. Blunt-Associate Professor C. P. Wendell-Smith (Renewal) The histochemistry of macroglia. The ultrastructure of developing glial elements. The ultrastructure and histochemistry ot retinal glial elements. Dr G. S. Molyneaux (Renewal) The ultrastructure and histochemistry of epitheloid cells in the carotid body and in the walls of arterio-venous anastomoses. School of Biological Sciences Dr K. G. Rienits-Mr J. F. Williams (Renewal) Carbohydrate metabolism in vertebrate iver. School of Hospital Administration Mr R. Gillam (New Grant) The effects of automation on the profession of nursing. Division of Neurology, Prince Henry Hospital Associate Professor J. W. Lance (New Grant) The relation between tonic and phasic spinal mechanisms in man. The humoral control of cranial arteries in man; in relation to changes in arterial blood pressure. School of Pathology Professor D. L. Wilhelm (Renewal) The inflammatory reaction to chemical
and
injury.
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Renewals and New Grants for the year 1967
187
School of Physiology Professor 1. Darian-Smith (Renewal) To study neu~onal inhibitory interaction in somatic afferent projections to the cerebral cortex by mteracellular recording and unitary analysis. To study interactions between parallel afferent projections via the rostral and caudal components of the trigeminal brainstem nuclei. School of Psychiatry Associate Professor J. E. Cawte (New G,ant) Human ecology of the arid zone. UNIVERSITY OF QUEENSLAND
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Department of Biochemistry Professor E. C. Webb (Renewal) Enzymology. Dr J. E. O·Hagan (Renewal) The relationship between structure and function of haemoglobins and myoglobins. Department at Medicine Professor J. H. Tyrer (New Grant) Quantitative histochemistry of oxidative enzymes in brain stem. Dr A. M. Parfitt (Renewal) The renal excretion and conservation of calcium and magnesium. Department of Parasitology Professor J. F. A. Sprent (Renewal) The pathogenesis and diagnosis of nemotode larva migrans in man with particular reference to eosinophilia and eosinophylic granulomatosis. Department at Physiology Dr A. Lipton (Renewal) Effect of steroid hormones on the fundamental properties of muscle. Department at Surgery Dr D. F. Hogg (New Grant) Gastro-intestinal motility studies by pressure transducer. Dr B. S. Mather (New Grant) The impact energy absorbing capacities of human long bones. The relationship between the strength and structure of bone.
UNIVERSITY OF SYDNEY
Department at Bacteriology Dr D. S. Nelson (Renewal) Macrophages and cytophilic antibodies in immunological reactions. The significance in transplantation immunity of humoral antibodies detectable by immune adherence.
188
Renewals and New Grants jar the year 1967
Dr A. L. Hunt (Renewal) Mechanism of induced synthesis of nicotinic acid hydroxylase respiratory complex in Ps. fluorescens. Dr R. G. Wake (Renewal) Studies on the B. subtilis chromosome. Department oj Histology Dr J. K. Pollak (Renewal) The dynamic state of the endoplasmic reticulum under various physiological conditions. Department of Medicine Professor C. R. B. Blackburn (Renewal) A study of chronic liver disease and chronic lung disease in the Territory of Papua and New Guinea. Associate Professor B. G. Firkin (Renewal) Platelet function and physiology. Mechanisms of anaemia. Study of cell defect in hereditary spherocytosis. Department of Obstetrics and Gynaecology Associate Professor R. F. Shearman (New Grant) Oestrogens in the biological fluids of pregnant women. Department of Ophthalmology Dr J. B. Cowie (Renewal) The pharmacology of enediols in aqueous drainage. Department of Pathology Professor D. A. Cameron (Renewal) Pattern of synthesis of collagen in bone cells. Fine structure of synovial cells. Origin and function of osteoclasts. Dr P. M. Ronai (Renewal) Quantitation of transplantation immunity in vivo using radio-isotope labelled cells. Dr B. J. Roser (New Grant) Macrophage migration and function in vivo. Department of Pharmacy Dr A. J. Ryan (Renewal) The enzymology of food additives and foreign molecule metabolism. Department of Physiology Professor P. O. Bishop-Associate Professor W. Burke-Dr C. W. Dunlop-Dr W. A. Hayhow (Renewal) Neurophysiology of vision. Neurohistological studies. Electrophysiological correlates of hearing in cats. Maintained activity of retinal ganglion cells. Dr W. R. Levick (Renewal) Receptive fields of primate retinal ganglion cells. ,-
Renewals and New Grants for the year 1967
189
Dr 1. A. Young (Renewal) A micropuncture and perfusion investigation of amino acid transport in the proximal tubules of the rat kidney.
Department of Preventive Dentistry Professor Noel D. Martin (New Grant) The structural changes in dental enamel when affected by idiopathic and fluoride opacties. Department of Surgery Associate Professor T. S. Reeve (New Grant) An evaluation of the effect of thyroidectomy on serum calcium. The roles of parathyroid impairment and thyrocalcitonin release. Mr J. A. Myhill (Renewal) Experimental tracer dynamics. UNIVERSITY OF TASMANIA Department of Biochemistry Professor E. S. Holdsworth (Renewal) Role of vitamin Da in bone and calcium metabolism. UNIVERSITY OF WESTERN AUSTRALIA Department of Biochemistry Dr 1. T. Oliver (Renewal) Biochemical aspects of development in neo-natal rat liver. Department of Medicine Dr M. G. McCall (New Grant) A study of differential mortality in migran!s. Department of Microbiology Professor N. F. Stanley (Renewal) The biological spectrum of reovirus. Department of Pathology Dr B. A. Kakulas (New Grant) A correlative c1inico-pathologic study of patients with spinal cord injury. Dr J. M. Papadimitriou (Renewal) Virus transport to target organs. Department of Pharmacology Professor Mary F. Lockett (Renewal) Sodium retaining protein hormones of blood. Department of Physiology Professor W. J. Simmonds (Renewal) Fat absorption studies. Dr B. M. Johnstone (Renewal) Physiology of the cochlea. 4275/67-14
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Renewals and New Grants for the year 1967 Dr I. Kaldor (Renewal) Kinetics of secretion and absorption of iron. Iron storage in the new born. Dr S. H. Morgan (Renewal) Plasma protein metabolism in pregnancy and lactation.
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NEW SOUTH WALES, INSTITUTES AND HOSPITALS Institute of Dental Research Dr K. W. Knox (Renewal) Antigenic components of oral micro-organisms. Dr Gwen J. Walker (Renewal) The enzymic mechanisms for the synthesis and degradation of polysaccarides in oral streptococci. Institute of Medical Research, Royal North Shore Hospital Dr M. R. Lemberg (Renewal) Chemistry and biochemistry of tetrapyrrolic compounds. Kanematsu Memorial Institute, Sydney Hospital Dr K. D. G. Edwards (Renewal) Cellular transport studies, particularly in the kidneys. Studies of renal acidification mechanism, and the role of citrate in hydrogen ion transport. Red Cross Blood Transfusion Service, Sydney Dr G. T. Archer (Renewal) Studies on the eosinophil leucocyte. Royal Alexandra Hospital for Children Dr D. C. Dorman-Dr J. D. Farley (New Grant) Virological and immunological aspects of congenital rubella infection. Royal Prince Alfred Hospital Dr A. J. Skyring (Renewal) To extend investigations in a preparation of isolated crypt cells from the small intestine of the rat. Dr P. M. Rountree (Renewal) The epidemiology of staphylococcal infection with special reference to the origin of newly identified strains and the control of infection in intensive care units. The genetics of antibiotic resistance in ,taphylococci. QUEENSLAND INSTITUTES AND HOSPITALS Cairns, Queensland Dr J. H. Barnes (Renewal) Prevention and treatment of marine stings. Queensland Institute of Medical Research Dr R. L. Doherty (Renewal) The epidemiology of arbovirus diseases in Quee~and, with special reference to Murray Valley encephalitis and epidemic polyarthritis.
Renewals and New Grants jor the year 1967
191
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SOUfH AUSTRALIA INSTITUTES AND HOSPITALS Institute 0/ Medical and Veterinary Science Dr J. R. Coulter-Dr C. S. Hann (New Grant) Amino acid sequences of staphylococcal alpha toxin and of fibrinopeptides. The Queen Elizabeth Hospital, Woodville Dr M. L. Wellby (Renewal) The chemical nature of circulating thyroid hormones. Free thyroxine assays following treatment of thyrotoxicosis with radioiodine. Red Cross Blood Transfusion Service, Adelaide Dr R. W. Beal (Renewal) Plasma protein binding of radioactive vitamin B.12. Neutrophile alkaline phosphates in pregnancy. South Australian Museum Dr R. V. Southcott (Renewal) Medical effects of marine invertebrates and other marine and terrestrial animals harmful to man, also of plants of clincal significance. VICTORIA INSTITUTES AND HOSPITALS Fairfield Hospital, Epidemiological Research Unit Dr A. A. Ferris (Renewal) Tissue culture studies with hepatitis viruses. Prince Henry's Hospital, Medical Research Centre Professor B. Hudson (Renewal) The secretion and metabolism of androgens. Royal Australasian College of Surgeons Dr G. A. Kune (New Grant) The surgical anatomy of the liver. Royal Children's Hospital, Gastroenterological Unit Dr Charlotte M. Anderson (Renewal) Digestion and absorption of sugars in the intestinal tract. Royal Children's Hospital, Surgical Research Unit Mr R. Fowler (New Grant) The preparation and use of heterologous antithymocyte antisera and its effect on survival of experimental renal homografts. The reactivity of lympocytes in culture. St. Vincent's Hospital, School 0/ Medical Research Dr P. Edman (Renewal) Structure of fibrinogen. Microheterogeneity in protein structure. Victorian College of Pharmacy Dr A. Stafford (New Grant) The physiological role of adenosine derivatives. Walter and Eliza Hall Institute of Medical Research, Melbourne Professor G. J. V. Nossal (Renewal) Experimental immunology and oncology. MISCELLANEOUS Traffic injury in Brisbane report.
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APPENDIX I L APPROPRIATIONS BY PARLIAMENT
Financial Year
Amount
Financial Year
Amount $ 258,000 259,000 279,500 300,000 340,000 410,000 410,000 483,000 537,000 597,000 597,000 637,000 826,000 878.000 1,065,000
1937-38 1938-39 1939-40 1940-41 1941-42 1942-43 1943-44 1944-45 1945-46 1946-47 1947-48 1948-49 1949-50 1950-51 1951-52
.. ..
S 60,000 60,000 20,000 40,000 40,000 40,000 40,000 40,000 80,000 64,000 100,000 120,000 120,000 170,000 289,000
1952-53 1953-54 1954-55 1955-56 1956--57 1957-58 1958-59 1959-60 1960-61 1961-62 1962-63 1963-64 1964-65 1965-66 1966--67
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APPENDIX
n FuND-1965-66
NATIONAL HEALTH AND MEDICAL RESEARCH COUNOL GRANTS MADE FROM THE MEDICAL REsEARCH ENDOWMENT
Universities, Institutions and Hospitals
I
Research Workers $
I
Scholarships $
Technical Maintednance I an A . sSlstance Equipment I $ I
1
Total $
-----------------1-------1-------1------1 ! UniversitiesUniversity of Adelaide .. University of Melbourne .. Monash University .. .. University of New South Wales .. University of Queensland University of Sydney .. University of Tasmania .. University of Western Australia Institutions and HospitalsNew South Wales .. Victoria .. .. Queensland .. South Australia .. Total .. 23,940 79,075 10,470 15,388 44,458 to,700 70,946 130,430 3,132 388,539 30,120 47,300 19,800 12,240 30,320 44,300 9,540 13,100 57,040 22,618 12,600 12,740 22,936
$
;
16,732 7,000 53,832 6,364 3,120 228,082
9,102 13,134 4,600 2,000 4,852 18,950 3,000 2,000 6,288 8,286 3,800 200 76,212
76,262 196,549 57,488 26,840 63,300 130,644 3,000 38,972 84,234 197,548 13,296 3,320 891,453
5,000
198,620
APPENDIX
m
NATIONAL HEALlH AND MEDICAL RESEARCH COUNCIL SALARY SCALES AND SCHOLARSHIP STIPEND RATES I. SALARY SCALES Scales used in connection with National Health and Medical Research Council grants providing the salaries of medical, dental and science graduates, as from 1 July, 1967.
Designation
Research Assistants Grade I Research Assistants Grade II Research Offi cers Senior Research Officers Research Fellows Senior Research Fellows Principal Research Fellows
$ 2,340 3.090 3.390 4,040 4,200 4,800 5,900 6,500 7,600 8,600 10,400
Per Annum Salary $ $ $ 2,490 2,640 2,790 3,390 3,240 3,520 3,650 3,780 4,170 4,300 4,320 4,440 4,560 5,460 5,020 5,240 6,120 6,340 6,720 6,940 7,160
S 2,940 3,910 4,680 5,680 7,380
:> -
Notes: (i) The normal entry point for Research Assistants shall be in accordance with postgraduate experience and ability. (ii) The normal entry point for medical and dental graduates is $4,800 p.a. as Senior Research Officer. (iii) Stipends for C. J. Martin Travelling Fellowships are in the Senior Research Officer or Research Fellow salary ranges. II. SCHOLARSHIP STIPEND RATES Per Annum Stipend Designation
$ Medical and Dental Postgraduate Research Scholars Medical and Dental Research Scholars
$
S
3,780 4,040 4,300 Within the range $260-$400 p.a.
(Reprinted from the Report of 64th Session of the National Health and Medical Research Council, April, 1967.)
APPENDIX IV
CONDITIONS ASSOCIATED WITH NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL GRANTS FOR MEDICAL RESEARCH, C. J. MARTIN TRAYELLING FELLOWSHIPS AND PUBLIC HEALTH TRAYELLING FELLOWSHIPS As FROM
1
JULY,
1967
Grants for Medical Research Preamble 1. These conditions shall be followed by the N.H. & M.R.C. in the administration of grants for medical research. The responsibililies relative to the grants to be undertaken by institutions receiving N.H. & M.R.C. grants are included in these conditions. 1.1 For the purposes of these conditions the N.H. & M.R.C. accepts as the responsible officers of institutions, the Registrars for Universities, the Directors of independent Institutes, and the Managers/Secretaries or Medical Superintendents for Hospitals or the individual recipients of grants not made to institutions. 1.2 All communications to and from the N.H. & M.R.C. relating to applications for grants, the award of grants, variations in grants, the conditions associated with grants, and the payment of grants, shall be through the responsible officer of the institution. 1.3 The award of any N.H. & M.R.C. grant is subject to the formal acceptance of the grant and the conditions associated 'vith the grant by the recipient of the grant, the Head of Department where the work is being carried out, and the responsible officer of the institution.
Award and Termination of Grants 2. The period of the grant including the continuance commitment shall be as notified in the award of a grant except for salary grants specified in condition 3. 3. The primary award of grants for salaries of Research Fellows, Senior Research Fellows and Principal Research Fellows shall be for five years unless otherwise specified. A five year award shall also normally be made on the promotion of a Research Fellow to Senior Resear;;h Fellow, and a Senior Research Fellow to Principle Research Fellow. After three years, each of these grants will be reviewed annually and a minimum of two years' notice will be given before termination of such a grant. 4. The period of notice of termination of grants other than salary grants in condition 3 shall normally be a minimum of one year for grants of more than two years duration, and a minimum of two years for grants of more than four years duration. 5. Notwithstanding the provisions in conditions 3 and 4 above, the Council may at any time terminate any grant providing the salary of a research worker with only six months notice on the grounds of permanent incapacity due to age or infirmity, inefficiency from causes other than age, infirmity or misconduct. Such a decision, however, shall not be taken unless the matter has been thoroughly investigated by the Council in consultation with the Medical Research Advisory Committee and the Head of the Institution in which the research worker is employed. 6. When a research worker leaves an institution to which a grant is paid for his support before the normal expiration of that grant, that grant shall be terminated except at the discretion of the Chairman of the Council, notwithstanding the provisions in condition 3 and 4.
196
Payment of Grants
7. Payment of money in respect of any grant shall be upon the terms and conditions specified in the grant, and shall, wherever possible, be made to the authorities of the institution at which the work is being performed. 7.1 Payment in respect of grants for salaries, all types of scholarships, technical assistance and maintenance expenses, and in respect of grants-in-aid, shall normally be paid half-yearly in advance. 7.2 Payment in respect of equipment costing $2,000 or more shall normally be paid upon receipt of an invoice for the equ ipment from the institution receiving the grant. Payment in respect of other equipment shall normally be paid at the beginning of the half-year period following the approval of the grant. 7.3 Payment of superannuation allowances for graduates shall be made annually in advance for annual payment of premiums. 7.4 Payment of travelling expenses allowed under condition 27 shall be made upon receipt of a claim following attendan~e at the congress. 7.5 Payment of travel expenses for sabbatical leave shall be made on application advising the date of departure from Australia.
Use of Grants 8. In accepting an N.H. & M.RC. grant, each institution undertakes to provide all overhead expenses and maintenance charges, and no portion of any grant shall be applied for these purposes, unless specifically appropriated by the Council. 9. Grants shall be used solely for the purposes specified in the awards, except with permission of the Chairman of Council to vary a grant. 9.1 Grants for salaries and scholarship stipends shall be used for the person specified in the award. 9.2 Grants for technical assistance are to provide salaries for assistant personnel other than those on N.H. & M.RC. graduate salary rates. 9.3 Grants for maintenance expenses are to provide9.3.1 Research materials including consumable supplies, apparatus, animals and minor equipment up to $400 per item of equipment. 9.3.2 Payroll tax relating to all salaries (graduate and non-graduate) derived from N.H. & M.RC. grants (see condition 14). 9.3.3 Superannuation allowances for eligible assistant personnel paid salaries from N.H. & M.RC. grants (see condition 14.) 9.4 Grants for equipment over $400 per item shall be used for the purchase of items specified in the award. 9.4.1 Equipment costing less than $2,000 becomes the property of the institution to which the grant is given. 9.4.2 Equipment costing $2,000 or more and purchased entirely from N.H. & M.Re. grants may be specified by the Council to be the property of the Commonwealth. Equipment not so specified becomes the property of the institution to which the grant is given. Equipment specified to be the property of the Commonwealth is subject to recall on demand, and is subject to return in any event upon completion of the research projects for which the equipment is granted.
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/
197 9.4.3 Institutions, to which the Commonwealth equipment is entrusted, undertake to retain the equipment under their control, maintain it in good condition, and where applicable, return it in the same condition in which it was received, subject to reasonable wear. Institutions to which the equipment is entrusted are eligible to receive a Council grant for costs of normal maintenance.
9.4.4
Accounting for Grants
to. Grants for periods not exceeding one year, which are not spent or committed by the recipients at the end of the specified periods, shall be refunded, except where the Chairman of Council approves funds to be carried forward. 11. Grants for periods exceeding one year provided for technical assistance, maintenance expenses or equipment, which are unspent and uncommitted at the end of each calendar year, may be carried forward into the following year in amounts not exceeding 50% of the grants, for the purposes specified, except where the Chairman of Council approves a greater amount to be carried forward. 12. The responsible officer of the institution receiving each grant shall certify for each year not later than 1st March of the year following that12.1 The grant has been expended solely upon the work and for the purposes specified in the award of the grant; 12.2 salaries and allowances, including superannuation if applicable, paid under the grant to personnel other than those on N.H. & M.R.C. graduate salary scales, have been in accordance with the general rates in force at the institution; 12.3 aU funds aUocated in the grant for each year not expended or carried forward under conditions 10 and 11 have been Teturned. 13. The account for each yearly grant shall be closed on 31st December of the year following the grant. Conditions of Employment of Personnel paid Salaries under N.H. & M.R.C. Grants 14. Research personnel receiving salaries under N.H. & M.R.C. grants are engaged and
employed by the institutions to which the grants are paid, and these institutions are respollsible for the administrative control of the personnel and all legal liabilities in connection with their employment. Their conditions of employment shaU be those obtaining in the institute or department where the personnel are working, unless otherwise specified. These conditions shall include the provision of superannuation for personnel, other than those paid a N.H. & M.R.C. graduate salary, eligible for inclusion in schemes established by the employing authority. 15. Graduates receiving fuU N.H. & M.R.C. salaries under Council grants shaU devote their time to the research projects supported by the grant and not engage in other work to the extent of an average of more than four hours per week, except with the permission of the Chairman of the Council. The remuneration for such work shall not exceed $400 per annum. 16. Graduates receiving full N.H. & M.R.C. salaries under Council grants may not receive additional personal remuneration or allowances from another source in respect of the work which is the subject of the Council grant, except with the approval of the Council or Chairman of the Council. 17. Graduates receiving full N.H. & M.R.C. salaries under Council grants are entitled to annual leave on full pay, within the period I)f appointment, similar to that obtaining in the Institute or Department where the grantee is working; but the working period in each year shaU be at least 11 calendar months, unless otherwise authorised by Council.
198 18. Approval by the Council or the Chairman of Council is required for graduat~s receiving full N.H. & M.R.C. salaries under Council grants to spend time away from their normal place of work, other than on annual leave and in attending recognised scientific congresses in Australia. 18.1 Approved leave shaIl be with or without pay as determined by the Council or the Chairman of Council. 18.2 A report on the activities of the graduate during overseas leave shall be submitted to the Secretary of the Council within one month of returning to normal duty. Superannuation 19. Graduates receiving full N.H. & M.R.C. salaries under Council grants are eligible for allowances for the purpose of superannuation, following probationary periods of employment in research approved by the Chairman of the Council. The probationary periods shall be three years for Research Assistants and one year for workers of Research Officer or higher rank. 20. The Superannuation allowance shall be an amount equal to 10% of salary to enable the recipient to take out an endowment assurance policy of a type and in a company approved by an Australian University F.S.S.U. Scheme. The payment of superannuation allowance is made conditional upon the recipient contributing at least 5% of salary to the premium. 21. The Policy shall be in the name of, assigned to, or held by the institution where the recipient is working, according to the provisions of the institution's staff superannuation scheme, or where there is no appropriate institution staff superannuation scheme the Policy shall be in the name of the recipient and held by the Secretary of the Council. 22. The Policy shall be on the life of the recipient, and shall mature when the recipient is not less than 60 years of age. 23. The appropriate administrative authority of the institution in which the recipient is working shall be responsible for carrying out all arrangements for the policy, including payment of premiums. 24. Superannuation allowance payments will be made to the institution concerned upon receipt by the Secretary of Council of evidence24.1 that a policy in accordance with conditions 21 and 22 has been effected on the life of the recipient; 24.2 that the total annual premium payable under the policy represents not less than 15% of the total salary of the recipient; 24.3 that the life office issuing the policy has certified that the policy conforms with the regulations governing F .S.S. U .-type policies; 24.4 that the policy is not encumbered in any way. 25. Superannuation allowances will cease when the salary grant under which the recipient is working terminates. The policy concerned shall then become the property and responsibility of the recipient. 26. If the recipient resigns before the normal termination date of the salary grant, the Council may require that the recipient or institution concerned shall reimburse the Council with a sum equal to the pro rata premium for the unexpired portion of the premium year. Travel Expenses for Anstralian Scientific Congresses 27. Graduates receiving full N.H. & M.R.C. salaries, N.H. & M.R.C. Postgraduate scholars, and N.H. & M.R.C. Medical and Dental Postgraduate Research scholars are eligible, upon prior approval of the Chairman of Council, for a travel allowance once a year to attend
1
199 recognised congresses in Australia. The expenses paid shall be fares up to a maximum of 80% of return tourist class air fare, and a travel allowance of $6 per day for a maximum of three days, and shall be paid in accordance with condition 7.4. Sabbatical Leave 28. Research workers of Research Fellow or higher rank shall be eligible for sabbatical leave to a maximum of twelve months, for the purposes of travel and study approved by the Council, after each six years period of service in Australia on full N.H. & M.R.C. salaries under Council grants. Leave may be taken for shorter periods at shorter intervals on approval by Council. 29. N. H. & M.RC. grants for full salary and superannuation allowance will continue during periods of approved sabbatical leave. 30. N. H. & M.RC. grants shall provide travelling expenses for approved sabbatical leave to cover30.1 The equivalent of tourist class air fare for the Fellows for travel on sabbaticll leave once every seven years. 30.2 A travel allowance of up to $500 over a seven year period. N.H. & M.R.C. Medical and Dental Postgraduate Research Scholarships 31. N.H. & M.RC. Medical and Dental postgraduate Research Scholarships are provid::d for medical and dental graduates undertaking full-time research studies, normally as candidates for higher degrees. N.H. & M.R.C. Medical and Dental Research Scholarships 32. N.H. & M.RC. Medical and Dental Research Scholarships are provided to assist medical and dental students to extend their undergraduate courses to study for the B.Med.Sc. or equivalent degrees. The Universities receiving grants for these Scholarships shall determine the students to receive the N.H. & M.RC. stipends appropriate to the Scholarship. Publication of Results 33. All publications of results achieved from research carried out with the assistance of grants from the Council shall state prominently that the work recorded has been supported by a grant from the National Health and Medical Research Council. One reprint of any Journal publication and one copy of any monograph or book on work supported by the Council shall be furnished to the Secretary of the Council. Patents 34. No work wholly or partly supported by Council research grants may be made subject to patent unless the written specific permission of the Chairman of the Council is obtained. Annual Reports 35. The recipient of each grant shall furnish a fuIl report to the Secretary of the Council by 15th December, describing the work performed by each person supported by the grant during the year, for the purpose of a general report to Parliament under the Medical Research ~ndowment Act. Each report shnll cover the nature and aim of the project, the results achieved, the future possibilities of !he project and the publications made.
200
c.
J. Martin Travelling Fellowships
Purpose 1. C. J. Martin Travelling Fellowships are awarded to enable Fellows to work on specific projects overseas under nominated advisers.
Eligibility 2. The Fellowships are open to all candidates who have been engaged in medical dental or related fields of research in Australia for a period of from two to seven years. They shall normally be awarded to workers intending to follow a research career in Australia. Tenure 3. The Fellowships are normally awarded for one or two years. A. C. J. Martin Fellow shall take up the Fellowship not later than 31st March of the year following the award, except with special permission of the Chairman of Council. Stipend 4. The stipend for a Fellow shall be in the Senior Research Officer or Research Fellow salary ranges. Fellows shall receive any increases of salary arising from adjustment to N.H. & M.R.C. salary scales during the tenure of their Fellowship, and superannuation allowance shall continue during the period of the Fellowship. Travelling Expenses 5. A tourist air fair will be provided to each Fellow for the journey to the overseas centre(s). A return tourist air fare will be provided when a Fellow returns to Australia within one month of completion of the Fellowship, or in other special circumstances approved by the Chairman of Council. 6. A travel allowance of $300 per annum shall be provided to each Fellow. 7. A family allowance at the rate of $600 for the Fellow's wife and $200 per child up to a total maximum of $1,000 per annum shall be provided. Report on Fellowship 8. A full report shall be submitted to the Secretary of the Council within three months of completion of the Fellowship. The report shall cover the work undertaken abroad, with details of any new knowledge gained in the ibId of study while abroad.
,..
Public Health Travelling Fellowships Purpose 1. Public Health Travelling Fellowships are awarded to enable Fellows to make postgraduate study tours abroad relating to their work and speciality. Eligibility 2. All medical graduates working and experienced in the field of public health are eligible to apply. Tenure 3. Each Fellowship is for a period not exceeding twelve months.
201
Value 4. The Council grant for a Public Health Fellowship shall not exceed $3,000 for twelve months Fellowship. Conditions 5. The granting of a Fellowship is conditional upon the employing authority maintaining the recipient's salary, allowances, and service benefits for the duration of the Fellowship. 6. Each Fellow shall undertake to return to the present employing authority for a period of at least three years following the completion of the Fellowship. Report on FeHowship 7. The recipient shall prepare a report of the study tour, giving, in particular, details of any new knowledge gained in the subjects studied, and shall forward 12 copies of the report to the Secretary of the Council within three months of returning from abroad. (Reprinted from the Report of 64th Session of the National Health and Medical Research Council, April. 1967.)
202
APPENDIX V MEMBERS OF THE MEDICAL RESEARCH ADVISORY COMMITIEE Professor S. Sunderland, Dean of the Faculty of Medicine, University of Melbourne. (Chairman. ) Dr J. J. Billings, Consultant Physician. (Deputy Chairman), 55 Collins Street, Melbourne. Dr C. J. Cummins, Director-General of PU..Jlic Health, New South Wales. Sir Norman Nock, an eminent layman appointed by the Commonwealth Government. Dr R. Reader, Medical Director, National Heart Foundation. Professor N. F. Stanley, Department of Microbiology, University of Western Australia. Mr K. W. Starr, Consultant Surgeon, 149 Macquarie Street, Sydney. Professor E. C. Webb, Department of Biochemistry, University of Queensland. Professor R. F. Whelan, Department of Human Physiology and Pharmacology, University of Adelaide. Dr P. S. Woodruff, Director-General of Public Health, South Australia. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. (Professor J. Loewenthal, Department of Surgery, University, co-opted member.)
,
-.
r r i I
APPENDIX VI MEMBERS OF TIlE STANDING GRANTS COMMITTEES
203
Standing Grants Committee A (Anatomy, Pathology and Microbiology) Professor S. Sunderland, Dean of Faculty of Medicine, University of Melbourne (Chairman). Professor G. S. Christie, Department of Pathology, University of Melbourne. Dr A. A. Ferris, Fairfield Infectious Diseases Hospital, Fairfield. Professor F. E. Magarey, Department of Pathology, University of Sydney. Professor J. S. Robertson, Department of Pathology, University of Adelaide. Professor N. F. Stanley, Department of Microbiology, University of Western Australia. Dr P. S. Woodruff, Director-General of Public Health, South Australia. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. Standing Grants Committee B (Biochemistry, Physiology and Pharmacology). Professor E. C. Webb, Department of Biochemistry, University of Queensland (Chairman) . Professor A. K. McIntyre, Department of Phyiology, Monash University. Professor A. G. Ogston, Department of Physical Biochemistry, Australian National University. Professor W. J. Simmonds, Department of Physiology, University of Western Australia. Professor S. Sunderland, Dean of Faculty of Medicine, University of Melbourne, or Dr J. J. Billings (Consultant Physician), 55 Collins Street, Melbourne. Professor R. F. Whelan, Department of Human Physiology and Pharmacology, University of Adelaide. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. Standing Grants Committee C (Clinical Sciences, Dentistry and Public Health) Dr J. J. BiIIings, 55 Collins Street, Melbourne (Chairman). Professor H. F. Atkinson, Department of Dental Prosthetics, University of Melbourne. Dr C. J. Cummins, Director-General of Public Health, New South Wales. Dr T. H. Hurley, Honorary Physician, Royal Melbourne Hospital. Professor J. Loewenthal, Department of Surgery, University of Sydney. Professor E. V. Mackay, Department of Obstetrics and Gynaecology, University of Queensland. Mr K. W. Starr (Consultant Surgeon), 149 Macquarie Street, Sydney. Professor H. M. Whyte, Department of Clinical Science, John Curtin School of Medical Research. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary.
~
204
APPENDIXVD NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL MEMBERS Major-General W. D. Refshauge, the DIrector-General of Health, Commonwealth (Chairman) . Professor Sir Edward Ford, Dr J. B. Mathieson, representing the Department of Health of the Commonwealth. Dr W. R. Lane, representing the Commonwealth Serum Laboratories Commission. Dr C. J. Cummins, the Director-General of Public Health, New South Wales. Dr R. J. Farnbach, the Chief Health Officer, Victoria. Dr A. Fryberg, the Director-General of Health and Medical Services, Queensland. Dr P. S. Woodruff, the Director-General of Public Health, South Australia. Dr W. S. Davidson, the Commissioner of Public Health, Western Australia. Dr J. Edis, the Director-General of Health Services, Tasmania. Dr R. F. R. Scragg, the Director of Public Health of the Territory of Papua and New Guinea. Dr T. H. Hurley, representing the Federal Council of the Australian Medical Association. Mr K. W. Starr, representing the Royal Australasian College of Surgeons. Dr J. J. Billings, representing the Royal Australasian College of Physicians. Professor J. Loewenthal, representing the Australian Universities having medical schools. Professor G. King, representing the Australian Council of the Royal College of Obstetricians and Gynaecologists. Dr J. G. Radford, representing the Australian College of General Practitioners. Dr A. V. Jackson, representing the College of Pathologists of Australia. Dr J. M. Wark, representing the Australian Dental Association. Dr D. G. Hamilton, representing the Australian Paediatric Association. Dr C. K. Hambly, representing the College of Radiologists of Australasia. Sir Norman Nock, an eminent layment appointed by the Commonwealth Government. Miss M. C. Nelson, an eminent laywoman appointed by the Commonwealth Government. Professor S. Sunderland, Chairman of Medical Research Advisory Committee, co-opted member. Dr R. H. C. Wells (Secretary of the Council).
By Authority: A. J. MTHUll, Commooweallb Go-.nnent PriDIer, CaubemI '~
NATIONAL HEALTH .. ~
-, .:..
--.;:,
AND MEDICAL RESEARCH COUNCIL
Sixty-third Session
, , ~
COMMONWEALTH OF AUSTRALIA
COMMONWEALTH OF AUSTRALIA
\ ~ """.,e -" ~~
National Health and Medical Research Council Sixty-third Session CANBERRA, 4 NOVEMBER 1966
r-
,
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•
BY A.UTIlOllrrY: A. J. A.llTHUR. COMMONWBALTH CtOVEllNMBNT PlllNTBR. CA.NBBllllA.
-CONTENTS Page
General .. Medical Research Advisory Committee Grants for Medical Research Medicine Advisory Committee Antibiotics Committee Dental Health Committee Public Health Advisory Committee Food Additives Committee Food Standards Committee Medical Statistics Committee Occupational Health Committee Veterinary Public Health Committee Committee Membership and Constitution ApPENDICES--
5 8 10
31 31 32 33 35 35 37
38 38 39
y
..
I Schedule of Walter and Eliza Hall Institute Scientific Establishment Recommended as a Basis for N.H. and M.R.C. Support in the 1968-70 Triennium II Additional Grant Recommendations for 1967.. III Amendments to the Uniform Poisons Schedules IV First Aid Measures in the Uniform Poisons Schedules " V Amendment of Index to the Uniform Poisons Schedules VI Procedure for Scheduling of Therapeutic and Non-Therapeutic Substances .. VII Recommended Tolerances for Residues of Agricultural Chemicals on Fruit and Vegetables, Both Fresh and Preserved, and on Grains VIII Standard for Artificial Sweetening Substances. . IX Standard for Baking Compounds X Standard for Edible Fats and Oils XI Code of Practice for the Handling of Frozen Foods XII Standard for the Sale, Service, Storage, Display and Transportation of Frozen Food XIII Standard for Jelly Crystals, Tablets, Cubes and Mix XIV Standard for Labelling XV Standard for Mineral and Carbonated Waters XVI Standard for Type Size in Labelling. . XVII Standard for Vitamins and Minerals XVIII Draft Paint Standard XIX General Organization and Administration of Council and Committees XX Constitution and Terms of Reference of Committees XXI Inter-relationship of Council and Committees XXII Membership of Committees
40 43 46 52 54 58
60 64 65 66 67 70 73
74 76 77 78 80 83 84 89 90
3
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REPORT OF THE NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL
Sixty-third Session, 4 November 1966 GENERAL The Sixty-third Session of the National Health and Medical Research Council was held in the Conference Room, Community Hospital, Canberra on Friday, 4 November 1966. The following members were present: Major-General Sir William Refshauge, the Commonwealth Director-Generhl of Health (Chairman); .. ... . Professor Sir Edward F o r d 1 . . Dr D. B Travers jrepresentmg the Commonwealth Department of Health; Dr W. R. Lane, representing the Commonwealth Serum Laboratories Commission; Dr C. J. Cummins, the Director-General of Public Health, New South Wales; Dr R. J. Farnbach, the Chief Health Officer, Victoria; Dr A. Fryberg, the Director-General of Health and Medical Services, Queensland; Dr G. H. McQueen, for the Director-General of Public Health, South Australia; Dr W. S. Davidson, the Commissioner of Public Health, Western Australia; Dr J. Edis, the Director-General of Health Services, Tasmania; Dr R. F. R. Scragg, The Director-General of Public Health, Territory of Papua and New Guinea; Dr T. H. Hurley, representing the Federal Council ()fthe Australian Medical Association; Mr B. K. Rank, representing the Royal Australasian College of Surgeons; Dr J. J. Billings, representing the Royal Australasian College of Physicians; Professor S. Sunderland, representing the Australian Universities having medical sChools; Professor S. L. Townsend, representing the Australian Council of the Royal College of Obstetricians and Gynaecologists; Dr J. G. Radford, representing the Australian College of General Practitioners; Dr A. V. Jackson, representing the College of Pathologists of Australia; Dr J. M. Wark, representing the Australian Dental Association; Dr D. G. Hamilton, representing the Australian Paediatric Association; Dr C. K. Hambly, representing the College of Radiologists of Australasia; Sir Norman Nock, an eminent layman appointed by the Commonwealth Government; Miss M. C. Nelson, an eminent laywoman appointed by the Commonwealth Government; Dr R. H. C. Wells (Secretary of the Council). Sir William Refshauge in the Chair, presented the apologies of Dr H. J. Ham, Dr J. B. Mathieson, Mr K. Starr, Dr T. G. Swinburne and Dr P. S. Woodruff who were unable to attend. The Chairman welcomed Dr G. H. McQueen, Dr T. H. Hurley, Mr B. K. Rank, Dr C. K. Hambly lind pr p. B. Travers who attended the meeting in the place of pr Woodruff, Dr Swinburne,
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Mr Starr, Dr Ham and Dr Mathieson respectively. The Chairman referred to the appointment of Dr C. K. Ham to the Chair of Radiotherapy in the University of Utrecht, Holland. The Council recorded its congratuations to Dr Ham and its appreciation of his valuable service to the Council. The Chairman presented the following message from the Honourable A. J. Forbes, Commonwealth Minister of State for Health, who was unable to personally open the Session due to the pressure of other Government business. 'At your meeting in Canberra last February, when I was kindly invited to address you, I expressed my admiration of the way in which this Council adapts itself to change. On that occasion you were gathered together to consider an important re-organisation of Medical Research Policy and Administration. The decisions taken at that meeting have since been implemented, as a result of much work on the part of the Committees concerned, and also of your Secretariat. No doubt you will be as pleased as J am with the manner in which the new organisation has been shown to function. I have already received the report of the Medical Research Advisory Committee which met in October, and in accordance with your wishes have approved the grants contained therein. The National Health and Medical Research Council was set up by an Order in Council made by the Governor-General in 1936. It has been found necessary, at various times, to amend this Order to enable the Council to meet the changing needs of the community with maximal effectiveness. The Order has recently been revised making new provisions in relation to the chairmanship of meetings of Council, the appointment of representatives of various organizations as members of the Council, an alteration to the function of the Council in a minor detail, and several alterations of drafting detail. This new Order makes provisions in relation to chairmanship of meetings of the Council when the person for the time being appointed or acting as the Commonwealth DirectorGeneral of Health (who is ex-officio chairman) is unable to attend a meeting. The Order will allow the Director-General to choose a deputy to represent him at the meeting and to occupy the chair. Provision is also made for the chairman to appoint a temporary chairman when he vacates the chair during a meeting. Under its present constitution the Council includes twelve representatives nominated by various associations such as the Australian Medical Association, the Australian Dental Association and the Royal Colleges. However, when the original Order was drafted, no provision was made for the actual appointment of these representatives as members. The new Order will provide for the Minister for Health to appoint such members on the nomination of the professional medical and dental organisations concerned. A further point is that the present constitution lists as one of the functions of the Council co-operation with the Commonwealth Council for National Fitness. In the past there has been no cause for the Council to carry out this function and it is considered that it should no longer be included. The new Order accordingly will delete that function from the constitution of the Council. At the meeting in July of Commonwealth and State Ministers of Health, two matters arose which I have asked you to consider at this meeting. The first is the formation of a Mental Health Committee. I am sure that you will all agree that the formation of such a committee would fill a gap in the organisation of the Council. I would confidently expect that a Mental Health Committee under your auspices would assist the Commonwealth and State Governments in helping the mentally ill, by providing the background knowledge on which successful administration can be built, and by giving expect advice on the development of facilities for cure. The second of the matters I have referred to you concerns smoking habits and attitudes in Australia. The question of smoking and its effects on health has been considered by you before, and you have agreed with health authorities in other countries that smoking can be harm~ul. Theproblem is 'How in a free democracy can we persuade people not to take up smoking, or If they already smoke how can we persuade them to reduce their tobacco consumption 1'. The State Ministers for Health have suggested that more information is
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needed on the reasons why Australians take up or continue smoking and on their attitudes to smoking and health, as a basis for planning effective health education programmes. I have asked for your advice on this matter, because I want to know if you think such a survey would be a good idea, and if so, how you think it could best be carried out. Now although this meeting of the Council is less concerned with the detailed allocation of medical research grants than in former years, I would like to take this opportunity, before closing, of commenting on this aspect of the Council's function. Earlier this year, in putting the case to Cabinet for an increased allocation to the Medical Research Endowment Fund, I had occasion to reappraise the work you and your medical research committees are doing in stimulating, guiding and supporting medical research in this country. With so many demands on the Budget it is no easy matter to obtain increased funds to support research, and I was therefore particularly pleased at being able to document a convincing case for increased medical research support based on the manifest experience and proven efficiency of the N.H and M.R.C. as a grant distribution agency and on your recent recommendations. The 25 per cent increase in the Government appropriation to the Medical Research Endowment Fund as announced in the Budget, raises the total appropriation to $1,065,000 per annum, and may be taken as an indication not only of the Government's realisation of the importance of and need for medical research but also as an acknowledgment of this Council's pre-eminence in this field. Finally, may I thank you on behalf of the Government and the people of Australia for what you have achieved in the past and for what I expect you to achieve in the future. May J also thank you for inviting me to open your Sixty-third Session in this way.'
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MEDICAL RESEARCH ADVISORY COMMIITEE The Committee met in the Conference Room of the Department of Health, Administration Building, Canberra on 5 and 6 October 1966. The report of the Committee was presented by its Chairman, Professor S. Sunderland, and Council approved the following recommendations arising from the Report. Support of Walter and Eliza H all Institute of Medical Research The Counetl, having interviewed Professor G. J. V. Nossal, the Director of the Walter and Eliza Hall Institute, and having considered his submission for N.H. and M.R.C. support of the Institute on a long-term basis, recommended that support for the Institute be provided through the Medical Research Endowment Fund on a triennial basis commencing on 1 January 1968 to support the scientific establishment shown in Appendix I, and further recommended that an additional allocation to the Medical Research Endowment Fund be sought to meet the increased grants required to support this recommended scientific establishment, estimated to be $253,300.68 in 1968, $258,644.70 in 1969 and $264,040.23 in 1970, subject to the following provisions: (i) that two N.H. and M.R.C. representatives be added to the Institute Board, (ii) that the N.H. and M.R.C. be informed officially and as soon as practicable if any radical change in the Institute's current field of research activity is proposed, (iii) that no increase is made in the permanent scientific establishment of the Institute requiring or likely to require additional N.H. and M.R.C. support unless and until the N.H. and M.R.C. has been approached and has endorsed the proposal. Policy on N.H. and M.R.C. grants The Council re-considered the proposal of the 62nd Session of Council concerning the exclusion from favourable consideration of applications for project grants to the School of General Studies at the Australian National University. Council recommended that until the areas of interest of other Government grant giving authorities are more clearly defined applications from the School of General Studies should be considered on the same basis as those from other universities and medical research institutes. Conditions Associated with N.H. and M.R.C. Grants for Medical Research Council recommended that condition 35 of the 'Conditions Associated with N.H. and M.R.C. Grants for Medical Research' (Report of 59th Session, Appendix II) be revised to read: 'Publication of Results 35. All publications of results achieved from research carried out with the assistance of grants' from:the' Council' shall state prominently that the work recorded has been supported by a grant from·the National Health- and Medical Research Council. One reprint of any Journarpublication·and·one"'copy"of any" monograph or book on work supported by the Council.shall.be.furnished.to.the.Secretary.of the.Council.' Medical Literature Analysis and Retrieval System (Medlars) Council considered that in view of the difficulties faced by research workers in keeping abreast of the current literature a medical literature retrieval system was desirable in Australia. Council recommended that an investigation be carried out into the costs involved in the retrieval aspects of the MedIars System developed by the National Library of Medicine in Washington. '.
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Variations In grants by Chairman of Council The Council recommended that the following additional grants and variations in grants in the period May 1966 to October 1966 approved by the Chairman of Council, be endorsed. The additional grants total $2,383.20. Additional Grants Dr G. T. STEVENSON, Department of Biochemistry, University of Sydney. Registration fee for Joint Congresses of the International Societies of Haematology and Blood Transfusion, Sydney, in lieu of claim under condition 27-$55.
Dr R. G. WAKE, Department of Biochemistry, University of Sydney. To provide full and correct salary for Research Assistant, Grade I (Miss M. Gray)-$I44. . -'!"
University of Queensland To provide for increase of grants for four Medical Research Scholarships from $1,320 to $1,600-$280.
Professor E. S. HOLDSWORTH, Department of BiochemiStry, University of Tasmania. Additional grant for equipment-$56. Dr M. R. LEMBERG, Institute of Medical Research, Royal North Shore Hospital, Sydney. To provide full sabbatical leave travel allowance for Dr J. Barrett-$297. 'Traffic Injury in Brisbane' Report. Additional grant for publication expenses-$5oo. Grants for travel expenses to attend meetings of Scientific associations Dr I. S. DE LA LANDE, Department of Human Physiology and Pharmacology, University of Adelaide. For Mrs J. Wanstall-$121.20.
Dr S. L. SKINNER, Department of Human Physiology and Pharmacology, University of Adelaide. For Dr S. L. Skinner-$50. 32. Dr P. C. READE, Department of Microbiology, University of Adelaide. For Dr P. C. Reade-$84.88. THE REGISTRAR, University of Adelaide. For Mr J. M. McIntyre-$84.88. Professor G. C. DE GRUCHY, Department of Medicine, University of Melbourne. For Mrs Loder-$52.56. Dr J. O'Hagan, Department of Biochemistry, University of Queensland. For Dr J. O'Hagan-$54.32. • >"
Dr M. R. LEMBERG, Institute of Medical Research, Royal North Shore Hospital, Sydney. For Mr W. H. Lockwood, Dr D. B. Morell_and.Miss J. Thompson-each $54.32-$162.96. Professor H. M. Whyte, Kanematsu Memorial Institute, Sydney Hospital. For Dr N. W. Alcock-$54.32. Professor G. J. V. Nossal, Walter and Eliza HaIl Institute of Medical Research, Melbourne. For Dr G. Goldstein, Dr J. F. A. P. Miller, Dr S. Whittingham-each $52.56; ($157.68); Dr G. L. Ada, Mrs J. Williams-each $88.88 ($177.76); Dr I. R. Mackay-$50.76; . Total-$385. 76.
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Grant Variations Dr S. L. SKINNER, Department of Human Physiology and Pharmacology, University of Adelaide. Use of an amount not exceeding $250 from maintenance grant, for travel expenses in connection with attendance at Third International Congress of Nephrology, Washington, U.S.A.
Kanematsu Memorial Institute, Sydney Hospital. Transfer of current grant to Dr K. D. G. Edwards, Acting Director, on the resignation of Professor H. M. Whyte. Grants/or Medical Research The Council noted that the Commonwealth appropriation to the Medical Research Endowment Fund is now $1,065,000, an increase of 25 per cent over the previous allocation, and recorded its appreciation of the efforts by the Minister to secure this increase.
In making recommendations on grants for medical research in 1967 the Council took into consideration the information available on grants being recommended and/or made by the Australian Research Grants Committee, National Heart Foundation and other research granting agencies, and noted that the quality of the applications has shown a marked and substantial improvement in recent years. The Council recommended grants for 1967 totalling $918,275 and (subject to funds being available) commitments for 1968 totalling $226,984 as listed below.
----------------------------------------------------------1967 $
Name and Project
Nature of Grant
Grant
Commitment
1968 $
1969 $
UNIVERSITY OF ADELAIDE Department of Biochemistry
Professor W. H. ELLIOTT (Renewal) Photovolt Densicord Model 524 Isolation of aminolevulinic acid synthetase densitometer with accessories Technical assistance and maintenance expenses
3,000 3,624 6,624 3,624 3,624 3,624 3,624
Department of Child Health
Professor G. M. MAXWELL Dr R. B. ELLIOTT (New Grant) Investigation of nutritional and microbiolOgical factors as causes of diarrhoea in Australian Aboriginal children
Beam scale Laboratory assistance, consumable supplies and maintenance expenses
850
5,500 6,350
Department of Dental Science
Professor J. C. THONARD (New Grant) Metabolism of human singival epithelium
'" Zeiss inverted microscope Technical assistance and mainten. IIIlce expenses
1,150 3,000
4,150
10
.,.
Name and Project
Nature of Grant
Grant 1967
. Commitment 1968 $ 1969
$ Department of Human Physiology and Pharmacology Professor R. F. WHELAN (Renewal) Harvard pump Nervous and humoral control of blood ves- Two Transducer pressure heads sels in man Tachometer unitfor Grass recorder Technical assistance and maintenance expenses
$
700 500 500 2,426 4,126
3,000 3,000
3,000 3,000
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Dr I. S. de la LANDE (Renewal) (i) Analysis of venon of Myrmecia pyriformis (ii) Analysis of the samlfly (family ceratopogonidae) Dr S. L. SKINNER (Renewal) Physiology of the renin angiotensin system
Salary, Research Assistant, Grade II, Mrs J. Wanstall Maintenance expenses
3,910 540 4,450
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Salary, Research Fellow, Dr S. L. Skinner Stipend, Medical Postgraduate Research Scholar, Dr E. R. Lumbers Technical assistance and maintenance expenses
7,160 4,040 3,000 14,200
7,380
7,600
3,000 10,380 7,600
Department of Medicine
Professor D. J. DELLER (New Grant) Studies of: (i) Mucoviscidosis (ii) Gall stone formation
Stipend, Medical Postgraduate Research Scholar, Dr P. L. Reilly Refrigerated fraction collector Maintenance expenses
3,780 1,200 500 5,480
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Professor B. S. HETZEL (Renewal) Thyroid function in health and disease Dr I. J. FORBES (Renewal) Studies of human lymphocyte function
Equipment and maintenance expenses Stipend, Postgraduate Scholar, Mr J. L. Smith Maintenance expenses
2,000
2,000
2,000
2,500 600 3,100
600 600
600 600
Department of Microbiology ,"".
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Professor D. ROWLEY (Renewal) Mechanism of acquired resistance to intracellular parasites
Salary, Research Fellow, Dr K. J. Turner Technical assistance and maintenanceexpenses
6,940 2,000 8,940
7,160
7,380
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7,160
7,380
Dr C. R. JENKIN (Renewal) Synthesis of artificial antigens
Salary, Senior Research Officer, Dr C. D. F. Jackson Maintenance expenses
4,800 200
5,020 200
5,240 200
.,.,.
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5,000
5,220
5,44Q
Nature of Grant 1967
Commltmmt 1968 1969
$
$
$
Departme/t of Obstetrics and Gynaecology DrI.R.COX (Renewal) Studies on the control of gonadal, adrenooortical and pituitary function Dr E. M. SYMONDS
Technical aSsistance and maib.tenance expenses
2,000
The correlation of foetal acid-base status
(New Grant)
Grant-in-aid heart action and
3,500
Department of Surgery Dr J. S. CHARNOCK
(Renewal) Mechanism of cation transport
Stipend, Postgraduate Schow, Miss H. Trebilcock Maintenance expeuses
2,500 1,280 3,780
Dr P. R. KNIGHT
(New Grant) Effect of homograft rejection on the reticulo-endothelial system
Humid incubator for tissue culture Technical assistance and maintenance expenses
500 3,500
4,000 Dr J. D. SALUS
(Renewal) Mechanism of action of parathyroid hormone
Refrigerated fraction collector Peristaltic perfusion pump Top-drive tissue macerator Technical assistance and maintenance expenses (Equipment to remain the property of the Commonwealth)
1,600 700 150
1,000 3,450
.. 2,000 1,000
Australian JourlUll of Experimental Biology and Medical Science Publication expenses
3,000
FLINDERS UNIVERSITY School of Biological Sciences Professor M. R. ATKINSON (New Grant) Nucleotide metabolism and control of growth
Grant-in-aid
8,500
UNIVERSITY OF MELBOURNE Dtpdrtmenl of AIUl/omy Professor K. C. BRADLEY (New Grant) Cerebrospinailluid circulation )}r
Technical assistance and maintenance expenses Grant-in-aid
4,000 7,500
A. F. ROCHE (Renewal) PIiYsical aspedi of child irowth
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MIme and hoJ«t
Nature of Grant
GrtmI
eommltmenl 1968 $ 1969 $
1967 $
Department of Biochemistry Professor V. M. TRIKOJUS (Renewal) Studies on thyroid enzymes and thyroglobulin Stipend, Postgraduate Mr G. D. Smith Maintenance expenses Scholar,
2,600 1,500 4,100
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Professor P. F. HALL (New Grant) The action of h,ormollCSon melanogenesis
Radiochromatogram scanner Packard 7201 Technical assistance and mainten. ance expenses
3,144 3,000 6,144
Dr F. D. COLLINS (Renewal) Studies on phospholipids
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Salary, Senior Research Fellow, Dr F. D. Collins Technical assistance and mainten· ance expenses
8,600 3,000
11,600
Department of Dental Prosthetics Professor H. F. ATKINSON (Renewal) Mandibular movements in speech and mastication Technical assistance, equipment and maintenance expenses
5,000
4,000
Department of Conservative Dentistry Professor E. STOREY Dr W. A. McDOUGALL (Renewal) (i) Factors effecting the development and metabolism of hard tissues (iI) The role of Iysommes in normal and inftamed tissues Dr H. 1. ORAMS (New Grant) A study of enamel structure and the cuticles attached to the enamel surface with particular reference to the initial carious process
Technical assistance and mainten· ance expenses
7,500
7,500
Two diamond knives (with holders) for microtome Maintenance expenses
380
500
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Department of Medicine (Austin Hospital) Professor A. B. DOYU\, (New GranO The pathogenesis of malignant hypertension
Salary, Senior Research Officer, Dr A. Ebringer MainteQance expell$l8
5,240 SOO 5,740
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Name and Project
Nature of Grant
Grant
Commitment
1967 $ Department of Medicine (Royal Melbourne Hospital) Dr J. K. DAWBORN (New Grant) Salary, Research Fellow, Dr J. K. Potassium/aldosterone relationships Dawbom
1968
S
1969 $
7,380
7,600
DrJ.R.E.FRASER (Renewal) Physiological and chemical studies of hyaluronic acid
Salary, Research Assistant, Grade II, Mr B. Clarriss Equipment and maintenance expenses
3,910 1,700 5,610
Dr P. KINCAID-SMITH (Renewal) (i) The aetiology and treatment of renal infection. (ii) Correlation of structure and function in renal disease. (iii) The treatment of chronic uraemia by diet, dialysis and renal transplantation. (iv) Analgesic abuse and renal disease. (v) Hypertension in pregnancy. (vi) Electron microscopy of the kidney with special reference to vascular and glomerular changes in homograft rejection.
60 per cent part-time salary, Senior Research Fellow, Dr P. KincaidSmith Technical assistance and maintenance expenses
5,160 6,400
11,560
Dr F. I. R. MARTIN (New Grant) (i) To determine the effect of insulin on peripheral glucose uptake and hepatic glucose output in patients with juvenile onset diabetes mellitus (ll) To investigate the relation between the immunological and biological activity of injected insulin in the plasma of juvenile onset diabetics
Technical assistance and maintenance expenses
2,500
Department of Medicine (St. Vincent's Hospital)
Professor G. C. DE GRUCHY DrJ. HIRSH (Renewal) (i) The metabolism and turnover of platelets in relation to their function (ii) Red cell metabolism in relationship to cell age and in haemolytic anaemia
Salary, Research Officer, Loder Maintenance expenses
Mrs 4,680 1,000
5,680
Dr J. G. D. RANKIN (New Grant) Natural history, treatment and prognosis of alcoholism
Data processing
600
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Name and Project -",
Nature of Grant
Grant
Commitment
1967 $
1968 $
1969 $
Department of Microbiology Professor S. D. RUBBO (Renewal) Prophylaxis against tetanus
Salary, Research Assistant, Grade II, Miss J. Franklin Maintenance expenses
3,780 700 4,480
3,910 700 4,610
4,040 700 4,740
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Professor F. W. E. GmSON (Renewal) (i) The biosynthesis of vitamin K and ubiquinone, in bacterial cells (ii) Other aspects of aromatic metabolism
Salary, Research Assistant, Grade II, Mr G. B. Cox for three months from I January 1967 at $3,910 per annum Payroll tax
978 24 1,002
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Dr B. W. HOLLOWAY (Renewal) Conjugation and the study of gene distribution in Pseudomonas aeruginosa
Brunswick-Gyrotory shaker bath with accessories Technical assistance and maintenanceexpenses
910 2,500 3,410 2,500 2,500 2,500 2,500
Dr I. H. HOLMES (Renewal) Electron microscopy of hepatitis viruses Dr D. O. WHITE (Renewal) Expression of the viral genome in cells infected with occogenic and non-occogenic adenoviruses
Grant-in-aid
4,000
Salary, Research Assistant, Grade II, Mrs M. Shew Maintenance expenses
3,650 \,000 4,650
3,780 \,000 4,780
3,910 1,000 4,910
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Dr A. J. PITTARD (Renewal) A genetic and biochemical investigation of aromatic biosynthesis in Escherichia coli
Stipend, Postgraduate Scholar, Mr B. Wallace
Maintenance expenses
2,600 600 3,200
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Department of Obstetrics and Gynaecology Dr J. B. BROWN (Renewal) Development of oestrogen, pregnanediol and gonadotrophin assays and study of ovarian and placental function in gynaecological and obstetrical disorders
Technical assistance and maintenance expenses
7,000
Dr I. J. HOPKINS (New Grant) Neonatal convulsions ~"
Beckman Offner Type T portable 8 channel E.E.G. machine
4,000
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Name and ProJect
Naturt o/Grant
Grant 1967
Commitment
Dtpar1ment 01 Pathology DrI.K.BUCKLEY (Renewal) A microscopic study of the mechanisms of progressive damage following focal heat Salary, Research Fellow, Dr I. K. Buckley Technical assistance and maintenance expenses
•
1968 $
1969
•
7,600 2,400 10,000
ilUury
Department of Pharmaeo!ogy Professor M. J. RAND (New Grant) Drugs affecting activity and release oC catecholamines
60 per cent part.time salary. Senior Research Offic:er, Dr J. O'Neill Salary. Research Assistant. Grade II, Mrs Genge 4-channel penwriter with accessories Technical assistance and main· tenance expenses
3,570 3,520 9,000 3,000 19,090
Department 0/ PhysiolOf1 ProfessorR.D.~GHT
(Renewal) Histological studies of salivary glands and other histological projects DrD. A. DENTON (Renewal) (i) Continuation of studies on ablation of kidneys in hypophysectomized animals in relation to site or origin of ASH (ii) Study of hypophysectomized sheep with adrenal transplant (ill) Effect of large or discrete ablations in the central nervous system on aldosterone secretion (iv) Effect of induction of emotional states in trained animals on the cortico· steroid secretion (v) Effect of local haemodynamic charIge$ in splanchnic and renal circulation on corticosteroid secretion (vi) Effect of changes of plasma and extra· cellular volume of corticosteroid secretion and renal haemodynamics (vii) Effects of Na + deficiency and physiological response of secretory tissues (viii) Continuation of studies on the biosynthesis of aldosterone (ix) Study of aldosterone of sheep bn· munized to give high titre of anti·renin in the circulation (x) Investigation of neural mechanisms involved in selective appetite for Na + shown by Na + deficient sheep-tho in1Iuence of hypertension on thia mechanism
Histological technical assistance and maintenance expenses
1,400
1,400
1,400
Salary, Principal Research Fellow, Dr D. A. Denton Salary, Research Fellow, Dr J. F. Blair-West Salary, Research Fellow, Dr J. P. Coghlan Technical assistance, equipment and maintenance expenses
10,400 7,380 7,380
10.400 7,600 7,600
10,400 7,600 7,600
15,000 40,160 25,600 25,600
I
r Name and Project io';
Nature-oJ Grant
Grant 1967
Commitment 1968 1969
$ Dr D. J. DEWHURST (Renewal) The precise control of human muscular movement Dr A. SHULMAN (Renewal) (i) The use of metal chelates in the investigation of biological mechanisms (ii) The mode of action of central nervous system stimulant and depressant drugs in the intact animal Technical assistance and maintenance expenses Salary, Senior Research Fellow, Dr A. Shulman Stipend, Postgraduate Scholar, Mrs Glenda Shulman Technical assistance and maintenance expenses
$
$
3,500
.~
, ;,-.~
8,600 2,700 915 12,215
8,600
Department oj Zoology Professor G. BURNSTOCK (Renewal) Autonomic nerve-smooth muscle transmission Technical assistance and maintenance expenses 5,000 5,000
5,000
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MONASH UNIVERSITY Department of Anatomy Professor G. C. SCHOFIELD (Renewal) Experimental studies on biologically active substances in the alimentary canal Technical assistance and maintenance expenses 4,400 4,400 4,400
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Department oj Biochemistry Professor J. BORNSTEIN (Renewal) The structure and mechanisms of action of insulin and its antagonists Stipend, Postgraduate Scholar, Mr R. E. H. Wettenhall Maintenance expenses 2,500 2,000 4,500
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Prore~ocA.W.LINNANE
(Renewal) The origin of mitochondria and the synthesis and organisation of mitochondrial enzymes
Stipend, Postgraduate Scholar, Miss M. Duncan Technical assistance and maintenance expenses
2,500 6,000 8,500
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Dr D. A. LOWTHER (Renewal) The macromolecular structure of cartilage and intervertbral disc tissues
Salary, Research Assistant, Grade I, Miss E. Baxter Maintenance expenses
3,090 600 3,690
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Department oj Microbiology Dr J. H. MARSHALL (New Grant) Physiology of pigment formation by staphylococci and lipid metabolism in mycoplasma Salary, Research Assistant, Grade II, Mrs Rodwell Maintenance expenses 3,650 400 4,050 3,780 400 4,180
W68/66-J
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Name and Project
Nature of Grant
Grant
Commitment
1967 $ Department of Obstetrics and Gynaecology
1968
S
1969 $
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Professor E. C. WOOD (Renewal) Influence of the autonomic nervous system upon the human uterus
Salary, Senior Research Officer, Dr. H. Nakanishi 2 Channel Offner type RP pressure recorder Maintenance expenses
5,020 3,300 1,000 9,320
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Department ofPathology
Professor R. C. NAIRN (Renewal) (i) Study of organ-specific antigens and autoantigens in man and experimental animals (ii) Investigation of autoimmune diseases
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Salary, Senior Research Officer, Mr H.A. Ward Technical assistance and maintenance expenses
5,460 4,000 9,460
Department ofPhysiology
Professor A. K. MclNTYRE (Renewal) Quantitative analysis of synaptic actions on central neurones
Salary, Electronics Technician Other technical assistance, equipment and maintenance expenses
3,180 3,000 6,180
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Dr M. E. HOLMAN (Renewal) The electrophysiology of autonomic effector mechanisms, cardiac muscle, and excitationcontraction coupling of mammalian smooth muscle Department ofPyschology
Technical assistance and maintenance expenses
3,000
DrR. H. DAY (New Grant) Electrophysiological correlates of attentional mechanisms Department of Surgery
Digitimer
1,200
DrJ. M. WATTS (New Grant) A study of the physiology of bile secretion and tests of hepatic function in the isolated perfused porcine liver
Grant-in-aid
3,000
UNIVERSITY OF NEW SOUTH WALES School of Anatomy
Professor M. J. BLUNT Associate Professor C. P. SMITH
WENDEL~
(Renewal) (i) The histochemistry of macroglia (ii) The ultrastructure of developing glial elements (iii) The ultrastructure and histochemistry of retinal glial elements
Technical assistance and main tenance expenses
2,500
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Name and Project
Nature of Grant
Grant
Commitment
1967 $ DrG. S. MOLYNEUX (Renewal) The ultrastructure and histochemistry of epitheloid cells in the carotid body and in the walls of arterio-venous anastomoses Dr K. G. RIENlTS Dr J. F. WILLIAMS (Renewal) Carbohydrate metabolism in vertebrate liver School of Hospital Administration Mr R. Gillam (New Grant) The effects of automation on the profession of nursing
1968 $
1969 $
Technical assistance and maintenance expenses
1,400
Technical assistance and maintenance expenses
3,000
Salary, Research, Assistant Grade II, Mr A. Cable at $4,040 per annum Travel and maintenance expenses
3,367· 500
673· 673
3,876 ·Salary for one year as from 3 March 1967 Division 0/ Neurology, Prince Henry Hospital Associate Professor J. W. LANCE Salary, Research Fellow, Dr C. A. (New Grant) (i) The relation between tonic and phasic Tassinari spinal mechanisms in man (ii) The humoral control of cranial arteries in man, in realtion to changes in arterial blood pressure School of Pathology Professor D. L. WILHELM (Renewal) The inflammatory reaction to chemical ilijury
6,500
Technical assistance and maintenance expenses
1,500
.,
..
School of Physiology Professor I. DARIAN-SMITH (Renewal) (i) Neuronal inhibitory interaction in somatic afferent projections to the cerebral cortex by intracellular recording and unitary analysis (ii) Interactions between parallel afferent projections via the rostral and caudal components of the trigeminal brainstem nuclei School of Psychiatry Associate Professor J. E. CAWTE (New Grant) Human ecology of the arid zone
Technical assistance and main tenance expenses
2,600
Salary, Research Fellow, Mr B. W. Ross Travel and secretarial expenses
6,500 4,400 10,900
6,720
1,000 7,700
19
Name and Project
Nature of Grant
Grant
Commitment
1967
1968
S
S
1969 $
UNIVERSITY OF QUEENSLAND Department of Biochemistry Professor E. C. WEBB (Renewal) Enzymology
r Preparative electrophoresis unit Recycling chromatographic apparatus Electrophoretogram Technical assistance and maintenance expenses
4,000 3,850 4,000 9,000 20,850
Dr J. E. O'HAGAN (Renewal) The relationship between structure and function of haemoglobins and myoglobins
Salary, R~search Fellow, Dr J. E. O'Hagan Maintenance expenses
7,600 500 8,100
7,600 500 8,100
Department of Medicine Professor J. H. TYRER (New Grant) Quantitative histochemistry of oJcidative enzymes in brain stem
Ferrand spectrofiuorometer and accessories MPV conversion accessories for Leitz MPE microscope photometer Maintenance expenses
3,800 1,900 500 6,200 500 500
Dr A. M. PARFITr (Renewal) Technical assistance and maintenRenal excretion and conservation of calcium ance expenses and magnesium
3,638
Department of Parasitology Professor J. F. A. SPRENT (Renewal» The pathogenesis and diagnosisofnemotode larva migrans in man with particular reference to eosinophilia and eosinophylic granulomatosis
Stipend, Postgraduate Scholar, Mr E. C. Warren Travel to University farm
2,500 100
2,600
Department of Physiology DrA.UPTON (Renewal) Effects of steroid hormone on the fundamental properties of muscle Department of Surgery DrD. F. HOGG (New Grant) Gastro-intestinal motility studies by pressure transducer
Grant-in-aid
1,000
Grant-in-aid
1,000
20
v
Name and Project
Nature olGrant
Grant 1967 $
Commitment 1968 $ 1969 $
• ~
Dr B. S. MATHER (New Grant) (i) The impact energy absorbing capacities of human long bones (ii) The relationship between the strength and structure of bone
Salary, Research Fellow, Dr B. S. Mather Maintenance expenses
7,160 850 8,010
UNIVERSITY OF SYDNEY .. ~
,-
Department 01 Bacteriology Dr D. S. NELSON Salary, Research Assistant, Grade (Renewal) (i) Macrophages and cytophilic antibodies I, Miss P. Cox objectives for Planachromat in immunological reactions Olympus microscope (ii) The significance in transplantation immunity of humoral antibodies detectable Maintenance expenses by immune adherence DrA. L. HUNT (Renewal) Mechanism of induced synthesis of nicotinic acid hydroxylase respiratory complex in Ps. ftuorescens DrR.G. WAKE (Renewal) Studies on the B. subtilis chromosome
2,490 200 1,000 3,690 300
2,640 1,000 3,640
..
-i·
Maintenance expenses
Research Assistant and maintenance expenses
3,000
"'.
Department 01 Histology Dr J. K. POLLAK (Renewal) The dynamic state of the endoplasmic reticulum under various physiological conditious
Beckman-Spinco L2 drive unit and accessories Maintenance expenses
550 450 1,000
Department of Medicine Professor C. R. B. BLACKBURN (Renewal) . A study of chronic liver disease and chromc lung disease in the Territory of Papua and New Guniea Associate Professor B. G. FIRKIN (Renewal) (i) Platelet function and p.hysiology (ii) Mechanisms of anaemia (iii) Study of cell defect in hereditary spherocytosis
Salary, Technician, Miss Mitchell Additional grant-in-aid
C.
3,176 1,000 4,176 4,800 4,142 8,942 5,020
Salary, Senior Research Officer, Dr J. S. Wiley Technical assistance and maintenance expenses
600 5,620
Department of Obstetrics and Gynaecology Associate Professor R. F. SHEARMAN (New Grant) .. Oestrogens in the biological flUids of pregnant women
Aminco-Bowman llle leT
spectroftuori-
5,600
21
Name and Project
Nature of Grant
Grant·
Commitment
1%7 $ Department of Ophthalmology Dr J. B. COWLE (Renewal) The pharmacology of enediols in aqueous drainage
1968 $
1969 $
Salary, Research Assistant, Grade I, Miss E. Rain Maintenance expenses
2,490 100 2,590
Department of Pathology Professor D. A. CAMERON (Renewal) (i) Pattern of synthesis of collagen in bone cells (ii) Fine structure of synovial cells (iii) Origin and function of osteoclasts Dr P. M. RONAl (Renewal) Quantitation of transplantation immunity in vivo using radio-isotope labelled cells
Salary, 4/5ths full-time Senior Research Officer, Dr. R. Tyrer Technical assistance and maintenance expenses
5,070
4,000 9,070
Salary, Senior Research Officer, Dr P. M. Ronai Technical assistance and maintenance expenses
5,020 2,500 7,520
t
Dr B. J. ROSER (New Grant) Macrophage migration and function in vivo
Technical assistance and maintenance expenses
2,000
Department of Pharmacy Dr A. J. RYAN (Renewal) The enzymology of food additives and foreign molecule metabolism Department of Physiology Professor P. O. BISHOP Associate Professor W. BURKE Dr C. W. DUNLOP Dr W. A. HAYHOW (Renewal) (i) Neurophysiology of vision (ii) Neurohistological studies (iii) Electrophysiological correlates of hearing in cats (iv) Maintained activity of retinal ganglion
Technical assistance and mainmaintenance expenses
7,300
cells
Salary, Electronics Technician Mr R. Brailey , Salary, Electronics Technician Mr A. Knight ' Salary, Research Assistant, Grade I, Miss Ooi Salary, Histology Technician, Miss G. Taylor Digitimer Strip chart recorder Hewlett Packard waveform generator Technical assistance and main. tenance expenses
3,452
3,584
2,940 2,040 1,200 1,064 760 3,600 18,640
.,
2Z
-
Name and Project 'f'_
Nature of Grant
Grant
Commitment
1967 $ Dr W. R. LEVICK (Renewal) Receptive fields of primate retinal ganglion cells Dr J. A. YOUNG (Renewal) A micropuncture and perfusion investigation of amino acid transport in the proximal tubules of the rat kidney Grass, C4 Oscilloscope 1,400
1968 $
1969 $
~
Ultra-micro flame photometer Minor equipment, technical assistance and maintenance expenses
2,840 1,500 4,340
.. -~' Department of Preventative Dentistry Professor Noel D. MARTIN (New Grant) The structural changes in dental enamel when affected by idiopathic and fluoride opacities
Salary, female laboratory assistant Maintenance expenses
1,685 500 2,185
--,.
Department of Surgery Associate Professor T. S. REEVE (New Grant) (i) An evaluation of the effect of thyroidectomy on serum calcium (ii) The roles of parathyroid impairment and thyrocalcitonin release
Salary, Research Assistant Grade I (to be appointed) Maintenance expenses
2,490 500 2,990
2,640 500 3,140
Mr J. A. MYHILL (Renewal) Experimental tracer dynamics
Salary, Laboratory Assistant, Miss Dvoskin X-ray accessories and maintenance expenses
1,945 2,300 4,245
"i'
UNIVERSITY OF TASMANIA Department of Biochemistry Professor E. S. HOLDSWORTH (Renewal) Role of vitamin Ds in bone and calcium metabolism ~-
Maintenance expenses
2,000
2,000
UNIVERSITY OF WESTERN AUSTRALIA Department of Biochemistry Dr I. T. OLIVER (Renewal) Biochemical aspects of development in neonatal rat liver
Gilford Model 207 linear thermosensor Gilford Model 212 ancillary recording channel Gilford Model 300 rnicrosample spectrophotometer Technical assistance and maintenance expenses
460 260 2,200 4,000 6,920
f'
23
Name and Project
Nature olGrant
Orant 1967 $
Commitment 1968 1969
"
S
$
Department 01 Medicine Dr M. G. McCALL (New Grant) A study of differential mortality in migrants Programming and coiling assistance Travel expenses 3,000 500 3,500
Department 01 Microbi%KY Professor N. F. STANLEY (Renewal) The biological spectrum of reovirus Part-time salary (20 hours per week) Research Officer, Dr K. T. Kathigasu Mettler P .1200 balance Technical assistance and maintenance expenses
2,399 400 17,309 20,108 17,309 17,309 17,309 17,309 ~
Department 01 Pathology Dr B. A. KAKULAS (New Grant) A correlative clinico-pathologic study of patients with spinal cord injury Dr J. M. PAPADIMITRIOU (Renewal) Virus transport to target organs Grant-in-aid 5,000
Salary, Senior Research Officer, Dr J. M. Papadimitriou Technical assistance, equipment, publication and maintenance expenses
5,680 3,800 9,480
Department 01 Pharmacology Professor Mary F. LOCKETT (Renewal) Sodium retaining protein hormones of blood Technical assistance and maintenance expenses 2,732
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Department 01 Physiology Professor W. J. SIMMONDS (Renewal) Fat absorption studies Dr B. M. JOHNSTONE (Renewal) Physiology of the cochlea DrI.KALDOR (Renewal) (i) Kinetics of secretion and absorption of iron (ii) Iron storage in the new born Dr S. H. MORGAN (Renewal) Plasma protein metabolism in pregnancy and lactation Technical assistance and maintenance expenses Technical assistance and maintenance expenses Technical assistance and maintenance expenses 4,000 ,i
1,000
1,250
Beckman electrophoresis equipment Technical assistance and maintenance expenses
390 1,250 1 1,640
24
!"
Name and PrIJJect
Nature of Grant
Grant
Commitment
1967 S
1968 S
1969 S
NEW SOUTH WALES INSTITUTES AND HOSPITALS Institute of Dental Research DrK. W. KNOX (Renewal) Antigenic components of oral microorganisms DrG.J. WALKER (Renewal) The enzyme mechanisms for the synthesis and degradation of polysaccharides in oral streptococci
Salary, Research Assistant, Grade I, Miss K. Bogsanyi
2,490
2,640
2,790
Salary, Research Assistant, Grade
II Miss J. Builder Beckman solution metering pump Maintenance expenses
3,520
340 100
3,960 Institute of Medical Research, Royal North Shore Hospital Dr M. R. LEMBERG (Renewal) Salary, part Principal Research Chemistry and biochemistry of tetrapyrrolic Fellow, Dr. M. R. Lemberg compounds Salary, Senior Research Fellow, Dr D. B. Morell Salary, Research Fellow, Dr W. H. Lockwood Salary, Research Fellow, Mr J. Barrett Salary, Research Assistant, Grade II, Miss Y. Chang Salary, Research Assistant, Grade II, Miss J. Thompson Salary, Research Assistant, Grade II, (to be appointed subject to approval of Chairman) Salary, part, Secretary Refrigerated centrifuge Sabbatica11eave expenses, Dr D. B. Morell Maintenance expenses
4,400 8,600 7,600
7,160 3,780 3,780
3,390 700
3,600
1,860 2,200
47,070 Kanematsu Memorial Institute, Sydney Hospital Dr K. D. G. EDWARDS Salary, Research Fellow, Dr N. W. (Renewal) (i) Cellular transport studies particularly Alcock Technical assistance and mainin the kidney (ii) Studies of the renal acidification tenance expenses mechanism, and the role of citrate in hydrogen ion transport
6,620 7,000
13,620
..
Red Cross Blood TransfltSion SerVice, Sydney Dr G. T. ARCHER Salary, Research Assistant, Grade (Renewal) II, Miss Angyal Studies on the eosinophilleucoeyte Travel expenses for Miss Angyal to visit C.S.I.R.O. Field Station at Woolongbar
3,520 90
3,610
2S
Name and Project
Nature of Grant
Grant
Commitment
1967 $ Royal Alexandra Hospital for Children Dr D. C. DORMAN Dr J. D. HARLEY (New Grant) Virological and immunological aspects of congenital rubella infection
1968 $
1969
S
Salary, Research Assistant, Grade I (to be appointed) Tissue culture roller drum Maintenance expenses
3,090 400 400 3,890
3,240 400 3,640
3,390 400 3,790
Royal Prince Alfred Hospital Dr A. P. SKYRING (Renewal) To extend investigations on a preparation of isolated crypt cells from the small intestine of the rat
Salary, Senior Research Officer, Miss D. D. Harrison Maintenance expenses
5,020 400 5,420
Dr P. M. ROUNTREE (Renewal) (i) The epidemiology of staphylococcal infection with special reference to the origin of newly identified strains and the control of infection in intensive care units (ii) The genetics of antibiotic resistance in staphylococci
Salary, Senior Research Officer, Miss M. A. Beard Maintenance expenses
5,240 500 5,740
QUEENSLAND INSTITUTES, HOSPITALS, ETC. Cairns, Queensland Dr J. H. BARNES (Renewal) Prevention and treatment of marine stings
Research and clerical assistance Personal remuneration, maintenance and travel expenses
1,750 2,100 3,850
Queensland Institute of Medical Research Dr R. L. DOHERTY (Renewal) The epidemiology of arboviruses in Queensland, with special reference to Murray Valley encephalitis and epidemic polyarthritis
Morris Mini-Moke (to remain the property of the Commonwealth) Laboratory and field study expenses
1,067 3,933
4,000 4,000
4,000 4,000
5,000
SOUTH AUSTRALIA INSTITUTES, HOSPITALS, ETC. Institute of Medical and Veterinary Science Dr J. R. COULTER DrC.S.HANN (New Grant) Aminoacid sequences of staphylococcal alpha toxin and of fibrinopeptides
Perkin-Elmer gas chromatograph and accessories (to remain the property of the Commonwealth)
4,281
..
..
,.
Name and Project
Nature of Grant
Grant 1967
Commitment 1968 1969
$ Queen Elizabeth Hospital, Woodville Dr M. L. WELLBY (Renewal) (i) Chemical nature of the circulating thyroid hormones (ii) Free thyroxine assays following treatment of throtoxicosis with radioiodine
$
$
Oven with circulating fan Technical assistance and maintenance expenses
400 1,665 2,065
Red Cross Blood Transfusion Service, Adelaide DrR. W. BEAL Technical assistance and main(Renewal) (i) Plasma protein binding of radioactive tenance expenses Vitamin BI2 (ii) Neutrophil alkaline phosphatase in pregnancy South Australian Museum Dr R. V. SOUTHCOTT (Renewal) Maintenance expenses Medical effects of marine invertebrates and other marine and terrestrial animals harmful to man, also of plants of clinical significance
2,250
200
VICTORIA INSTITUTES, HOSPITALS, ETC. Fairfield Hospital, Epidemiological Research Unit Dr A. A. FERRIS (Renewal) Salary, Research Assistant, Grade Tissue culture studies with hepatitis viruses n Miss E. E. Kidd Technical assistance and maintenance expenses
3,780 2,965 6,745
Prince Henry's Hospital, Medical Reserach Centre Professor B. HUDSON Salary, Research Assistant, Grade (Renewal) The secretion and metabolism of androgens I, Mrs A. Mirovics F & M Model 402 gas-liquid Chromatograph Technical assistance, equipment and maintenance expenses
4,300 4,500
6,000 14,800
.¥
Royal Australasian College of Surgeons
DrG.A.KUNE (New Grant) The surgical anatomy of the liver
Part-time salary, Senior Research Officer, Dr G. A. KUNE Maintenance expenses
1,600 400
..
2,000 Royal ChlIdren's Hospital, Gastroenterological Unit
Dr C. ANDERSON (Renewal) Digestion and absorption of sugars in the intestinal tract
Salary, Research Assistant, Grade n, Mr K. Kerry Maintenance expenses
3,910
200 4,110
27
Name and Project
Nature of Grant
Grant 1967
Commitment 1968 $ 1969 $
S Royal Children's Hospital, Surgical Research Unit MrR.FOWLER (New Grant) Salary, Senior Research Officer, (i) Thepreparation and use ofheterologous Dr M. J. Simons antithymocyte antisera and its effect on Maintenance expenses survival of experimental renal homografts (il) The reactivity of lymphocytes in culture St. Vincent's School of Medical Research DrP.EDMAN (Renewal) Microheterogeneity in protein structure Victorian College of Pharmacy Dr A. STAFFORD (New Grant) The physiological role of adenosine derivatives
5,680 800 6,480
5,900
800 6,700
Technical assistance and maintenance expenses
6,000
Grant-in-aid
2,000
Walter and Eliza Hall Institute of Medical Research Professor G. J. V. NOSSAL (Renewal) Salary, Principal Research Fellow, Experimental immunology and oncology Dr G. L. Ada Salary, Principal Research Fellow, Dr I. R. Mackay Salary, Principal Research Fellow, Dr J. F. A. P. Miller Salary, Research Fellow, Dr J. Pye Salary, Research Fellow, Dr A. Szenberg Salary, Research Fellow, Dr K. Shortman Salary, Research Fellow, Dr. N. L. Warner Salary, Senior Research Officer, Dr P. Lind Salary, Senior Research Officer, Dr S. Whittingham Salary, Senior Research Officer, Dr T. A. McPherson Salary, Senior Research Officer, DrG. Robson Salary, Medical Postgraduate Scholar, Dr W. J. Martin Stipend, Postgraduate Scholar, MrN. Kraft Stipend, Postgraduate Scholar, Miss M. Smalley Block grant, other graduate research assistance Technical assistance and maintenance expenses
",..-',
10,400 10,400 10,400 7,600 7,600 6,940 3,360 6,340 5,900 5,020t 5,020 3,780 2,700 2,500 20,000 75,000 182,960
10,400 10,400 10,400 7,600 7,600 7,160
10,400 10,400 10,400 7,600 7,600 7,380
1
MISCELLANEOUS Traffic IJ:Uury in Brisbane Report Additional publication expenses 600
t First assistant to clinical research unit.
..
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28
Mrs Precila May Bowling Bequest
The late Mrs Precila May Bowling stated in her will that the residue of her estate should be applied for the assistance and support of medical or scientific research. The trustees have previously taken the advice of Council in making distributions of the estate and the council recommended that the trustees be advised to make the following grant, representing the final residue of the estate for distribution. Professor R. F. WHELAN, Department of Human Physiology and Pharmacology, University of Adelaide. Study of the nervous and humoral control of blood vessels in man. Additional maintenance expenses $574.01. The Council recommended that a letter of appreciation be sent to the trustees on behalf of the Council and the recipients of grants from the Bowling Estate. Additional Grant Recommendations for 1967
The Council took into account the need to reserve funds for the award of scholarships, travelling fellowships and other commitments following recommendations to be made at the 64th Session early next year, and considered the maximum amount that should be made available for project grants at this stage from the present appropriation to the Medical Research Endowment Fund was $918,275. On the basis of current estimates this would leave less than $20,000 for allocation as project grants at the 64th Session. However, if an additional allocation to the Medical Research Endowment Fund could be obtained, the Council recommended additional project grants totalling $80,845 as shown in Appendix II. Coordination with the Australian Research Grants Committee
..
Arrangements for coordinating the consideration and award of grants for medical research by the National Health and Medical Research Council and the Australian Research Grants Committee were discussed, and Council was informed of discussions that had taken place between representatives of the two bodies. Council endorsed a recommendation of the Medical Research Advisory Committee that arrangements for the support of medical research in Australia should ensure (i) that medical research is adequately supported on a long-term basis; (li) that the National Health and Medical Research Council can continue to exercise its beneficial influence in this field; and (iii) that the activities of the Australian Research Grants Committee should not prejudice the future functions of the National Health and Medical Research Council. The Council also endorsed the following recommendations made at a meeting of representatives of the Council and of the Australian Research Grants Committee. (i) Biological research with application to medical problems will be supported by the N.H. and M.R.C. and general biological research which does not have a bearing on medical problems will be supported by A.R.G.C. Clearly, no sharp dividing line distinguishes medical research from biological research with possible medical importance, and there will be many borderline cases. Generally speaking, medical research will be defined as including all research in which human subjects are involved and all investigations in physiology, biochemistry, pathology and other medical sciences reasonably likely to have close bearing on problems of human health. This definition means that N.H. and M.R.C. will deal with research proposals which come from hospitals, medical and dental research institutes and university clinical departments, except where a project in such a department or institution can be shown to have no bearing on problems of human health; such a problem should be considered by A.R.G.C. Under this definition too, it will be likely that nearly aU the research in universities' pre-clinical departments of the medical and dental faculties (e.g. anatomy, pathology, physiology, pharmacology) will be dealt with by N.H. and M.R.C. In other university departments, such as those 29
(ii)
(iii)
(iv)
(v)
of biochemistry and microbiology, research which has mainly a medical or dental application will be dealt with by N.H. and M.R.C. and that mainly of general biological interest by A.R.G.C. Ajoint A.R.G.C. and N.H. and M.R.C. form of application for grants will be produced, and this form will indicate to applicants that their applications may be channelled from either one to the other organisation for consideration. The closing date for receipt of applications on this joint form will be the 1 June each ye-ar. (For exceptions, see (iii) and (iv) below). Special arrangements sbould be made for the receipt of applications for N.H. and M.R.C. C. J. Martin Travelling Fellowships, Public Health Travelling Fellowsbips, Medical and Dental Research Scholarships, and Medical and Dental Postgraduate Research Scholarships. Pending a fuller consideration of these special cases by the Council in Mayor June next year the present methods of calling and receiving applications for these Scholarships and Fellowships should continue unchanged. Where the N.H. and M.R.C. bas commitments to continue the support after 1967 of rese-arch which, in accordance with the definitions in (i) above, sbould be supported by the A.R.G.C. ratber than by the N.H. and M.R.C., a transition period of several years may be necessary to effect complete transfer of support responsibility and safeguard the interests of the research workers concerned. A small co-ordination committee will be formed with the following membership and functions: Memberhips The Chairman or Acting Chairman of the A.R.G.C. The Cbairman or Acting Chairman of the N.H. and M.R.C. Medical Research Advisory Committee. The Secretary of the National Health and Medical Research Council. The Secretary of the A.R.G.C. Functions To consider grant applications which do not fall easily into one or other groups (A.R.G.C. or N.H. and M.R.C.) and to channel these applications to the most appropriate organisation or to both.
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30
MEDICINE ADVISORY COMMITTEE A meeting of the Medicine Advisory Committee was held on Thursday, 3 November 1966. The Chairman of the Committee, Dr J. G. Radford, presented the report of the Committee to Council. Recommendations arising out of the report received from the Antibiotics Committee are recorded under the appropriate Committee heading. A matter referred to the Medicine Advisory Committee by the Dental Health Committee is also recorded in this part of the report. Diagnosis of Brucellosis Following requests to Council by a number of pathologists for further information concerning the availability ofW.H.O.literature on this subject, it was recommended that pathologists be informed by means of a letter to the Medical Journal of Australia and to the College of Pathologists that the W.H.O. Brucellosis Reference Centre, maintained by the Commonwealth Serum Laboratories, is able to supply information from W.H.O. working papers and publications concerning brucellosis. A list of interested laboratories is kept and any pathologist wishing to obtain such information is requested to write to; W.H.O. Brucellosis Reference Centre, C/o Commonwealth Serum Laboratories, 45 Poplar Road, PARKVILLE, N.2. VIC.
+,
asking that the name of his laboratory be added to the list. Pilot Study on Automation in the Nursing Profession Council noted that an application for a grant by Mr R. Gillam, Senior Lecturer in Hospital Administration, University of New South Wales, to carry out a study on the effects of automation upon the nursing profession has been recommended by the Medical Research Advisory Committee and approved by the Minister. Shortage of Radiotherapists Council noted that a Sub-Committee of the College of Radiologists had been formed to consider this subject and recommended that the College be asked in addition to consider whether there is any shortage of radiodiagnosticians. Teratogenic Effect of Antihistamines Council noted that the new scheduling of antihistamine drugs recommended at the 62nd Session overcomes some of the dangers of self-medication, by requiring that those drugs which may have a teratogenic effect be supplied only on prescription. The Chairman of Council was requested to refer the question of teratogenicity of these drugs to the Australian Drug Evaluation Committee.
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..
ANTIBIOTICS COMMITTEE The report of the Antibiotics Committee was received and Council approved the following recommendations arising from the report; Definition of Chemotherapeutic Agents, Including Antibiotics Council approved an amendment to the definition of an antibiotic as recommended at its 62nd Session. The amended definition reads as follows;The term 'chemotherapeutic agents including antibiotics' as use~ in Cou~cil. reports and recommendations means substances derived from micro-orgamsms, ~envatlves of ~uch substances produced wholly or partially by synthesis and other synthetiC substances Wlth a 31
specific therapeutic effect, for example sulphonamides and nalidixic acid, which may be used for the specific treatment of human or animal infections. The term does not include non-specific disinfectants. In this context, non-specific disinfectants may be defined as nonspecific anti-bacterial substances not derived from micro-organisms and used exclusively for tropical application, for example lyso!. Erythromvcin as a Livestock Feed Additive Council recommended that due to the possible development of sensitivity in persons handling the material, and due to the possible development of resistant strains of susceptible organisms, erythromycin should not be used as a livestock feed additive.
••
DENTAL HEALTH COMMITTEE The following matter was referred to the Medicine Advisory Committee by the Dental Health Committee for discussion. Sympathomimetic Drugs and Monoamine Oxidase Inhibitors Council considered that there were possible dangers in giving local anaesthetic injections containing sympathomimetic drugs to patients who were receiving monoamine oxidase inhibitors. Because of practical problems involved in implementing any recommendation, the Chairman of Council was requested to refer the matter to the Australian Drug Evaluation Committee for further consideration.
~
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32 ),.
PUBLIC HEALTH ADVISORY COMMITTEE A meeting of the Public Health Advisory Committee was held on 31 October, 1 and 2 November 1966. The Chairman of the Committee, Professor Sir Edward Ford presented the report to Council. Reports were received from the Dental Health, Food Additives, Food Standards, Medical Statistics, Occupational Health and Veterinary Public Health Committees. Recommendations arising from these reports are considered under the appropriate committee headings. A recommendation by the Dental Health Committee which was referred to the Medicine Advisory Committee is considered in the report of that Committee. Bottles for Eyedrops It was decided that the requirements for bottles for eye drops, stated in the Report of the 62nd Session of the National Health and Medical Research Council, be amended to read: (i) Capable of being autoclaved. (ii) Have a locking cap with either a screw or bayonet type fitting capable of delivering drops. (iii) Need not be of a particular colour. (iv) Distinguishable by touch by fluting, ribbing, or stars, if of 15m!. or more in capacity. Fluoridation of Water Supplies
At its 52nd Session in November 1961, Council made the following recommendation regarding the fluoridation of public water supplies: 'That fluoridation of public water supplies has been shown in a number of countries to result in a significant reduction in dental caries in the popUlation supplied and that the procedure is safe. The Council recommends that public authorities give early consideration to the necessity of fluoridating their water supplies.' Council reaffirmed this recommendation, expressed concern at the delay in the introduction of fluoridation of public water supplies and, in the interests of the health of children, strongly urged the relevant water authorities of Australia to give urgent consideration to the implementation of this important measure. Public Health Travelling Fellowship
Council approved the award of a Public Health Travelling Fellowship to the value of $3,000 to: Dr Noel Kevin Dougan, Department of Health, Western Australia, for a study ofpsychiatrlc problems in geriatrics. Scheduling and Labelling of Poisons Amendments to Uniform Poisons Schedules
r
Council approved a number of amendments to the Uniform Poisons Schedules as published in Appendix II of the Report of the 60th Session and as amended at the 62nd Session. These appear in Appendix III to this report. First Aid Directions
Council recommended a revision of the 'First Aid' directions as appearing in the Report of the 62nd Session. The revised list, together with suitable combinations for specific substances appears in Appendix IV to this report. 21568/66-3
33
Index to Schedules
Council noted that it has been decided to list each substance included in the blanket entries in the schedules by its specific name in the index. In order to keep the actual schedules within manageable size 'blanket' entries will be continued including therein typical specific names as at present. The wording in such 'blanket' entries should read 'including' instead of 'such as'. A list is attached (see Appendix V) of approximately 350 specific names which are covered by some of the present blanket entries. These items will be included in the index to the Schedules, and not in the Schedules themselves. Label Warnings Council considered the labelling requirement in the Uniform Poisons Schedules for veterinary preparations. It was recommended that the label requirement for exempt veterinary preparations should be:
'WARNING-SHOULD NOT BE USED FOR HUMAN BEINGS.' Procedure for Scheduling The question of information required for the scheduling of therapeutic and non-therapeutic substances has been reviewed. A revised set of instructions and a single consolidated list which sets out the information required for scheduling of both therapeutic and non-therapeutic substances, appears in Appendix VI to this report. Prohibited Substances Council considered that the definition of a prohibited substance should be widened to permit use of such substances for research. The following definition of prohibited substances was accepted: 'Substances or preparations thereof, the manufacture, use, possession or sale of which is prohibited except for amounts which may be necessary for medical and other scientific research only, including clinical trials therewith to be conducted with the approval of Commonwealth or State Health Departments.' Schedules 5 and 6 Council recommended that Schedules 5 and 6 be reviewed and re-arranged as to toxicity rather than use. Less toxic substances will be placed in Schedule 5, to be labelled with the signal word WARNING. More toxic substances will be placed in Schedule 6 to be labelled with the signal word POISON. Smallpox Vaccination Council re-affirmed its current recommendations on smallpox vaccination and considered maximum publicity should be given to the following statement:(i) That an increased rate of vaccination against smallpox is to be encouraged, especially in childhood. (n) That the optimum age at which primary smallpox vaccination should be given is from 6 months to 4 years. (iii) All persons likely to be exposed if a case of smallpox develops unexpectedly should be vaccinated and should be re-vaccinated every three years. This group would include medical practitioners and their families, medical students, all hospital and ambulance personnel, health inspectors, persons employed in aircraft and on airports, policemen, wharf labourers, taxi drivers, crews of Australian vessels, employees of air and shipping companies who come in contact with overseas traffic, sea pilots, press reporters and all persons who are likely to come in contact with persons or vessels from overseas. (iv) Pregnant women should be excluded from general vaccination programmes but should be vaccinated if they are exposed or are likely to be exposed to smallpox.
; ....
,
34
FOOD ADDITIVES COMMITTEE Council received the report of the Food Additives Committee and approved the following recommendations. Dried Instant Mashed Potatoes Dried instant mashed potatoes should be permitted to contain 0.01 per cent by weight of antioxidant and 0.5 per cent by weight calculated on the moisture-free basis, of modifying agents in Group IV of the Jist set out in Appendix VI to the Report of the 62nd Session. Glyceryl Lacto Stearate Glyceryllacto stearate should be added to Group IV of the list of prescribed modifying agents set out in Appendix VI to the ReIort of the 62nd Session. Nisin Nisin should be permitted to be used in canned soups which are in hermetically sealed containers and which have been sufficiently heat processed to destroy any Clostridium botulinum present. Residues on Fruit and Vegetables The tolerances for residues of agricultural chemicais on fruit and vegetables, both fresh and preserved, and on grains as set out in Appendix VII to this report should be adopted. Sulphur Dioxide in Dried Peas Sulphur dioxide should be permitted in dehydrated green peas up to a maximum of 1,000 p.p.m.
FOOD STANDARDS COMMITTEE Council approved the fonowing recommendations arising out of the report of the Food Standards Committee. Artificial Sweetening Substances A standard for artificial sweetening substances was recommended and appears as Appendix VIII to this report. Baking Compounds Council recommended that the standard for baking compounds approved at the 46th Session (page 20) be amended as fonows;(i) In the paragraph fonowing the heading 'Acid Phosphate Powder or Phosphate Aerator' after the words 'any suitable acid phosphate' add '(including sodium aluminium phosphate)' . (ii) In the fonowing paragraph delete the words 'not more than three-tenths of one part per centum of compounds of aluminium, calculated as alumina (AI 20 a),. (iii) In the paragraph fonowing the heading 'Baking Powder' delete the words 'no more than one-tenth of one part per centum of aluminium compounds calculated as alumina (AI 203)'. A revised standard appears as Appendix IX. Cheese It was recommended that the Standard for Cheese as amended by Council at its 57th Session (Appendix V to that report) and again at the 59th Session (page 30), be further amended as follows;(i) To clause 3 add new sub-clause (d) 'Cream cheese, when heat processed, may contain prescribed antioxidants as prescribed in Regulation . . . . . '. (ii) The addition to clause 5 (a) of the words 'and no more than 0.1 per cent of lactose'. (iii) At the end of clauses Sea), 6(a) and 7(a) after the words 'and/or sodium citrate' add the words 'and/or sodium alginate provided the proportion of the sodium alginate in the cheese does not exceed 1 per cent'.
35
Dried Milks
Council recommended the following amendment to the Standard for Dried Milk Products which appeared as Appendix VII to the Report of the 62nd Session. Mter clause 2 add the following new clause with the heading 'Permitted additions' and reading:'Milk powder as used in hot drink dispensing machines may contain not more than 0.4 per cent sodium alumino silicate or 0.4 per cent calcium sodium alumino silicate provided that O. 1 per cent of edible bone phosphate is also present.' Edible Fats and Oils
A standard for edible fats and oils was recommended by Council and appears as Appendix X to this report. Fish and Fish Products
It was recommended that the Standard for Fish and Fish Products, as amended by Council at its 58th Session, and set out as Appendix V to the report of that Session, be further amended as follows:Clause 3 to be renumbered 3(a) and tpe following two new sub-clauses added:'3(b) Frozen fish fillets may contain alkali metal polyphosphates in proportion not exceeding O. 3 per cent calculated as phosphorus pentoxide. 3(c) Frozen fish fillets and frozen prawns may contain ascorbic acid or erythorbic acid (iso-ascorbic acid) or their sodium salts as an antioxidant in an amount not exceeding 400 p.p.m. No reference shall be made on the label or in any advertisement to the presence of any such addition." Frozen Foods Code of Practice for Handling
Council recommended a Code of Practice for the handling of Frozen Foods, which appears as Appendix XI to this report. Sale, Service, Display and Transportation
A new Standard for the Sale, Service, Display and Transportation of Frozen Foods was recommended and appears as Appendix XII to this report. Council also recommended that as from I January, 1970 this Standard should be amended by substituting OaF for each temperature in Schedule I. Ice Cream and Related Products It was recommended that the standard for Ice Cream and Related Products as set out as Appendix III to tbe Report of tbe 55th Session amended by Council at its 60th Session be further amended by the addition to clause 1 (b) of:'The addition of fat other than milk fat to ice cream is not permitted'.
Jelly Crystals, Tablets, Cubes and Mixes
A Standard for Jelly Crystals, Tablets, Cubes and Mixes was recommended by Council and appears as Appendix XIII to this report. Labelling
A new Standard for Labelling was recommended and appears as Appendix XIV to this report. Meat and Meat Products It was recommended that the Standard for Meat and Meat Products as amended by Council at
the 57th Session (Appendix VII) and at the 59th Session (page 31) be further amended as follows: To clause 9 add new sub-clause '(e) Frozen poultry meat may contain alkali metal polyphosphates in proportion not exceeding 0.3 per cent calculated as phophorus pent oxide.'
36
'-I-
Substitute for the present Clause 9(a) dealing with the use of sulphur dioxide in uncooked sausage meat, the following: '(a) Uncooked sausage meat when enclosed in a casing may contain sulphur dioxide in proportion not exceeding 525 p.p.m. Uncooked sausage meat when not enclosed in a casing may contain sulphur dioxide in proportion not exceeding 525 p.p.m. provided that the total meat content is not more than 85 per cent; the provisions of this clause of the regulation shall not, however, prohibit the sale of a chopped or comminuted meat containing more than 85 per cent of meat and not more than 6 per cent of starch with or without herbs, salt, sugar, spices, salt-petre and water provided that such uncooked chopped or comminuted meat does not contain any preservatives whether it be sold under the name of sausages or sausage meat or not.' Delete from Clause 5(a) ,the reference to the minimum content of starch, Clause 5(b) replaced by:'A sausage is sausage meat enclosed in a casing or formed by other means', Mineral and Carbonated Waters A new Standard for Mineral and Carbonated Waters was approved and appears as Appendix XV to this report. Type Size in Labelling It was recommended that the Standard for Type Size in Labelling as set out in Appendix IX to the Report of the 57th Session of Council be amended to include a table for converting the existing point size measurements into the decimal system. With the adoption of this system of measurement of type size it will not be necessary to set out exemplary type sizes in the Regulations as exist at present in most States legislation. An amended standard appears as Appendix XVI to this report. Vitamins and Minerals A further amendment was recommended to the Standard for Vitamins and Minerals as recommended by Council at its 54th Session (Appendix E to that Report) and previously amended at the 57th Session (page 25), the 58th Session (page 38) and the 59th Session (page 31). An amended standard appears as Appendix XVII to this report.
MEDICAL STATISTICS COMMITTEE Council approved the following recommendations arising out of the Report of the Medical Statistics Committee. Population Data as a Basis for Analysis Council commended the work of the Bureau of Census and Statistics in preparing a definitive series of age estimates for intercensal years, and recommended that the Bureau be encouraged to publish the estimates preferably in stages, and taken back as far as it is reasonable, ultimately to 1881 if possible. Publication and distribution of Eighth Revision Manual of the International Classification of Diseases Council recommended that all organisations likely to require copies of the manuals of the Eighth Revision of the International Classification of Diseases be circularised to ascertain their requirements. Consideration should be given to means whereby the Commonwealth Government could purchase copies of the manuals for distribution and sale to the appropriate Commonwealth and State departments and instrumentalities in order to take advantage of the special bulk order price offered by the World Health Organization to governments of member countries, Use of the International Classification of Diseases by Hospitals Council recommended that hospitals should use the World Health Organization'S adaptation of the ICD for indexing hospital records when this becomes available. This adaption, while leaving untouched the three-digit structure of the lCD, will provide greater detail at the fourth digit level.
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37
Survey of Australian Smoking Habits On the 25th and 26th July 1966, the Commonwealth and State Ministers for Health held a meeting in Canberra. They agreed that the National Health and Medical Research Council be asked to examine the practicability of undertaking a survey of smoking habits and attitudes in Australia.
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Council recommended the establishment of an ad hoc Smoking Survey Sub-Committee with the following terms of reference:'To consider and submit proposals to the Medical Statistics Committee for a survey of smoking habits and attitudes in Australia.' OCCUPATIONAL HEALTH COMMITTEE Council approved the following recommendations arising out of the Report of the Occupational Health Committee. Ion Smoke Detectors incorporating Krypton-85 Council recommended that subject to a satisfactory safety assessment by a central laboratory, e.g. the Commonwealth X-ray and Radium Laboratory or the Australian Atomic Energy Commission, the use of ion smoke detectors containing krypton-85 be permitted in Australia. It was recommended that the owners of buildings in which these devices are installed might be exempted from the licensing requirements of Radioactive Substances Acts and Regulations but that any firm selling and maintaining the devices should be licensed and be required to keep a register of sales and installations of the devices, and further that each person servicing the equipment should be licensed. Draft Paint Standard Council approved the amended draft paint standard as set out in Appendix XVIII to this report.
VETERINARY PUBLIC HEALTH COMMITTEE The following recommendation of the Veterinary Public Health Committee was approved by Council. Cysticercus bovis Viable cysts of Cysticercus bovis are being found in increasing numbers in Australia. Council was of the opinion that when Cysticercus bovis is found on meat inspection examination, the meat and offal of the carcass concerned should either be destroyed, or, when infestation is slight, should be allowed for sale only after subjection to freezing and holding for an appropriate period of time at a suitable temperature to ensure that cysts are no longer viable. Conditions which have been shown to be effective are 14°P for 14 days or 200P for 21 days.
COMMITTEE MEMBERSHIP AND CONSTITUTION Review of Committees and Sub-Committees A meeting of an ad hoc Committee to review the Committees and Sub-Committees of Council was held in Sydney on 20 July 1966. Council received the report of the ad hoc Committee and approved the amended organisation and terms or reference and the reconstitution of committees which are incorporated in Appendix XIX 'General Organisations and Administration of Council and Committees', Appendix XX 'Constitution and Terms of Reference of Committees', Appendix XXI 'Inter-relationship of Council and Committees' and Appendix XXII 'Membership of Committees'. Amendments to Constitution Council noted the Amendments to the Constitution of the National Health and Medical Research Council contained in the Order in Council which received Royal Assent on 1 September 1966 and was published in the Commonwealth of Australia Gazette of 15 September 1966 (No. 78 of 1966)
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TIME AND PLACE OF NEXT MEETING Council recommended that consideration be given to holding the 64th Session of Council in Perth towards the end of April 1966, closely preceding or following the meeting of Commonwealth and State Ministers for Health which will take place in that city. R. H. C. WELLS, Secretary W. D. REFSHAUGE, Chairman
39
APPENDIX I SCHEDULE OF WALTER AND ELIZA HALL INSTITUTE SCIENTIFIC ESTABLISHMENT RECOMMENDED AS THE BASIS FOR N.H. AND M.R.C. SUPPORT IN THE 1968-70 TRIENNIUM Position No. Classificatio" and salary rtll/lfe(s) Likely occupant 0" 1 Ja1I1IQI")1 1968 Proposed classificatio" and salary
1968 $ 10,400.00 10,400.00 10,400. 00 6,940.00 6,SOO.OO 5,020.00 7,600.00 7,600.00 7,160.00 6,720.00 6,120.00 6,500.00 6,340.00 6,340.00 4,170.00 108,210.00 16,231.50 124,441.50
1969 $ 10,400.00 10,400.00 10,400.00 7,160.00 6,720.00 5,240.00 7,600.00 7,600.00 7,380.00 6,940.00 6,340.00 6,720.00 6,340.00 6,340.00 4,320.00 109,900.00 16,485 .00 126,385.00
1970 $ 10,400.00 10,400.00 10,400.00 8,600.00 6,940.00 5,460.00 7,600.00 7,600.00 7,600.00 7,160.00 6,500.00 6,940.00 6,340.00 6,340.00 4,440.00 112,720.00 16,908.00 129,628.00
2
3 4 5 6 7 8
$
9
10
11 12 13 14 15
Research Fellow-Principal Research Fellow ($6,500-$7,600) ($8,600) ($10,400) Research Fellow-Principal Research Fellow ($6,500-$7,600) ($8,600) ($10,400) Research Fellow-Principal Research Fellow ($6,500-$7,600) ($8,600) ($10,400) Senior Research Officer-Senior Research Fellow ($4,800-$6,340) ($6,500-$7,600) ($8,600) Senior Research Officer-Research Fellow ($4,800-$6,340) ($6,500-$7,600) Senior Research Officer-Research Fellow ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200$4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200($4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200$4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200$4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200$4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Research Fellow ($4,200$4,680) ($4,800-$6,340) ($6,500-$7,600) Research Officer-Senior Research Officer $4,200-$4,680) ($4,800-$6,340) Research Officer-Senior Research Officer ($4,200-$4,680) ($4,800-$6,340) Research Assistant, Grade II-Research Officer (S3,390-$4,300) ($4,200-$4,680)
DrG. L. Ada
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Principal Research Fellow Principal Research Fellow Principal Research Fellow Research Fellow(i) Research Fellow Senior Research Officer Research Fellow Research Fellow Research Fellow Research Fellow Senior Research Officer{ii) Research Fellow Senior Research Officer Senior Research Officer Research Assistant, Grade II(iii)
Dr I. R. Mackay Dr J. F. A. P. Miller Dr N. L. Warner To be appointed 1st Assistant to Dr I. R. Mackay Dr G. Robson, Pathologist to Clinical Research Unit Dr A. Szenberg Mr J. Pye Dr K. Shortman
Dr M. C. Holmes Dr S. Whittingham To be appointed Dr P. Lind To be appointed Miss Austin
Sub-totals Plus 15 per cent to cover superannuation, payroll tax, sabbaticalleave and travel expenses (in accordance with usual N.H. and M.R.C. conditions) Totals (i) Provision for possible promotion to Senior Research F.now in 1970. (Ii) Provision for possible promotion 10 Research Fellow in 1970. (iii) Provision for possible promotion 10 R_arcb OIBcer ill 1969.
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Position No.
Classification and salary range(s)
Likely occupant on 1 January 1968
Proposed classification and salary
1968
1970
16 17 18 19 20 21 22
23 24 oil-
...
2S
26
Senior Technical Officer, Grade ll-Grade ill (Electron microscopy) Technical Officer, Grade I (Electron microscopy) Technical Officer, Grade I (Senior Biochemistry Technician) Technical Officer, Grade I (Senior Electronics Technician) Technical Officer, Grade I (Senior Histology Technician) Technical Officer, Grade I (Head Animal Caretaker) Technical Officer, Grade I (Senior Media and Tissue Culture Technician) Foreman Animal Attendant Technical Assistant, Grade III (Foreman Mouse Breeding) Technical Assistant, Grade ill (Senior Pathology Technician) Assistant Librarian
MrA.Abbott MrJ. NaHon MrK. Clarke Mr M. S. Grant Mr A. Bargebos Mr J. Sheridan .. Miss H. Simpson Mr H. Hansen .. Miss A. J. Parsons Miss W. House Mrs A. Seymour
Senior Technical Officer, Grade ll(iv) Technical Officer, Grade I Technical Officer, Grade I Technical Officer, Grade I Technical Officer, Grade I Technical Officer, Grade I Technical Officer, Grade I Foreman Animal Attendant Technical Assistant, Grade ill Technical Assistant, Grade Assistant Librarian •.
$ 5,011.00 3,465.00 3,669.00 3,669.00 3,669.00 3,567.00 3,241.00 2,681.00 2,835.00 2,835.00 2,563.00 37,205.00 5,480.75 42,785.75
$ 5,253.00 3,567.00 3,771.00 3,771.00 3,771.00 3,669.00 3,353.00 2,681.00 2,835.00 2,835.00 2,687.00 38,193.00 5,728.95 43,921.95
$ 5,437.00 3,669.00 3,771.00 3,771.00 3,771.00 3,771.00 3,465.00 2,681.00 2,835.00 2,835.00 2,811.00 38,817.00 5,822.55 44,639.55
m
Sub-totals Plus 15 per cent to cover superannuation, payroll tax, etc., in accordance with local awards Totals .. (Iv) Provision for possible promotion to Grade III in 1969.
Position No.
Classification and salary range(s)
Likely occupant on 1 January 1968
Proposed classification and salary
1968
1969
1970
Zl-37 3~
47-55 56
Technical Assistants, Grade I Anima1 Attendants Assistants, Grade I Drafting Assistant, Grade I
Not named Not named Not named Not named
Technical Assistants, Grade I(v) Animal Attendants(v) Assistants, Grade I(v) Drafting Assistant, Grade I
$ 18,377.00 19,860.00 14,909.00 2,021.00 55,167.00 2,758.35 57,925.35 225,152.60 28,148.08 253,300.68
$ 18,928.31 20,455.80 15,356.27 2,021.00 56,761.38 2,838.07 59,599.45 229,906.40 28,738.30 258,644.70
$ 19,496.16 21,069.47 15,816.96 2,021.00 58,403.59 2,920.18 61,323.77 235,591.32 28,448.91 264,040.23
Sub-totals Plus 5 per cent to cover payroll tax and otber liabilities in accordance witb local awards(vi) Totals Total Salaries and Associated Liabilities Plus 12-!- per cent for consumable supplies and otber scientific expenses Grant Totals(vii) ~
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(v) Computation adds 3 per cent per annum on 1968 base. (vi) Most of tbese personnel are not eligible for superannuation. (vii) Adjustmeots to the total payable in anyone year. woUld be made on the basis of the salaries actually paid.
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APPENDIX II ADDITIONAL GRANT RECOMMENDATIONS FOR 1967 The Council recommended additional grants for medical research for 1967 totalling $80,845 as listed below, subject to an additional allocation to the Medical Research Endowment Fund.
Name and Project
Nature of Grant
Grant Commitment 1967 1968 $ $
UNIVERSITY OF ADELAIDE Department of Dental Science Dr B. G. RADDEN (New Grant) (i) The study of collagenase in mammalian tissues (ii) The effects of steroids on the inhibition of collagenase MrM. R. SIMS (New Grant) The metabolism of osteoblasts and osteoclasts Department of Medicine Dr I. J. FORBES (Renewal) Studies of human lymphocyte function Grant-in-aid 1,000
/.,
Maintenance expenses
750
s.<:
Additional maintenance expenses
600
UNIVERSITY OF MELBOURNE Department of Physiology Dr A. A. KENNEY (New Grant) A study of the renal tubular handling of electrolytes and the nephron processes in the elaboration of osmotic stratification in the kidney Department of Psychiatry Professor B. M. DAVIES (New Grant) (i) Mineral metabolism, adrenocortical functions and salivary secretion in depressive illness (ii) A study of catecholamine metabolism in psychiatric disorders Technical assistance and maintenance expenses
3,000
-J
-
Salary, Research Assistant Grade II, (to be appointed) Payroll tax
3,390 85 3,475
3,520 88 3,608
MONASH UNIVERSITY Department of Biochemistry Dr I. AUSTIN (New Grant) Sub-cellular localization of the synthesis of adrenergic neuromuscular transmitter substances Dr D. A. LOWTHER (Renewal) The macromolecu1ar structure of cartilage and intervertebral disc tissues Department of Pathology DrT. GROSE (New Grant) (i) Immune reactions against cancer and normal cells in vitro (ii) Eillctron spin resonance in normal and irradiated tissues and radiation-induced tumours Equipment and maintenance expenses
2,000
Salary, Research Assistant Grade I,
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Mrs A. T. W. Goh
3,090
Electron cell counter with automatic plotter Maintenance expenses
7,800 500 8,300
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Name and Project
Nature of Grant
Grant Commitment 1967 1968 $ S
UNIVERSITY OF NEW SOUTII WALES School of Bwlogical Sciences Dr J. B. ADAMS (New Grant) Enzymatic sulphation of steroids in the human with particular emphasis on its possible significance in carcinoma of the breast School of Physiology Dr R. A. B. HOLLAND (New Grant) Chemical kinetics of haemoglobin gas reactions in solution and in the red cell.
Technical assistance and maintenance expenses
2,000
Salary, Research Officer, Miss H. Robin Maintenance expenses
4,440 SOO
5,940
UNIVERSITY OF QUEENSLAND Department of Anatomy Dr H. W. WHITTING (New Grant) The mechanism of peritoneal adhesion formation Department of Microbwlogy DrG. H. DAVIS (New Grant) (i) Ecology and systematics of gram-positive diphtheroid bacteria indigenous to man (ii) The application of gel electrophoresis to the classification and diagnosis of human bacterial amphibionts Department of Pharmacy Dr G. A. GROVES (New Grant) The stability of drugs in the solid state
Technical assistance and maintenance expenses
2,000
Technical assistance, minor equipment and maintenance expenses
2,000
Controlled environment chamber Maintenance expenses
2,500 SOO 3,000
DrW. R. OWEN (New Grant) An investigation into absolute determination of purity using a differential scanning calorimeter Equipment: Perkin Elmer differential scanning calorimeter-Model DSC-IB Recorder Accessories for calorimeter Colora ultra thermostat Zone melting apparatus T.L.C. oven Maintenance expenses 6,760 1,144
704 400
r
206 224
562 10,000
Department of Physiology Professor R. W. HAWKER (New Grant) Thyroid stimulating hormone studies Dr C. C. KRATZING (New Grant) Pb,ysioloaicalloadiog and lipid transport
..
Technical assistance and maintenance expenses Grant-in-aid
2,500 1,000
44
Name-of Project
Nature-of Grant
Grant ·COmmllmnlt 1967 1968
S Department 0/ Psychological Medicine Dr M. A. HARPER (New Grant) Affective responses in Korsakoff's syndrome Psychogalvanic skin response recorder Maintenance expenses
S
790 210
1,000
UNIVERSITY OF SYDNEY Department of Medicine Professor C. R. B. BLACKBURN (Renewal) A study of chronic liver disease and chronic lung disease in the Territory of Papua and New Guinea Dr M. R. PLAYOUST DrN.GALLAGHER (New Grant) Absorption and intramucosal metabolism of fatty acids in the rat Additional Grant-in-aid
1,500
Grant-in-aid
2,000
Department of Surgery Dr A. H. GOODMAN (New Grant) An investigation of blood flow and blood flow measurement in health and disease Salary, Senior Research Officer, Dr A. H. Goodman Maintenance expenses 5,240 400
5,640
UNIVERSITY OF WESTERN AUSTRALIA Department of Obstetrics and Gynaeco!ogy Mr H. A. JONES (New Grant) Steroid-acid reaction mechanism Maintenance expenses
1,000
NEW SOUTH WALES INSTITUTES AND HOSPITALS Institute of Dental Research DrK. W.KNOX (Renewal) Antigenic components of oral tnicro-organisms Spinco L2-6S centrifuge preparative ultra-
11,000
..
VICTORIA INSTITUTES AND HOSPITALS St. Vincent's Hospital, School of Medical Research DrP.EDMAN (Renewal) Structure of fibrinogen Salary, Dr A. Henschen, six months
3,250
Walter and Eliza Hall Institute of Medical Research Professor G. J. V. NOSSAL (Renewal) Experimental immunology and oncology
Salary, Senior Research Officer, Dr A. J. Cunningham
4,800
45
APPENDIX III AMENDMENTS TO THE UNIFORM POISONS SCHEDULES The following amendments have been approved by the 63rd Session of Council, November 1966. Acetic Acid The entry under 'Acid Acetic Glacial' in Schedule 2 should be deleted. A new entry should be inserted in Schedule 2 to read: 'Acetic Acid and substances containing more than 80 per cent acetic acid for therapeutic use.' A new entry should be inserted in Schedule 6 to read: 'Acetic Acid and substances containing more than 80 per cent of acetic acid except for therapeutic use.' Allopurinol
New entries should be made in Schedule 4 to read: 'Xanthine oxidase inhibitors including Allopurinol.' Amphetamine
The entry under' Amphetamine' in Schedule 2 should be deleted. Amytriptyline
A new entry should be placed in Schedule 4 to read:'Amytriptyline and other compounds structurally derived therefrom by substitution in the side chain.' Anaesthetics local
The entries under 'Cocaine Synthetic Substitutes' in Schedules 2 and 4 should be deleted: (a) A new entry should be placed in Schedule 2 to read: 'Anaesthetics local, being synthetic cocaine substitutes when included in: (i) lozenges, pastilles, tablets and capsules containing 30 mg or less of such substance; (ii) Suppositories or bougies containing 200 mg or less in each; (iii) Preparations for external use containing 10 per cent or less. (b) A new entry should be placed in Schedule 4 to read: 'Anaesthetics local, being synthetic cocaine substitutes except when included in Schedule 2.' Antimony The entry in Schedule 4 should be amended to read: •Antimony, organic compounds of, for therapeutic use.' Antithyroid Substances The entry in Schedule 4 under 'Antithyroid Substances' should be amended to read: 'Antithyroid Substances including Carbimazole, Methimazole and Thiouracil, and its derivatives and including Thiourea when used for therapeutic purposes.' ' Arsenic
The entry in Schedule 4 should be amended to read: 'Arsenic, organic compounds of, for therapeutic use.' Arnica
The entry in Schedule 5 under 'Arnica' should be deleted. Atropine Methonitrate
A new entry should be made in Schedule 4 to read: 'Atropine Methonitrate.' The entry under Atropine in Schedule 1 should be amended to read: 'Atropine and substances containing more than 0.25 per cent of Atropine except Atropine Methonitrate.' The entry under Atropine in Schedule 2 should be amended to read: 'Atropine;n substances containing 0.25 per cent or less of atropine except Atropine Methonitrate.'
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46
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Beryllium A new entry should be placed in Schedule 6 to read: 'Beryllium.'
and Beryllium should be added to the list requiring warning (b) in the preamble to Schedule 6. Beta-Aminopropylbenzene The entry in Schedule 4 under Beta-aminopropylbenzene should be amended to read: 'Beta-aminopropylbenzene (amphetamine) and beta-aminoisopropylbenzene and any compound structurally derived from either of those substances by substitution in the side chain or by ring closure therein (or by both such substitution and such closure), except ephedrine, etaphedrine, N-methylephedrine, N-diethylaminoethylephedrine, phenylpropanolamine and prenylamine; and salt of any substance falling within this item.' Binapacryl A new entry should be made in Schedule 6 to read: 'Binapacryl.' 8utacarb
A new entry should be made in Schedule 6 to read: 'Butacarb. ' Carbon Tetrachloride A new entry should be made in Schedule 4 to read: 'Carbon tetrachloride for human therapeutic use.' The entry in Schedule 7 under: 'Carbon tetrachloride . should be amended to read: 'Carbon tetrachloride except when used in fire extinguishers or in refill containers for such extinguishers or except for human therapeutic use.' ChIormequat A new entry should be made in Schedule 6: Chlormequat. Chlorpromazine The entry in Schedule 4 under 'Chlorpromazine' should be amended to read: 'Chlorpromazine and its salts and other derivatives of phenothiazine and their salts when used for therapeutic purposes, except in preparations labelled and packed for the treatment of motion sickness in packs of 10 doses or less.' Chromates and Dicbromates of Alkali Metals The entry in Schedule 6 regarding Chromates should be amended to read: 'Chromates and dichromates of alkali metals and ammonium.' Coloured Chalks The entry in Schedule 5 under 'Coloured Chalks' should be amended to read: 'Coloured Chalks, Crayons, School Pastels, Finger Colours and Show Card Colours, containing any scheduled poison.' Coniine A new entry should be made in Schedule 2 to read: 'Coniine in substances containing 0.1 per cent or less of coniine'. Copper Salts The entry under 'Copper Salts' in Schedule 5 should be deleted. Coumarin The entry in Schedule 4 under 'Coumarin' should be amended to read: 'Coumarin derivatives and phenylindanedione derivatives for therapeutic use'. A new entry should be placed in Schedule 5 to read: 'Coumarin derivatives and phenylindanedione derivatives in all substances containing 0.1 per cent or less except for therapeutic use'.
47
A new entry should be placed in Schedule 6 to read: 'Coumarin derivatives and phenylindanedione derivatives in all substances containing more than 0.1 per cent except for therapeutic use'. Cytotoxic Substances The entry in Schedule 4 under 'Cytotoxic Substances' should be amended to read: 'Cytotoxic substances including busulphan, mustin and tretamin'.
Dlclorao A new entry should be made in Schedule 6: 'Dicloran'. Dicydomloe A new entry should be made in Schedule 3 to read: 'Dicyclomine and its salts in preparations containing 0.1 per cent or less'. The entry under Dicyclomine in Schedule 4 should be amended to read: 'Dicyclomine and its salts in preparations containing more than O. 1 per cent' .
Dimethyl Sulphoxide 1be entry in Schedule 6 under 'Dimethyl Sulphoxide' should be amended to read: 'Dimethyl sulphoxide except for therapeutic use'. and dimethyl sulphoxide be added to the list requiring warning b, in the preamble to Schedule 6. Dlpbacloooe A new entry should be placed in Schedule 4 to read: 'Diphacinone for therapeutic use'. A new entry should be placed in Schedule S to read: 'Diphacinone in all substances containing 0.1 per cent or less except for therapeutic use'. A new entry should be placed in Schedule 6 to read: 'Diphacinone in all substances containing more than 0.1 per cent except for therapeutic use'. Dlpheuldol A new entry should be made in Schedule 4 to read: 'Diphenidol' . Dlsulphoton The entry under 'Organa-Phosphorous Compounds' in Schedule 7 should be amended by the addition of 'Disulphoton'.
DithIaooo A new entry should be made in Schedule 6 to read: 'Dithianon' •
•
Eodosulfao A new entry should be made in Schedule 6 to read: 'Endosulfan'. Ephedrine and Pseudoephedrine The entry under 'Ephedra' in Schedule 3 should be amended to read: 'Ephedrine and pseudoephedrine except preparations containing 0 • S per cent or less and except in substances for external use containing I per cent or less'. r
Etafedrloe A new entry should be made in Schedule 3 to read: 'Etafedrine'.
Ethyl-m-am!nobenzoate The entry under 'Ethyl m-aminobenzoate •.. ' in Schedule 2 should be deleted and the entry in Schedule 4 be amended to read: 'Ethyl m-aminobenzoate except when included in Schedule 2 under the entry for anaesthetics local'.
48
!Ji.--
Hyoscine N·butyl.bromlde A new entry should be made in Schedule 4 to read: 'Hyoscine N-butyl-bromide'. The entry under Hyoscine in Schedule I should be amended to read: 'Hyos~ine and substances containing more than 0.25 per cent of hyoscine except Hyoscine N-butylBromide'. The entry under Hyoscine in Schedule 2 should be amended to read: 'Hyoscine and its derivatives in substances containing 0.25 per cent or less of hyoscine and its derivatives except Hyoscine N-butyl-bromide'.
Ibufenae A new entry should be placed in Schedule 4 to read: 'Ibufenac'. Lead Salts
The entry in Schedule 2 should be amended to read: 'Lead salts and compounds of lead for medicinal or cosmetic Mebeverlne HydrodIloride A new entry should be placed in Schedule 4 to read: 'Mebeverine Hydrochloride'.
use'.
Mercuric Chloride The entry in Schedule 6 under 'Mercuric Chloride' should be amended to read: 'Mercuric chloride when used for agricultural, industrial, pastoral or horticulturaI purposes'.
Mercury The entry in Schedule 4 should be amended to read: 'Mercury, organic compounds of, for therapeutic use'. Methylperldol Hydrochloride A new entry should be made in Schedule 4 to read: 'Droperidol, haloperidol, methylperidol, triperidol and their salts'. Metronidazole A new entry should be made in Schedule 4 to read: 'Metronidazole'.
Narcotic Control Council considered that the Uniform Poisons Schedules should be brought into line with the Single Convention on Narcotics 1961, as far as possible. Items in Schedules I and II of the Single Convention on Narcotic Drugs 1961 should be included in Schedule 8. Items in Schedule III of the Single Convention on Narcotic Drugs 1961 should be included in Schedule 4 if over 1 per cent and in Schedule 2 if I per cent or less.
Schedule 8 Entries The following new entries should be made in Schedule 8: 'Acetyldihydrocodeine and in preparations containing more than 2.5 per cent of acetyldihydrocodeine.' 'Codeine (3-methylmorphine) and in preparations containing more than 2.5 per cent of codeine.' 'Dihydrocodeine and in preparations containing more than 2.5 per cent of dihydrocodeine.' 'Ethyl morphine (3-ethylmorphine) and in preparations containing more than 2.5 per cent of ethylmorphine: 'Nicocodine (6-nicotinylcodeine) and in preparations containing more than 2.5 per cent of nicocodine.' 'Norcodeine (N-demethylcodeine) and in preparations containing more than 2.5 per cent of norcodeine.' 'Pholcodine (morpholinylethyl morphine) and in preparations containing more than 2.5 per cent of pholcodine.' 'Nicodicodine. ' The entry under 'Morphine Derivatives' should be amended to read: 'Morphine derivatives not specificaJly included in this Schedule.'
22568/66-4
49
Schedule 4 Entries
The entries in Schedule 4 under Acetyldihydrocodeine, codeine, dihydrocodeine, ethylmorphine, nicocodine, pho1codine, should be amended to read: 'Acetyldihydrocodeine in substances containing more than I per cent and not more than 2.5 per cent of acetyldihydrocodeine.' 'Codeine, its salts, and substances containing more than 1 per cent and not more than 2.5 per cent of codeine.' 'Dihydrocodeine in substances containing more than 1 per cent and not more than 2.5 per cent of dihydrocodeine. ' 'Ethyhnorphine in substances containing more than 1 per cent and not more than 2.5 per cent of ethyhnorphine.' 'Nicocodine in substances containing more than 1 per cent and not more than 2.5 per cent of nicocodine." 'Pholcodine in substances containing more than 1 per cent and not more than 2.5 per cent of pholcodine. A new entry be made in Schedule 4: 'Norcodeine in substances containing more than 1 per cent and not more than 2.5 per cent of norcodeine.' Schednle 2 Entry A new entry should be made in Schedule 2 as follows: 'Norcodeine in substances containing 1 per cent or less of norcodeine.' N.Methylepbedrine A new entry should be made in Schedule 3 to read: 'N.Methylephedrine. ' Phenylpropanolamine
r
A new entry should be made in Schedule 3 to read: 'Phenylpropanolamine. ' Propanidid A new entry should be made in Schedule 4 to read: 'Propanidid. ' Prosd\laridln A
A new entry should be placed in Schedule 4 to read: 'Cardiac glycosides not elsewhere specified in these Schedules.' Protokylol Hydrochloride
The entry under 'Nor-adrenaline' in Schedule 4 should be amended to read: 'Nor-adrenaline and substances structurally derived therefrom by substitution in the amine group, their salts, in preparations containing more than I per cent of the base.' The entry under 'Nor-adrenaline' in Schedule 3 should be amended to read: 'Nor-~enaline ~nd subst~n.ces structurally derived therefrom by substitution in the amine group, their salts ill preparatIOns contammg 1 per cent or less and more than 0.01 per cent of the base.'
Sex Hormones The entry in Schedule 4 should be amended to read: 'Sex hormones, natural or synthetic, their derivatives and their substitutes except those without sex hormonal activity, in all preparations, including cosmetics.' Sulpbaquinoxaiine The entry in Schedule 4 for Sulphanilamide should be amended to read: 'Sulphanilamide, its salts, its derivatives, their salts, except sulphaquinoxaline when incorporated in baits for the destruction of vermin.' TrImIpramIne Maleate T
A new entry should be made in Schedule 4 to read: 'Trimipramine and other compounds structurally derived therefrom by substitution in the side chain.'
50
,
-
Veterinary Preparations (Exemptions) The footnote to Schedule 4 should be amended to read: Notwithstanding anything contained elsewhere in this Schedule, a person may sell by retail for veterinary therapeutic and propyhlactic purposes without a written prescription of a medical practitioner, dental practitioner or veterinary surgeon the following preparations of: (a) Sulphanilamide, its salts, its derivatives, their salts. Testosterone propionate and testosterone dipropionate, when such preparations are contained in the original unopened container as supplied by the manufacturer and clearly and distinctly labelled with the words 'Warning unsafe for use in human beings' and with the statement that the contents are to be used only for veterinary purposes ... (b) Antibiotic substances approved by the Minister by notice in the Gazette which are: (i) Penicillin, streptomycin, tetracycline, their salts, their derivatives, their salts, when suitably coloured with Brilliant Blue FCF or other approved colour as a marker and when specially packed in applicator devices designed for intra-mammary infusion in the treatment of animals; Oi) Chloramphenicol for tropical application for foot rot and ocular use only; (iii) Tetracycline, their salts, their derivatives and their salts, prepared for topical application for ocular use only. and which are contained in the original unopened container as supplied by the manufacturer and clearly and distinctly labelled with the words, 'Warning should not be used for human beings,' and with the statement that the contents are to be used only for veterinary purposes. These substances which have been exempted from the necessity of a prescription when specially prepared, packed and labelled as stated above, shall be labelled in accordance with Schedule 6. A new entry should be made in the preamble to Schedule 6: '(f) Warning should not be used for human beings. For veterinary purposes only'. Choramphenicol for the topical treatment of foot rot and for ocular use. Sulphanilamide, its salts, its derivatives, their salts. Testosterone propionate and testosterone dipropionate. Tetracycline, its salts, its derivatives and their salts for ocular use.' A fourth paragraph should be added to the requirements in Schedule 6 for containers of preparations for veterinary purposes. 'Preparations must be contained in the original unopened containers as supplied by the manufacturer in respect of: Chloramphenicol for the topical treatment of foot rot and for ocular use. Sulphanilamide, its salts, its derivatives, their salts. Testosterone propionate and testosterone dipropionate. Tetracycline, its salts, its derivatives and their salts for ocular use'. New entries should be made in Schedule 6 as follows: 'Chloramphenicol for veterinary purposes for the topical treatment of foot rot and for ocular use.' 'Penicillin, its salts, their derivatives, their salts for veterinary purposes when suitably coloured with Brilliant Blue FCF or other approved colour as a marker and when specially packed in applicator devices designed for intramammary infusion in the treatment of animals'. 'Streptomycin, its salts, their derivatives, their salts for veterinary purposes when suitably coloured with Brilliant Blue FCF or other approved colour as a marker and when specially packed in applicator devices designed for intramammary infusion in the treatment of animals'. 'Sulphanilamide, its salts, its derivatives, their salts for veterinary purposes'. 'Testosterone propionate and testosterone dipropionate for veterinary purposes'. 'Tetracycline, its salts, their derivatives, their salts for veterinary purposes when prepared for topical application for ocular use only, and when suitably coloured with Brilliant Blue FCF or other approved colour as a marker and when specially packed in applicator devices designed for intramammary infusion in the treatment of animals'.
".
51
APPENDIX IV FIRST AID MEASURES IN THE UNIFORM POISONS SCHEDULES The Uniform Poisons Schedules I, 2, 3, 5, 6 and 7 make reference to the need for antidotes or special precautions when indicated. The term 'Pirst Aid' should be used to describe emergency treatment and use of antidotes. One or more of the following simple directions or a suitable combination should be assigned to all items in the manner indicated below. (a) Bathe thoroughly-remove contaminated clothing (b) Give water or milk (c) Give water, NOT milk or oils (d) Induce vomiting if conscious (e) Do not induce vomiting (f) Contact a doctor or poisons information centre (g) Remove from contaminated area. Apply artificial respiration. NOTE: These first aid measures apply to individual substances. Combinations of substances will be dealt with at a later date. Acetonyl beuzyl-4-hydroxycoumarin b, d, f. Acid acetic glacial a, b, e, f. Aconite b, d, f. Ammonia a, b, e, f, g. Aniline a, b, d, f. Antimony b, d, f. Arsenic b, d, f. Atropine a, b, d, f. Barium salts b, d, f. Belladonna a, b, d, f. Benzene a, b, e, f, g. Brucine b, d, f. Carbon bisulphide a, b, d, f, g. Carbon tetrachloride a, b, d, f, g. Chlordane (See 4:7 Methanoindene) a, c, d, f. Chlorine a, f, g. ChIoroallydiethylthiocarbamate (CD.E.C.) a, b, d, f. 2-ChIoro-N-N-diallylacetamide (CD.A.A.) a, b, d, f. Chloroform a, b, d, f, g. Chloropicrin a, b, d, f, g. Colchicine b, d, f. Copper Salts a, b, d, f. Creosote a, b, e, f. Cresol a, b, e, f. Cyanide a, b, d, f, g. Diarnines b, d, f. Dicophane a, c, d, f. Dieldrin a, b, d, f. Dintethanonaphthalene a, b, d, f. Dinocap (Karathane) b, d, f. Dinitrocresols a, b, d, f. Dinitrophenols a, b, d, f. Disulfiram b, d, f. Pluoracetic acid b, d, f. Gamma benzene hexachloride a, Co d, f. Hydrochloric acid a, b, e, f. Hydrocyanic acid a, b, d, f, g. Hyoscine b, d, f. Iodine a, b, d, f. Kerosene b, e, f. Lead salts a, b, d, f. Mercuric chloride a, b, d, f. Mercuric iodide a, b, d, f. Mercuric nitrate a, b, d, f. Mercuric-potassium iodide a, b, d, f. Metaldehyde b, d, f. 4:7 Methanoindene a, c, d, f. Methyl bromide a, f, g. Nicotine a, b, d, f.
..
S2
,
Nitric acid a. b. e. f. Nitrobenzene a. b. d. f. Nitrophenols. ortho. meta para. a. b. d, f. Organo-phosphorus compounds a. b. d. f. Oxalic acid a. b, e. f. Pentachlorphenol a, c, d. f. Phenol (Carbolic acid). Immediate irrigation with vegetable oil (if readily available) or water, remove contaminated clothing, c.e.f. Phosphides (Metallic). Bathe thoroughly with oil, remove contaminated clothing b, d, f. Phosphorus, yellow a, b, d, f. Potassium bromate b, d, f. Potassium hydroxide a, b, e, f. Santonin b, d, f. Selenium a, c, d, f. Sodium bromate b, d. f. Sodium hydroxide a, b, e. f. Sodium nitrite b, d, f. Strychnine b, d, f. Sulphuric acid a, b, e, f. Tetramethyl-thiuram-disulphide (Thiram) a, b, d, f. Tetrachlorethane a, b, d, f. g. Thallium b, d, f. Toxaphene a, c, d, f. Zinc chloride b, d, f. Zinc dimethyl dithiocarbamate (Ziram) a, c. d, f.
53
APPENDIX V AMENDMENT OF INDEX TO THE UNIFORM POISONS SCHEDULES LISTING OF SUBSTANCES BY SPECIFIC NAME The following Jist includes specific names of substances at present covered by the blanket entries in the uniform poisons schedules. It has been decided to list each substance covered by the blanket entries in the schedules by its specific name in the index. In order to keep the actual schedules within manageable size 'blanket' entries will be continued including therein with typical specific names as already appearing. The wording in such 'blanket' entries should read 'including' instead of 'such as'. Acepromazine Acetazolamide Acetophenazine Acetylphenyl hydrazine Actinomycin D Aldosterone Allopurinol AIIyl oestranol Aloxidine Alpha-hydroxy progesterone Alseroxylon Ambenonium Amethocaine Amino g1uthethimide Aminopterin p-Amino salicylic acid Aminphenazole Amphomycin Amphotericin B Ampicillin Amylocaine Androisoxazole Androstanolone Antazoline Azacyclonol Azathioprine Bacitracin Bamipine Beclamide Bemegride Benoxinate Benzactyzine Benzamine Benzchlorpropamide Benzdiazepoxide Benzhexol Benzocaine Benzoestrol Benzpyrinium Benztropine Betamethasone Bethamidine Biperiden Bretylium Bromazine Bromodiphenhydramine Bromothen Brompheniramine Buclizine Busulphan Butacaine Butethamine Butyl amino benzoate Calcium benzoyl P.A.S. Captodiame Caramiphen Carbamazepine Carbimazole Carbinoxamine Carbomycin Carphenazine Cephalosporin Cetoxine Chlorambucil Chloramphenicol Chlorcyclizine Chlordiazepoxide Chlorisondamine Chlormadinone Chlormezanone Chloroprocaine Chlorothen Chlortrianisene Chlorpheniramine Chlorphenoxamine Chlorpromazine Chlorprothixene Chlorpyrilene Chlortetracycline Cinchocaine Cinnarizine Clemizole Cloxacillin Colchicine Colistin Corticosterone Corticotrophin Cortisone Crytenamine
..
,
Cyanoacetohydrazide Cyclizine Cyclomethycaine Cyclophosphamide Cycloserine Cycrimine Cyproheptadene o,p'DDD Dehydroepiandrosterone Demecarium Demecolcine Demethyl chlortetracycline Deoxycortone Deserpidine
54
y
~,,--,.
Desoxycorticosterone Dexamethasone Dexbromphenimethdilazine Dextrochlorpheniramine Diazepam Dibucaine Dichlorisone Dienoestrol Diethazine Diethyl stilboestrol Dimenhydrinate Dimethindene Dimethisterone Dimethoisoquin Dimethoxydiethyl stilboestrol Diphenhydramine Diphenylpyraline Doxylamine Dromostanolone Dyclonine Dydrogesterone Dyfios Echothiophate Ectyl urea Edriphonium Emylcamate Erythromycin Ethambutol Ethinyl oestradiol Ethinyl testosterone Ethionamide Ethiosuximide Ethisterone Ethoxzolamide Ethopropazine Ethotoin Ethylnodrel Ethyloestranol Fludrocortisone F1uocinolone F1uormethalone Fluorouracil Fluoxymesterone Fluphenazine Fluprednisolone F1urandrolone F1urodesoxyuridine Framycetin Fungacillin Fusidic acid Gentamicin Gramicidin Griseofulvin Guaiacol glycerol ether Guanethidine Haloperidol Halopyramine Hetrazine Hexafiuorodiethyl ether Hexamethonium Hexoestrol Hexylcaine Hydralazine Hydrocortamate
Hydrocortisone Hydroxy phenamate Hydroxyprogesterone Hydroxyzine Iodothiouracil Iproniazid Isobutylaminobenzoate Isocarboxazid Isoniazid Isothipendyl Kanamycin Leptazol Levallorphan Lignocaine Lincomycin Lymecycline Lynoestrinol Mebamazine Mebhydrolin Mebutamate Mecamylamine Mechlorethamine Mec10zine Medroxyprogesterone Megestrol Melphalen Mepazine Mephenesin Mephenoxalone Mepivacaine Meptobamate Mepyramine Mercaptopurine Mestranol Metaxalone Methacycline Methallenoestril Methaminodiazepoxide Methandriol Methanedienone Methaphenilene Methapyrilene Methaqualone Methdilazine Methenalone Methicillin Methimazole Methoin Methoserpidine Methotrexate Methotrimeprazine Methoxalen Methsuximide Methylacetoxy progesterone Methylandrostenediol Methylandrostandone Methylandrostanopyrazole Methyldopa Methylnortestosterone Methylpentynol Methylphenidate Methylprednisolone Methyltestosterone Methylthiouracil
-----
t.."f
,:,..,
.~
0:_... .....-
55
Monobenzone Mustine Naepaine Nafcillin Nalorphine Nandrolone Neomycin Neostigmine Nialamide Nikethamide Norethandrolone Norethindrome Norethisterone Norethynodrel Nortestosterone Novobiocin Nystatin Oestradiol Oestriol Oestrone Oleandomycin OMPA Orphenadrine Orthocaine Oxacillin Oxanamide Oxandrolone Oxymesterone Osymethalone ()xyphenabu~e
Physostigmine PiCrotoxin Pimaricin Piperocaine Pipethanate Pivazide Polymixins Polyoestradiol Pramoxine Prednisolone Prednisone Pregnenolone Prethcamide Prilocaine Primidone Procaine Prochlorperazine Procyclidine Progesterone Promazine Promethoestrol Proparacaine Propyl thiouracil Proxymetacaine Puromycin Pyrathiazine Pyrazinamide Pyridostigmine Pyrilamine Pyrrobutamine Pyrrolodino methyl tetracycline Quinacrine Quinoestradiol Reserpine Ristocetin Sodium nitroprusside Spiromycin Spironolactone Stanolone Stanozomel Stilboestrol Streptomycins Streptonivicin Sulthiame Syrosingopine Tacrine TEPP Teropterin Testosterone Tetracaine Tetrabenzamine Tetracycline Thenalidine Thenyldiamine Thiacetazone Thioridazine Thiopropozate Thioproperazine Thiouracil Thonzylamine Tocopherol Tolpropamine Tranylcypromine
Oxytetracycline Panlhesin Paramethadione Paramethasone Pargyline Paromomycin pecazine Pempidine Penicillin Penicillin 0 Pentametbonium Pentolinium PentyJene tetrazol Perphenazine Pemitone Phenacemide Phenacaine Phenaglycodol Phenel7.ine Phenethicillin Pheneturide Phenglutarimide Phenindamine Pheniprazine Pheniramine Phenoxymethyl penicillin Phenoxy propazine Phensuximide Phentolamine Phenyl acetyl urea Phenyl amino salicylate Phenylbutazone Phenyl hydrazine Phenytoin
56
•
Tretamine Triacetyl oleandomycin Triamcinolone Trichomycin Triethylene melamine Triethylene thiophosphoramide Trifluoperazine Triftupromazine Trihexyphenidyl Trimeprazine Trimetaphan camphor sulphonate Trimethadione Trimethidinium Trimustine Tripelennamine
Triprolidine Toxidone Tyrothricin Uracil mustard Urethane Vancomycin Vanillic acid diethylamide Vinblastine Vincristine Viomycin Xanthocillin
APPENDIX VI PROCEDURE FOR SCHEDULING OF THERAPEUTIC AND NON THERAPEUTIC SUBSTANCES The following information is provided in order to assist officers of the State Health Departments and industry concerned with applications for the scheduling of therapeutic and non therapeutic substances. Applications should be marked 'Attention, Chairman, Poisons Schedule Sub-Committee' and sent to: The Secretary, National Health and Medical Research Council, P.O. Box 93, Canberra, A.C.T. Information is sought by the Poisons Schedule Sub-Committee as shown below. The information in items I to 14 inclusive, should be covered in summary form in a few pages and 15 copies are required. In the case of new substances the information in item 14 (Toxicity Studies) is required inconsiderable detailfor pharmacological appraisal and 4 copies are sufficient. It is requested that this material be indexed as a guide to the information sought. If the information is not available this should be noted in the index. Acknowledgment of each application will be made. The Chairman of the Poisons Schedule Sub-Committee or, in his absence, the Convener, are readily available to discuss methods of application for scheduling. The proceedings of the Poisons Schedule Sub-Committee are confidential and are not for publication. When considered by Council and approved, with or without modification, the findings are published in the Council Reports. Council meetings are held twice each year, usually in May, in one of the capital cities, and in November in Canberra. The recommendations of Council will be passed on to the applicants as soon as possible thereafter. It should be noted that the National Health and Medical Research Council is an advisory body and its recommendations have no legal standing unless implemented in the States or Territories of the Commonwealth. However, the recommendations do act as a guide to uniformity in the control and labelling of poisons. INFORMATION REQUIRED FOR SCHEDULING Name Manufacturer
1. Applicant:
2. 3. 4. 5. 6. 7. 8. 9. 10.
11. 12. 13.
Address: Approved or common name: Proprietary name: Purpose: Chemical name: Chemical formula and structure: Chemical and physical characteristics: Formulation and presentation: Standards: Tests for potency, purity and safety in manufacture and storage when applicable. Uses: In the case of therapeutic substances; dosage, route of administration, special precautions, claims regarding effect and antidote or antagonist. In the case of non therapeutic substances; strength of preparations, methods of handling special ' precautions and claims regarding effectiveness and antidote or antagonist. Labelling and packaging: Indicate proposed details. Action by other authorities: Evidence of approval or rejection by any other statutory body or authority. Bibliography: . . Complete bibliograp~y of any publications relating to pharmacological and therapeutic actions, including cJirucaJ trials, should be gIven.
58
14. Toxicity studies: .S~ow /ubll de!ails .o~ investigations made with respect to the toxicity of the substance including tests came ou y UDlvetsltJes and/or research institutions and clinical trials. ' NOTE: FUl~reports are required of adequate tests which will show whether or not the substance will be safe to t e. human. ~he rep~:>rts s~all include detailed data derived from appropriate animal and other bIOlogical experiments III which the methods used and the results obtained are clearly set forth. Details of any reports which could bias an evaluation of the safety of the substance shall NOT be omitted. The dose levels at which the tests are carried out should always include a level based on the expected normal exposure of the human. In tests (i) (b) (ii) and (v) the dose level which produces toxic or physiological changes is specifically required. Toxicity data should also include tests conducted with the formulated substance. Toxicological data should also include the results of full histological examination. Information required should include: (i) Acute Toxicity: (a) L.D. 50 in two species by both the oral and parenteral routes. (b) Local and systemic toxicity by topical and inhalation routes. (ii) Sub-acute Toxicity: 6-14 weeks administration to rats and dogs by each of oral, parenteral (and topical) routes. (iii) Chronic Toxicity: Daily administration for at least two years in the rat. Information should also be supplied regarding: (iv) Uniformity of response within a species and among different species. (v) Behavioural, cardiovascular, neural, and respiratory effects in the cat or dog. (vi) Occurrence of unusual or alarming reactions, such as carcinogenesis, or teratogenesis. (vii) Occurrence of sensitivity, tolerance or idiosyncrasy in response to the substance. (viii) Metabolism, rate, extent and mode of elimination of the substance in mammal or human. (ix) Any tendency towards accumulation in the body. (x) Any special incompatability. (xi) Method of assay. (xii) Known side effects (in the case of therapeutic substances).
, • , /
59
APPENDIX
vn
RECOMMENDED TOLERANCES FOR RESIDUES OF AGRICULTURAL CHEMICALS ON FRUIT AND VEGETABLES, BOTH FRESH AND PRESERVED, AND ON GRAINS Agricultural chemicals have been divided into five sectionS:a(follows:
Section I Substances which are deemed unlikely to produce harmful or poisonous residues when used in accordance with good agricultural practice, prior to harvest and when used as directed. This includes seeds and tubers when treated prior to planting. The foods in any case must not contain residues of these substances in excess of those for which at present tolerance levels are set in State legislation. Alum Aluminium silicates Anthracene oil Anthraquinone Benzol Boracic acid
Borax Bordeaux mixture Boron trioxide Butoxy polypropylene glycol Calcium polysulphide Copper carbonate Copper oxychloride Copper sulphate Creosote Cresylic acid Cuprous oxide Derris Ferrous sulphate Formalin Hexachlorobenzene Kerosene Lethane 384 Lime sulphur Lysol MetaldehYde Mineral oil Pentachloronitrobenzene Petroleum oil Quassia infusion Quinoxine benzoyl hydrazone Rotenone Sodium borate Sulphur Tar acids Tar distillates Tar oils Thanite Tobacco dust
Section
n
Volatile post-harvest fumigants which, when used as directed on stored products, will disappear before foods as collSumed
the food reaches the consumer. Residues of the unchanged compound must not be present in or upon Aluminium phosphide Ammonia Carbon disulphide Carbon tetrachloride Chloropicrin o-Dichlorobenzene p-Dichlorobenzene Dichloro-diethyl ether Ethyl dichloride
60
Ethyl fonnate Ethylene dibromide Ethylene dichloride Methyl bromide Phosphine Trichlorethylene t
Section
m
Soil fumigants and herbicides which when used as directed do not leave any residue in or upon food. Residues of the unchanged compound must not be present in or upon foods as consumed. 2,4-DB 2,4,5-T Allyl alcohol Amitrol Ametryne Ammonium sulphamate Atrazine CDAA CDEC p-Chlorobenzene Chlorinated benezene sulphonates Chlorxylenoi 4-CPA Dalapon DD Diallate Diquat EPTC Fenuron Linuron MCPA MCPB Nemagon Paraquat Pentachlomitrobenzene Pentachlorphenol Potassium cyanate Prometryne Propazine Simazine Sodium chlorate Sodium N-methyl dithiocarhamate Sodium pentachlorphenate Sodium trichloracetate TCA Triazines
Section IV Other substances which are highly toxic and residues must not be present in or upon foods. Amiton Aramite Dinoseb DNOC HETP (TEPP) Hydrazines and substituted hydrazines Sodium fluoroacetate
..
Section V Substances which when used as directed usually result in detectable residues in or upon foods and for which the following tolerances apply.
Tolerance Aateck Aldrin Arsenic anhydride Arsenic oxide Arsenicpentoxide (ppm) 7
0.1 1. 5 (as ASIO~ 1.5 (as AsIO~ 1.5 (as AsiJ~
61
Arsenic trioxide Azinphos ethyl L Azinphos methyl f BHC and its isomers Bromoxynil Calcium cyanide Captan Carbaryl Carbophenothion Chlorbenside Chlordane .. Chlorofenson Chloropropylate Chlorpropham 2,4-D DDT (including DDD and DDE) 2,4-DES Demeton (including demeton-O, demetonS, demeton methyl S-sulphoxide and methyl demeton) Diazinon Dibrom Dichlone Dichlorvos Dicloran Dicofol Dieldrin Dimecron Dimethoate Dinocap Diphenylamine Dithianon Diuron Dodine Endosulfan .. Endrin Ethion Ethoxyquin .. Fenson Fenthion Ferbam Folpet Gibberellic acid Glyodin Heptachlor •• Hydrocyanic acid lsobenzan .. Lead arsenate Lindane Malathion Maleic hydrazide Maneb Menazon Mercury containing compounds Methoxychlor Methyl parathion Mevinphos .. Monuron NAA B-naphthoxy acetic acid Nicotine Nicotine sulphate
1.5 (as As2O.) (fruit) (all others) \) 2 (total isomers) 0.5 75 (as HCN-grain) 25 (as HCN-other) 20 5 1 3 0.1 3 5 50 5 2 2
f2
• •
.....
.;
0.5 0.75 2 15 3 2 10 5 0.1 1 2 7 7 2 2 5 1 0.1 1 3 3 2 7 20 2 5 0.1 75 25 0.1 1.5 4 2 8 2 50 7 1 0.01 5 1 0.25 5 1 1 2 2
(strawberries) (other fruit and vegetables) (beans, lettuces, tomatoes) ~
(apples and pears) (fruit)
(vegetables) (apples and pears) (as zineb)
..... ,
(grain) (other) (as As.O.> (as Pb) (see BHC) (grain) (fruit and vegetables) (potatoes) (as zineb) (apples and pears)
(as nicotine) ):~
62
,
,. ~
~
£
Oxythioquinox Parathion
Paris green .. Perthane Phenkaptone o-Phenylphenol Piperonyl butoxide Propham Pyrethrins .. Schradan Sodium aluminium flouride Sodium arsenate Sodium arsenite Sodium cyanide Sodium fluoride Sodium silicofluoride Strobane Sulphoxide .. Tartar emetic Tetradifon Thimet Thiometon Thiram Toxaphene Trichlorphon Zineb Ziram
,.
• ...,-
lit
0.5 0.5 1.5 5 1 20 8 50 1 0.1 7 1.5 1.5 75 25 7 7 3 8 1.5 5 0.5 1 7 3 2 7 7
(fruit and vegetables) (as AS 20 3) (citrus fruits)
(as F) (as AsPal (as As.03) (as HCN)-(grain) (as HCN)---{other) (as F) (as F) (as Sb)
I ~
..41'
I.. r
63
APPENDIX
vm
STANDARD FOR ARTIFICIAL SWEETENING SUBSTANCES 1. An' Artificial Sweetening Substance' is any substance other than a saccharide which is added to food for the purpose of sweetening. 2. For the purpose of these Regulations the following are prescribed artificial sweetening substances: a) Saccharin (b) Cyclamate (cyclohexylsulpharnic acid and/or its sodium and/or calcium salt.) 3. No person shall sell or offer for sale any food to which has been added an artificial sweetening substance other than a prescribed one. 4. Prescribed artificial sweetening substances may be added for the purpose of sweetening to: (i) Low Calorie Dietetic Foods, (ii) Any food described or sold as suitable for the use of persons suffering from diabetes mellitus, (iii) Any beverage, other than those included in (i) or (ii), where the addition of an artificial sweetening substance is specifically allowed by the regulations, but in respect to the following only in proportions not exceedingCyclamate calculated as cyclohexylsulphamic acid per cent
-(i) and (ti) Low Calorie Dietetic Foods and foods sold as suitable for diabetes mellitus sufferers " (iii) Beverages other than those included in (i) or (ii)
Saccharin
~1
per cent
0.1S
2.0 0.06
where addition is allowed
..
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O.OOS
When the foods are sold ready for consumption or when the foods are prepared ready for consumption in accordance with directions given on the label. Wbere a combination of artificial sweetening substances is used, the sum of the fractions obtained by dividing the quantity of artificial sweetening substances used by the maximum quantity of each such substance permitted to be present if used alone shall not exceed unity. 5. No person shall sell or offer for sale any food to which an artificial sweetening substance has been added except as specifically permitted by the Regulations. 6. No person shall sell or offer for sale any food containing an artificial sweetening substance unless the package containing such food bears a label, in which shall he written in bold face sans serif capital letters with a face depth of not less than 0.06 inch the following words: (i) THIS FOOD CONTAINS (here insert the names of all artificial sweetening substances in the food), A NON-NUTRmVE SWEETENING SUBSTANCE (OR MIXTURE) as the case may be, and (ti) CONTAINS ADDED SUGAR or NO ADDED SUGAR, as the case may be.
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APPENDIX IX STANDARD FOR BAKING COMPOUNDS CREAM OF TARTAR
Cream of Tartar shall contain not less than ninety-nine parts per centum of acid tartrates, calculated as potassium acid tartrate (KHC,H,O,.). ACID PHOSPHATE POWDER OR PHOSPHATE AERATOR Acid phosphate powder or phosphate aerator is any suitable acid phosphate including sodium aluminium phosphate which, with or without starch or other wholesome farinaceous substances, can be used in the preparation of a chemical leaven for baking purposes. Its neutralising value, calculated as parts NaHCO s per 100 parts powder, shall be not less than 44 when determined by the method of the Association of Official Agricultural Chemists (1955 Edition, para. 7, 8). It shall contain not more than two parts per centum of sulphates, calculated as calcium sulphate (CaSO,) and not more than twenty parts per million of fluorine.
Labelling Every package of Cream of Tartar, or of Acid Phosphate Powder, or of a mixture of the two, shall have in the label the words CREAM OF TARTAR and/or ACID PHOSPHATE POWDER (OR PHOSPHATE AERATOR) as the case may be, in bold faced sans serif capital letters with a face depth of not less than 0.11 of an inch. In the case of a mixture sold in one container the substance greater in proportion by weight shall appear first on the label, and the label shall bear in bold faced sans serif capital letters with a face depth of not less than 0.06 of an inch a statement of the percentage of Cream of Tartar and Acid Phosphate in the mixture. BAKING POWDER Baking Powder is a salt or a mixture of salts with or without farinaceous diluent substance which evolves carbon dioxide on being moistened and heated, and which may be used as a chemical leaven in the preparation of food. It shall yield not less than 10 parts per centum by weight of carbon dioxide. It shall contain not more than one and five tenth parts per centum of sulphates calculated as calcium sulphate (CaSO,) and not more than 10 parts per million of fluorine.
Labelling The word 'egg' or expressions or devices which imply or suggest the presence of egg or the eqnivalent of egg shall not appear on or be attached to any package which contains baking powder. Every package of baking powder shall have in the label either (i) immediately preceding the name of the product, the words: CREAM OF TARTAR
andlor PHOSPHATE AERATOR (OR ACID PHOSPHATE) or (ii) immediately following the name of the product the words: CONTAINS CREAM OF TARTAR and/or PHOSPHATE AERATOR (OR ACID PHOSPHATE) as the case may be, in bold-faced sans-serif capital letters with a face depth of not less than 0.06 of an inch. In the case of a mixture sold in one container the substance greater in proportion by weight shall appear first on the label, and the label shall bear in bold faced sans serif capital letters with a face depth of not less than 0.06 of an inch a statement of the percentage of Cream of Tartar and Acid Phosphate in the mixture.
6S
APPENDIX X STANDARD FOR EDIBLE FATS AND OILS GENERAL STANDARD 1. (a) Edible fats and edible oils are the fats and oils modified or not and commonly recognised as wholesome foodstuffs. They shall be free from rancidity and from decomposition and from offensive odour and taste, and unless otherwise specified in these regulations, shall contain not more than one part per centum of free fatty acids calculated as oleic acid. They shall not contain any mineral oil but may contain prescribed antioxidants in accordance with the provisions of Regulation .... (b) Vegetable fats and oils packed and sold for use as shortenings may contain propylene glycol stearate. Labelling
)
I
2. (a) There shall be written in the label attached to every package which contains any edible fat or any edible oil which is not a mixture of two or more edible fats or oils in bold-faced sans serif capital letters with a face depth of not less than 0.06 of an inch the true descriptive name of the oil or fat. (b) Notwithstanding anything to the contrary in general labelling provisions for blended or mixed food in these regulations where there is a mixture of edible fats or edible oils or a mixture of both, there shall be written in the label of every package which contains such a mixture in bold-faced sans serif capital letters with a face depth of not less than 0.06 of an inch the words 'BLENDED EDIBLE (here state whether ANIMAL, VEGETABLE or ANIMAL AND VEGETABLE) FAT' or 'BLENDED EDIBLE (here state whether ANIMAL, VEGETABLE or ANIMAL and VEGETABLE) OIL' as the case may be. OLIVE OIL 3. Olive oil is the oil obtained by expression from the sound mature fruit of the cultivated olive tree (Olea europea L.). It shall conform with the requirements of the British Pharmacopoeia. LUCCA, OIL, SUBLIME SALAD OIL AND VIRGIN OIL 4. Lucca oil, sublime salad oil or virgin oil, is an oil which conforms with the standard for olive oil. Labelling 5. The word 'olive' or the word 'lucca' or the words 'Sublime Salad' or the word 'virgin' or any expression or device or representation which resembles the said words or any of them, or suggests the presence of olive oil, shall not appear in the label of any package of oil which does not conform with the standard for olive oil. ,-
.
DRIPPING 5. Dripping is clean fat rendered from meat other than that of swine. It shall not contain more than two parts per centum of free fatty acid calculated as oleic acid, nor more than one part per centum of foreign matter, including salt, unavoidably incorporated in the course of rendering nor more than two parts per centum of water. H it bears a name descriptive of its origin it shall correspond thereto. LARD 6. Lard is the clean fat rendered from the meat of swine. It shall not contain more than two parts per centum of free fatty acid calculated as oleic acid, nor more than one part per centum of foreign matter including salt, unavoidably incorporated in the course of rendering, nor more than one part per centum of water.
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APPENDIX XI CODE OF PRACTICE AND RECOMMENDATIONS FOR THE HANDLING OF FROZEN FOODS (
Ideally, frozen food should always be held at a product temperature of 0° F. Of lower. Some deviation from this rule is permissible for defrost cycles, loading and unloading or other short-term conditions beyond the immediate control of the person or company under whose care the frozen food is held. For such brief periods the air temperature should not exceed 10° F. and that air temperature should be reduced to 0° F. or lower as quickly as possible. Whilst the present standard specifies temperatures above 0" F. future amendments to the Standard will require all product temperatures to be at 0° F. A. Handling Code for those engaged in production 1. Freezing is a highly efficient method of food preservation. It does not, however, add to or improve product quality which is unchanged by the process and depends entirely on the quality of the food at the time of freezing. Intake of the selected raw material should therefore be planned in such a way that all foods processed are at the maximum level of freshness. 2. Quality control of raw materials and of products during processing is essential to ensure both high product quality and safety for human consumption. 3. The temperature of raw materials, where stored before processing, should be below 40° F., consistent with bacteriological and processing requirements. Fish should be well iced and stored in a chill-room at 32°_35° F. Prepared foods after processing or cooking should be cooled as rapidly as possible, consistent with processing requirements to a temperature below 40° F. 4. The food should be frozen by a method so designed and operated that the temperature of the CENTRE of the food is reduced to a temperature not exceeding the recommended storage temperature for that product at such a rate as is consistent with good product quality. 5. Should the time interval between removal of the product from the freezing plant and its delivery to cold store be likely to exceed 30 minutes, pre-cooled refrigerated vehicles or pre-cooled insulated vehicles should be used to maintain the product temperature of 0° F. or below during transit. 6. The time interval between the commencement of preparation and processing and freezing of frozen food should not exceed two hours. 7. Cold stores should be operated at a CONSTANT temperature of 0° F. or below. 8. Efficient circulation of air in cold stores is essential, if the temperature of goods entering the processor's stores exceeds the storage temperature. It is assumed that the temperature of goods entering the processor's store will not exceed the recommended storage temperature. Under these conditions the product should be stored on pallets or dunnage in such a manner as to allow not less than 3 in clearance between it and the floor of the cold store, and there should be spaces left of not less than 4 in from walls or refrigerated pipes located on walls, and not less than 12 in from ceilings or refrigerated pi pes located on ceilings. 9. A system of controlled stock rotation should be employed at all frozen food stores. 'Pirst in First Out' is the basic principle. 10. All frozen foods should be offered for sale in a good quality, odour, and taste-free package in order to: (a) Prevent contamination of the product by exposure or handling The product should be totally enclosed in a container (e.g. carton, pack, wrapper, etc.) which should be tamper-proof (i.e. not capable of being opened without recognisable damage). (b) Protect the product against damage by shock Outer containers should be of adquate strength. The Standards Association of Australia specification is recom;nended as a guide to the weight and type of material required. (c) Inhibit dehydration This com be achieved by incorporating a moisture vapour barrier: recommended materials include waxed board, cellulose film, polythene, or foil of a standard approved by the Standards Association of Australia. 11. All outer cases should be clearly coded so that stock rotation can be carried out. It is also desirable that the inner pack or carton should bear a code number to permit subsequent reference to the production source as required. 12. The in"er pack should carry advice to the consumer on how the product is to be stored and defrosted, and such cooking instructions as may be necessary to enable the consumer to use the product satisfactorily. 13. Transfer from factory or other non-terminal store to terminal cold store should be made in refrigerated vehicles or insulated vehicles capable of maintaining a product temperature of 0° F. or less and the product temperature should be maintained at O°F. or below during transit. Loading into vehicles and into store from vehicles on arrival should be as fast as is practicable and the methods employed should be such as to ensure that the temperature of any part of the product does not rise above 5° F.
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14. Suitable equipment for measuring product temperatures should be obtained and should be regularly checked in a laboratory approved by the National Association of Testing Authorities. B. Handling Code for those engaged in wholesale distribution 1. It is essential for a distributor to have at his disposal a low temperature cold store which can be operated at a constant air temperature of 0° F. or below. For the storage of fish for a period exceeding 6 months the air temperature should be maintained at _10° F. 2. Where goods are received at the recommended storage temperature, they should be stored on pallets 0 r dunnage in such a manner as to allow not less than 3 in clearance between them and the floor of the cold store, and there should be spaces left of not less than 4 in from walls or refrigerated pipes located on walls and not less than 12 in from ceilings or refrigerated pipes located on ceilings. Air circulation within the stack is not necessary under these conditons. 3. However, when the temperature of goods entering the store exceeds their recommended storage temperature, the temperature of the goods must be reduced to the recommended storage temperature before they can be block stacked. The best conditions for cooling require open stacking of cases, particularly in the vertical plane. 4. A system of controlled stock rotation should be employed at all distribution frozen food stores. 'First in First out' is the basic principle. S. The temperature of any part of the product should not be allowed to rise above So F. during assembly and packing of customers orders. 6. Distributors or carriers of frozen foods should provide efficient refrigeration for the product whilst in transit between their store and retailers' cabinets, so that at no time does the temperature of any part of the product rise above So F. or preferably 00 F. The means of transport recommended are: (a) Insulated containers of suitable thermal efficiency, provided with effective refrigeration. (b) Insulated vehicles provided with effective refrigeration. 7. Storage overnight in non-refrigerated vehicles should not be permitted. 8. Should there be residual stocks in distribution vehicles at the end of a journey, product temperatures should be checked before these stocks are returned to cold stores and if found to be above 5° F. steps should be taken to reduce the temperature before reloading. 9. Distributors should provide a service for the return to cold stores of stocks in retailers' cabinets in an emergency such as cabinet breakdown. 10. Distributors should preserve intact the inner container (carton, pack or wrapper) as provided by the processor and should ensure that damaged or faulty stock is not permitted to reach retail outlets. 11. Records of the codes of outer containers should be kept and should be quoted in all references back to the processor. 12. Air temperatures should be monitored continuously and automatically controlled. C. HandIlng Code for 1bose engaged in retalling 1. Frozen foods must not be offered for sale except through a refrigerated cabinet designed for the purpose and capable of maintaining a constant product temperature of 0° F. as tested by methods laid down by specification No .•• of the Standards Association of Australia. 2. Regular maintenance of the refrigerated cabinet or retailers' storage facilities for frozen foods to be carried out by a qualified refrigeration service agent. 3. Air and product temperature checks should be made daily. The refrigerated cabinets should be fitted with an accurate thermometer properly located and visible at all times thus ensuring that the recommended temperature is being held. Under no circumstances should an air temperature of more than 100 F. be allowed anywhere within the load lines. 4. For efficient operation of the cabinet, the inner walls and floor must be kept clean and clear of ice. They should be defrosted once a week or more frequently if necessary and, during the operation of defrosting, stocks should never be kept outside the cabinet for more than ten minutes. S. As required by the Regulation: (a) The contents of the cabinet must always be stacked within the load lines. (b) New stocks must be placed in the cabinet or other appropriate frozen storage immediately on receipt. Delivery should be refused of any frozen food, the product temperature of which exceeds 10° F. or such lower temperature as may be prescribed by any amendment of the present Regulation. (c) The package of frozen food as delivered to the retail outlet must be sold intact. The package in which the product was originally packed by the manufacturer has been designed to preserve the high quality and hygiene standard set in the factory, and repacking should not be carried out.
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(d) Non-frozen foods and unwrapped products must never be stored in the frozen food cabinet since they introduce the risks of temperature rise and contamination of frozen foods. (e) Frozen foods which have thawed must not be refrozen and offered for sale.
6. Stocks should be rotated to ensure that the earliest deliveries are sold first. The fullest use of the distributors' frequent delivery service is recommended to ensure the maximum rate of turnover through the frozen food cabinet ( ,
7. If, because of breakdown, or for any other cause, the air temperature rises above 10· F., technical assistance should be sought to correct it. Frozen food distributors are generally prepared to help with temporary storage of cabinet contents and to advise on whether or not goods remain fit for sale. (Insurance against the risk is available).
APPENDIX XII DISPLAY AND TRANSPORTATION OF FROZEN FOOD Application of Standard
This Standard shall apply to: (i) Places in which frozen food is sold, or displayed for sale as frozen food, and (ii) Food Service establishments in which frozen food is used in. the service C?f meals. or refreshments for sale, either in the ready to eat frozen state or m a state which reqUIres thawing and/or heating or cooking prior to service, and (iii) Places in which frozen food for sale is prepared, processed, packed, repacked or stored prior to transport or sale to all places within the provisions of this Standard, and (iv) Vehicles used for the transportation of frozen food for sale or vehicles which are used for sale of frozen foods. For the purpose of this Standard: is food as listed in Schedule I for sale for human consumption or intended for sale for human consumption in raw, processed or packaged form, preserved by freezing. Such food shall be subsequently handled and stored until its sale or service so that the temperature of no part of the produce shall rise above the product temperature as prescribed in Schedule I of this Standard for the particular frozen food. is the calibrated temperature of frozen food in situ obtained by the reading of an accurate thermometer in the following manner: (a) In the case of single packages: By inserting the thermometer in the frozen food to the correct depth of immersion and by reading the temperature after a lapse of five minutes and then subsequently reading the thermometer at intervals of one minute until the difference between consecutive readings is less than -top. The produce temperature is calculated from the temperature reading so obtained by applying the calibration correction of the thermometer; or (b) In the case of packaged frozen food packed in an outer container: (i) By inserting the thermometer to the correct depth of immersion between the 2nd and 3rd packages of at least four packages in the outer container; and (ii) By placing two full containers on top of the one being measured and then reading the temperature after a lapse of five minutes and then subsequently reading the thermometer at intervals of one minute until the difference between consecutive readings is less than -t oF. The product temperature is calculated from the temperature reading so obtained by applying the calibration correction of the thermometer; or (c) In the case offood not specified by (a) and (b) above: (i) by inserting the thermometer to the correct depth of immersion between the second and third packages of at least four packages, and (ii) By placing two packages on top of the one being measured and then reading the temperature after a lapse of at least five minutes, and then subsequently reading the thermometer at intervals of one minute until the difference between consecutive readings is less than -top. The product temperature is calculated from the temperature reading so obtained by applying the calibration correction of the thermometer. is one which is clearly graduated at intervals of l°F and has been calibrated to an accuracy of +2°F or better by a laboratory approved by the National Association of Testing Authorities in the field of thermometry. is the depth of immersion which is marked by the calibration laboratory on the thermometer. includes buildings, rooms, premises or parts thereof. includes restaurants, cafes, cafeterias, coffee shops, diners, milk bars, sandwich shops, caterers, hotels, motels, clubs, guest houses and all other public eating or drinking places. is any case, cabinet or other facility used for displaying or storing frozen food for sale. is frozen food for sale or display: (a) which does not confirm either wholly or in part with the definition prescribed by this Standard for Prozen Food, or (b) which is in package form and the package label or written matter attached thereto or enclosed therewith bears a statement, design or device regarding such frozen food which is false or misleading in any particular. define the spatial limits within which the specified product temperature can \>e maintained. i '
Definitions Frozen Food
Product Temperature
Accurate Thermometer Correct Depth of Immersion Plaus Food Service Establishments
Frozen Food Cabinet
Falsely Described
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Frozen Food
Product Load J-ines
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Outer Container Sale of Falsely Described Frozen Food Labelling
is the container used for the transportation or storage of a number of unit packages. (1) No person shall sell frozen food which is falsely described. (2) (a) No person shall sell frozen food in a package unless, in addition to such information
required by this Standard to be indicated upon such package, there is legibly and durably written thereon immediately above or contiguous with the designation of the article the word 'Frozen'. Such word shall be uniformly written in bold faced sans serif capital letters with a face depth of not less than 0.06 of an inch and in such colour or colours as to afford a distinct contrast to the ground. (b) There shall be written in the label on or attached to every package of frozen food in bold faced sans serif capital letters with a face depth of not less than 0.11 of an inch the words 'Store at or below O°F.' Ingredient (3) No person shall process pre-cooked frozen food for sale from ingredients that are capable of Temperature supporting rapid bacterial growth inless such ingredients are maintained continuously at a product temperature which is either above 160°F, or below 40°F up to the time of commencement of processing and incorporation of the ingredients in the product to be frozen. The term pre-cooked does not include food only blanched before freezing. Requirements (4) No person shall store frozen food for sale in any place or for service in any Food Service for the Storage Establishment unless the following requirements are observed: of Frozen Food (a) All frozen food shall be stored at the product temperature prescribed in Schedule I of this Standard or lower. (b) Every Frozen Food Cabinet shall be marked with distinctive, legible and permanent markings to indicate the product load lines (c) Frozen Food Cabinets in Retail premises must be capable of maintaining a steady temperature of OaF as tested by methods laid down by Specification No ... of the Standards Association of Australia. (5) No person shall sell any frozen food which is not contained in its original package as received by him or which is contained in only portion of its original package as received. (6) No person shall receive into any place or into any food service establishment frozen food for Immediate sale or for service, unless such frozen food is immediately placed in the storage facilities Storage of Frozen prescribed by the aforementioned Clause of this Standard. Food on Reception (7) No person shall store or display frozen food for sale or for service in any cabinet or display Display of unit outside the product load lines. Frozen Food outside Cabinet Load Lines. (8) No person shall store or display any food which is not frozen food in any frozen food Prohibition of cabinet or other freezer in which frozen food for sale or for service is stored or displayed. Storage of Other Foods with Frozen Food (9) No person shall refreeze food described as frozen food, provided that frozen food may be Re-Jreezing of used in the preparation of a pre-cooked frozen food without contravention of this Regulation. Thawed Foods (10) No person shall carry or deliver food described as frozen food for sale or for service in a Transport of Food Service Establishment unless such food at all times during its carriage and at the time Frozen Food of delivery conforms with the product temperature prescribed in Schedule I of this Standard for such frozen food. ":\:..-
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SCHEDULE 1 DRAFr SCHEDULE OF MAXIMUM PRODUCT TEMPERATURES APPLICABLE TO FROZEN FOODS AT EACH STAGE OF MARKETING Definitions 1. Maximum Product Temperature: The highest temperature in degrees Fahrenheit which a frozen food will be permitted to attain. 2. Terminal Store: The last bulk cold (frozen) storage facility in which the food is held prior to distribution to retailers. (
Kind of frozen food
In ship's refrigerated cargo In retail store During delivery space, proces- During delivery In Terminal store or frozen food sor's and other to terminal)store to Retailer cabinet non-terminal stores OF. OF. OF. OF. OF.
Frozen foods as follows: Fruits Vegetables .. Fruit juices .. Fish and other freshwater and marine products .. Poultry .. Pre-cooked foods Pastry products
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S
S
S
10
10
Pre-packaged edible meat and offal derived from cattle, sheep and pillS .. Egg pulp ..
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APPENDIX XIII STANDARD FOR JELLY CRYSTALS, TABLETS, CUBES AND MIX l. Jelly Crystals and Jelly Tablets Jelly Crystals and Jelly Tablets are preparations of gelatine with sugar and/or glucose and with citric acid and/or tartaric acid and/or lactic acid with flavouring and with or without permitted colouring matter. 2. Jelly Cubes
Jelly Cubes are preparations of gelatine and water with sugar and/or glucose and with citric acid and/or tartaric acid and/or lactic acid with flavouring and with or without permitted colouring matter. 3. Jelly Mix
Jelly Mix is a mixture of vegetable gelling substance (alginate, pectin, agar or edible gum) with or without gelatine, with sugar and/or glucose and citric acid and/or tartaric acid and/or lactic acid and/or tri-potassium citrate and/or calcium sulphate with flavouring and with or without permitted colouring matter. 4. Labelling (a) There shall be written in bold faced sans serif capital letters with a face depth of not less than 0.09 of an inch in the label attached to every package of Jelly Crystals or Jelly Tablets the words JELLY CRYSTALS or the words JELLY TABLETS as the case may be. (b) There shall be written in bold faced sans serif capital letters with a face depth of not less than 0.09 of an inch in the label attached to every package of Jelly Cubes the words JELLY CUBES. (c) There shall be written in bold faced sans serif capital letters with a face depth of not less than 0.09 of an inch in the label attached to every package of Jelly Mix the words:
JELLY MIX and the statement
CONTAINS A VEGETABLE GELLING SUBSTANCE or the statement
CONTAINS A VEGETABLE GELLING SUBSTANCE AND GELATINE as the case may be (d) Where Jelly Crystals, Jelly Tablets, Jelly Cubes or Jelly Mix contain a permitted colouring and/or flavouring other than a concentrated flavouring wholly derived from fruit, there shall be written in the label attached to the package in bold faced sans serif capital letters with a face depth of not less than 0.06 of an inch either the words: ARTIFICIALLY COLOURED
ARTIFICIALLY FLAVOURED
or
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ARTIFICIALLY COLOURED AND FLAVOURED as the case may be. (e) There shall be written in the label attached to every package of Jelly Crystals, Jelly Tablets, Jelly Cubes or Jelly Mix, a statement declaring either the amount (in pints and/or fluid ounces) of water to be added to the contents of the package to prepare the jelly, or the amount (in pints and/or fluid ounces) of jelly that the contents of the package will make. (/) The word 'fruit' or any design or device suggesting the presence of fruit, shall not awe:rr on any label attached to any package containing Jelly Crystals, Jelly Tablets, Jelly Cubes or Ielly Mix.
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APPENDIX XIV STANDARD FOR LABELLING I. (a) 'Label' includes every tag, brand, mark, pictorial or other descriptive matter written, printed, stencilled,
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marked, embossed or impressed on or attached to any food or with any package containing any food. (b) 'Package' includes any form of packaging of food for sale as a single item, whether by completely or
partially enclosing the food and i neIudes wrappers, confining bands, jars, cans and boxes. (c) 'Common Name' means a name or description which indicates the true nature of the food, ingredient
or constituent, as the case may be, to which it is applied, which does not include any word claiming or implying superior quality or purity and which is, where appropriate a specific and not a generic name or description, provided that where a regulation lays down a compositional standard and specifies the name of a product to which the standard applies, that name shall be deemed to be a common name for the purpose of this regulation, but nothing in this sub-paragraph shall prevent the use of a more specific name than that specified in the said standard except where regulations lay down a precise designation that must be used for a specific product. (d) 'Trade name' in relation to a food is a distinctive arbitrary, or fancy name which clearly distinguishes a food from any other food but shall not be one: (i) representing any single constituent of the food; or (ii) misrepresenting the composition or any property or quality of a food; or (iii) giving false implication or origin, character, or place of manufacture_ 2. (a) Unless exempted by these regulations, every package of food packed or enclosed for sale shall bear a
label attached to it containing such particulars, statements, information or words in English as are required by the Act or these Regulations. (b) The said statement shall appear conspicuously and in a prominent position on the label, and shall be clearly discernible to the purchaser or consumer under the customary conditions of purchase and use. 3. Unless exempted by these Regulations the label shall include: (i) the common name of the product; (ii) (a) the name of the manufacturer or packer or importer or vendor and his business or registered address, not being a post office, cable, telegraphic or code address. Provided that where a company is incorporated in accordance with the appropriate law of any State or Territory of the Commonwealth of Australia, or a firm is registered under the Business Names Act of any State or Territory, the inclusion in the label of the registered name of the corporation or firm and the city or town in which a registered office is situated shall be deemed to comply with the requirements of this paragraph. (b) Where the name of the vendor is used on the label or package, not that of the manufacturer or packer, there shall be an identifying mark on the label, whereby the name of the manufacturer or packer can be identified provided that this information shall be made available by the vendor on demand to (here insert instrumentality). (iii) such other information as is required by these regulations. (iii) such other information as is required by these regulations. 4. Subject to the labelling requirements of these Regulations relating to flavouring, colouring, preservative, antioxidant, artificial sweetener, or medication or directions for preparation, packages of food named or indicated hereunder shall unless otherwise specifically provided for in these Regulations, be exempted from the need to bear a label. (i) Food weighed, counted, or measured in the presence of the purchaser; (iii) Meat and meat products except when packed in closed or sealed packages.
S. (a) Where specifically required by these Regulations the label shall include: (i) Statement of ingredients and the quantity or proportion in which they are present, in descending order of their relative proportion; (ii) The place of manufacture and/or the country of origin of the packed food. (b) Where these regulations do not specifically require any statement of ingredients to be made and ingredients are separately declared, they shall be declared in the descending order of their reiative proportion and without any qualifying statement. Any emphasis or statement in relation to any particular ingredient or ingredients in the products, shall not be made unless the proportion of such ingredients is stated.
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6. Any statement required by the Act or these regulations shall appear in the label: (a) (i) in bold faced sans serif capital letters of at least the prescribed size. Except where otherwise prescribed in these Regulations the name of the manufacturer, packer or vendor may appear in letters other than sans serif capital letters, which are of uniform height apart from initial letters, of uniform colour and the smallest letter shall be not less than the prescribed size. Oi) in such colour or colours as to afford a distinct colour contrast to the ground; (iii) unless otherwise prescribed, in letters with a face depth of not less than 0.06 of an inch, provided that when the package or container is so small as to prevent the use of letters of the prescribed size, smaller letters, of proportionally reduced size may be used, provided no letters have a face depth of less than 0.06 of an inch. This provision shall only apply if none other than statutory information appears on the label. (b) Each statement required by a particular labelling provision shall wherever occurring appear thereon in letters of uniform size, style and colour.
7. (a) A label shall not contain any statement, claim explicit or implicit, design, device, fancy name or abbreviation which is false or misleading in any particular concerning any food, or the ingredients or substances contained in the package, or concerning the quality or the physiological action or the food value of, or the place of origin of such a food. Unless specifically provided otherwise in the Regulations, claims for therapeutic or prophylactic action or words of similar import shall not be made for any food. The word 'health' or a word of similar import shall not be used in conjunction with the name of the food in the label. (b) A label shall not include any comment on, reference to, or explanation of any statements required by the Act or these Regulations which directly or by implication, contradicts, qualifies, or modifies such statement. (c) There shall not be written or printed, on the statement or label attached to any package containing any article of food the word 'imitation' or any word implying that the article is a substitute for any food, unless the use of such word is specifically permitted by these Regulations. (d) The word 'pure' or any word or words of the same significance shall not be included in the label of a package. (e) Unless specifically provided otherwise in the Regulations, a label shall not contain any words, claim, explicit or implicit, design or device which could be interpreted as advice of a medical nature from any person whatsoever. (f) No person shall include or cause to be included in the label any certificate of analysis or part thereof or report or any statement purporting to be a certificate of analysis or report of any chemist or analyst or other person. (g) Where the registered name of the manufacturer, vendor or packer contains a common name of a food different from that of the food in the package, the registered name of the company shall be written in letters of not greater than half of the face depth of the common name of the food. 8. There shall not be included in the label any statement or advertisement relating to any poisonous substance except as specifically required by these regulations.
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APPENDIX XV STANDARD FOR MINERAL AND CARBONATED WATERS GENERAL STANDARD
1. Mineral and carbonated waters are potable waters impregnated with carbon dioxide under pressnre and they may contain salts of sodium, potassium, lithium, magnesium and calcium. LITHIA, SELTZER AND SODA WATER.
2. (a) Soda water is a mineral water which may contain sodium or potassium carbonate. (b) Lithia water is a mineral water containing not less than 570 ppm wIv lithium carbonate. (c) Seltzer water is a mineral water containing not less than 1700 ppm w/v of sodium chloride, not less than 230 ppm w/v of sodium bicarbonate, not less than 450 ppm w/v of magnesium chloride, and not less than 450 ppm w/v of calcium chloride. (d) Mineral and carbonated waters not otherwise standardised shall conform with the general standard for mineral and carbonated waters.
Lobellblg 3. Every person who sells any package of a mineral or carbonated water containing a salt or salts, sha11 attach thereto a label which shall include in letters with a face depth of not less than 0.06 of an inch the name or names of such salts and the percentage proportion in which each is present, provided that where lithia, seltzer or soda water complies with the prescribed standard it shall not be necessary to include in the label the name or names of the salt or salts present or the proportion or proportions thereof.
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APPENDIX XVI STANDARD FOR TYPE SIZE IN LABELUNG FACE DEPTH A reference to the size in which letters, words or figures mayor shall be printed shall, unless the contrary intention appears, be expressed in terms of decimal divisions of an inch and be read as a reference to the size of a capital letter printed in that size and measured in full depth. The full depth of the printed capital letter shall be measured without regard to the size of the type body from which the letter may be printed or to the size of any beard or, shoulder on the type body. Where a lower-case letter is required to be, or may be printed, the 'x' height of the lower-case letter shall be not less than one-half of the full depth of the capital letter with which it is associated in the printing of the letters or words required to be printed in a specific size. Wherever the wording 'of not less than (number) point measurement' or the wording 'of not less than (number) point face measurement' appears in State food legislation it shall be replaced by the wording 'with a face depth of not less than . . . of an inch', the face depth to be expressed in decimal divisions of an inch.
TYPE SIZE Sizes of type expressed in States Food legislation should be amended by substituting the following face depth size of letters to be used for labelling specific items of food wherever occuring in such legislation: 72 point by substituting 0.68 inch 48 point by substituting 0.46 inch 36 point by substituting 0.34 inch 24 point by substituting 0.23 inch 18 point by substituting 0.17 inch 12 point by substituting 0.11 inch 10 point by substituting 0.09 inch 6 point by substituting 0.06 inch
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APPENDIX XVII STANDARD FOR VITAMINS AND MINERALS 1. The addition of a vitamin to any article of food, except as specifically permitted by the Regulations is hereby prohibited. Articles of food prepared in part from food in which vitamins are naturally present or to which vitamins are permitted to be added shal~ not cO!ltain more vitamins than result from the addition of such food containing or permitted to contam vitamms. Claims regardmg the presence of vltamms III a food shall not be made unless the food is listed under Table 2.
2. (a) No claim based upon the presence of a vitamin or mineral or implying the presence of a vitamin or a mineral in a food, shall be made in any advertisement or printed label except by the use of one or marc of the names specified in Column 1 of Table 1, and unless the reference quantity as laid down in Table 2 contains at least one sixth of the daily allowance as laid down in Table I. (b) When a claim for a vitamin or mineral is based upon the presence in the reference quantity as laid down in Table 2 of more than one-sixth Of less than one half of the daily allowance specified in Column 3 of Table 1, such claim shall be restricted to a statement of the proportion of the Vitamin or Mineral present in terms as set out in Clause 4 below. (c) No claim stating or implying that the food is a good source of a vitamin or mineral shall be made unless the reference quantity as laid down in Table 2 contains not less than one half of the daily allowance as laid down in Table I. (d) No claim stating or implying that the food is of value for the prevention or cure of disease due to lack of a vitamin or mineral shall be made unless the reference quantity as laid down in Table 2 contains not less than the daily allowance as laid down in Table I. (e) This Regulation shall not apply to food in its natural state or as standardised by these Regulations to which vitamins and minerals have not been added, with regard to vitamins and minerals naturally present in such foods where the claims are restricted to statements to the effect or suggesting that the foods are a source of a vitamin or mineral. No such claim shall be made unless the food contributes in a reasonable daily intake, as ordinarily consumed, or prepared as directed on the label, not less of the vitamin or mineral in respect of which the claim is made than one-sixth of the amount listed under Column 3 of Table 1. 3. Oaims based on the presence of more than one vitamin or mineral shall not be made unless the content of each vitamin or mineral present conforms with clause 2 (a) or 2 (b) or 2 (c) or 2 (d) as the case may be. 4. There shall be written on the label attached to every foodstuff in which claims regarding vitamins as outlined in 2(a), 2(b), 2(c) or 2(d) are made, a statement of the reference quantity of the foodstuff as outlined in Table 2 and the content of each vitamin or mineral contained in the reference quantity, as in the following example: '(here state the amount of the reference quantity) of this food contains (here state the quantity of units prescribed in Table I and the proportion) of the daily allowance of Vitamin A'. 5. Claims such as 'vitamin enriched' or 'vitamin fortified' implying that the food contains added vitamins are prohibited. 6. Statements in any advertisement or label comparing the vitamin content of the foodstuff with that of any other foodstuff are prohibited. 7. Where the regulations permit the addition of a vitamin or mineral to a food, such addition must not increase the vitamin A content to more than 2,500 I. U. per reference quantity as specified in Table 2 nor increase the content of Vitamin D to more than 400 1. U. or of minerals to more than three times the daily allowance (as laid down in Table I) per reference quantity as specified in Table 2. 8. Clauses I, 2. 3 and 4 of this regulation shall not apply to infants' foods or any food when such exemption is specifically prescribed in the regulations. 9. The addition of vitamins and minerals as set out in Table I to the foods specified in Table 2 is hereby permitted.
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TABLE 1 Column 1 Substances
Column 2 To be Calculated As
Column 3 Daily Allowance
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PART 1: VITAMINS Vitamin A, vitamin A alcohol and esters, Carotenes Vitamin B, Aneurin, Thiamine, thiamine hydrochloride, mononitrate International Unit Vitamin A Milligrams of thiamine Milligrams of Riboflavin Micrograms of Cyanocobalamin Milligrams of Niacin Milligrams of ascorbic acid International Units Vitamin D PART 2: MINERALS Calcium Iodine Iron Phosphorus Milligrams of Calcium Micrograms of Iodine Milligrams of Iron Milligrams of Phosphorus • Limited to milk substitutes of vegetable origin.
, , -
2,500 International Units 1 . 1 milligrams 1 . 6 milligrams 2 micrograms 11 milligrams 30 milligrams 400 International Units
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Vitamin B2 Riboflavin ·Vitamin BI2 , Cyanocobalamin Niacin, Niacinamide, Nicotinic Acid, Nicotinamide Vitamin C, Ascorbic Acid Vitamin D, Vitamin D., Vitamin D3
-.;.t-
700 milligrams 100 micrograms 10 milligrams 1,000 milligrams
TABLE 2
Foodstuff
Reference Quantity
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Biscuits containing not more than 20 per cent fat nor more than 5 per cent sugar .. Milk powder (full cream or skim) and food containing not less than 51 per cent of milk powder Butter or Margarine Breakfast Cereals (as purchased) Bread Flour (wheaten) and food containing not less than 51 per cent of flour (wheaten) .. Fruit and Vegetable Juices and food containing not less than 90 per cent of fruit and vegetable juices .. Fruit Juice Concentrates (diluted according to label) .. Fruit Cordials (diluted according to label) Extracts of Meat or Vegetables or Yeast (modified or not) and substances containing not less than 90 per cent of extract of meat or vegetables or yeast (modified or not) .. Foods described as invalids' Foods .. Milk substitutes of vegetable origin (diluted according to label) ..
40z 20z 20z 20z 80z 40z 1 pint
1 pint loz 2 oz in the case of solid foods or 1 pint in the case of liquid food. 1 pint
1 pint
I • I
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APPENDIX XVIII DRAFI' PAINT STANDARD 1. Scope These regulations refer to imported paints as well as locally produced paints. 2. Definitions 'Paint'-without limiting the ordinary meaning, includes any substance used or intended to be used for application as a colouring or protective coating to any surface. The term includes the following: oil paint, water paint, enamel, varnish, lacquer and thinners, solvents, driers, stainers, tinters, curing agents but does not exclude any substance used or intended to be used in the composition of any paint. Curing agents, when separately packed, must be labelled in accordance with the appropriate State poisons legislation. 'Lead' means the total lead content calculated as a percentage of the non-volatile content of the paint. 'Non-volatile content' means that portion of the paint as determined by the method laid down in S.A.A.K. 41 Method 301.1. This method is attached as the Appendix to this Standard. 3. Prohibition No person shall manufacture, sell or use any paint containing basic carbonate white lead. 4. Classification Paint containing any material shown in Schedule I shall be classified as Schedule I Paint. Paint containing any material shown in Schedule 2 shall be classified as Schedule 2 Paint.
5. Labelling (a) No person shall sell any paint unless the container of such paint has attached thereto a label which(i) shows the trade name or description; (ii) shows the net weight or true measure of volume of the contents; (iii) shows the name and address of the vendor or manufacture of the contents; (iv) shows the maximum lead content of the paint, for example, 'Lead content not more than 1 per cent', 'Lead content not more than 5 per cent'; (v) contains the statements: 'KEEP AWAY FROM CHILDREN', 'PROVIDE ADEQUATE VENTILATION DURING APPLICATION'. (b) No person shall seJl any paint which is classified as a Schedule I Paint or as a Schedule 2 Paint unless the container of such paint has attached thereto a label containing a statement as specified below, which shall be headed by the word 'WARNING' which shall appear in red letters with a face depth of not less than 6/32nd of an inch. * Immediately below this heading shall appear, in black or other suitable contrasting colour, in letters with a face depth of not less than 3/32nd of an inch *, one or both of the following statements according to the classification of the paint: Schedule 1: This paint presents a danger to young children from eating the dried paint, and should not be used on parts of buildings easily accessible to young children or on toys, or furniture or any other articles likely to come within the reach of young children. Schedule 2: Breathing in of vapour may be dangerous. When applying by brush or roller in a poorly ventilated space, wear suitable respiratory protective equipment at all times. When spraying always provide adequate exhaust ventilation or wear a supplied air respirator or hood. Do not use in the presence of a naked flame. Do not smoke. (c) No person shall sell any Schedule I Paint unless the container of such paint has attached thereto a label which shows the name of the ingredient covered by Schedule I and the percentage of this ingredient calculated on the non-volatile content of the paint. 6. Restrictions on sale of certain painted articles No person shall sell any toys, wallpaper, pencils, wraps, containers or furniture of which any Part has been painted with a Schedule 1 Paint. 7. Restrictions on use of Schedule 1 Paints No person shall use or put or permit to be used or to be put any paint classified as a Schedule 1 Paint on(a) the roof of a house or other building or structure whatsoever; (b) any exterior portion, other than the roof of any house or other building whatsoever; • Except where it can be shown that this size is excessive in relation 10 the size of tho container.
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(c) any fence, wall, post or gate whatsoever; (d) any interior portion of a house, or other building whatsoever intended for the use of human beings; (e) any household or other furniture or part thereof; (f) any toys, wallpaper, pencils, wraps and containers, or any surface which will come into contact with food.
8. Powers to order removal of paint or destruction of articles Upon proof to the satisfaction of the Director-General that any Schedule 1 Paint is on any house or other structure or article whereon the use or putting of that paint is prohibited by a provision of these Regulations then the Director-General may by notice in writing given to the owner of that place or that article, require that owner to clean down and remove from the house, structure or article in question that paint. Provided that in the case of toys, pencils, paper or any other article from which the removal of the offending paint is impracticable, the Director-General may order the destruction or disposal of such article in such a manner as may be satisfactory to him.
SCHEDULE 1 Lead and compounds of lead exceeding 1 per cent calculated as Pb on the non volatile content of the paint. Arsenic and compounds of arsenic exceeding 0.1 per cent calculated as As on the non-volatile content of the paint. Antimony and compounds of antimony exceeding 5.0 per cent calculated as Sb on the non-volatile content of the paint. Cadmium and compounds of cadmium exceeding O. I per cent calculated as Cd on the non-volatile content of the paint. Selenium and compounds of selenium exceeding 0.1 per cent calculated as Se on the non-volatile content of the paint. Mercury and compounds of mercury exceeding 0.5 per cent calculated as Hg on the non-volatile content of the paint. SCHEDULE 2 Over 1 per cent by weight on total weight of the paint Over 5 per cent by weight on total weight of the paint Over 10 per cent by weight on total weight of the paint Over 5 per cent by weight on total weight of the paint Over 5 per cent by weight on total weight of the paint Over 1 per cent by weight on total weight of the paint Over 1 per cent by weight on total weight of the paint Over 2 per cent by weight on total weight of the paint Over 5 per cent by weight on total weight of the paint Over O. 1 per cent by weight on total weight of the paint
Benzene Dichlorethane Dichlorethylene Dichlorbenzene Dichlormethane Methanol .. Nitrobenzene Pyridine Trichlorethylene Free Organic Isocyanates
INSECTICIDES IN PAINTS The following recommendations were made by the National Health and Medical Research Council (62nd Session, May 1966): 1. That the sale of paints containing insecticides be subject to a qualified prohibition which would allow the sale of any new formulation of such paints only after examination of its merits by the appropriate authority. 2. That in the case of formulations at present on the market which are considered to be undesirable by the appropriate authority, a time limit should be set after which sale would be illegal. 3. That where State Governments are considering paint formulations containing insecticide, the matter should be referred to the National Health and Medical Research Council with the object of achieving uniformity of action in all States. " -;---"
APPENDIX TO DRAFT PAINT STANDARD NON VOLATILE CONTENT This method may not be suitable for lacquers containing camphor or for material which includes nitrogen-containing resins, or for dry paints. Apparatus A shallow fiat-bottomed circular dish of approximately 3 in diameter. A well ventilated oven capable of being maintained at 105 ± 3°e. 22568/66-6
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Procedure 1. Dry the dish (and stirring rod if one is used-see step 3) at 105 ± 3°C within the working space. Cool and weigh.2. Transfer 1 .0--2.0 g of the well mixed sample to the dish by: (i) weighing by difference from a stoppered weighing bottle, or (ii) if the sample is a viscous liquid and, or a material of known low volatility, weighing- directly into the dish, which shall be suitably covered during the weighing operation. 3. Spread the material evenly over the bottom of the dish by tilting and, if necessary, by the addition of 3 ml of a suitably volatile diluent and the use of a stirring rod. Suitable diluents are: benzol for oil base paints, water for water paints, acetone for nitro-cellulose lacquers. 4. Heat the dish and contents (including the stirring rod if one is used) in the oven at 105 withour stirring; cool and weigh.· 5. Determine by difference the weight of the residue. Calculation and Report
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± JOC for 3 hours
"1.._ .....
Calculate the percentage of non-volatile matter as follows: 100 . Weight of residue Non volatIle matter percentage = W'gh f I x I el to samp e
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* All weighing shall be carried out to the nearest mg, and the non-;olatile conte~~e~~~d --;-~ the --;'eare-s-;O-.i per cent~--
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APPENDIX XIX GENERAL ORGANISATION AND ADMINISTRATION OF COUNCIL AND COMMITTEES (i) Council should continue to meet regularly twice a year. (ii) Each regular meeting of Council should be preceded by meetings of three Advisory Committees (Medical
Research, Public Health, and Medicine). (iii) Each Standing Committee and Standing Sub-Committee should meet at least once in each calendar year.
(iv) The Chairmen or Conveners of meetings of Committees and Sub-Committees must make written requests to the Secretary of the Council for approval to hold such meetings, setting out the agenda, dates and places of the intended meetings, and the members, co-opted members (if any) and observers (if any) who will be attending. (v) All Committees of Council may set up Sub-Committees with such terms of reference and membership as may be required, subject to the prior agreement of the Chairman of the Council. (vi) The Chairman and Secretary of the Council are to be ex officio members of all Committees and SubCommittees of Council. (vii) The Chairmen of all Committees of Council should be appointed by Council. (Exception-see (xi) below). (viii) The Chairmen of all Committees and Sub-Committees may co-opt members and invite observers to attend specific meetings of their Committees and Sub-Committees, providing that the prior permission of the Chairman of Council is obtained (see (iv) above). Such co-opted members should be eligible for the fees and allowances payable to regular members, and may take part in but may not vote in the business of the meetings. Observers invited to attend meetings of Committees and Sub-Committees may not take part in the business of meetings except on the invitation of the Chairmen. They may not vote and will not be eligible for members' fees and allowances. (ix) With the exception of co-opted members and members apPOinted by the Chairman of Council under clause (xi), all other members of Committees of Council must be appointed by Council. (x) The members of the Standing and Reference Committees and Sub-Committees of Council should be selected on the basis of their value to Committees and Sub-Committees as individuals and not as representatives of particular groups or organisations. (xi) Notwithstanding clause (vii) the Chairman of Council (Commonwealth Director-General of Health) may terminate the appointment of members of the Commonwealth Health Department staff to Committees and Sub-Committees and replace them by other members as necessary. (xii) Notwithstanding the normal terms of appointment of members of Committees and Sub-Committees, the Council may terminate the appointment of any member at any time. (xiii) The functions and membership of the Committees and Sub-Committees of Council should be formally reviewed every three years. (xiv) As soon as practicable after each meeting of a Committee or Sub-Committee a report of matters dealt with at the meeting must be forwarded to the Secretary of the Council. (xv) Whenever possible, the dates of Committee and Sub-Committee meetings should be arranged to allow reports of the meetings (60 copies desirable) to reach the Secretary at least six weeks prior to the subsequent Council meetings. (Exception-see (in above). (xvi) Chairmen of Committees of Council should present their reports in person to the relevant AdVisory Committees, wherever it is convenient to do so. (xvii) The meetings and reports of all Committees and Sub-Conunittees of Council are confidential. (Exceptions -see (xviii) and (xix) below), (xviii) All material derived from unpublished proceedings or reports of Council, its Committees, and SubConunittees must be approved by Council, or by the Chairman of Council in consultation with the Chairman of the relevant Advisory Conunittee of Council, before being submitted for publication. (xix) When urgently necessary, a Conunittee or Sub-Committee reconunendation may, at the request of the Chairman, be forwarded to State Health or other appropriate authorities providing permission is obtained from both the Chairman of Council and the Chairman of the relevant Advisory Conunittee of Council.
22568/66-1
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APPENDIX XX CONSTITUTION AND TERMS OF REFERENCE OF COMMITTEES MEDICAL RESEARCH ADVISORY COMMITTEE
Constitution (i) The Committee should consist of not less than six and not more than ten members appointed by the Council. (ii) The Chairman, Deputy Chairman and at least three other members of the Committee should be selected from members of the Council. (iii) The Chairman of the Medical Research Advisory Committee should remain a member of the Council for the full term of his appointment as Chairman of the Committee. (iv) The functions and membership of the Committee should be formally reviewed every three years, but members of the Council appointed as members of the Committee, other than the Chairman, should only retain membership of the Committee so long as they remain members of the Council. (v) Meetings of the Committee should normally be held twice a year in May and October. The May meetings should closely precede meetings of the Council. (vi) In all other respects the normal arrangements for Committees of the Council should apply to the Medical Research Advisory Committee. Terms of Reference (i) To advise Council on all matters connected with the application of the Medical Research Endowment Fund for the purposes of the Medical Research Endowment Act of 1937, and to make recommendations to the Council in May each year in the form of budget proposals for the distribution of grants the following year between the various disciplines of medical and dental research. (ii) To receive and consider all applications for National Health and Medical Research Council research grants, scholarships and fellowships, except 'Public Health Travelling Fellowships', to authorise grants, scholarships and fellowships in accordance with delegated authority, and where no delegation of authority is made to make recommendations in respect of grants, scholarships and fellowships to Council. (iii) To investigate, keep under review and report to Council upon medical research in Australia as a whole, to estimate its trends and developments and direct support where it is specially needed.
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MEDICINE ADVISORY COMMITTEE
Constitution The membership of the Committee is as follows: (i) The representative on Council of the Australasian Medical Association; (ii) The representative on Council of the Royal Australasian College of Surgeons; (iii) The representative on Council of the Royal Australasian College of Physicians; (iv) The representative on Council of the Australian Council of the Royal College of Obstetricians and Gynaecologists; (v) The representative on Council of the Australian College of General Practitioners; (vi) The representative on Council of the College of Pathologists of Australia; (vii) The representative on Council of the College of Radiologists of Australasia; (viii) The representative on Council of the Australian Paediatric Association; (ix) The representative on Council of the Australian Dental Association; (x) The prominent laywoman member of the Council, providing she is a qualified nurse; (xi) The representative on Council of the Commonwealth Serum Laboratories Commission; and (xii) The Chief Director (Medical Services), Commonwealth Repatriation Department. Terms of Reference (i) To inquire into and advise the Council on matters relating to medical and dental care. (ii) To inquire into and advise the Council upon the merits of reputed cures or methods of treatment which are from time to time brought forward for recognition. (iii) To receive, consider and transmit to Council the reports of the following Committees(a) Antibiotics (Reference) Committee (b) Child Health (Standing) Committee (e) Maternal Health (Standing) Committee (d) Nursing (Reference) Committee (e) Nutrition (Reference) Committee (f) Radio Isotopes (Standing) Committee and o.ther comm~ttees that Council may direct to report through the Medicine Advisory Committee (IV) To receive, conSider and report to Council upon the recommendations of all the other Committees of Council insofar as they affect medical and dental care.
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PUBLIC HEALTH ADVISORY COMMITTEE Constitution The membership of the Committee is as follows: (i) The Director, School of Public Health and Tropical Medicine, Sydney; (ii) The Director-General of Public Health, New South Wales; (iii) The Director-General of Health and Medical Services, Queensland; (iv) The Director-General of Public Health, South Australia; (v) The Director of Public Health, Tasmania; (vi) The Chief Health Officer, Victoria; (vii) The Commissioner of Public Health, Western Australia; (viii) The Director of Public Health for the Territory of Papua and New Guinea; (ix) The First Assistant Director-General, National Health Division, Commonwealth Department of Health, Canberra; (x) The Commonwealth Director of Health, Northern Territory. Terms of Reference (i) To inquire into and advise the Council on all matters of public health and preventive medicine, and matters involving health legislation and administration by the Commonwealth and State Governments. (ii) To receive, consider and transmit to Council its recommendations on the reports of the following committeesDental Health Committee (g) Occupational Health Committee Epidemiology Committee (h) Radiation Health Committee (i) Traffic Injury Committee Food Additives Committee (j) Tropical Medicine and Health Committee Food Standards Committee (k) Veterinary Public Health Committee, Medical Statistics Committee (I) Mental Health Committee and other Committees that Council may direct to report through the Public Health Advisory Committee. (iii) To receive, consider and report to Council upon the recommendations of all the other committees of Council, insofar as they involve legislation or administration by the Commonwealth and/or State Governments. (iv) To receive and consider all applications for 'Public Health Travelling Fellowships' and make recommendations in respect thereof to Council. (a) (b) (c) (d) (e)
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ANTIBIOTICS (REFERENCE) COMMITTEE Terms of Reference To inquire into and advise Council through the Medicine Advisory Committee on all matters concerning antibiotics referred to it by Council and/or by the Chairman of Council. CHILD HEALTH (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Medicine Advisory Committee on the causation and prevention of infant and child ill health and mortality. DENTAL HEALTH (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on all matters relating to the prevention, control and treatment of dental diseases and abnormalities. EPIDEMIOLOGY (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on human epidemiology and the control of epidemic diseases. FOOD ADDITIVES (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on additives, chemical contaminants and dye stuffs in food for human consumption. FOOD STANDARDS (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on all aspects of food legislation, inctuding the standards necessary for the safe manufacture, labelling, packaging, storage, advertising and sale of food for human consumption.
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MATERNAL HEALTH (STANDING) COMMITI'EE TenDS of Reference To inquire into and advise Council through the Medicine Advisory COmmittee on the causation and prevention of maternal ill health and mortality. MEDICAL STATISTICS (STANDING) COMMITI'EE Terms of Reference To inquire into and advise the Council through the Public Health Advisory Committee on matters relating to the collection and interpretation of human vital health and medical statistics. MENTAL HEALTH (STANDING) COMMITTEE TenDS of Reference To inquire into and advise Council through the Public Health Advisory Committee on medical matters relating to the prevention and control of mental illness and to the care and rehabilitation of patients with mental illness. NURSING (REFERENCE) COMMITTEE TenDS of Reference To investigate and consider any matters referred to the Committee by the Council concerning the training and functions of nurses, and to report to Council through the Medicine Advisory Committee. NUTRITION (REFERENCE) COMMITTEE Terms of Reference To inquire into and consider any matters concerning nutrition referred to the Committee by the Council and to report to Council through the Medicine Advisory Committee. :;
OCCUPATIONAL HEALTH (STANDING) COMMITTEE
TenDS of Reference To inquire into and advise Council through the Public Health Advisory Committee on all matters relating to industrial hygiene and occupational health. RADIATION HEALTH (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on all matters relating to (a) the effects in man of naturally occurring ionising radiation and of artificial ionising radiations used in industry, commerce, scientific research and medical investigation, treatment and research; (b) the levels of, and the measures necessary to minimise the radiation exposure of individuals and the Australian population from, such radiations; and (c) procedures and practices which would assist the Commonwealth and States in the implementation of their public health legislation relating to radioactive substances and irradiating apparatus. RADIO ISOTOPES (STANDING) COMMITTEE Terms of Reference (i) To inquire into and advise Council through the Medicine Advisory Committee on the utilisation and control of radio isotopes in medical research, clinical investigation and therapy. (ii) To provide advice to the Director, Commonwealth X-ray and Radium Laboratory, in connection with requests for the use of radio isotopes on the safety for persons being investigated or treated and the usefulness of the methods. RESEARCH GRANTS CO-ORDINATION (STANDING) COMMITTEE Terms of Reference To consider grant applications which do not fall easily into one or other of the Australian Research Grants Committees or National Health and Medical Research Council groups and to channel these applications to the most appropriate organisation or both. STANDING GRANTS COMMITTEES Constitution (i) The three Standing Grants Committees should be as follows: A. Anatomy, Pathology and Microbiology. B. Biochemistry, Physiology and Pharmacology. C. Clinical Sciences, Dentistry and Public Health. (ii) Each Committee should consist of five to eight members, including the Chairman or Deputy Chairman of the Medical Research Advisory Committee, and at least one other member of the Medical Research Advisory Committee. (iii) The normal term of membership for the Standing Grants Committees should be seven years and members would then be ineligible for reappointment for one year. '
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Terms of Reference
(i) To receive and consider all applications for National Health and Medical Research Council research grants, scholarships and fellowships referred by the Medical Research Advisory Committee and/or the Secretary of Council and to make recommendations in respect thereof to the Medical Research Advisory Committee. (ii) To investigate, keep under review and make recommendations to the Medical Research Advisory Committee upon the national needs for research and research support in the fields of medical knowledge covered by the individual Committees. TRAFFIC INJURY (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on the factors of medical significance in the causation, prevention and treatment of injuries in traffic accidents. TROPICAL MEDICINE AND HEALm (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on all matters relating to the aetiology, treatment, control and prevention of essentially tropical ill health and disease. VETERINARY PUBLIC HEALm (STANDING) COMMITTEE Terms of Reference To inquire into and advise Council through the Public Health Advisory Committee on matters relating to the infection, use, husbandry and control of animals and animal products, which may directly or indirectly affect human health. ad hoc DIABETES SURVEY SUB-COMMITTEE Terms of Reference To consider, arrange and report to the Public Health Advisory Committee upon the organisation and results of diabetes surveys in Goulburn, New South Wales and Toowoomba, Queensland.
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EXPERIMENTS IN ANIMALS (REFERENCE) SUB-COMMITTEE Terms of Reference To study and report to the Medical Research Advisory Committee upon matters relating to experiments in animals referred to the Sub-Committee by the Medical Research Advisory Committee or Chairman of Council. FOOD ANALYSTS (REFERENCE) SUB-COMMITTEE Terms of Reference To consider matters concerning methods of analysis of foods and food additives referred to the Sub-Committee by the Public Health Advisory Committee and to make recommendations to the Public Health Advisory Committee. FOOD AND COSMETIC COLOURS (STANDING) SUB-COMMITTEE Terms of Reference To inquire into and advise the Food Additives Committee on the colouring matter and dye stuffs in food for human consumption and cosmetics. FOOD IRRADIATION (STANDING) SUB-COMMITTEE Terms of Reference To inquire into and advise the Food Additives Committee on the nutritive value, safety and possible alterations in the constituents of food treated by ionising radiation.
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FOOD MICROBIOLOGY (REFERENCE) SUB-COMMITTEE Terms of Reference To consider and make recommendations to the Food Standards Committee on matters referred to the SubCommittee by the Food Standards Committee concerning microbiological standards for foods.
HOSPITAL MORBIDITY STATISTICS (STANDING) SUB-COMMITTEE Terms of Reference To inquire into and advise the Medical Statistics Committee on the hospital morbi~ty. statistics available in Australia and the possibilities and priorities for further development and use of these statistics.
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MEDICAL RESEARCH IN ABORIGINES (REFERENCE) SUB-COMMITTEE Terms of Reference To consider proposals for medical research projects involving Aborigines referred to the Sub-Committee by the Chairman of Council or Medical Research Advisory Committee, and to make recommendations to the Medical Research Advisory Committee on the research value and medical ethics of the projects and their effect on the people being studied. ad hoc NATIONAL MORBIDITY SURVEY SUB-COMMITTEE Terms of Reference To prepare for publication an interpretative commentary on the results of the National Morbidity Survey, as published in Part I of the report of the Survey, and to submit the manuscript through the Medical Statistics Committee. PESTICIDES AND AGRICULTURAL CHEMICALS (STANDING) SUB-COMMITTEE Terms of Reference To inquire into and make recommendations to the Public Health Advisory Committee upon(i) the hazards to health associated with the manufacture, distribution and use of pesticides and agricultural chemicals; and (ii) the problems associated with and safe tolerances for pesticide and incidental agricultural chemical residues in food for human consumption. POISONS SCHEDULE (STANDING) SUB-COMMITTEE Terms of Reference To inquire into the scheduling and labelling of drugs, poisons and other substances hazardous to human health in the States and Territories and to make recommendations to the Public Health Advisory Committee. POLIOMYELITIS (STANDING) SUB-COMMITTEE Terms of Reference (i) To assess the clinical and pathological records of all cases of poliomyelitis and of cases of suspected poliomyelitis. (ii) When requested by the Chairman to receive and adjudicate upon reports of untoward reactions or illnesses which might be associated with polio immunisation. (iii) To continue evaluation of the efficacy of poliomyelitis vaccines. (iv) To submit reports periodically on the incidence of pOliomyelitis in Australia. (v) To report all findings and recommendations to the Public Health Advisory Committee. PREVENTIVE MEDICINE IN GENERAL PRACTICE (STANDING) SUB-COMMITTEE Terms of Reference To inquire into and advise the Medicine Advisory Committee on problems of preventive medicine in general practice, and to assist in the application of preventive medicine programmes approved by Council. ad hoc REGIONAL GRANTS SUB-COMMITTEES Constitution (i) Five ad hoc Regional Grants Sub-Committees should be appointed each year by the Chairman of Council acting upon the advice of the Medical Research Advisory Committee. (ii) Each Regional Grants Sub-Committee should be composed of three or four members, including at least one member from each of the three Standing Grants Committees. Terms of Reference To visit persons and institutions applying for National Health and Medical Research Council grants for medical research and interview persons working with the support of and/or applying for these grants, and to report to the Standing Grants Committees and Medical Research Advisory Committee. (The Sub-Committees' investigations will be concerned, with the facilities available to applicants, the ability and experience of the applicants and the responsibilities of the applicants apart from their research). ad hoc SMOKING SURVEY SUB-COMMITTEE Terms of Reference To consider and submit detailed proposals to the Medical Statistics Committee for a survey of smoking habits and attitudes in Australia. Terms of Reference THERAPEUTIC METHODS (REFERENCE) SUB-COMMITTEE
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To consider reputed cures or methods of treatment referred to the Sub-Committee by the Chairman or Adv!sory Committ~s of Council.and to make recommednations to the Medicine Advisory Committee and to the Chlllrman of Councd on the meflts of these therapeutic methods.
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APPENDIX XXI INTER-RELATIONSHIP OF COUNCIL AND COMMITTEES Advisory Committees Committees Sub-Committees
Research Grants Co-ordination Adelaide Regional Grants Brisbane Regional Grants - - - Melbourne Regional Grants Perth Regional Grants Sydney Regional Grants
Medical Research
Standing Grants A Standing Grants B Standing Grants C
Experiments in Animals Medical Research in Aborigines -1-
.------------1 Antibiotics Child Health Medicinle-e---I Maternal Health Nursing Nutrition Radio Isotopes
Preventive Medicine in General Practice Lerapeutic Methods
CouncilDental Health Epidemiology
Diabetes Surveys Food Analysts Pesticides and Agricultural Chemicals Poisons Schedule Poliomeylitis
Food Additives - - - - - - 1 Food Irradiation Food and Cosmetic Colours
Food Standards.-----I Food Microbiology Public Health-Medical Statistics - - - Mental Health Occupational Health Radiation Health Traffic Injury Tropical Medicine and Health Veterinary Public Health Hospital Morbidity Statistics National Morbidity Survey Smoking Survey
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APPENDIX XXII NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL MEMBERS FOR 1967 Major-General Sir William Refshauge, the Director-General of Health, Commonwealth (Chairman). Professor Sir E~ward Ford } representing the Department of Health of the Commonwealth. Dr. J. B. MathIeson Dr W. R. Lane, representing the Commonwealth Serum Laboratories Commission. Dr C. J. Cummins, the Director-General of Public Health, New South Wales. Dr R. J. Farnbach, the Chief Health Officer, Victoria. Dr A. Fryberg, the Director-General of Health and Medical Services, Queensland. Dr P. S. Woodruff, the Director-General of Public Health, South Australia. Dr W. S. Davidson, the Commissioner of Public Health, Western Australia. Dr J. Edis, the Director-General of Health Services, Tasmania. Dr R. F. R. Scragg, the Director of Public Health of the Territory of Papua and New Guinea. Dr T. G. Swinburne, representing the Federal Council of the Australian Medical Association. Mr K. W. Starr, representing the Royal Australasian College of Surgeons. Dr J. J. Billings, representing the Royal Australasian College of Physicians. Professor J. Loewenthal, representing the Australian Universities having Medical Schools. Professor G. King, representing the Australian Council of the Royal College of Obstetricians and Gynaecologists. Dr J. G. Radford, representing the Australian College of General Practitioners. Dr A. V. Jackson, representing the College of Pathologists of Australia. Dr J. M. Wark, representing the Australian Dental Association. Dr D. G. Hamilton, representing the Australian Paediatric Association. Dr C. K. Hambly, representing the College of Radiologists of Australasia. Sir Norman Nock, an eminent layman appointed by the Commonwealth Government. Miss M. C. Nelson, an eminent laywoman appointed by the Commonwealth Government. Professor S. Sunderland, the Chairman of the Medical Research Advisory Committee, co-opted member. Dr R. H. C. Wells (Secretary of the Council).
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MEMBERSHIP OF COMMITTEES OF THE COUNCIL (UNTIL 31 DECEMBER 1969 UNLESS OTHERWISE STATED) MEDICAL RESEARCH ADVISORY COMMITTEE Professor S. Sunderland, Dean of the Faculty of Medicine, University of Melbourne, (Chairman). Dr J. J. Billings, 55 Collins Street, Melbourne, (Deputy Chairman). Dr C. J. Cummins, Director-General of Public Health, N.S.W. Sir Norman Nock, 1 Lindsay Avenue, Darling Point, N.S.W. Dr R. Reader, Medical Director, National Heart Foundation. Professor N. F. Stanley, Department of Microbiology, University of Western Australia. Mr K. W. Starr, 149 Macquarie Street, Sydney. Professor E. C. Webb, Department of Biochemistry, University of Queensland. Professor R. F. Whelan, Department of Human Physiology and Pharmacology, University of Adelaide. Dr P. S. Woodruff, Director-General of Public Health, South Australia. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. (Professor J. Loewenthal, Department of Surgery, University, Co-opted member). MEDICINE ADVISORY COMMITTEE Dr J. G. Radford, the representative on Council of the Australian College of General Practitioners (Chairman). Dr T. G. Swinburne, the representative on Council of the Australian Medical Association. Mr K. W. Starr, the representative on Council of the Royal Australasian College of Surgeons. Dr J. J. Billings, the representative on Council of the Royal Australasian College of Physicians. Professor G. King, the representative on Council of the Australian Council of the Royal College of Obstetricians and Gynaecologists. Dr A. V. Jackson, the representative on Council of the College of Pathologists of Australia. Dr C. K. Hambly, the representative on Council of the College of Radiologists of Australasia. Dr D. G. Hamilton, the representative on Council of the Australian Paediatric Association. Dr J. M. Wark, the representative on Council of the Australian Dental Association. Miss M. Nelson, the prominent laywoman member of the Council, being a qualified nurse. Dr W. R. Lane, the representative on Council of the Commonwealth Serum Laboratories Commission. Dr W. E. E. Langford, the Chief Director (Medical Services), Commonwealth Repatriation Department. Dr R. H. C. Wells (Convener).
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PUBUC HEALTH ADVISORY COMMITI'EE Professor Sir Edward Ford, the Director, School of Public Health and Tropical Medicine, Sydney (Chairman). Dr C. J. Cummins, the Director-General of Public Health, New South Wales. Dr A. Fryberg, the Director-General of Health and Medical Services, Queensland. Dr P. S. Woodruff, the Director-General of Public Health, South Australia. Dr A. D. Ross, the Director of Public Health, Tasmania. Dr R. J. Farnbach, the Chief Health Officer, Victoria. Dr W. S. Davidson, the Commissioner of Public Health, Western Australia. Dr R. F. R. Scragg, the Director of Public Health for the Territory of Papua and New Guinea. Dr J. B. Mathieson, the First Assistant Director-General, National Health Division, Commonwealth Department of Health, Canberra (Deputy Chairman and Convener). Dr W. A. Langsford, the Commonwealth Director of Health, Northern Territory. Dr R. H. C. Wells (Convener). ANTIBIOTICS (REFERENCE) COMMfITEE Dr K. W. Edmondson, Department of Health, Canberra, (Chairman, Convener and Secretary). Dr K. F. Anderson, Institute of Medical and Veterinary Science, Adelaide. Sir William Morrow, 185 Macquarie Street, Sydney. Mr B. K. Rank, 29 Royal Parade, Parkville, N.2. Victoria. Dr Phyllis Rountree, Fairfax Institute, Royal Prince Alfred Hospital, Sydney. Dr S. W. Williams, Royal Children's Hospital, Parkville N. 2. Victoria. CHILD HEALTH (STANDING) COMMITTEE Professor V. L. Collins, Department of Child Health, University of Melbourne, (Chairman). Dr A. C. Green, Commonwealth Department of Health, Canberra (Convener and Secretary). Dr D. G. Hamilton, 135 Macquarie Street, Sydney. Professor W. B. Macdonald, Department of Child Health, University of Western Australia. Dr C. H. Mair, Medical Officer for Child Health, Tasmania. Professor G. M. Maxwell, Department of Child Health, University of Adelaide. Dr D. P. McCloskey, Assistant Chief Health Officer (Child Health), Victoria. Professor T. J. Rendle-Short, Department of Child Health, University of Queensland. Professor T. Stapleton, Director, Institute of Child Health, Royal Alexandra Hospital for Children, Camperdown, N.S.W. Dr J. Storey, 534 Forest Road, Penshurst, N.S.W. DENTAL HEALTH (STANDING) COMMITI'EE Dr J. M. Wark, 147 Collins Street, Melbourne C.l. Victoria, (Chairman) Professor Sir Arthur Amies, Department of Dental Medicine and Surgery, University of Melbourne. Professor H. F. Atkinson, Department of Dental Prosthetics, University of Melbourne. Dr D. E. Barrnes, Chief Dental Officer, Department of Public Health, Territory of Papua and New Guinea. Mr L. M. carr, Chief Dental Officer, Australian capital Territory, (Convener and Secretary). Professor G. N. Davies, Faculty of Dentistry, University of Queensland. Mr A. R. Docking, Director, Bureau of Dental Standards, Melbourne. Mr W. A. Grainger, T. & G. Building, 49 Park Street, Sydney. Mr R. Harris, Director, Institute of Dental Research, Sydney. Professor A. M. Horsnell, Department of Dental Science, University of Adelaide. Professor N. D. Martin, Department of Preventive Dentistry, University of Sydney. Professor E. Storey, Department of Conservative Dentistry, University of Melbourne. Professor K. J. Sutherland, Faculty of Dental Science, University of Western Australia. EPIDEMIOLOGY (STANDING) COMMITTEE Professor Sir Edward Ford, Director, School of Public Health and Tropical Medicine, Sydney, (Chairman). Dr J. B. Mathieson, Department of Health, Canberra, (Convener and Secretary). Dr C. E. A. Cook, 23 Killarney Street, Mosman, N.S.W. Professor F. Fenner, Department of Microbiology, Australian National University. Dr A. A. Ferris, Director, Epidemiological Research Unit, Fairfield Hospital, Victoria. Dr E. L. French, Senior Principal Research Officer, Animal Health Research Laboratory, Melbourne. Dr R. W. Greville, Department of Health, Canberra. Dr W. R. Lane, Director, Commonwealth Serum Laboratories, Melbourne. Dr W. Stevenson, Public Health Department, Victoria. FOOD ADDITIVIES (STANDING) COMMITTEE Dr D. B. Travers, Department of Health, Canberra, (Chairman and Convener). Dr R. A. Bottomley, Vice-President of Research, Mauri Bros. & Thompson Ltd. Dr K. T. H. Farrer, Kraft Foods Ltd, Melbourne. Dr P. E. Hughes, Department of Pathology, University of Melbourne.
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Dr R. C. Hutchinson, Director, Defence Food Science Laboratory, Scottsdale, Tasmania. Mr W. R. Jewell, Flat I, 1483 High Street, Glen Iris, Victoria. Mr E. S. Ogg, Government Analyst, Department of Public Health, Sydney. Professor M. J. Rand, Department of Pharmacology, University of Melbourne. Professor F. H. Reuter, Department of Food Technology, University of N.S.W. Dr A. J.Ryan, Department of Pharmacy, University of Sydney. Mr J. P. Warry, Chemist, Department of Health, Canberra, (Secretary).
FOOD STANDARDS (STANDING) COMMITTEE Professor F. H. Reuter, Department of Food Technology, University of New South Wales (Chairman). Dr D. B. Travers, Department of Health, Canberra, (Deputy Chairman and Convener.) Mr W. R. Jewell, Flat 1, 1483 High Street, Glen Iris, Victoria. Mr K. F. Kelford, Division of Food Preservation, C.S.I.R.O., New South Wales. Mr C. Murray, Chief Food Inspector, Department of Health, Queensland. Mr J. G. Krigsman, Albright and Wilson Pty Ltd. Mr D. Kruger, Department of Health, Canberra. Dr V. M. Lewis, Director, Henry Lewis and Sons Pty Ltd. Mr R. C. McCarthy, Secretary, Food and Drug Advisory Committee, South Australia. Mr W. Madgwick, Chief Food Inspector, Department of Public Health, New South Wales. Mr L. E. Nichols, Commonwealth Dairy Expert Department of Primary Industry, Canberra. Mr E. S. Ogg, Government Analyst, Department of Public Health, New South Wales. Mr I. H. Smith, Assistant Secretary, Department of Primary Industry, Canberra. Mr J. P. Warry, Chemist, Department of Health, Canberra, (Secretary). MATERNAL HEALTH (STANDING) COMMITTEE Professor S. L. Townsend, Department of Obstetrics and Gynaecology, University of Melburne, (Chairman). Professor L. W. Cox, Department of Obstetrics and Gynaecology, University of Adelaide. Dr R. C. Gill, 235 Macquarie Street, Sydney. Dr A. C. Green, Commonwealth Department of Health, Canberra (Convener and Secretary). Dr D. -F. Lawson, 12 Collins Street, Melbourne, c.l. Victoria. Professor E. V. Mackay, Department of Obstetrics and Gynaecology, University of Queensland. Dr S. Devenish Mears, 149 Macquarie Street, Sydney. MEDICAL STATISTICS (STANDING) COMMITTEE Dr R. H. C. Wells, Commonwealth Department of Health, Canberra (Chairman and Convener). Mr L. G. Hopkins, Assistant Statistician, Commonwealth Bureau of Census and Statistics, Canberra Dr D. L. Jones, Department of Public Health, New South Wales, (until 31 December 1967). Dr Norma McArthur, Professional Fellow in Demography, Australian National University A.C.T. Professor P. Moran, Department of Mathematical Statistics, Australian National University, A.C.T. Mr V. E. Pickering, Bureau of Census and Statistics, Canberra, (Secretary). Dr G. C. Scott, School of Public Health and Tropical Medicine, Sydney. MENTAL HEALTH (STANDING) COMMITTEE Dr R. H. C. Wells, Commonwealth Department of Health, Canberra (Chairman and Convener). Dr W. Barclay, Director of Psychiatric Services, New South Wales. Dr J. J. Billings, 55 Collins Street, Melbourne, Professor W. A. Cramond, Department of Psychiatry, University of Adelaide. Dr E. Cunningham Dax, Chairman, Victorian Mental Health Authority. Dr A. S. Ellis, Director of Mental Health Services, Western Australia. Dr T. G. H. Dick, Acting Director of Psychiatric Services, Tasmania. Dr W. S. Davidson, Commissioner of Public Health, Western Australia. Dr B. J. Shea, Director of Psychiatric Services, South Australia. Dr J. H. Hurt, Assistant Chief Director (psychiatric Services), Repatriation Commission. Dr A. J. M. Sinclair, Epworth Hospital, Richmond, Victoria. Dr I. G. Simpson, Royal Prince Alfred Hospital Medical Centre, Sydney. Dr G. Urquhart, Director of State Psychiatric Services, Queensland. NURSING (REFERENCE) COMMITTEE Miss M. Nelson, Matron, Royal Prince Alfred Hospital, Sydney (Chairman). Miss I. M. Copley, Department of Health, Canberra (Convener and Secretary). Dr K. W. Edmondson, Commonwealth Department of Health, Canberra. Miss V. Holland, Registrar, Nurses' Registration Board, Department of Health, Tasmania. Miss P. F. Lee, Principal Matron, Department of Health, Western Australia. Miss B. Lyons, Adviser in Nursing, Department of Public Health, New South Wales. Miss C. A. E. Michehnore, Deputy Matron, Children's Hospital, Adelaide. Miss J. E. Muntz, Nurse Adviser, Department of Health, Victoria. Mrs E. W. Sullivan, Adviser in Nursing, Department of Health and Home Affairs, Queensland. -t
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NUTRITION (REFERENCE) COMMITTEE Dr F. W. Clements, Senior Lecturer, Institute of Child Health, Sydney (Chairman). Professor V. L. Collins, Department of Child Health University of Melbourne. Dr E. Hipsley, Director, Australian Institute of Anatomy, Canberra (Convener and Secretary). Professor E. J. Underwood, Director, Institute of Agricultural Research, University of Western Australia. Dr D. M. Walker, Reader in Animal Husbandry, University of Sydney. Dr J. Woodhill, Nutritionist, Prince Henry Hospital, Sydney. OCCUPATIONAL HEALTH (STANDING) COMMITTEE Dr H. E. Downes, Deputy Commonwealth Director-General of Health (Chairman). Dr A. J. Christophers, Chief Industrial Hygiene Officer, Victoria. Mr A. W. Findlay, Senior Chemist, Occupational Health Division, School of Public Health and Tropical Medicine, Sydney. Professor D. Gordon, Department of Social and Preventive Medicine, University of Queensland. Dr D. D. Letham, Industrial Medical Officer, Public Health Department, Western Australia. Dr E. O. Longley, Department of Public Health, New South Wales. Dr G. H. McQueen, Principal Medical Officer (Public Health), Department of Public Health, South Australia. Dr E. M. Rathus, Director of Industrial Medicine, Department of Health, Queensland. Dr G. C. Smith, Director ofIndustrial Hygiene, School of Public Health and Tropical Medicine, Sydney (Convener and Secretary). Dr K. M. Williams, Department of Public Health, Tasmania. RADIATION HEALTH (STANDING) COMMITTEE Mr D. J. Stevens, Director, Commonwealth X-ray and Radium Laboratory, Melbourne (Chairman and Convener). Dr A. J. Christophers, Chief Industrial Hygiene Officer, Victoria. Mr M. G. S. Donnan, Consultant Radiologist to Army and Honorary Diagnostic Radiologist, St. Vincent's Hospital, III Collins Street, Melbourne. Dr C. K. Hambly, Director, Institute of Radiotherapy, Sydney Hospital, Sydney. Dr P. L. T. Ilbery, Radiation Biologist, School of Public Health and Tropical Medicine, Sydney. Dr G. R. Kurrle, Director, McCallum Institute, Melbourne. Professor J. McRae, Department of Medicine, University of Sydney. Dr R. Motteram, Pathologist, Cancer Institute Board of Victoria. Dr K. S. Mowatt, Director, Queensland Radium Institute, Queensland. Mr J. F. Richardson, Assistant Director, Commonwealth X-ray and Radium Laboratory, Melbourne. Dr A. D. Ross, Director of Public Health, Tasmania. Dr G. C. Smith, Director of Industrial Hygiene, School of Public Health and Tropical Medicine, Sydney. Mr R. W. Stanford, Department of Medical Physics, Royal Perth Hospital. Mr K. A. Stevens, Radiation Health Physicist, Department of Health, Queensland. Dr G. M. Watson, Australian Atomic Energy Commission. Mr J. M. Whaite, Occupational Health Division, Department of Public Health, New South Wales. Dr K. Wilson, Department of Public Health, South Australia. RADIO ISOTOPES (STANDING) COMMITTEE Mr D. J. Stevens, Director, Commonwealth X-ray and Radium Laboratory, Melbourne (Chairman and Convener). Dr J. T. Andrews, Medical Officer-in-Charge, Radio Isotopes Section, Royal Melbourne Hospital. Dr A. G. Baikie, Department of Medicine, St. Vincent's Hospital, Melbourne. Professor A. L. Clarke, Department of Paediatrics, Monash University, Victoria. Mr D. W. Kearn, Physicist, Commonwealth X-ray and Radium Laboratory, Melbourne. Professor J. McRae, Department of Medicine, University of Sydney. Professor R. Nairn, Department of Pathology, University of Monash. Dr D. P. Pearce, Epworth Hospital, Erin Street, Richmond, Victoria. RESEARCH GRANTS CO-ORDINATION (STANDING) COMMITTEE Chairman or Acting Chairman, Australian Research Grants Committee (Professor R. N. Robertson). Chairman or Acting Chairman, Medical Research Advisory Committee (Professor S. Sunderland). Secretary, National Health and Medical Research Council (Dr R. H. C. Wells). Secretary, Australian Research Grants Committee (Mr T. J. Carmody) .
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STANDING GRANTS COMMITTEE A. (ANATOMY, PATHOLOGY AND MICROBIOLOGY) Professor S. Sunderland, Dean of Faculty of Medicine, University of Melbourne (Chairman). Until 31 December 1969. Professor G. S. Christie, Department of Pathology, University of Melbourne. Until 31 December 1973. Dr A. A. Ferris, Fairfield Infectious Diseases Hospital, Fairfield. Until 31 December 1972. Professor F. E. Magarey, Department of Pathology, University of Sydney. Until 31 December 1972. STANDING GRANTS COMMITTEE
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Professor J. S. Robertson, Department of Pathology, University of Adelaide. Until 31 December 1971. Professor N. F. Stanley, Department of Microbiology, University of Western Australia. Until 31 December 1972. Dr P. S. Woodruff, Director-General of Public Health, South Australia. Until 31 December 1969. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. STANDING GRANTS CoMMITTEE
B.
(BIOCHEMISTRY, PHYSIOLOGY AND PHARMACOLOGY)
Professor E. C. Webb, Department of Biochemistry, University of Queensland (Chairman). Until 31 December 1970. Professor A. K. McIntyre, Department of Physiology, Monash University. Until 31 December 1973. Professor A. G. Ogston, Department of Physical Biochemistry, Australian National University. Until 31 December 1972. Professor W. J. Simmonds, Department of Physiology, University of Western Australia. Until 31 December 1967. Professor S. Sunderland, Dean of Faculty of Medicine, University of Melbourne, until 31 December 1969, or Dr J. J. Billings, 55 Collins Street, Melbourne, until 31 December 1972. Professor R. F. Whelan, Department of Human Physiology and Pharmacology, University of Adelaide. Until 31 December 1971. The Secretary of the Council (Dr R. H. C. Wells), Convener and Secretary. STANDING GRANTS CoMMITTEE C. (CLINICAL SCIENCES, DENTISTRY AND PuBLIC REALm) Dr J. J. Billings, 55 Collins Street, Melbourne (Chairman). Until 31 December 1972. Professor H. F. Atkinson, Department of Dental Prosthetics, University of Melbourne. Until 31 December 1969. Dr Cummins, Director-General of Public Health, New South Wales. Until 31 December 1969. Dr T. H. Hurley, Honorary Physician, Royal Melbourne Hospital. Until 31 December 1973. Professor J. Loewenthal, Department of Surgery, University of Sydney. Until 31 December 1969. Professor E. V. Mackay, Department of Obstetrics and Gynaecology, University of Queensland. Until 31 December 1972. Mr K. W. Starr, 149 Macquarie Street, Sydney. Until 31 December 1969. Professor H. M. Whyte, Department of Clinical Science, John Curtin School of Medical Research. Until 31 December 1967. The Secretary of the Council (Dr R. H. C. Wells), Convenor and Secretary.
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TRAFFIC INJURY (STANDING) COMMITTEE Professor J. S. Robertson, Department of Pathology, University of Adelaide (Chairman). Dr J. H. W. Birrell, Police Surgeon, Melbourne. Dr A. C. Green, Department of Health, Canberra (Convener and Secretary). Dr K. G. Jamieson, Neurosurgeon, Brisbane General Hospital. Dr J. C. Lane, Director of Aviation Medicine, Department of Civil Aviation. Mr R. A. Money, Neurosurgeon, Sydney, Royal Prince Alfred Hospital, Sydney. Dr I. I. Tonge, Director, Laboratory of Microbiology and Pathology, Brisbane. TROPICAL MEDIONE AND HEALTH (STANDING) COMMITTEE Professor R. H. Black, School of Public Health and Tropical Medicine, Sydney (Chairman). Professor C. H. Campbell, School of Public Health and Tropical Medicine, Sydney. Dr C. E. A. Cook, 23 Killarney Street, Mosman, New South Wales. Dr R. L. Doherty, Deputy Director, Queensland Institute of Medical Research. Professor Sir Edward Ford, Director, School of Public Health and Tropical Medicine, Sydney. Dr A. C. Green, Commonwealth Department of Health, Canberra (Convener and Secretary). Dr W. A. Langsford, Commonwealth Director of Health, Northern Territory. Professor W. V. Macfarlane, Waite Institure, Glen Osmond, South Australia. Professor R. K. Macpherson, Chief of the Environmental Health Section, School of Public Health and Tropical Medicine, Sydney. VETERINARY PUBLIC HEALTH (STANDING) COMMITTEE Dr R. W. Greville, Commonwealth Department of Health, Canberra (Chairman). Mr J. L. Anderson, Chief, Division of Animal Industry, Department of Agriculture Stock and Fisheries, Port Moresby, New Guinea. Mr A. L. Qay, Director of Animal Industry, Queensland. Mr J. C. Keast, Director of Veterinary Research, Veterinary Research Station, Glenfield, New South Wales. Mr K. S. McIntosh, Director of Veterinary Hygiene, Commonwealth Department of Health, Canberra. Mr H. R. Peisley, Commonwealth Department of Health, Canberra, (Convener and Secretary). Mr W. S. Smith, Chief Inspector of Stock, Department of Agriculture, Adelaide. Mr D. F. Stewart, McMaster Laboratory, Division of Animal Health, e.S.I.R.O., P.O., Glebe, New South Wales. Dr W. I. Stevenson, Department of Public Health, Melbourne. Mr L. N. Thornton, Chief Veterinary Officer, Department of Primary Industry, Canberra.
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ad hoc DIABETES SURVEY SUB-COMMI'ITEE Dr. A. J. P. Proust, Commonwealth Department of Health, Canberra (Chairman and Convener). Dr P. J. D'Arbon, 79a Croydon Street, Lakemba, New South Wales. Dr H. S. Patterson, Corner East and South Streets, Ipswich, Queensland. Dr G. C. Scott, School of Public Health and Tropical Medicine, Sydney. Dr B. Smithurst, Senior Lecturer, Department of Social and Preventive Medicine, Medical School, University of Queensland, Brisbane.
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EXPERIMENTS IN ANIMALS (REFERENCE) SUB-COMMITrEE Professor A. K. McIntyre, Department of Physiology, Monash University, Victoria (Chairman). Professor D. Blood, Dean, Faculty of Veterinary Science, Melbourne University . Dr Margaret C. Holmes, Senior Research Officer and Assistant Manager, Walter and Eliza Hall Institute, Melbourne Mr P. F. Lewis, Chief of Veterinary Services, Commonwealth Serum Laboratries, Melbourne. Mr K. O'Brien, Commonwealth Department of Health, Canberra (Convener and Secretary). FOOD ANALYSTS (REFERENCE) SUB-COMMITTEE Dr D. B. Travers, Commonwealth Department of Health, Canberra (Chairman). Mr H. Dunstan, Chief Chemist, Department of Health, Queensland. Mr R. Hetherington, Deputy Government Analyst, South Australia. Mr N. Houghton, Government Chemical Laboratories, Perth, Western Australia. Mr E. S. Ogg, Government Analyst, Department of Health, New South Wales. Mr M. Shipp, Government Analyst, Government Analyst Laboratories, Hobart, Tasmania. Mr R. Stanhope, Chief Analyst, Department of Public Health, Victoria. Mr J. P. Warry, Chemist, Commonwealth Department of Health, Canberra (Convener and Secretary). FOOD AND COSMETICS (STANDING) SUB-COMMITTEE Dr D. B. Travers, Commonwealth Department of Health, Canberra (Chairman). Dr. R. A. Bottomley, Vice-President of Research Mauri Bros and Thompson Ltd. Mr E. S. Ogg, Government Analyst, Department of Public Health, New South Wales. Dr A. J. Ryan, Department of Pharmacy, University of Sydney. Mr J. P. Warry, Chemist, Commonwealth Department of Health, Canberra (Convener and Secretary). FOOD IRRADIATION (STANDING) SUB-COMMITTEE Mr D. J. Stevens, Director, Commonwealth X-ray and Radium Laboratory, Melbourne (Chairman and Convener}, Mrs Audrey Cahn, Department of Biochemistry, University of Melbourne. Mr K. W. Kearn, Commonwealth X-ray and Radium Laboratory, Melbourne (Secretary). Professor F. H. Reuter, Department of Food Technology, University of New South Wales. Dr W. Scott, Food Preservation Division, C.S.I.R.O., Ryde, New South Wales. Dr B. D. Travers, Commonwealth Department of Health, Canberra.
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FOOD MICROBIOLOGY (REFERENCE) SUB-COMMITTEE Dr D. B. Travers, Commonwealth Department of Health, Canberra (Chairman and Convener). Dr K. F. Anderson, Institute of Medical and Veterinary Science, South Australia. Dr G. Cooper, Department of Microbiology, University of Melbourne. Dr J. M. Crotty, Commonwealth Health Laboratory, Canberra, A.C.T. Miss M. Dick, Kraft Foods Ltd., Melbourne. Dr W. J. Scott, Division of Food Preservation, C.S.I.R.O., Ryde, New South Wales. HOSPITAL MORBIDITY STATISTICS (STANDING) SUB-COMMITTEE Professor H. A. F. Dudley, Department of Surgery, Monash University (Chairman). Dr D. S. Child, Assistant General Superintendent, Royal Prince Alfred Hopsitai, Sydney. Dr W. S. Davidson, Commissioner of Public Health, Perth. Dr G. Freed, Senior Medical Officer, Department of Repatriation, Melbourne. Professor J. Griffith, School of Hospital Administration, University of New South Wales. Professor B. S. Hetzel, University Department of Medicine, Queen Elizabeth Hospital, South Australia. Mr L. G. Hopkins, Assistant Statistician, Bureau of Census and Statistics, Canberra. Dr J. R. McIntyre, Chief Medical Officer, Department of Health Services, Tasmania. Mr V. E. Pickering, Bureau of Census and Statistics, Canberra (Secretary). Dr O. Powell, Medical Superintendent, Princess Alexandra Hospital, Queensland. Dr B. J. Shea, Director, of Psychiatric Services, South Australia. Dr D. M. Storey, Hospitals Commission, New South Wales. Mr P. B. Stringer, Repatriation Department, Melbourne. Dr R. H. C. Wells, Department of Health, Canberra (Convener).
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MEDICAL RESEARCH IN ABORIGINES (REFERENCE) SUB-COMMITTEE Dr R. H. C. Wells, Commonwealth Department of Health, Canberra (Chairman and Convener). Professor R. H. Black, School of Public Health and Tropical Medicine, Sydney. Dr C. J. Cummins, Director-General of Public Health, New South Wales. Dr W. S. Davidson, Commissioner of Public Health, Perth, Western Australia. Dr A. Fryberg, Director-General of Health and Medical Services, Queensland. Dr W. A. Langsford, Commonwealth Director of Health, Darwin. Dr P. S. Woodruff, Director-General of Public Health, South Australia. ad hoc NATIONAL MORBIDITY SURVEY SUB-COMMITTEE Dr J. G. Radford, Honorary Secretary, Australian College of General Practitioners (Chairman). Dr W. Breinl, Secretary, Australian College of General Practitioners Research Committee. Dr K. W. Edmondson, Commonwealth Department of Health, Canberra (Convener and Secretary). Mr V. E. Pickering, Commonwealth Bureau of Census and Statistics. Dr G. C. Scott, School of Public Health and Tropical Medicine, Sydney. PESTICIDES AND AGRICULTURAL CHEMICALS (STANDING) SUB-COMMITTEE Dr A. M. Walshe, Commonwealth Department of Health, Canberra (Chairman). Dr A. J. Christophers, Chief Industrial Hygiene Officer, Victoria. Mr P. C. Hely, Chief Entomologist, Department of Agriculture, New South Wales. Mr J. D. Macfarlane, First Assistant Secretary, Department of Primary Industry, Canberra. Mr H. Nardin, Pesticide Chemist, Department of Agriculture, New South Wales. . Professor M. J. Rand, Department of Pharmacology, University of Melbourne. Dr G. C. Smith, School of Public Health and Tropical Medicine, Sydney. Dr J. R. Vickery, Chief of Division of Food Preservation, C.S.I.R.O., Ryde, New South Wales. Mr J. P. Warry, Chemist, Commonwealth Department of Health, Canberra (Convener and Secretary). Person to be appointed as Pesticides Activity Control Officer, Department of Primary Industry. POISONS SCHEDULE (STANDING) SUB-COMMITTEE Dr A. M. Walshe, Commonwealth Department of Health, Canberra (Chairman). Mr R. Borowski, Senior Pharmaceutical Chemist, Department of Public Health, Victoria. Mr H. A. Braithwaite, Australian Pharmaceutical Association. Mr R. M. Dash, Secretary, New South Wales Poisons Advisory Committee. Dr I. S. de la Lande, Reader, Department of Human Physiology and Pharmacology, University of Adelaide. Dr K. D. Fairley, 421 St Kilda, Road Melbourne, Victoria. Mr W. H. Kelly, Chief Food and Drugs Inspector, Department of Public Health, Queensland. Mr R. C. McCarthy, Poisons Administration, Department of Public Health, South Australia. Professor M. J. Rand, Department of Pharmacology, University of Melbourne. Mr J. P. Warry, Chemist, Commonwealth Department of Health, Canberra (Convener and Secretary). POLIOMYELITIS (STANDING) SUB-COMMITTEE Dr A. C. Green, Commonwealth Department of Health, Canberra (Chairman and Convener). Dr A. A. Ferris, Director, Epidemiological Research Unit, Fairfield Hospital, Victoria. Dr J. A. Forbes, Medical Superintendent, Fairfield Hospital, Victoria. Dr J. Graydon, Statistician at Commonwealth Serum Laboratories. Dr S. W. Williams, Hon. Physician, Children's Hospital, Melbourne. PREVENTIVE MEDICINE IN GENERAL PRACTICE (STANDING) SUB-COMMITTEE Dr K. W. Edmondson, Commonwealth Department of Health, Canberra (Chairman and Convener). Dr J. A. C. Bamford, 150 Douglas Avenue, South Port, Western Australia. Dr T. C. Beard, Queen Street, Campbell Town, Tasmania. Dr F. N. Bouvier, Maryvale Road, Morewell, Victoria. Dr J. P. Little, 42 Cathcart Street, Goulburn, New South Wales. Dr J. Pacy, Hough Street, Tea Gardens, New South Wales. ad hoc REGIONAL GRANTS SUB-COMMITTEE Members appointed annually upon advice of Medical Research Advisory Committee. ad hoc SMOKING SURVEY SUB-COMMITTEE Dr K. W. Edmondson, Commonwealth Department of Health, Canberra (Chairman and Convener). Professor T. Brennan, Department of Social Work, University of Sydney. Dr F. W. Clements, School of Public Health and Tropical Medicine, Sydney. Dr S. J. Krister, Department of Public Health, New South Wales.
96
THERAPEUTIC METHODS (REFERENCE) SUB-COMMITTEE Dr K. W. Edmondson, Department of Health, Canberra (Chairman and Convener). Dr J. J. Billings, 55 Collins Street, Melbourne. Dr J. G. Radford, 94 Woniora Road, Hurstville, New South Wales. Professor H. M. Whyte, Department of Clinical Sciences, Australian National University.
97
, , , ENGLISH OIlLY GU.A!1 IS 1EJl..LTH ACTIVITIES1
1967
-J'
During the past year, t..1-te state of health of the people of Guam has remained good. Ho.Tever, there have been some significant changes in the problems faced by the territory in the axes of health =--n the past yeE':r. In February, 1967, a mass measles vaccin~.tion campaign .las held, and 18 000 children were vaccL~ated against measles. This num0er exceeded the anticipated number of susceptible cL:l.lcJ.ren. Heasles should no loni~er be a threat of the children of Guam. In March, 1967, rabies v'...rus rTas demonstrated in a dog from Guam for the first time. .As of AU[;ust 1, 1967, 25 an:il"..als have had laboratory diagnosis of rabies made. None have had clinical s:;-r.ytoms of rabies. Ho human cases have occurred. The findi.,.,t: of rabies in the community prompted a masflive dog control program til-dch is still in :i.ts infancy. 'l'here nere 5055 dogs and 181 cats vaccinated for rabies in vaccination clinics held thro'lghout the island from March 27 through April 15, 1967. Be·tMeen }1arch 27 and August 1, 1967, 4802 dogs and 664 cats Here destroyed. Guam has had a very large stray or IIbonniell dog popUlation for a long time. As "the animal control pro~;ram "!-Tent on, it became ob-vious that the techniques being utilized, i.e., night shooting of s"crays, voltmtary sU."""Tencier of umranted animals, and capture and subsequ6.i."1t disposal of stray dogs, lrere not resulting in a great enough reduction of the stray dog population. Assistance in this area vas obtained from the United States Public Health Service, Department of Interior , Division of Fish and vTildlife; and a public health veterinarian and fish and ;:Iildlife officer will be on duty in Guam shortly to aid in this program.
I~
The Department of Public Health and Felf~.re uas also fortunate in obtaining the services of a Public Health Educator and a Tu'0erculosis Control Officer during the year, both on loan from the United Stat,es Pu;;'lic Health Service. The services of a Sani"Cary Engineer from the United Sta:o.es Public Health Service 'vere again available in the past year. The incidence of enteric diseases, particularly infectious hepatitis has decreased by 50 per cent. since the assignment of the Sanitary Engineer. The incidence of in"testinal parasit.es remains about 20 per cent • The birth rate has remained high; 55 for the island as a whole, but 50.97 l-lhen"based on the civilian population only. However, the infant mortality rate of 21.4 is 10.ler than that of the United Ste.tes as a 'Thole. There were only 50 home deliveries; the rest liere all delivered in hospitals by qualified physicians. Family planning services initiated in 1966 shot·red a modest increase, but this program is still in its infancy.
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,
fA
plan to •••
lsubmitted by the Depa.rbnent of Health Education and Helfare, Public Health Service, Washington, 1 September 1967
J ~ 1
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, ~
A plan to offer cripple children f s serv:i.ces on GUe!ll or Halmii for children from the Trust Territory lIas in:i..tiated this past year, financed entirely by the United States Children's Bureau. Diseases of the heart and blood vessels and accidents remained tre leading causes of death. An NIN!lB Research Unit has continued its Horlc i.'l" the study of amyotrophic lateral. sclerosis and Parkinson I s dementia.
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ORIGINAL: ENGLISH HONG KONG
r
BRIEF REPORT ON TEE PROGRESS OF H:E:Al1PH ACTIVITIES
19661
1.
GENERAL HEALTH
The genera~ health of the population continued to be good during 1966 despite the conditions of urban overcrowding and the occurrence of a severe rainstorm in June, which caused the most disastrous floods and landslides ever experienced in Hong Kong. 2. VITAL STATISTICS
The estimated mid-year population in 1966 ,.,as 3 732 400, approximately 4C!fo being below the age of 15 years and only 6% over the age of 60.
Improvement in the gener~l state of health of the population is satisfactorily reflected by the progress in vital statistics. The crude death rate in 1966 was 5.0 per thousand population, and the crude birth rate fell further from 27.7 in the previous year to 24.8 per thousand population in the year under revievl. The reduction in general mortality in the post-,lUr years 1s accounted largely by a reduction in mortality from infectious~ respiratory and intestinal diseases, follOwing improvements in the standard of living and development of medical and health services.
I
I
J4-
The infant mortality dropped further to 24.9 per 1000 live births. The steady decline ininf'ant mortality has been due to improvement in environmental conditions and development of maternal and child health services, as reflected bygre~t reductions in mort~ity from the preventable diseases of later infancy particularly tuberculosis, bronchopneumonia and gastro-enteritis. The maternal mortallty has also shown a continuing reduction and the rate in 1966 was 0.43 per 1000 total births. During recent years there have been continuing reductions in deaths from toxaemia, haemorrhage and puerperal sepsis.
3. 3.1 Cholera
COMMUNICABLE DISEASES
, r l , I ,
A single case of cholera ,IUS notified on 24 November 1966, the first to occur after an absence of the disease for more than two years, the kst :(-
I.
lSUbmitted by the Colonial Secretariat, Hong Kong, 17 August 1967
• - 2-
case baving been report.ed in June ~964. All the necessary public heal.t.h prevent.ive measures which bad been undertaken ~s a matt.er of routine before the outbreak ,[ere reinforced. A mass immunization campaign against cholera vrhich was com;p~eted ear~ier in the year was repeated in November. No further case was subsequently report.ed. The Colony was dechred free from infection on 5 December 1966, and continued t.o re~in free from t.his and other quarantinable diseases.
3.2 Smallpox The disease has been absent from Hong Kong since ~952 but vacc~tion cc.m;paigns against. the disease Mve been conducted e.:ch year. The cam;paign is usually he~d during the Chinese New Year period, t~aditionally an auspicious time for receiving this iIllDlUIlization. The increasing im;portance of: Hong Kong in international travel by sea and. air and the prevalence of smallpox in nearby countries under~ine the need to maintain a high leve~ of: community protection against the disease.
3.3 Tuberculosis Tuberculosis remains the major hea~th problem of Hong Kong although considerable progress is nOIT being made. The policy for control of the disease has been to protect, by vaccination with BCG, those most vulnerable to serious post-pr~ manifest~tions, to provide out-patient facilit.ies f:or the ambuhtory treatment of as many tuberculosis patients as :possib~e and to reserve the limited hospit~ accommoddtion for patients not responding to ambuhtory t.reatment or in need of surgical. intervention. In executing this :policy there continues to be a high degree of co-o:pe~dtion between the Government Chest Service which maintains the BCG vaccination and out-patient treatment programme on the one hand, and the volunt~y agenCies, partiCularly the Hong l~ng Anti-tuberculosis dOd Thoracic Diseases Association which Illi..cintain most or the hospit.;.l.s, on the other. During the year, i;i. total of 28 365 patients received continuous anti-tuberculosis chemotherapy on an ambulatory basis at government chest clinics, and 4763 patients were admitted to hospitals for treatment. The Colony has now 1951 beds available specifically for the t.reat.ment of tuberculosis. During 1966, 90.Z/o of babies born in the Colony received BCG vacc~ tion within 48 hours of birth. This measure is believed to have been largely responsible for t.hevery im;pressive reduction in infcntile IOOrtality from t.his disease since the inception of t.he vaccin~tion programme. During t.he year t.here was a slight increa.se in mortality r8.te from an. forms of tuberculosis, which ,-ras 40.6 per 100 000 population as com;pared with 34.6 in 1965. Notifications of tuberculosis also showed an increase over the previous ye<Jr, llhich may have been, at least in part, u result of the intensified case-finding progr~, especially the increased contact examinations. Increasing attention is being ~id to the public health aspect of tuberculosis and he<h visitors have been posted to the Government Chest Service to guide <.:nd direct tuberculosisvTorkers in their vork on health education at home, contact examination, home visiting and follow. up of: defaulters.
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3.4
Diphtheria
The incidence has shovill a continuous decline due to vigorous annual immunization campaigns. The incidence in 1966 vTaS 8.3 per 100 000 population as compared with 73.0 in 1959.
3.5 Poliosrelitis Incidence of the dise~se remained low during 1966 after a recrudescence in e~rly 1965, possibly due to a variation in the composition of the trivalent vaccine used, the protective functions of which were further augmented by the commencement in April 1966 of a programme of administration of Type I vaccine soon utter birth. Approx1m.::l.tely 8afo of infants born after 1 April 1966 received one dose of Type I poliovuccine at 4-7 days after birth, and protection against the disease was further reinforced in more than half of these children vho subsequently received <.l full course of tyro doses of trivalent vaccine ~t maternal and child health centres at the ~ge of 3 and 5 months. Virological investigation of the disease is maintained on a routine and year-round basis. Polio~elitis virus Type I remained the predominant organism in clinical cases.
3.6 Enteric Fever The incidence remained .:.t about the s~me level compared ,lith previous year. The peak incidence continued to occur in children of school age and young adolescents.
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3.7
Mllaria
The incidence of ~r~ continued to decline, the disease being restricted mainly to certain parts of the uncontrolled rural areas in the New' Territories. Plasmodium vivwc remained the predominant parasite responsible for the infection.
3.8
:r.-~asles
The disease is usually most prevalent during the cooler lOOnths and outbreaks normally occur in Qlternate years. The 1966/67 epidemic started earlier than in the previous years with rising notifications from June 1966 onwards and reaching a peak in January and Februury 1967. The true value of the recorded mortality as related to incidence is difficult to assess as notification is very incomplete and many cases only present at hospital after the onset of complications. MOrtality is mainly due to bronchopneumonia encountered too late for treatment to be effective. During the epidemic parents of children suffering from measles "ere exhorted thrOugh press and radio to seelt early medical advice. Trials of measles vaccines "\lere undertaken during the yeur, and consideration is being given of making the vaccine available to children in the susceptible age group.
,.9
Venereal Diseases
The incidence of early infectious syphilis sho,led u considerable reduction in 1966, marking the third consecutive year of reduction.
- 4 The number of latent syphi1it1c cases was about the same as in the previous
year whi1e the incidence of gonorrhoea showed a s1ight increase. It is encouraging to note that the incidence in teenage group of the population has not risen in the manner experienced in many other parts of the world. The maintenance of this satisfactory position is partly due to energetic epidemic contr01 by contact tracing, follow-up of defau1ters and routine free ante-natal bJ.ood tests. 3.10 Leprosy
The incidence of this disease in 1966 was 4.1 per 100 000 population 'Thich is the 10west recorded since 1959. Tubercu10id manifestations predominated. Prejudices against empJ.oyment or rehabi11tation of cured 1eprosy patients are gradua1ly but steadily disappearing and widespread publicity is leading to a IlPre hllll1/;l.D.e and progressive approach to the prob1em by the cotm:m.mity. .,L- -
4.
MA!rERNAL liND CHILD HEALTH SERVICES
The M3.terna1 and Child Heul.th Services offer free materna1 and chiJ.d care at 31 centres, 17 of which are fu11 time and. 22 of them are provided ,lith maternity beds. 75.5% of children born attended an loCH centre on at 1east one occasionj this compares with a figure of 63.1% in 1965. Approximately 9B<1> of births took place in institutions and 43 new maternity beds vrere provided follo,ling the opening of the new Jockey C1ub Health Centre at Yuen IDng and the Cheung Sha Han Jockey C1ub Health Centre. 5. MENTAL HEALTH SERVICES
With the addition of enrol 240 beds by the comp1etion of two new blocks during the year, the bed capacity of the Cast1e Peak Hospital for psychiatric patients has increased to 1359 beds. This hospital was sti11 overcrowded over the revised bed capacity, and deta11ed p1anning has commenced for a new mental hospital in North-Hest KowJ.oon.
,mro.
The Drug Addiction Treatment Centre, formerly situated at Cast1e Peak Hospital, continues to provide treatment for ma1e drug addicts at a rehabilitation centre on Shek I~TU Chau Island. This institution 1s run by the Society for the Aid and Rehabilitation of Drug Addicts, a vo1untary organization subsidized by the Government. Drug addicts are .adm1tted to the Centre vo1untarily, their stay varying from four to six IlPnths. .After they (U'e discharaed, the SOciety provides further assistunce in their rehabilitation.
6.
HOSPITALS
At the end of 1966, there was a total. of 12 851 beds available in all hospitals in Hong Kong, excluding those maintained by Her Mijesty' s
". - 5Armed Forces. PJJ. additional 515 beds in private maternity and nursing homes 1fere also available. The total of l.3 366 beds av-ailabl.e in Hong Kong represents 3.6 beds per thousand of the population. Work on the year the doctors, the professorial the extensions to Queen Mlry Hospital continued and during projects compl.eted include the nev quarters for nurses and new nurses' training school, new oper.J.ting theatres and suites and the greatly-e~anded radiodiagnostic department.
The Queen Elizabeth Hospital. serving a population of upproximately 2-1/2 mil.l1on people living in Kowloon and the New Territories entered its third year of operation. A fe<lture of note w.::.s the increased number of attendances at the Casual.ty Dep,,-rtment, which rose by 4.9% compared with the previOUS year. PJJ.other Casuulty Department was opened in Kwong Wah Hospital in 1965 in order to relieve some of the he<lVY pressure on the Casual.ty Department in Queen Elizabeth Hospital. 2Ild to provide additional casuaJ.ty facilities for the public in Kowloon and. Ne,., Territories.
The Tung Wah Group of Hospitals continued its programme of modernization and. e~ansion. The neiT infirmary at Wong Tai Sin had. compl.eted Phase I of its construction, providing 350 beds; and fo~tion stone of Phases II und III of the project to give un overall total of 700 beds w1l.l be l.aid e<ll'ly in 1967. Construction of £.llother infirm.::;.ry .::.t Sandy Bay on Hong Kong Island prOviding Zl5 beds is e~ected to be completed early in l.967.
7.
Ot1r-PATIml' SERVICES
Pressure remained heavy throughout the ye8.r, a total of 6 849 596 out-patient attendances at Government Out-patient Depcrtments being recorded. Three new government clinics were opened and the Government now mdintuins 40 out-patient clinics as well. as mobil.e dispensaries, floating clinics and. a flying doctor service. In dddition, the Government al.so provides evening and. public holiday out-patient sessions at seven clinics in the more densely-po~ted ~reas.
ORIGINAL: ENGLISH
JAPAN REFOR!! ON THE PROGRESS OF ImAIlI'H ACTIVITIES FOR THE FISCAL YEAR 1966 (April 1966 - March 1967)1 1.
OOOANIZAi'ION OF NATIONAL AND LOCAL HE'.AIIl'H ADMINISTRATION
There were no changes in the organization of the Ministry of Health and lTelt'are during the period under review as far us the health service is concerned. The prefectural and municipal health centres continued to carry out their routine functions as local community health service agencies. There were 829 health centres throughout Japan at the end of l-hrch 1967, an increase of 3 centres over the previous year. (In order to meet the increased problems of public nuisance and environmental pollution, the Environmental Control Division ,ras created in the Environmental Sanitation Bureau of the Ministry of Health and Welfare on 20 June 1967.) 2. HE:AIIrH BUDGET
~ ··115
The total national health budget for the fisc~ year 1966 was 144 million, whereas it u ...s ~ 110 475 million for the fisccl. year
1965.
3.
VITAL STATISTICS
,
The estimated population as of 1 October 1966 W<lS 99 056 000. The following table gives some of the vital statistics data for the calen~ year 1966 with a cOllq)arison ,lith 1965.
.!.2§2 Births: Number Rate (per 1000 population) Number Rate (per 1000 population) 1823 697 18.6 700 438 7·l. 33 742 18·5 1 597 8.8 161617 88.6
1 359 221 13.7 670 135 6.8
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lq66
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Deaths:
Infant deaths: Number Rate (per 1000 :otal live births) Maternal deaths: Number Rate (per 10 000 total live births) Still-births: Number Rate (per 1000 total live births) .:(
26 206 19.3 1245 9.2 148 1.68 109·0
lSubmitted by the Ministry of Health and Uelf;;..re, Tokyo, 17 AugUst 1967
1 The average life expect~cy at birth for the Japanese people, prepared
on the basis of the 1966 data, indicates 68.35 years for ma:Les and 73.61 years for females; the cOIllpw.rable figures for the previous year being 67.73 years for males and 72.95 yeurs for females. 4. MATERNAL lIND CHILD HEALTH
During the calendar year 1966, 817 344 visits uere made to the clinics by mothers, and 4 983 207 by children. Public heal.th nurses paid 286 190 home visits on mothers and 735 211 on children. At the end of March 1967, there were 459 maternal and child health centres in the rural areas (404 centres in 1966). During the calendar year 1966, 58 657 low weight babies .rere reported, indicating a decrease of 18 624 compared with that of 1965.
5.
TUBERCULOSIS CONTROL
In the calendar year 1966, the number of deaths from tuberculosis decreased further, there being only 20 028 deaths, at a rate of 20.2 per 100 000 (22 259 deaths, at a rate of 22.6 for 1965). During 1966, 42 822 000 persons (42 709 000 persons for 1965) received heal.th examinations for casefinding purposes. Among them, 37 381 000 (37 269 000 for 1965) were examined by photofluorography. The case-finding rate for 1966 was 0.15% (0.16% for 1965). Among those tuberculin negative, 4 681 000 lrere vaccinated with l3CG. The total number of registered tuberculosis patients as of the end of 1966 was 1405 283 (1 469 583 for 1965), 63.1% of l,hom were active cases; 21.4% of the active cases were hospitalized, 60.9% were under domiciliary treatment, 15.8% did not receive complete medical treatment and the remaining 1.8% could not be traced. During the same period, 279 833 cases were newly registered. In 1965, the total expenditure on tuberculosis treatment was estimated to be 110 billion yen (108 billion yen for 1964). This is equivalent to 9.4% (11.0% for 1964) of the total expenditure on medical care for all kinds of illness. At the end of 1966, there were 211 527 beds allocated to tuberculosis patients and the bed occupancy rate was 73.8%.
6.
LEPROSY CONTROL
The number of newly reported cases of leprosy has been decreasing yearly. In the calendar year 1966, it lras 1<:6 (125 for 1965). The total. number of reported leprosy patients at the end of 1966 vIas 10 404 (10 607 for 1965) ldth a prevalence rG.te of 1.0 per 10 000 population (1.1 for 1965); 9715 patients were institutionalized at 11 national and 3 private leprosaria. The total number of beds available in those leprosaria were 12 950 .and 280 beds, respectively.
- 37. COMMUNICABLE DISEASE CONl'ROL
The tota~ number of persons "Tho received immunization during the 3 ~55 000 for smallpox; 16 252 000 for typhoid and pa:t:atyphoid fever; ~ 830 000 for diphtheria; 3 58~ 000 for diphtheria-whooping cough cOllibined, and 2 519 000 for poli~litis (attenuated vaccine). ca~endar yea:t: ~966 l'TaS as follOlTS:
In ~966, there lms a marl;:ed decrease in mst of the acute diseases, except for Japanese encephalitis and dysentery. The of polio~elitis was dramatically reduced after the successful tration of Sabin-type polio~litis vaccine. In 1966, only 38 reported. The decrease of polio~litis cases during the past is as folloylS: 56a5 for the year 1960, 2436 for 1961, 289 for 1963, 86 for 1964, and 76 for 1965. ~.
communicable incidence oral adminiscases "Tere several years 1962, 131 for
The nulliber of Japanese encephalitis cases has increased compared with 1965, and vas estimated at 2l63, including 1442 deaths, although voluntary immunization against Japanese encephalitis has been carried out every yea:t:. The ou;;break in 1966 occurred in the western part of Japan. As to dysentery, in spite of a gradual decrease since 1960, there was a small increase in 1966, and 65 108 cases "ere reported.
8.
INTmIATIONAL QUARANTINE
During the calendur ye~r 1966, 28 ll7 vessels and 14 657 aircrafts (for 1965, 25 577 and I I 227, respectively) involving 1 156 955 and 1 044 856 persons, respectively, were subjected to quarantine inspection; 150 065 persons received preventive vaccination for q~ranti~ble diseases; 1056 vessels underwent deratting, and 5387 vessels received deratting exemption certificates. Fortunately, no case of quarantinable disease vTaS introduced during the year 1966.
9.
ENVIRONMENTAL SANITATION
1\'S of the end of l>E.rch 1966, a population of 68 241 682 (about 69.4% of the tot<.:-l population) was covered by some Idond of public water supply. At the end of IIhrch 1966, there 1-Tere 108 cities opcruting sewage tre::ctment plants and a population of 13 480 000 benefitted from these services. At the end of Mlrch 1966, there lrere 792 cities operating nightsoil disposal plants. At the end of March 1965, a population of 45 322 991 was covered by the garbage disposal progr~, either by incineration or composting methods. The insect and rodent control programme, supported by the community organizations, has been continued, und routine sc.nitary inspections bilve been carried out continuously.
t.
- 4 In order to cope with the uir pollution problem, so far sixteen large or newly industrialized citie3 huve been designated as the specific smolre control areas under the Smoke Control Law. A study on the effect of polluted air on human health commenced in several industrialized cities. Twenty rivers 1fere designated as control basins under the ilater Pollution Control unTo
In the past, the administrative responsibility for sewage disposal c.nd its facilities has been jointly in the h.<;:..nds of the Ministry of Health ;md Heli'are and the Ministry of Construction, i. e., operation of sewage treatment pJ.ants was under the jurisdiction of the former and maintenance .:.nd construction of sewerc.ge pipes of the latter. However, with a vie" to simplifying administration, the Ministry of Construction became the single ",gency responsible for Sei'Tagc disposal ,lork as far as its budget and operation are concerned (as from 21 June 1967), although it still requires to obtain the consent of the Minister of Health und lleli'are "hen approving the new construction cf se"er;;,.ge facilities and their extension.
10.
FOOD S.ANITATION
During the year 1966, 5097 food inspectors ,/ere stationed in 829 health centres to deal with 2 530 519 food-handling establishments. For the same year, the total number of food pOiSOning cases reported was 1400, involving 31 204 patients ..md resulting in 117 deaths. Chemical synthetics to be used as food additives &re fully controlled under an c.uthorization system by the Government. At the end of 1966, a total of 350 chemical synthetic food additives "ere included in the list of authorized synthetic food additives.
11.
NUTRITION
During the calendar year 1966, 1 324 903 cases of personal nutrition guidance and 85 702 group seSSions, including demonstrations by kitchencars, "ere given by the nutrition staff of the health centres. /.s of the end of Mll-ch 1967, there were 197 authorized nutrition training schools and about 10 458 licensed nutritionists.
12. DENTAL HEALTH One hundred and twenty-one of the 829 health centres ,Tere equipped with dental facilities and dentists, and continued to play an important role in the preventive dental health programme. During the year 1966, 215 557 dental health guidance consultations ;,ere given to pregnant .romen and 1 638 629 to children.
-5 .:. l3. MENTAL HEAIlL'H
• Continuous efforts were IDD.de to iIqprove the mental health programme during the year 1966, including care of the mental cases. The number of mental hospitals, mental beds, etc. at the end of June 1966 as compared with the same data in 1964 and 1965 is shovffi belov: 1964 ~ntal
1965 7 05 363 163910
1966 746 399 181 709
hospitals
649 329 144 823
Units in general hospitals ~ntal
beds
There are many governmental facilities carrying out the programme for the promotion of mental health guidance for the public as ve11 as for the mentally retarded children and adults. The Government is expecting to receive expert advice in the field of conmn.mity mental health care from a WHO short-term consultant for a period of three months starting November this year. l4. MEDICAL SERVICE
At the end of calendar year 1966, there vere 7308 hospitals (7047 for 1965) with a total bed capacity of 918 233 (873 652 for 1.965), showing an increase of 26l hospitals and 44 581 beds against those available in 1965. At the end of calendar year 1965, there vere 64 524 general clinics (63 296 for 1964) and 28 602 dental clinics (28 1.50 for 1.964), showing an increase of 1.228 general clinics and 452 dental clinics. (Data for 1966 are not yet available.) At the end of calendar year 1965, there vere 109 369 physicians (11.1 per 10 000 population), 35 558 dentists (3.6 per 10 000 population), 68 673 pharmaCists (7.0 per 10 000 population) and 245 211 nurses (24.9 per 10 000 population). This means an increase of 1281 physicians, 479 dentists, 2074 pharmacists and 15 41.4 nurses. (Data for 1966 are not yet ..lvailable. ) In order to cope ,nth the increase in traffic and other accidents, the ambulance medical care system vTaS revised in February 1964. As a result, a network of ambulance medical care has been established throughout the country; at the end of lfurch 1.966, the number of such faci1.ities,. either public or private, reached 3532.
15.
l.oo:lICAL REHABILITATION
The School of Rehabilitation attached to the National Tokyo Chest Hospital and established in 1963 for the purpose of training and educating
- 6 physical. therapists and occupational. therapists, has continued successful.ly its teaching activities under I/HO's eJlllert assistance. There are now a total. of 493 physical. therapists and 72 occupational therapists who have passed the national exalllillation for their respeotive professions under the tau f'or Physical. Therapists and Occupational Therapists.
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16.
PHARMACEUCICAL CONTROL
During the calendar year 1966, 1956 pharmaceutical inspectors visited 202 980 pharmaceutical facilities (out of a total. of 26l 993 such facilities), such as drug and medical supply manufacturers, pharmaCies and blood banks. The control of ~hetami.ne preparations and narcotics ,laS also maintained, and the measures for narcotic addicts were also carried out. The blood supply service had in the past depended chiefly on the socalled "professional blood donors It. This practice had caused not only social evils but had also increased the risk of' serum hepatitis among the population. The Government, recognizing the seriousness of' the above situation, made a decision in """ugust 1964 to develop voluntary blood donations further to normalize the blood supply service programme. Under the nation~wide campaign for voluntary blood donation, the ratiO of' voluntary donations to total donations increased, reaching 48.5% during the year 1966, while it was only 7.7% in 1964. The revision of' Part I of the Japanese Pharmacopoeia is in progress f'or publication on 1 April 1970. A monitoring system for adverse drug reaction was established in M;.rch 1967. Under this system, medical and dental professions are nOll requested to send in information on unexpected und adverse reaction of' drugs. Proper administrative action will be talren to ensure safety of' drugs after reviewing those reports.
--
17.
INTERNATIONAL CO-OPERATION
m
THE HEALTH PROGRAMME
During the calendur year 1966, the Government extended its services and co-operation in connexion llith the international. health programme, and received and trained 64 vlHO f'ellcnTs, 42 trainees under the Colombo Plan, and 6 trainees under other schemes. It also arranged for 9 short-tern consultants to \fork with \-lHO, 38 .,ith the Colombo Plan and 1 with-another scheme.
~I'''''' .,;
l.,. ." .'
A Brief Report on Public Health Administration in Japan 1967 (January 1966 - August 1967)
----~======-----
With Pertinent Informations on Social Welfare and Insurance Programme (
Ministry of Health and Welfare Japanese (;overnrnent
31 August 1967
CONTENTS ~~ ~ 1. Organization of National Health Administration ............................................. 1 2. Main Laws under the Jurisdiction of the Ministry of Health & Welfare ......... 3 3. Finance of the Ministry of Health & Welfare ................................................ 5 4. Organization of Local Health Administration ................ · ...... · .................. · ........ 5 5. Health Center ................................................................................................ 5 6. Population················· ...................................... · .............................................. 8 7. Vital Statistics···· .. ············ .. · .. ··········· .... · .................. · .......... · .............. · ............ 9 8. Life Tables .................................................................................................. ·13 9. Deaths by Leading Causes .................................... · .............. · .. · .. · .................... 15 10. Maternal and Child Health· .... · .. · .... · .... ··· .. ·· .. · .. ···· .. ······ ........ ·· .. · .. ·· .. · .... ······· .. · .. 18 11. Family Planning .................................................................................... · ........ 20 12. Health Education ......................................................................................... ·21 13. Tuberculosis Control···· .. ·········· .. ······ ............................................................... 22 14. Leprosy Control ........ ·· .. ····· ...... ······· ........................................................ ····· .. 24 15. Adult Disease Control ................................................................................... ·25 16. Communicable Disease Control· .. · .. · ............................................................... ··27 17. Port Quarantine Service ...................................................... ······················ .. · .. 34 18. Environmental Sanitation· ..................................................... '" ·················· .. · .. ·35 19. Environmental Pollution Control .. ·· .......... · .. · .. ·· ...... · ....................................... ·38 20. Food and Veterinary Sanitation· .. · .. · .... · .. · .. ·.. · .. ···· .. · ........ ·· .... · .. · ................ ·· ...... 39 21. Nutrition········································································································ ·41 22. Dental Health ............................................................................................... ·43 23. Mental Health································································································44 24. Medical and Social Rehabilitation Service· .... · ............ · ........ · .. · .. · .. · .. · ........ · ........ 48 25. Radioactive Isotope and Peaceful Use of Atomic Energy ...... · .................. · ...... ·49 26. Occupational Health ...................................................................................... ·50 27. Medical Service ............................................................................................ ·51 28. Pharmaceutical Affairs ........................................... ·········································57 29. Major Research and Training Institutes in Public Health Programme .... ·...... ·60 30. International Cooperation on Health Programmes ...... · ........ · ...... ·.................. ·62 31. Public Assistance, Child Welfare and Social Insurances· .. · ...... · .. · .... · ........ · ........ 63
-1-
1.
Organization of National Health Administration
The chart below shows the organizational structure of the national health and welfare administration in Japan as of 1 August 1967. On 20 June 1967, the Environmental Control Division was created in the Environmental Sanitation Bureau in order to meet the increased problems on public nuisance and environmental pollution. The idea of close coordination among the fields of preventive medicine, medical care, social welfare and social insurance is maintained. The Publi: Health Bureau, Environmental Sanitation Bureau, Environmental Control Division, Medical Affairs Bureau, Pharmaceutical and Supply Bureau, Maternal and Child Health Section of the Children and Families Bureau, Rehabilitation Section of the Social Affairs Bureau, and the Health and Welfare Statistics Division, of the Ministry of Health and Welfare, share responsibilities on planning national health policy and programmes in the field of preventive medicine, environmental sanitation, control of public nuisance and environmental pollution, medical care, pharmaceutical control, maternal and child health, and social health, respectively. These Bureaus direct the health programmes by giving orders to the 46 Prefectural Governments and 29 larger Municipal Governments.
Minister's Secretariat -
,-Personnel Affairs Section General Affairs Section Accounts Section Office of the Personnel Welfare Officer Office of the Programme Evaluation and Planning I Office of the Counsellor for Liaison in International Affairs '-Office of the Counsellor for Scientific and Technical Affairs
I , Vi tal Statistics Section Health & Welfare Statistics Division-Health Statistics Section Social Statistics Section Mechanical Counting Section -Office of the Statistical Investigator
-Administration Section
:-Public Health Bureau I
,-Planning Section I Nutrition Section Health Center Section Tuberculosis Prevention Section Communicable Disease Control Sechon Mental Health Section -Quarantine Section
,-
-Environmental Sanitation Section Water-Works Section Food Sanitation Section !-Environmental Sanitation Bureau - - - Veterinary Sanitation Section -Food Chemistry Section -General Affairs Section I Environmental Control Division - - - - Environmental Pollution Control Section I-Sanitation Facilities Section -General Affairs Section Medical Affairs Section I Hospital Guidance Section Administration Section National Hospital Section I-Medical Affairs Bureau National Sanatorium Section Supply and Equipment Section I Nursing Section I -Dental Health Section -Technical Counsellor for Pharmaceutical Affairs Enterprise Section Pharmaceutical Affairs Section Drug Manufacturing Section I-Pharmaceutical & Supply Bureau Inspection Section Biologics and Antibiotics Section First Narcotic Section -Second Narcotic Section CCon'd) I
-----'1
-2-Administration Section 'I,-National Parks Bureau-i Planning Section '-Recreation Facilities Section -General Affairs Section Public Assistance Section Rehabilitation Section Life Improvement Section Affairs Bureau I-social Institution Section Office of the Counsellor for the Investigation on Public Assistance Programme
-Section for the Welfare of the Aged -Planning Section I Child Protection Section Children & Families Bureau--- Maternal and Child Welfare Section -Maternal and Child Health Section ,
I I
I I-Insurance Bureau -.-- i
-Planning Section Health Insurance Section National Health Insurance Section Medical Care Section -Acturial Research Affairs Section
-Pension Bureau
-Planning Section Pension Section Pension Fund Operation Section I-Acturial Affairs Section -General Affairs Section Bereaved Families Relief Section Demobilization Section First Pension Affairs Section First Allowance Screening Section Second Pension Affairs Section Second Allowance Screening Section -Investigation Section
-Repatriation Bureau-
-
·-Director's Secretariat
-I
I Accounts Section
-General Affairs Section
'-Inspection Section ,. . SOCIal Insurance _,_ MedIcal Care Agency Insurance I
... DIvISIOn
_
I-Health Insurance Section Seamen's Insurance Section -Welfare Pension Insurance Section -National Pension Section Welfare Pension Section -Accounting Section -Institute of Population Problems Institute of Public Health National Institute of Mental Health National Institute of Nutrition National Institute of Health Port Quarantine Offices National Hospitals National Sanatoria National Institute of Hospital Administration National Institute of Leprosy Research National Cancer Center National Institute of Hygienic Science3 National Homes for the Blind National Rehabilitation Center for the Physically Handicapped National Rehabilitation Center for the Deaf and Mute National Recuperation Homes National Homes for the Juvenile Training and Education I National Home for Mentally Retarded I Social Insurance Appeals Committee ,-Social Insurance Service Training Institute
!
Pension Insurance Division
Affiliated Institutions
Local Branch Offices__ I-Regional Branch Offices of Medical Affairs Bureau -RegIOnal NarcotIc InvestIgators' Offices
-3-
2.
Main Laws under the Jurisdiction of the Ministry of Health & Welfare
1. Laws on Administration: Health Center Law (1947)
2.
3.
r' I 4.
5.
Ministry of Health and Welfare Establishment Law (1949) Laws on Preventive Medicine: Infectious Disease Prevention Law (1897) Leprosy Prevention Law (1907) Trachoma Prevention Law (1919) Parasitosis Prevention Law (1931) Venereal Disease Prevention Law (1948) Preventive Vaccination Law (1948) Rabies Prevention Law (1950) Quarantine Law (1951) Tuberculosis Control Law (1951) Laws on Environmental Sanitation: Natural Park Law (1931) Friseur Artists Law (1947) Food Sanitation Law (1947) Entertainment Facilities Law (1948) Public Bath House Law (1948) Hotel Business Law (1948) Law Relating to Processing Plants of Dead Animals and Others (1948) Law Regarding Graveyards, Burial and Others (1948) Hot Spring Law (1948) Cleaning Business Law (1950) Slaughter House Law (1953) Wastes Disposal Law (1954) Beauty Artists Law (1957) Water-Works Law (1957) Law Concerning Impr()ved Management of Business Dealing with Sanitation (1957) Sewerages Law (1958) Water Pollution Control Law (1958) Law for Cooks (1958) Smoke Control Law (1962) Environmental Pollution Control Service Corporation Law (1965) L3.W for Confectioners (1966) Fundamental L3.w for Environmental Pollution Control (1967) Laws on Health Statistics: Regulations Regarding Declaration of Still-birth (1946) Ordinance Regarding Vital Statistics (1946) Other Laws on Public Health: Nutritionists Law (1948) Eugenics and Maternal Protection Law (1948) Mental Health Law (1950)
-
4
Nutrition Improvement Law (1952) Law for Loan of Scholarship for Studies in Public Health (1957) Law for Health Protection and Medical Care for A-Bomb Explosion Sufferers(1957) Maternal and Child Health Law (1965) 6. Laws on Medical Care: Law for Masseurs, Acupuncturists, Moxa-cauterists and Judo-orthopaedists (1947) Medical Service Law (1948) Medical Practitioners Law (1948) Dentists Law (1948) Dental Hygienists Law (1948) Public Health Nurse, Midwife and Nurse Law (1948) Law for Dissection and Preservation of Dead Body (1949) Law for Medical X-Ray Technicians (1951) Law for Dental Technique (1955) Cornea Transplantation Law (1958) Law for Health Laboratory Technicians (1958) Law for Medical Care Facilities Finance Corporation (1960) Law for Physical Therapists and Occupational Therapists (1965) 7. Laws on Pharmaceutical Affairs: Poisonous and Deleterious Substances Control Law (1950) Awakening Drug Control Law (1951) Narcotic Control Law (1953) Taima (Marihuana) Control Law (1953) Opium Law (1954) Bleeding and Blood Donor Supply Service Control Law (1956) Pharmaceutical Affairs Law (1960) Pharmacists Law (1960) 8. Laws on Social Welfare: Child Welfare Law (1947) Disaster Relief Law (1947) Welfare Commissioners Law (1948) Consumers' Livelihood Cooperative Association Law (1948) Law for the Welfare of Disabled Persons (1949) Daily Life Security Law (1950) Social Welfare Service Law (1951) Law for the Welfare of Mentally Retarded Persons (1960) Law for the Welfare of the Aged (1963) Widowed Mother and Child Welfare Law (1964) Special Child Allowance Law (1966) 9. Laws on Social Insurance: Health Insurance Law (1922) National Health Insurance Law (1938)
"
-5-
Seamens' Insurance Law (1939) Welfare Pension Insurance Law (1941) Social Insurance Medical Fee Payment Fund Law (1948) Health Insurance Law for Daily Workers (1953) National Pension Law (1959)
3. Finance of the Ministry of Health & Welfare Annual budget of the Ministry of Health and Welfare and its health budget for the past several years is shown in the following table as compared with the total National Government expenditures. This budget includes those subsidy granted to the Local Governments. Our fiscal year covers the period from April 1 through March 31 the following year. Table 1. ... -~----
Budgetary Expenditure of the Ministry of Health and Welfare and its Health Budget. --------
-~---~.-
Fiscal Year
Expenditure of All National Government Agencies Million Yen
Total Expenditure of Ministry of Health & Welfare -------. -_._ .. ,.-Million Yen
Amount of Health Budget Million Yen
1962 1963 1964 1965 1966 1967
2 2 3 3 4 4
426 850 255 658 314 950
801 008 438 080 271 911
272 331 398 481 580 671
316 313 980 942 241 373
54 761 71 236 84 787 98 720 110475 115 144
4. Organization of Local Health Administration Each Prefectural Government and larger Municipal Government have their own Health Department in order to carry out their health programmes in compliance with the national policies and programmes directed by the Ministry of Health and Welfare. These Prefectural and Municipal Governments divide their administrative boundaries into several "health center districts," and the Health Center is established in each one of those districts. For the reason of geographical conditions, most of the Health Centers have their branch health units within their health center districts. Further details on the Health Center are described in the following chapter.
5. Outline
Health Center
The first Health Center in Japan was established in Tokyo in 1935. Then, in 1937, the original Health Center Law was enacted, and the 10-year programme for health center construction started, which resulted in bringing the total number of health center up to 306 in 1943. The number had further increased to 770 in 1944 as a result of amalgamation
t
-6-
of all governmental health consultation agencies. The Health Center in pre·war days had only health consultation in tuberculosis control, maternal and child health, and mainte· nance of health of pre-service men. However, in 1947, public health programme in this country was reorganized, and the Health Center Law was completely revised, whereby the new health center programme had started. Legal Basis According to the Health Center Law, the Local Government is required to establish the Health Center, and the National Government is responsible to share the cost. 46 prefectures, and those 29 larger municipalities specially designated, have their own Health Centers. The Director of Health Center is specified to be the medical doctor by law. The role of Health Center as defined by law is primarily to function as the community health service agency, and secondarily as the health administration supervising agency based on the authority delegated by the governor or mayor. Number, Standard Scale and Organization As of the end of March 1967, there are 829 Health Centers throughout Japan. All Health Centers are classified by the size of health center district, its population, extent of urbanization, and its industrial component. There are 4 basic types, i.e., Urban Health Center, Rural Health Center, Urban·Rural Health Center, and Health Center with small population in big area. These are abbreviated as U, R, UR, L type. As the exceptional type health center, the Health Center with small population in small area is classified as S type. According to this classification, there are 222 U type Health Centers, 80 UR type, 384 R type, 121 L type, and 22 S type health centers. It was reported that the total number of health center personnel subsidized under health center grants was 22,626. This includes 1,624 physicians, 110 dentists, 6,170 public health nurses, 874 nutritionists, 1,313 X-ray technicians, 1, 267 laboratory technicians, 1,067 health statisticians, 609 health educators, 361 social case workers as the main technical personnel. In addition to those, there are also 2,015 food inspectors, 1, 412 sanitary inspectors, and 1, 039 veterinarians for veterinary sanitation. Therefore, 27,092 technical staff are now working in all the Health Centers. It is about 32.4 per health center and 27.3 per 100, 000 population. Function and Programme The function and programme of Health Center include activities in the different fields. Thus, all community health programmes have been integrated into the health center activities. Followings are the basic functions defined by the law: Health education; vital and health statistics; improvement of nutrition and food sanitation; environmental sanitation; public health nursing; medical social service; laboratory service; mental health; prevention of tuberculosis; control of venereal diseases and other communicable diseases; maternal and child health; dental hygiene, and other local health programmes as required, such as endemic disease control, etc. As a routine programme, the health consultation clinic, well·baby conference, mass chest survey, home visit, community health education, inspection and field supervision
-7-
on sanitary operation are carried out. The health education is integrated into every phase of routine programme. TB control, insect and rodent control, and maternal and child health promotion are highlight programmes. Recently, the community organization process has been extensively developed for performance of all health programmes. The following table shows the main health center activities during the year 1966. Table 2. Main Health Center Activities. CJan.~Dec.
1966)
Total number of health consultation session Inside of health center At district Activities of ~anitary in~pectors Total number of sanitary establishments Total labour used for environmental sanitation field work (person)( day) Total number of food establishments inspected by food inspectors Total number of inspection days by food inspectors Carrier investigation in dysentery control Prevention of tuberculosis X-ray examination 35mm and 6x6 large film Immunization (periodical) Parasite examination Maternal and child health Care of expectant and nursing mothers Actual number of attendances at health clinic Total number of attendances at health clinic Care of infants and children, 1~5 years of age Actual number of attendances at health clinic Total number of attendances at health clinic Care of physically handicapped children Actual number of attendances at health center Total number of dental examination Nutnti)n consultation Total numb~r of attendances to personal nutrition consultation Total number of attendances to mass nutrition consultation session Total number of health education session Total number of visits bv social case workers Total number of househo'ld visited by public health nurses Actual number Accumulated number Laboratory examination Bacteriological examination Clinical examination Water examination
252 177 135 106 837 420 450 170
2 183 819 503 350
7 380 640 38 555 062 37 380 881 1 174 181 11 635 558 3 383 679 377 490 525 364 2 472 215 3 591 452
81 548 1 700 678 1 324 903 2 444 695 158 064 84 620
1 124 124 1 603010 7 845 105 8 129 179 602 369
Finance
The Health Center is financed by Local and National Governments. The item of national subsidy is divided into 2 categories; one is the health center subsidy based on Health Center Law and the other is the programme subsidy based on the respective legislation concerned. According to the Health Center Law, the National Government is responsible to share the cost of health center expenditure both recurrent and non·recurrent ones. When the Health Center is newly established, the National Government shares one half of the expenditure for construction and necessary equipments, and it also subsidizes one third of running expenses. Local Government pays the rest of expenses. For 1967 fiscal year, the total amount of national health center subsidy is 5,511 million yen. For 1965 fiscal year, it was 5,037 million yen,
-8-
6.
Population
Fig. 1 below shows the trends of population in Japan, including the estimated popula· tion in the future calculated by the Institute of Population Problems of Ministry of Health and Welfare. The latest population census conducted as of Oct. I, 1965 revealed that the population of Japan amounted to 98,274,961. In 1967, it is expected to increase beyond 100 million, and the aged population of 65 years and over will constitute a larger proportion of the total population. The population pyramids in the future will be shaping broader form in the aged population. Fig. 2 shows the comparison of population pyramids for 1935 and 1966. Fig. 1. Trends of population in Japan. A"
Male
Female
- -1935
----·-.I0-·----·H
,,, Fig. 2.
. . . . .:::. . -1 :1~-..-_-=-===j,.....J'-r-__ 300 10(1 0 0 100 200 300 400 500 600 ]0 thousands
Population Pyramids for 1935 and 1966.
---'0.
Year
-9-
7. Vital Statistics The nation-wide vital statistics survey has been yearly carried out since 1899 in Japan, except for the period between 1944 and 1946, during which no reliable data were available due to the confusion resulting from the last World War_
Live Births Annual Change of Birth Rate_ Between 1900 and 1919, the birth rate III Japan was between 30 and 35 per 1,000 population, but it rapidly rose to 36_2 in 1920, which was the highest rate since 1900_ But after this peak, it started to decrease and kept declining every year until 1939 when the rate reached the lowest point (26.6), and from about 1940 it again started to rise. This Fig. 3. Annual Change of Live Birth Rate. rise is considered to be due to the (per 1,000 population) pro-natalist policy supported by the Government at that time. During 3 years from 1944 to 1946, the birth rate seems to be considerably low, judged from various reasons, although no accurate data were available because of the confusion caused by the war. The rate in 1947 was abnormaIIy high, showing 34.3, but such an I extraordinary rise is considered to be L, [ [ U'l due to a sudden increase of postpoU'l U'l <::> 0 <D ~ U'l U'l <D .". 0> <> 0'> 0'> 0'> 0'> ned marriages and reunited couples Year of demobilized or repatriated families of the people after the termination ~
~
--
~
.:
of the war. After such extraordinary rise, the birth rate started to decline rapidly, and reached 17.2 in 1957. This rapid decrease seems to be due to the decrease of marriage, the extensive use of contraceptive measures, and the prevalence of artificialIy induced abortions as weII as the changing attitude of people toward family size. However, in 1958, the rate was recorded as 18.0, indicating sign of halting its declining for the first time in the postwar years. However, it again started to decrease since then and reached 16.9 in 1961, showing the lowest rate ever experienced by that time_ Since 1962, the rate again started to increase, and it reached 18.5 in 1965. However in 1966, the births were noticeably decreased to about 1, 360 thousand and the birth rate became 13. 7, showing the lowest one ever recorded. This is judged to be due to the fact that the married couples avoided giving birth to children in the year 1966, which happened to be the year caIled "Hinoe-Uma"_ This comes round every 60 years under sexagenary cycle and has been traditionalIy believed' to bring bad luck to female babies, because they may face difficulty in finding husbands when they grow up. Deaths Annual Change of Death Rate_ From 1900 to about 1930, the annual death rate had been around 20 per 1,000 population, excepting the high rates of 27. 3 in 1918 and 25.4 in 1920, respectively, because of the world-wide pandemic of influenza. It kept
-10Table 3. Vital Statistics in Japan. (Number) ,
(19DD~1966)
I Year' Population 1
,
1
Births
L~iv~e-~~eaths 910' 7441
I Increase I (under i(un~er s
I Natural I t'::t!:s I
~{f~~ Deaths Ma~"JJ-1 S~i\l: Marria-j DivorbIrths ges ' ces I'
'I'
1 yr')j28 days) 19 0'0' " 43 847 0'0'0' 1 420' 5341 50'9 790" 220' 211, 112 259' 648 623i 276 1361126 910', 60'3 468 335 6131 139 6811 914 2341258 70'31 10'4 101 81 8691 77 829
I
I
1 63 828
1
6 20'0", 137 9871346 528 1
1910 I 49 184 DDQi 1 712 857 1 0'64 234 1920' ' 55 963 0'53'1 2 0'25 564 1 422 096 ' 1 1930' 64 450' 0'0'5 2 0'85 101 1 170' 8671' I'
6 2281157 392 441 222' 7 158 144 0'38 546 20'7: 5 681! 117 730' 50'6 674' 5 070'; 102 0'34 666 575 4 929, 10'3 40'0', 791 625
59 432 55 511 51 259 48 556 49 424,
71 933 0'0'0' 2 115 867 1 186 595 929 272 190' 50'9 1940' 41 71 680' 20'0',1 2 277 283 1 149 559 1 127 724, 191 420' 42 , 43 44 , 1945 46 47 48 49
~~ g~ ~~' ~ ~~~ ~~.~I ~ ~~~ g~·gl ~ g~r ~~~I ~~g ~~~i ~~ ~~~ ! ~~'~I ~~ ~'~I ~r~ ~~.~! !~ ~?·.~ I ~~ ~6i !~g, 2 678 7;;2]1 138 238, 1 540' 55'4 199 573 852 0'33 293 275 259 0'88 OlD 971 6371' 2 337 5Q7! ODD 2 137 689 0'0'0' 2 0'0'5 162 QQQ~ 1 868 Q4Di 0'0'0': 1 769 580'1 529 1 0'00' 1 0'0'0'11 00'0'" 1 0'00', 1 50'1 000' 0'0'0' 0'00' 0'00' 1 1 1 1 1 730' 665 566 653 626 60'6 589 618 659 716 6921 278' 7131 469 0'88 0'41,1 372' 616! 521 761 90'4 838 765 772 721 693 724 752 684 689 70'6 695 710' 670' 673 876 998' 0'68' 5471 491, 1 1 1 1 1 432 298 240' 0'95 0'48 71 998 100' ... 1 "'1 ...
""1
:::I 64 58 51 47 42 38 38 33 32 30' 27 26 24 22 21 1421 686 0'15 580' 726 646 232, 8471 237 235 362 255; 7771 965 343 1
...
...
..·1 1;:6' 999 170' 0'81'1 90'5 995!, 077, 809 79 55'i 79 0'32 82 575 83 82 79 75 76 75 72 71 74 72 689 331 0'21 255 759 267 0'40' 651 0'0'4 455 f
80' 0'0'2 50'0' 2 681 6241 81 772 60'0' 2 696 638,
20'5 360 83 Q47j 950' 610' 1 731 0'14 165 40'6, 72 90'71 945 44411 751 194 168 467 71 485 631 140' 515' 691 122 869 0'94 99 114 493 91 4241 0'89 78 944, 68 67 62 57 54 80'11' 691 678 0'52 1 768 1
1950' 83 51 84 52 85 53 ' 87 54 88 1955 56 57 58 59 89 90' 91 92 92
4 4881123 837 934 4 4371, 143 963 953 4 60'1' 192 677 842 1 4 117' 216 974 715 3 6911 217 2311671 3 4171 20'3 824 676 3 373 193 274, 682 3 262, 187 119 697 3 2 2 2 2 2 1 1 1 1 0'95 183 838 179 677, 176 560' 185 3811181 097 914' 813 70'1 699 179 179 177 175 168 265 0'0'7 353 148 893 714 715 773 826 847
1
i
5zsj 1 0'37 169 46Qj 940' 818 445 , 814 268 , 189 939 2801 959 936 1291 1 1
861 9341 362 90'2 135' 115 158 341 1 516, 130'
1960' 93 418 61 94 285 62 95 178 63 ' 96 156 1 , 64 97 186
599 ' 644 265 770' 0'67 1
899 893 90'8 988 0'43
49 728 45 351' 42 7511 38 694 34
442'
293 , 465 797 442 967
98 274 961 1 823 697 11965 , 66, 99 0'56 000' 1 359 221' Note:
70'0' 438 1 123 259 , 33 742 670' 135 689 0'86, 26 20'6
21 260' 16 287
281 866 1 895; 890' 363' 928 4241 937 0'46 963 1 1 597 161 6171 954 1 245 148 168 940'
69 410' 69 323 71 394'1' 69 996 72 30'6 '
852i 77 195 0'72, 79 0991
Figures for 1966 are provisional. Annual Change of Death Rate.
decreasing in the following years until 1941, showing 16.0, in spite of the war. (per 1,0'00 population) In 1948, just 3 yeras after the ending of war, the deaths decreased under 1 million and its rate dropped. to 11.9, in spite of the fact that considerable number of deaths must have occurred during the war and immediately after the ending of war. It further continued Og",,~-,o,-~---;~*-:±c-;*-,,*--+k-'-,,*---,k--±-~""'-'-<> to decrease as low as to 7.8 in 1955. :::: ;: However, in 1957, because of the A, ~Year Influenza epidemic, it became 8.3, showing a slight increase. Then, it again decreased in 1958 and kept on the same level of approximately 7.5 until 1962. In 1964, the death rate of 6.9 was recorded, which was the lowest one ever recorded in our Fig. 4.
-11Table 4. Live Birth Rate Year Death i Natural Rate Increase Rate Vital Statistics in Japan. (Rates) Infant Death Rate (l900~1966)
'Neo-natall Maternal! . . I . I Death Death IStIll'blrth Marriage Rate Rate Rate Rate
Divorce Rate ------
!Per 10.000 I Per 1,000! total total! Per 1,000 Per 1.000 ,Per 1,000, Per 1,000 , Per 1,000 I births births Per 1,000! Per 1,000 popu· popu· popu· I live I !lve. I(live birth (live birth' popu·. ! popu-_ I births and and i latlOn: lahon I lation I lation I lation I births ; I I still-birth)still-birth)' -
,~-- ---~~--
I
---
1900 1910 1920
32.41 34.8 36.2 32.4 i , '
20.8 21. 6 25.4 18.2 16.5 16.0 16.1 16. 7
11.61 13.2 I 10.8 • 14.2 12.9 15. 7 14. 7 14.2 I
155.0 161. 2 1 165. 7 124.1 90.0 84. 1 85.5 86.6 I !
79.0 74.1 69.0 49.9 38. 7 34.2 34.1 33.8
39.81 33.3 i 33.0 I i
88.51 84.2 66.4 53.4 46.0 ' 43.4 41. 0 39.6 '"
7.91 9.0 9.81 7.9
1. 46 1. 21 0.99 0.80 0.68 0.69 0.64 0.68
i
;,-
1930 1940 41 42 43 44 1945 46 47 48 49 1950 51 52 53 54 1955 56 57 58 59 1960 61 62 63 64 1965 66 Note:
25.8 ; 22.9 20.7 19. 7 19.4
1
29.4 , 31. 8 30.9 30.9
...
...
11. 0 ; 9.4 10.2 !
9.3,I
34.3 33.5 33.0 28.1 25.3 23.4 21. 5 20.0 19.4 I 18.4 17.2 18.0 ' 17.5 17.2 I 16.9 ' 17.0 : 17.3 i 17.7' 18. 6 13. 7
14.6 11. 9 11. 6 10.9 9.9 8.9 : 8.9 i 8.2 7.8 8.0 8.3 7.4, 7.4 7.6 7.4 7.5 7.0 6.9 7. 1 6.8
19. 7 21. 6 21. 4 17.2 15.4 14.4 12.6 11. 9 11.6 10.4 8.9 10.5 10.1 9.6 9.5 9.5 10.3 10.7 11. 4 7.0
76. 7 61. 7 62.5 60.1 57.5 49.4 48.9 44.6 39.8 40.6 40.0 34.5 33. 7 30. 7 28.6 26.4 23.2 20.4 18.5 19. 3
... ... 31. 0 27.2 26.5
... ... 16.0 15. 7 15.9 '
... 44.2 50.9 66. 7 84.9 92.2 92.3 93.8 95.6 95.8 97.1 101. 2 100. 7 100.6
'"
... ... ...
I
... ... ...
12.0 11. 9 10.3 8.6 7.9 7.9 7.8 7.9 8.0 7.9 8.5 9.0 9.1 9.3 9.4 9.8 9.7 9.9 9. 7 9.5
1.02 0.99 1. 01 1. 01 0.97 0.92 0.86 0.87 0.84 0.80 0.79 0.80 0.78 0.74 0.74 0.75 0.73 0.74 O. 79 0.80
27.4 27.5 25.4 25.5 24.1 22.3 23.0 21. 6 19.5 18.6 17.0 16.5 15.3 13.8 12.4 11. 7 12.0
16.1 15. 7 15.5 16.4 16. 7 16.2 15.4 15.4 13.9 13.2 I
11. 6 :
i
10.8 10.0 9.2 9.0 8.0 8.3
I !
100.4 101.7 98.8 95.6 89.2 81. 4 98.3 I I
Figures for 1966 are provisional.
history of vital statistics. However, in 1965, it increased slightly, showing 7. 1, resulting from the influenza epidemic which affected the adult·age groups. On the contrary, the mortality revealed 6.8 in 1966 (Refer Fig. 4)
Infant Deaths Annual Change of Infant Death Rate. The changes of infant death rate have been almost the same as the death rates for all ages. Before 1925, the yearly infant death rate had been around 160 per 1,000 live births excepting the high rate in 1918 (188.6) due to the pandemic of influenza. It declined in the course of the years after 1925 until it became below 100 in 1940, and reached 39.8 in 1955. The decreasing tendency halted some· what in 1956 and 1957, but in 1960, it remarkably decreased to 30.7, and went down further, reaching 18.5 in 1965. In 1966, it again increased to 19.3. (Refer Fig. 5, next page)
-12~
Maternal Deaths Annual Change of Maternal Death Rate. The maternal death rate around 1900 was approximately 40 per 10,000 total births (live births and still-births), but it decreased every year until it reached the low rate in 1943, showing 19.4. Although some sharp increase of maternal death rate was expected after the war due to the increase of artificially induced abortions, it remained at the level of 16.0 in 1947. Thereafter, it kept a decreasing trend, reaching 8. 0 in 1965, and 8. 3 in 1966. Foetal Deaths
Fig. 5. Annual Change of Infant Death Rate. (per 1,000 live births)
___ Year
Annual Change of Still-birth Rate. In the vital statistics of Japan, a still-birth is defined as a foetal death in the fourth or more later month of gestation. The still-birth rate in Japan in early 1900's was around 90 per 1,000 total births (live births and still-births), and it kept decreasing until it became about 40 in 1943. After the ending of war, it again started to show the high rate of 44.2 in 1947, and rapidly increased in the following years, and became 101.2 in 1957. Since then, it kept on almost the same level of 100 or so. In 1961, it increased suddenly to 101.7, showing the highest rate ever recorded. However, it dropped to 98.8 in 1962, keeping a decreasing trend and reached 81.4 in 1965. In 1966, it went up again, showing 98. 3. The increasing trend seen before 1957 was believed to be due to the influence of enforcement of Eugenics and Maternal Protection Law. This is proved by the fact that the proportion of artificially induced abortion to the total still-births had increased to 51.6% in 1956 and 50.2% in 1958, respectively, from 21.6% in 1948, though it again decreased to 43.9% in 1966. This is enough to prove how widely the artificial abortions have been carried out in Japan, and this fact explains that the increasing number of population are becoming aware of the heavy burden of a big family. However, as the increase of artificially induced abortions is not desirous from the viewpoint of maternal health, the Government is making efforts to educate people to use safer methods of con traception.
Marriages Annual Change of Marriage Rate. The marriage rate since 1900 up to about 1935 had been approximately between 7 and 8 per 1,000 population, excepting some slight fluctuations before and after 1920. It went up to 9.5 in 1937 due to the war which started in the same year. Although the marriage rate went down rapidly, it again rose to 9-11 after 1940, as the marriage was encouraged by the Government in the course of development of war. Then in 1947, it became 12.0, showing the highest rate since 1900, which was considered to be a temporary state caused by family reunion and increase of
-
13-
postponed marriages after the war. It started to decrease in 1949, showing 10.3, and went further down to 8.0 in 1955, and 7.9 in 1956, respectively, to the normal level recorded in the pre-war days. However, after 1957 it kept an increasing trend, reaching 9.9 in 1964, although it again started to decrease from 1965 and reached 9.5 in 1966. Divorce3
r,
Annual Change of Divorce Rate. The divorce rate in 1900 was 1.46 per 1,000 population, and since then it kept decreasing until it became 0.63 in 1938. But after the war, it suddenly rose again, showing about 1.0. This was partly because of the increase of marriages after the war, and partly because of the new attitude of the people toward divorce. After 1959, however, the rate had been slightly decreasing year after year, and it reached 0.73 in 1963. From 1965, it again started to increase and reached 0.80 in 1966.
8.
Life Tables
Average life expectancy at birth for the Japanese people, according to the Abridged Life Tables prepared on the basis of 1966 data, indicates 68.35 years for male and 73.61 years for female, showing a slight increase compared with that of 1965. According to the 11th Life Tables (complete) based on the population census and vital statistics for the period of calendar year 1960, it was 65.32 years for male and 70.19 years for female, showing a slight difference from the data by the Abridged Life Tables. Table 6. Year *1891~1898 *1899~1903 *1909~1913 *1921~1925
Expectation of life. (eo).
(a)
Male.
Age ------~--·~i--~--~--~--~------~:----
I
01115,10120130140150160701 42.8 1 49.2 43.97 51.11 44.25 51. 61 42.06 49.14 51. 07 1 44.82 46.92 51. 951 23.9 I 28.8 42.6 47.7 ; 50.06 I 53.74 55.6 . 58.4 56.2 I 59.2 1 59.57 I 62 '14 58.0 60.6 60.8 63.5 61. 9 I 64.2 61. 9 64.3 1 63.41 I 65.45 63.60 65. 37 63.88j 65.64 63.59 65.28 I, 1' 'I'
*1926~1930 *1935~1936
."
1945 1946 *1947 1948 1949 *1950~1952
50.7 51. 90 52.57 50.35 51. 85 52.22 28.5 47.1 53.61 56.8 57.7 60.10 58.7 61. 7 61. 8 61. 8 62.80 62.45 62. 73 62.28
~
~
."
1950 1951 1952 1953 1954 *1955 1955 1956 1957 1958 1959 *1960 1960 1961 1962 1963
1964 1965 1966
*
Note:
63.24 65.01 I 61. 96 64.98 63.32 66.51 63.45 65.21 I 66.66 66.56 63. 26 65.32 65.37 66.62 I 63.32 63. 78 66.03 I 67. 18 66.23 67.21 63.75 64.45 67.21 I 67.67 64.68 67.73 , 68.16 64.58 68.35 68. 78 65.16 1 Complete life tables. I' 1'
~~:~~
!I
! 47.5 1 48. 23 48.82 46.53 I 47. 93 I 48.25 25.0 43.1 I 49.49 52.5 I 53.4 I 55.68 54.4 57.2 57.3 I 57.3 I 23 58. 57.89 58. 19 , 57.67 57.32 1 68 58. 58. 81 1 58.57 1 58.64 59.08 59.00 I 59. 70 I 59.93 59.80 60.38 I 1
I 39. 8
40.35'
1
~lli
33. 0 I 25. 7 I 18. 8 I 33.441 26.03 18. 97 41.~1 um a~ m611 39. 10 I 32.59. 25. 131 18.02 I I
12. 8 I 12.76 I ll~
40. 41 I 18. 5 I 34. 8 , I ~MI 43. 6
33. 89 20. 7 29. 5 I U~I 36.6 I 37.0 1
nal
~U
~G
11. 87
ll~
I
8. 0 I 7.89 8.W 7. 11 I I'
~al
aMI 29. 1 29.2
26. 221 18. 7 23. 1
I 44.3 I I
~~
45.3
I
!~: ~
37.4 I 29.4
~1O
affil ~6: ~
18. 85 I 12. 55 i 13. 6 ; 8. 7 I 16. 4 I 10. 4 I m44 ll~ 21. 5 I 14.8 I I
7. 62 5. 0 5. 9 I ~n 9.7 I 9.4 9.3 9.4 fiN I I
' 21. 5
~~: ~
21. 4 ' 14.4 I
21.~:
14.6
I
U~
8.~ I I
I
~~: * ! t~: ~
I 10. 1
48.0 1
48.47 48. 77
~~
~'W'I 31.~1 22.41 ~MiI 14.97 I~MIi 39.70 30.85 40. 00 31. 15 22. 72 i 15. 33 I ~211 ~~ m~1 21.%1 Uffi ~m 38.98 I'
39.3
30.6 I 22.2
15.0
, 47.87 1
~31i
~W
30.04 31.30 31.001 31. 05 31.~
49. 13, 40. 10 49.58' ~441 ~1O 1
~MI ~w
~311
31.~
21. 53 ~®
~UI ~~
14.14 ' ~w
9. 13 9. 56 8.58 8.31! 1
~~
1
22. 42 I
UM
14. 87 I 15.17 Uffi ~~ I'
a10 8. ffi l 8. 86 , 9.05 8.72 a~
a~1
40.521 ~30 ~w
31. 44 22.77 31.mj ~511 ~1O
50.33 I 41. 10 I 31. 96 50. 17 40.88 31. 72. 1
~nl UGI n~, ~~I ~U
23.25 I 15.51 I 22.99 15. 19 I'
9.30 8.97 a511
-14 -
Table 6. Expectation of life. (eo). Age Year
(b) Female.
o 44.3 44.85 44.73 43.20 46.54 49.63 37.5 51. 1 53.96 59. 4 59. 8
1
5
10
W
w i
40
50
I
*1891~1898 *1899~1903
*1909~ 1913 *1921~1925 *1926~ 1930
*1935~ 1936 1945 1946 *1947 1948 1949
*WW~W~ 1950 1951 1952 1953 1954 *1955 1955 1956 1957 1958 WW *1960 1960 1961
24. 65 16.59 26.44 18.38 &~ 71.~ ~n ~OO ~45 ~211 ~M m24 lli.1O 70.19 1 I 71. 17 67.79 63. 04 53.39 44.10 34.90 26. 03 17.83 71. 25 67.88 63.13 53.48 44.19 34.98 I 26.11 17.91 70.26 71. 63 68.17 63.39 53.72 44.35, 35.10 26.16117.90 70.79 W~ 71,WI 71.89 .~ ~W ~~ ~~I mlli ~OO wa n34 n~ &_\' M45 MW ~~ ~89 m89 lliMI 1964 72. 87 73. 22 69. 59 64. 761 54. 99 45. 48 36. 11 I 27. 09' 18. 69 W65 72.% &51 M65 M~ ~34 ~W m~1 lli.45 11. 10 -,-__1::-9"."6___ 6 _ _ _7",3"-.6:-:1"--,-,___7",3",.8"'2'-------'7-"-o.'-'1"'5---'---~6""5.'_"3"'0_'____"_5,,5:.~5"'3__'_'____'45e_._"9_'__7-.e;---"36. 5~. 45__ 18. 99 _ 11. 61 1 1
34.4 27.8 I 28. 19 34.84 35.72 , 29.03 34.69 28. 09 35.98 1 29.01 29.65 36.88 29.9 24.0 1 28. 8 36. 0 30.39 37.95 40. 2 32.5 32.6 40.5 ~~I ffi~ ~~ ~~I' ~~ ~W 32.771 32. 7 61. 5 63.9 62. 1 57.8 48. 7 I 40.8 64.9 67.3 65.6 61. 1 51. 9 43. 6 I 35.4 65. 5 ' 67. 6 65. 3 60. 8 I 51. 4 42. 8 34.2 I 33.9 65. 7 67.7 65. 3 60.8 51. 4 1 42.6 67. 69 69. 52 66. 921 62. 31 52. 86 I 44. 00 I 35.22 34.34 I 67.75 69.34 66.41 61. 781 52.25 43.25 68.41 'I 69. 99 67. 09 62.47 52.95 44.01 I 35.11 I 33.85 67.54 69. 131 66. 151 61. 49 51. 92 42. 84 1 67. 70 68. 75 65. 69 61. 021 51. 48 42. 39 33.391 67.80 63.08 53.48 4~33 35.23 69.61 70.99 I'
1 50.1 I 51. 5 I 48.1 40.8 I 51. 17 51. 97 48. 34 41. 06 51. 24 52. 16 48. 51 41. 671 1 49.42 50.71 'I 47. 00 40.38 1 52. 10 53. 00 49. 181 42. 12, I 54.07 54.40 50.47 43.221 43.4 43.6 40. 5 I 34. 8 55.5 54. 7 50. 7 42. 6 I 57.40 57.45 53.31 44.87 61. 9 60. 3 56.0 I 47.3 62.5 61. 1 56. 8 47.9 I
I
I
1
I'
1
20.8 21. 11 I 21. 84 20. 95 21. 671 22. 15 17.7 1 21. 4 22. 64 24.7 1 24.6 47 24. 24.6 27.3 25.9 25.4 I 1
26.58 25. 70 26.49 25. 14
60 14.2 14.32 14.99 14. 12 14.68 15.07 11. 8 14.6 15. 39 17.4 17.2 16.81 17.1 20.0 18.3 17.7 18.54 17.72 18.59 17.12
70 8.8 8.77 9.28 8.44 8.88 9.04 6.8 9.0 9.41 11.5 11. 2 10.34
11.1 12.0 11. 3 11. 82 10.95 12. 05 1 10. 34 9. 65 11. 48 11. 05 10. 78 10.85 ' 10. 69 10. 67 11. 26 11. 35
44441 (a)
nw
_,__I
Table 7. Year I *1891~1898 *1899~1903 *1909~1913
Number of Living (Ix). Age
Male.
0
I
: 100 000, 100 000 , 100 0001 1
1 1,~~5~~1~0_~~2~0 , 85 105, 76 239 73 6551 69 716' 83 9795601' 83
64314In~ln8917131~65~60101~~4116024~
30 I 40 I 50 60 70 639171'58178j5<J534-:W 073i23 1491 59 889 57 6181 52 999 50 267 42 1361 26 014 38 517,' 21 591,
*1921~1925 *1926~1930
100 OOOi 1
*1935~1936
1945 1946 *1947 1948 1949 *1950~1952
100 100 100 100 100 1 100 I 100
1950 1951 1952 1953 1954 *1955 1955 1956 1957 1958 1959 *1960 1960 1961 1962 1963 1964 1965 1966 • Note:
I
lCO
i~g ~~~I
100
100 100 100 100 100 OOO!
000 85~n4~n~72~65721IM~M~I'~~24DI 000, 88 697, 81 788, 80 141 76 189' 69 441 64 242 57 034 44 712 26 434 9 2531 3 572' 000 80 1301 70 6741 66 3771 55 709' 29 8411 19 997 14 7821 000', 87 530 81 477 79 668 76 1161 65 705 57 410: 48 596 35 499 17 481 ' 000 91~85~~_81~nl~m9~60~~~~~ 1 1 OOO! 93 500, 89 747' 88 589 86 3951 80 187'1 74 432 67 648' 56 111 36 6861 1 1 0001 93 370 89 514' 88 449 86 609 81 079 75 9021 69 331 1 58 026 38 1101 94 331 91 382 , 90 4811 89 1321 85 653 81 802 ' 75 859 64 481, 42 9971 1 W~OOm89mg~~~llm~72~MD~~ 1 000 ' 000 1 COO W~~EW91817100m~~64~mM6682llil~44~ 000 95 380 93 4111 92 776 91 6371 88 945 85 8411 80 7651 69 658 49 870 000 95 8171 94 2151 93 537, 92 499 89 9381 87 047 81 963' 71 115 49 434 oeo 95 830 94 230 93 533 92 498 89 972i 87 080 82 0321 71 1931 49 82 1
76 410 74 564, 70 846 65 0201 75 5671 73 749, 69 336', 62 950
'.
:=~~I~~:=,=~~m,~~~=~®
1
%9'Wm~81~~wIOOW~~~~713illl'~~
100 OCO, 95 767, 94 355! 93 766 92 7811 90 437, 87 6771 82 6241 70 947 47 8721 100 000, 96 216 95 030 94 494 93 586 91 364, 88 751 83 991 73 095 51 448 100 00° ' 100 COO 100 0001 96 637 95 616 95 130 94 238 92 217 89 750 85 168 74 2801' 52 114 100 oeo 96 826 95 936 95 481 94 590, 92 640 90 2851 85 836j 75 257 53 6471 1 100 000 1 100 000 100 000 97 719 97 082' 96 710 , 95 992 94 3841 92 1511 87 858 77 813 56 404 ' 100 000 97 918 1 97 3131 96 9671 96 2931 94 812 92 598 88 3191 78 330 56 251 I 100 000 ~W8~m~OOI%ww_~_g~n~~~ 1 Complete life tables.
==i=~i=~=llil~m'=~==~~~=I'
~==m===~==~=:~~ml'~~I'
/:;,;,
Year 0
Table 7. Number of Living C1x). (b) Female. ---- - - ----------Age 5 I
-
15-
----
10 ,
20 I ,
I
30 64 64 63 61 66 70 55 73 76 81 I
40
50
*1891",1898 # *1899~1903 *1909~1913 *1921~1925 *1926~1930 *1935~1936
1100 100 100 100 100
000: 000' 000 000, OOOi
71 85 908 78 3391 76 2451 71 1 85 496, 77 818 75 770 70 85 600, 77 1lO' 75 102 69 87 586 79 866 78 0531 73 90 84 90 92 94 83 2291 76 731 85 189 86 101 90664 1 94 110 90 3041 95 027 92 079 94 740, 91 382 94 910i 91 759 95 5801 93 119 95 510' 93 237, 95 950 94 016 96 311 94 800 96 340 94 817 1 96 278' 94 849, 1
86 62O, 78 028! 75 482,
I
60
70 27 28 29 27 31 35 17 34 40 46
I I , ,
073: 652 540[ 3791 069 792 266 346, 0671 367 329 978 819 664 315
479' 57 773! 51 874 58 3081 51 555 57 373, 51 885 55 536 49 215 60 3121 54 130 703 608,1 195 704 64 47 67 70 76 77 83 80 82 85 86 87 88 88 89 5151 893: 513 945 717, 58 39 60 65 71
OGG 41 826 1 794/ 42 9981 352 43 113 411 41 055, 285 45 819, 5371 959 781, 129; 100 49 30 50 56 62 63 69 66 69 72 73 76 77 77 77 78 79 80 81 81 82 8621 113 825 170, 1631 746 713 639 099: 345[, 529: 5991 213 219 641
745 783 465 1 544 328 204' 258 014 348 1
5941
1945 1946 *1947 1948 1949 *1950~1952
100 000 100 000 100000 100 000 1 100 0001 100 i 100 , 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 i
083 3101 350, 336/ 360[,
1950 1951 1952 1953 1954 *1955 1955 1956 1957 1958 1959 *1960 1960 1961 1962 1963 1964 1965 1966
000 0001 000, 000, 000, 000 000 000 000 000:
81 564 73278 83 630 84 793 89 676 1 89 3201 91 275 90 477: 90 979 92 402 92 93 94 94 94 95 95 95 96 96 96 547 461 271 2771 346, 076 163 562 029 0001 395 1
76 65 80 82 87 87 89 88 89 91 91 92 93 93 93
1
,
82 329 86 813 84 737 86411 88 686 89 90 91 91 91 92 92 93 94 94 94 257 412 525 451 799
728[ 72 359 189 78 325 528 75 347 736j 77 765, 426, 80 857, 319' 648 969 917 405 1 077 777 410 152 151 820
47 799 53 063 49 317 55 734 56 61 60 60 525 115 960 9371
1
1
I' 100 000: 96 895: 000 000 000 000 000 96 96 97 97 97 6751 969 261 238 456
1
"
95 5561 95 566 95 969 96394 96 366 96 707 955 363 663 880 ,
596 556 473 477 621 1 1 94 315, 94 507 g4 925 95 448 95 416 95852 96 1981 96708 97 041 97 298j
i
1
81 921 83 833 84968 84 959 85 518 86 87 87 88 88 89 90 91 91 92 153 196 949 741 750 621 1
1
503 90 874 90 450 91 058 92 045 92 6071 92
1
208 777 672 533[ 567 607
64 65 65 65 67
:~ :::1 165 161 624 761 246 823 717! 761 968
0001 97 618 96 000 97 919 97 0001 98 175[ 97 000 98 357 97 1
96673 97 117 97 423 97 661 97724 1
,
95 038, 95 677 96 087 96393 96 490
93 342 94 117 94 596 94964 95138
206 105 649 104
83 256 84544 85 308 85 789 1
67 69 70 70
100 000;
98 378,
97 9361
97 3461
I
I
I
I
92 433, 863591 72 088 I I 1
The prolongation of average life expectancy at birth for both men and women has been remarkable in the recent years. This is particularly due to the sharp decrease of mortality rates of younger population.
9.
Deaths by Leading Causes
,
- -....
As a recent trend, the deaths from those infectious diseases such as tuberculosis, pneumonia and bronchitis, etc. have decreased greatly, whereas the deaths from malignant neoplasms and other degenerative diseases have been gradually increasing, comprising more important proportion in the total deaths, particularly, the so·called adult diseases such as vascular lesions affecting central nervous system, malignant neoplasms, heart diseases, and some others have been increasing.
-
16-
Table 8.
Annual Change of Deaths and Death Rates by Leading Causes. (Rate per 100,000 population)
(1900~1966)
(Con'd to the next page)
, Vascular Lesions!
'00'00
Malignant Neoplasms
100 Heart Diseases
@® I Senility
Accidental Deaths
i affecting Central' Year I Nervous System
,--;,- B2~~R----N- B1 I I,
~:~~---:~ ~:: r ~~~:! I---~~ ::: :~. ~ 1- ~~ ~~~ 1920 1930 1940 41 42 43 44 1945 46 47 48
Ii--
88 186 104 942 127 125 125 120 8471 124 349 : 985 I
157.6 I 162.8 177.7 174.6 173. 2
40 648 45 488 51 52 53 53
r I
-;~<;~IB~2_7;---N B45!a ~ __ ,' __ ,i
:;±7'
BE~8
I
:::
~ 1- :~ ~~~--~~~-~ ~~ :~~: !!: ~ 73 468 76 591 89 540 89 673 1
72.6 70.6
35 540 41 138' 45 542 42543 43 487 45 428
63.5 63.8 63.3 59.2 60.1 62.3
131. 3 118.8 124.5 125. ]
26 198 I 26 295' 28 408 I I 28 808 ' 31 134 33 519 'I
46.8 40.8 39.5 40.2 43.1 46.0
166.0
879 949 897 I 580 :
72.1 73.9 74.5 73.5
95 9981 132.6 99 162 136. 1
I ... I ,
49 1950 51 52 53 54
101 095 94 329 100 278 105 105 110 116 116 121 133 138 136 142 728 858 359 351 925 504 931 181 767 858
129.4 117.9 122.6 : 127.1 125.2 128.5 133. 7 132.4 136. 1 148.4 151. 7 148.6 153.71 160.7 165.4 169.4 171. 4 171.7 I
53 886 56 633 59 889 64 428: 66 354 69 488 i
69.0 70.8 73.2
48 575 49 046 52 763 53 53 52 56 53 377 750 603 477 128
62.2 61. 3
64.5 64.2 63.6 61. 3
78 342 63 639 65 574 58 412
100.3 79.5 80.2 70.2 70. 7 69.3 77.6 69.5 67.1 75.8 80.5 55.5 56. 7 58.0 58.2 i 57.5 I 50.4, 48.4
38 533 38 975 34 277 32 850 31 968 31 215 34236 34812 33265 33258 34 528 35 785 41 662 38 964 41 38 39 40 6141 393
49.3 48. 7 41. 9 39.5 37.8 36.4 39.3 39.4 37.3 36.8 37.9
77.4 78.5 80.9 82.2 85.3 87.1 90.7 91. 3
71 578.
75 309 77721
64.9 60.2 60.9 66.0 73.1 64.8 67.7 73.2 72.1 76.2 70.4 70.3 77.0 71.1
59 59 67 61 59 68 73 51 52 54 54 54 48 46
796 514 514 334 932 414 283 046 6871 139 880 738 466 I 995 1
1955 56 57 58
81 879 83 155 87895 91 286 93 773 96 442 98 224 101 426 'I
54 351 59 543 66571
59 1960 61 62 63 64 1965
95.5 98.2 ' ]00.41 102.3 103.2 105.5 107.3 108.4 110.81
59 603 62 954 68400 68 0171 72 493 67672 68 328 75 672 70 417
38.9 44.8 41. 7
150 109 155 966
161 228 164 818 166 901
44.1 40.3 41.3 41. 6
104 324 106536 109 708
698 437 '
172 773 ' 175.8 173.4 _6_6_1171 716 I Note: 1) 2) 3)
49092 , 44 175 i I
50.0 40188 44.61 42 251
40.9 42. 7
In the upper column, "N" and "R" stand for "number" and "rates," respectively. Figures for 1966 are provisional. The encirled figure in the upper column as leading causes of deaths.
00, 00,
etc. indicates therank among
'~~-"@5 -~~~--'~(J)
17-
®--'----® Tuberculosis (aU forms) I
------,,' - - @ ) - _ . _ -
i
Year
Pneumonia and Bronchitis
Hypertensive Diseases ---
Suicide
Gastritis, Duo- I denitis, Enteritis " ---
~31,.,Jl32,- B4~a
Bl, B2
B28, B29
-
BE49 N ---~
N i R N R ,------ -----1'--- --' 1900 1905 1910 1915 1920 1925 1930 1935 1940 41 42 43 44 1945 46 47 48 49 1950 51 52 53 54 1955 56 57 58 59 1960 61 62 63 64 1965 66 99 115 128 137 130 326 877 730 1
and Colitis B36, B43b --
I
N - - - I... I
R
-I
R
N I
R 1
226.1 I 71 771 247.4 96 030 262.0 1113 ZU3 261. 1 115 913 408.0 125165 275.6' 115 956 200.1 119 635 186.7 132 151 185.8 175.9 177.4 191.8 153154 154344 161484 171 473
163.7' 2G6.0 I 230.2 219.7 223.7 194. I I 185.6 190.8, I
... ... I
I
5 863 8089 9 372 10 153
58 13. 4 17.4 I 63 19. 1 : 104 19. Z 117 1
664 9,9 950 988
I
133.8 137.2 213.4 223. 7 254.2 238.2 221. 4 173.2 159.2 142.8 142.0 153.2
228330 164 649 128 976 129 318 133649 126120 128438 139762
! ••• i
I'
10 630 I 12 249, 13 942 14172 i 9 877 9 713 9 393 8 7::: I
212.9 215.3 223.1 235.3
... i
19.0 142 278 I 20.5, 142 288 21. 6 142 673 20.5 119 931 I 13.7 114 538 13.6 102 13.0 102 387 784 111 688 12.1 I 'I'
I
136 524 174.8 78911 98.6 81 812 I 100.0 77 565! 93.2 69555 82.2 57586 67.1 62091 71.3 48256 54.7 43 154 48.3 43683 48.4 53923 59.2 43832 47.6 42018 45.2 46045 49.3 39245 41.6 42 861 I 45.0 31 899 I 33.2 31 212! 32. 1 36 663 27844 37.31 28.1
146 241 143909 138 113 121 769 93307 70558 57849 55124 46735 43874 42718 36274 32 992 31 959 27916 27 852 23 302 22 929 22 366 20028
187.2 179.9 168.8 146.4 110.3 82.2 66.5 62.4 52.3 48.6 46.9 39.4 35.5 34.2 29.6 29.3 24.2 23.6 22.8 20.2
9935 8865 8 950 9 343 9 100 9 073 10 371 11 158 12 565 13 503 15 115 16 083 17 547 17 469 18 207 18 987 18 377 'I'
12 262 12 753 14 201 11. 9 16 311 10.5 15 415 10.4 15 776 10. 7 17 731 10.3 20 635 10.2 22 477 11.5 22 107 12.2 22 136 13. 7 23 641 14.5 21 090 16.2 20 143 17.1 18446 18.4 16 724 18.2 , 15 490 18.7 I 14 707 19.31 14 444 18.6 14 837 ::: I'
...
!
15. 7 15.9 17.4 19.6 18.2 18.4 20.4 23.4 25.2 24.5 24.3 25. 7 22. 7 21. 6 19.6 17.6 16. 1 15. 1 14. 7 15.0
106 838 136.8 87 890 109.9 75 748 92.6 68540 82.4 57 214 67.7 45 552 53.1 40 139 46.1 34 436 39.0 28 289 31. 7 27 077 30.0 23 425 25. 7 23 128 15. 1 21 674 23.3 19 791 21. 2 19.5 18 383 17 143 I 18.0 15 449 , 16.1 14 180 14.6 12.9 12 705 11 152 11. 3
I
----------------~~
..- - - - - - - - - .
Table 9. Int'l Abbreviated List Number
Percentage of the Selected Causes to the Total Deaths. -----------
Causes of Death Tuberculosis (all forms) Malignant Neoplasms Vascular Lesions affecting Central Nervous System Heart Diseases Hypertensive Diseases
1950 , 1960 . 1965119661 13.5· 4.5 7.1 11.7 5.9 3.2 I
Bl,2 B18 B22 B25~27 B28~29
3. 0
13.3115.2 21. 2 ,. 24.7 9.7 10.8 1
16.4 25.6 10, 5
B31, 32, 43a B36, 43b B38 B45a
Pneumonia and Bronchitis Gastritis, Duodenitis, Enteritis, and Colitj.s Nephritis and Nephrosis Senility
- ; 2. 1 I 2.7, 2. 7 I 8. 6 i 6. 5. 5. 2 I 4. 2 ;
7.6: 2.8 1.8: 1.71 3.0 ! 2.2, 1. 6 1. 5 6.5 3.6 1. 8 30.8 I I
BE47, 48 BE49 Note:
Accidents Suicide Others
7.71 7.0 5.5 I 5.7 2.9 21. 6 I
I
6.6 6. 3
i
2 1 20 0
I'
2.2 19.31 1
The total deaths of each year are calculated as 100%.
-
18-
10. Maternal and Child Health Statistics As stated in Chapter 7, "Vital Statistics" (page 9) of this report, there has been a steady decline in the numbers and rates of neo-natal and infant deaths in the recent years, while the figures for still-birth have remained considerably high. Maternal deaths also have been gradually decreasing in numbers and rates, but still it should be noted that there is a great deal to be done to improve maternal health in Japan. Of a total of 1,823,697 live births reported during 1965, number of live births which took place in hospitals, clinics or maternity homes, was 1,531,812, representing a percentage of 84.0 to the total. This is a remarkable rise in the rate of institutional delivery for these 14 years; the figure being 4.6 for 1950. Analysis of maternal and infant deaths by leading causes of death for the year 1966 with the comparison for the past several years is shown in the following tables. Table 10. Infant Deaths and Death Rates by Leading Causes of Death. Infant Deaths ____ I
.~
(1955~1966)
Infant Death Rates (per 1,000 live births) 196511966 i
11955 All Causes Infectious and parasitic diseases Pneumonia and bronchitis Gastro-enteritis 1
i
1960--1964
1965, 196611955 1960 11964 30.7! 0.9 8.6 2.3 1 9 . I
'I " 168 80149 29334 96733 73726 206 39.8 i
20 4' O' 4
18.5 0.3 3.6 1. 0 2.0 1. 8 6.9 2.8
19. 3 0.41 3.4 1.
2 491 1 396
1
735!
582
542'
1. 41 9.4i 3.4'1' 2.1 0.8 , 16.2 6.5
1
16 325 13 761 7 479 6 615 4 633 5 821 3 772 2 214 1 912 1 437 3 564 ' 3 05613 368 3 587 3 062 1 325 2 494 3 050 3 256 2 731 1 1
i
4: 3' 1 3 1
~I
Congenital malformations Birth injuries, post-natal asphyxia and atelectasis Other diseases peculiar to early infancy and immaturity unqualified Others Note:
2: oil' 1. 8 1 '
2 3
.~
1.6 10.8 4.7
2. _I 731' 2.91 I
28037172791295712 6d 9 861, 11
I i i 238, 7 535 5 162 5 132, 3 ! I
7.5, 3.0
1
940
1
1
"
Figures for 1966 are provisional. Maternal Deaths and Death Rates by Leading Causes of Death. Maternal Deaths 1955 11960 11963 1964 (l955~1965)
__ ,_ t
Table 11.
Maternal Death Rates (per 10,000 live births)
i 1965 1955 11960 I 1963 i 1964 1965 i
All Causes Puerperal fever Toxaemias of pregnancy
3 095' 2 097 1 701; 1 69911 597
17.9 0.8 6.5 4.8 1
13.1
10.2' 0.5 4.0 2.5 1.0 0.4 1.8
9.9, 0.4 3.5
i
8.8 0.3
I
1411 1 1241 I
108 809 507 232 63 378 1
82 662 411 1
681 608 '
52, 628 387 145 I
O. 7 1
5.0 1 3.21 1 1. 41 1
3.41 2.1 1
Haemorrhages Ectopic pregnancy
1
1
831 373 1211
423 , I
2.5 1.0 0.4 2.1
__ L
Abortion without sepsis
1
!
Others
1711 69 306,1
180 62 358
2.2
0.81 0.4,
641
0.7[ 2.9
0.4 2.4
-
19-
Clinics for Mothers and Children
'_r
Every expectant woman is required to report on her pregnancy to the local authority in accordance with the Maternal and Child Health Law. All expectant and nursing mothers and guardians of young children are encouraged to receive health guidance concerning pregnancy, child-bearing and child care from the medical, dental and nursing staff. To this effect, the Prefectural and Municipal Health Centers regularly provide the ante-natal, post-natal and child health clinics, where mothers and young children can obtain advice and preventive treatment. In addition, an increasing number of local government authorities is providing such clinics for mothers and children living in their areas. The reports indicated that these health clinics had been mostly attended by the infants under 1 year of age, while attendances at clinics were falling off as the child grew older. To cope with such situation, a special programme has been in operation since 1961 for all 3year-old children to attend clinical sessions arranged by the Prefectural Government. The main purpose of those special clinics is not only to give routine medical examinations and advices on the general health of children, but also to find the children with physical and/or mental defects which require medical or protective treatments. During the calendar year 1965, 817,344 visits were made to the clinics by mothers, and 4, 983, 207 by children. Home Visiting Activities In addition to the provision of clinical services at the Health Centers, the home visiting for mothers and children is generally conducted by the nursing staff of the Health Centers and of other health agencies. The number of home visiting conducted by the public health nurses was 286,190 for mothers, and 765,211 for children during the calendar year 1966. As it seems to be of a great importance to provide more sufficient care for the newborn infants in order to reduce the high neo-natal death rates, the Health Centers have been making special arrangements for midwives in private practice and public health nurses to pay frequent home visits to the newborn infants since 1961. The number of visiting cases was 699, 332 during the calendar year 1966. A special project to provide the home visiting services to the pregnant mothers has been in operation since 1962. Because of a lack of nursing staff in the Health Centers, the midwives in private practice are employed on part· time basis for these home visiting. 286,190 cases were visited during the calendar year 1966 under this service. A new programme was commenced from 1963 in order that the patients of serious toxaemias of pregnancy could receive medical treatment in hospital mostly through the public expense.
...
. ---
Voluntary Activities The voluntary community activities have been encouraged for maternal and child health programme in rural as well as in urban areas. A large number of community organizations have been working in close co-operation with the local health authorities, and have been taking part in mothercraft training and in other various services.
-
20-
MCH Centers in Rural Areas
In the rural areas, where mothers and children had to travel their long way for receiving health guidances and consultations at Health Centers, the provision of maternal and child health services presented great difficulties. In order to relieve the proble ms and to meet the needs of mothers and children in such areas, the Maternal and Child Health Centers have been established in the rural villages and towns since 1958. Though it is small, the building includes rooms for ante-natal and post-natal clinics, class-room, demonstration room for nutrition guidance, and accommodations and facilities for childbearing mothers. Now, the total number of MCH Centers reached 459, and additional 44 centers will be constructed during the year 1967_ Premature Births
" •
Every infant born with the weight of 2,500 grammes or less has to be reported to the respective Health Center immediately after its birth. Public health nurses or midwives of the Health Center may visit the families with premature infant to advise them on the proper care of such infant at home, and if necessary, the baby-incubators of open type are lent to the family. The premature infants requiring more complicated care are treated in hospitals designated for this purpose, and the costs of hospitalization are mostly supported by the national and local authorities' subsidy_ During the calendar year 1966, 58,657 low-weight birth babies were reported, (77, 281 for 1965)_ Public health nurses paid visits for 55,019 cases (77,196 for 1965) of premature infants during the same period_ Tuberculous Children
Children staying in tuberculosis sanatoria for a long-term treatment of bone and joint tuberculosis as well as other tuberculosis may receive financial aids from national and prefectural authorities for all expenses for medical treatment, school education and other daily living costs required for the children. Approximately, 2,300 children were aided under this scheme during the year 1966_ Other Services In order to improve the condition of nutrition of expectant and nursing mothers and infants, a special programme started from 1965, enabling mothers and infants in indigent families to receive milk free of charge every day. As for the informations regarding rehabilitation of the physically handicapped childlen, they can be found in Chapter 24, page 48 of this report.
11. Family Planning Under the general social confusion and economic distress followed after termination of the last World War, there were unbalanced situation between population and national economy. People paid usual attention to the overpopulation and the need for limiting family-size was recognized among the people, thus the induced abortion became prevalent among the people, and undesirable effects were caused by the obstetric operation. In
,
-.
-
21-
such days in 1948, a law was carried into effect, the provisions of which made the induced abortion legal under certain conditions, i.e., the qualification of doctor in charge, medical and social indications of the women to undergo operation, etc. The reported number of induced abortion was increasing upto the year of 1955, when it reached 1.17 million. In 1952, the Government decided to provide the movement for the promotion of conception control instead of induced abortion. In the beginning of the movement thus resumed, the voluntary organizations performed introductory work to the general public, and in 1955, the Ministry of Health and Welfare launched a special programme to dissemintate the practice of contraception among the indigent families. The Prefectural and Municipal Governments have been playing leading and supervising parts in family planning services under public and voluntary basis in the areas. The Health Center not only routinely provides consultation clinics, but also frequently organizes mother's class, discussion group, newly married couple class, and other group meetings on the subject of family planning. Personal guidance is conducted by the doctors and those "contraception instructors," who are the qualified midwives, public health nurses, and clinical nurses received particular training through attendance at formal course given by the Government. In the above-stated special programme for the indigent families, who desire to practice contraception, the costs needed for personal guidance, the contraceptive appliances and drugs are aided through the expenditures of the Central and Local Governments. Besides the services provided through governmental scheme, some of the enterprises have been taking up the guidance on family planning as one of the welfare measures for their workers. The yearly reported number of induced abortion has been decreasing after the promotion of those measures, and in 1966, it was 808,378 cases. According to the sampling survey carried out by the Government and some press authorities, it is estimated that the current users of contraceptives reached more than 53% of the total couples, and more than 90% of couples have the know lege of contraception. The economic and social situation of Japan has been improved, and there is a fundamental idea that the problem of health and family planning should be the first one to be solved as personal aspects, and Government prepares several facilities for the people. Thus the meaning of family planning is understood in a way to construct happy family by keeping mothers' health and children's welfare in Japan.
12. Health Education The Health Centers perform extensive health education programme m the field of communicable disease prevention, care of infants, insect and rodent control and improvement of environmental sanitation. In addition, the school health education is performed by the school authorities under the direction of the local Education Board, whereas the industrial hygiene education is conducted by the local Labor Standards Offices. In the rural area, agricultural extension service is carried out under the direction of Ministry of Agriculture and Forestry which includes health education programme for the farmers.
-
22-
Radio and TV broadcast, movies, slides and exhibits are employed extensively. National congress on health education has been held annually for training and for conference, and the regional discussion groups on health education meet often for the exchange of views and ideas.
13.
Tuberculosis Control
Tuberculosis Control Programme in General The tuberculosis control programme is completely defined in the Tuberculosis Control Law, covering the responsibility of national and prefectural health authorities on the expenses for prevention of diseases and medical treatment of the patients. This law also provides for the health examination for case· finding, BCG immunization, reporting and registration of new cases. The voluntary activities for tuberculosis control has assisted the Government for carrying out the programme a great deal. Because of development of chemotherapy and technique of surgical operation, during the last 19 years, a good result has been obtained in slowing down the tuberculosis death rate yearly as shown in Fig. 6, which gives the comparison with the death rates of vascular lesions affecting central nervous system and malignant neoplasms during the years 1947-1966. Furthermore, the decrease of tuberculosis death rate is remarkable among younger age-group compared with the older age-group as shown in Fig. 7. Fig. 6. Annual Death Rate of Tuberculosis. Fig. 7. Annual Change of Tuberculosis Death Rate by Age-groups.
-Vas~ull1r
lo~kn8
af!8":)~g
t9'lt;a.1
J,\ ------ ......... \~._/
I
nerVCllSs~8tell
500 ~;a
-,,~
----
H;~
----;~6Ij
r.
(
'. '~--
1""
l
19,0
1",5
1%(1
1965
': .'. ; C _-.t' )0
_.-.-.-.--- _/ • 30 40 per Ion ~ ~
/ "'>\" iP ~
•
Al"_ V.. th Rde
OOOpop"la"~n
There were 20,028 deaths (20.2 per 100,000 population), during the calendar year 1966. Although the tuberculosis death rate for whole Japan has been gradually decreasing, we have noted an indication of difference of death rates among prefectures. We conducted three tuberculosis prevalence surveys, i.e., in 1953, 1958 and 1963,
-
23-
to obtain the nation-wide information on the existing status of tuberculosis, and the valuable data were obtained on a statistical sampling basis. According to the 3rd tuberculosis prevalence survey, it was revealed that there were 2.03 million active cases and 1.41 million inactive cases. When we compare the decrease of tuberculosis cases during the period of 1953-1958 with the period of 1958-1963, the decrease of tuberculosis cases during the latter 5-year period is larger than that of the former one. Early Case Finding and Preventive Vaccination The health examination for case-finding consists of routine and extraordinary examination; the former is applied to all the people above 6 years old once a year free of charge, and the latter is applied to some professional groups such as barbers, foodhandlers, and family member of patients, etc. During the calendar year 1966, 42, 822, 000 persons (42, 709, 000 persons for 1965) received the health examination for case-finding purpose. Among them 37,381,000 persons (37,269,000 for 1965) were examined by photofluorography. The case finding rate for 1966 was 0.15% (0.16% for 1965). Among those negative reactors against tuberculin, 4,081,000 persons (4,829,000 for 1965) were immunized with BCG vaccine during the same period. The statistical figures for various health examination and BCG vaccination for the past several years are shown in the following table. Table 12. Tuberculosis Health Examination and Preventive Vaccination.
'.,
(1955-1966) (in thousand persons)
II
Year .
IN f P~~s~ns 26 33 35 38 37 39 42 38
Examined
Tuberculin Test Examined j Persons I Reactor3
I Examined I Examined i Persons i Pers,onswith , with i diagnosed i received . Po;iti~' PhotofluoroRadiograph i as TB Case' BCG VaccI~~y y
,--------~.-
20 24 21 21 19 19 18 15
nU~
-------
1955 I 57 59 60 61 62 63 64
531 152 714 I
838 165 380 621 876
439 889 120 411 140 216 574 807
_:_:-,-_:_~_~~: _1- ~: ~~: Note:
13 117 16 280 13 896 13 346 12607 12866 12 055 10 409 10 758 10 821
17 24 29 32 31 34 33 33 37 37
923 589 679 625 837 070 699 678 269 381
755 1 000 1 205 1 269 1 180 1 211 1 315 1 207 1 172 1 174
130 108 132 142 117 106
6 6 6 6
094 690 279 346
5 590
97 77
5 412 5 061 4 605
69 62
4 829 4 681
----'-- - - - - - - - - - - - - - - - - - - -
A year stands for the calendar year period.
Reporting and Registration The law requires the physicians to report to the respective Health Center when they detect tuberculous patients. These reported cases are registered in the Health Centers. The total number of registered patients as of the end of 1966 was 1,405,289 (1, 469, 583 for 1965), and 63.1% (63.396 for 1965) of which were active cases. 21. 4% of active
- 24-
cases were hospitalized, 60.9% were under domiciliary treatment, 15.8% did not receive complete medical treatment, and the remaining 1.8% (2.7% for 1965) was unknown of any disposition. The number of newly registered cases during the calendar year 1966 was 279,833 (282.5 per 100,000 population), 18.0% (50,506 cases) of those were infectious. (Refer Table 13).
Table 13. Rate of Newly Reported Tuberculosis Cases. - I- -
Year 1950 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65
Rate of Newly Registered TUberculosis Cases (per 100,000 population) 636 698 683 583 593 580 574 572 542 538 524 446 407 387 356 310 283
Medical Treatment The law specifies that a half of the treatmet expense of patients requiring chemotherapy and surgical operation is to be paid out of the local government fund, a half of which is subsidized through the national treasury. The rest of the expense may be covered by social insurance or public assistance. The law requires that, in the case when a person engaging in certain occupation such as barber, food-handler, etc, is found 66 to have infectious case, he may be prohibited to Table 14. Number of TB Beds and continue his work, and in the case Occupancy Rates. where there is a danger of infecting Occupancy his family, he may be compulsorily Year I Number of TB Beds Rate (%) hospi talized. In these cases, the ex1951 125 204 penses of medical treatment will be 96 52 153 861 96 born by the Government. 53 178 424 96 The total amount of expenses for 54 210 062 95 the treatment of tuberculous patients 55 236 183 91 in the country is estimated to be 56 252 803 86 about 110 billion yen in 1965 (108 billi57 261 375 83 58 263 235 82 on yen in 1964), which is equivalent 59 260 124 77 to 9.496 (11.0% for 1964) of the total 60 252 208 76 amount of expenses spent for medical 61 245 975 78 care of all kinds of illness. 62 241 305 80 Facilities As of the end of 1966, total number of tuberculosis beds amounted to 211,527 and the occupancy rate was 73.8%. (Refer Table 14). 63 64 65 66 --------.-
"'-
235 227 220 211
150 454 757 527
80 78 75 74
--, -'
I
y'
/-
14_
Leprosy· Control
Basic policy on leprosy control is completely defined in the Leprosy Prevention Law. The original Leprosy Prevention Law was promulgated in 1907 and was amended
-
25-
._'
twice thereafter. Now, the current Leprosy Prevention Law provides not only the prevention of leprosy, medical care and promotion of welfare of the leprosy patients, but also the financial assistance of the needy families of the institutionalized patients. In addition to these provisions, the programme for leprosy has been greatly promoted by the patronage of the Imperial Family and the activities of religious and voluntary groups. The decrease of number of leprosy patients in our country by means of a half century's efforts for the leprosy control programme has been remarkable, and the gradual decrease of the number has been well proven by the fact that, according to the first nation·wide prevalence survey in 1900, there were 30,359 leprosy patients identified, whereas the present number of leprosy patients decreased to about 1/3, and the prevalence rate became about 1/6. In the calendar year 1966, the number of newly reported cases of leprosy was 106 (125 for 1965). The total number of reported leprosy patients as of the end of 1966 was 10,404 (10,607 for 1965) with a prevalence rate of 10 per 100,000 population, 9,715 patients of which were institutionalized at 11 national and 3 private leprosaria. The following table indicates the yearly changes of leprosy patients and newly reported cases. Table 15. -
<~
Number of Leprosy Patients and Newly Reported Cases. Prevalence Rate i • d I Newly Reporte per 100000 , ' Cases Population 22 21 18 12 12 12 11 11 10 10 257 235 211 175 135 125 106
..".
Year
Number of Patients --,No;ho~pitalized Total Hospitalized I
I I
---------
1930 40 50 60 61 62 63 64 65
14 261 11 326 11 094 11 11 11 10 587 414 215 983
3 261 8855 8325 10 645 10 492 10 339 10 163 9994 9 874 9715 -------
11 000 2 471 2 769 988 922 876 820 754 733 689
66
10 748 10 607 10 404 -------
• --
The total number of beds available in those leprosaria were 12, 950 and 280 beds, respectively. All expenses necessary for those patients in leprosaria are wholely met by the Government. As for the type of leprosy, 7,207 (74.2%) patients in leprosaria were lepromatous type, 1,418 (14.6%) tuberculoid neural, 983 (10.1%) tuberculoid macular, and other 105 atypical type, as of the end of 1966. In speaking of geographical and age distribution of leprosy patients, more patients are found in southern part of Japan than in northern part, and the average age of those institutionalized patients is about 50 years old and the one for those uninstitutionalized patients is abDut 10 years older than the former. Besides, the average age of leprosy patients has been getting older year by year.
15.
Adult Disease Control
Because of decrease of infectious diseases and aging of population, the death rate of vascular lesions affecting central nervous system, malignant neoplasms, and heart diseases
-
26-
have been increasing in the recent years, and they have been occupying a leading position among various causes of death, and they are now coming up to 60% of all deaths. They are treated as "adult diseases," and in 1958, the Government established the "AntiAdult Disease Council" in order to set up the plans for preventing and controlling these adult diseases. Surveys The Government carried out a survey on malignant neoplasms in 1958 on nationwide scale for a total of 13,127 patients discharged from 4,594 general hospitals for the period of September-October 1958. By this survey, we found that, out of all patients received operation, 70.6% of them were able to be radically operated and that 70.8% of them were discharged successfully. There were big differences among live discharge rates according to organs affected with cancer. We found that the live discharge rate of uterus cancer was high, inspite of the low rate of stomach cancer. After this survey, the similar surveys were made in 1960 and 1963, and we found new characteristics on cancers, for example, regional and age·group differences, relation between stomach cancer and the feeding habit of people and so on. As to hypertension, the Government carried out, in 1961 and 1962, a nation·wide sampling survey of population of 30 years old and over on the distribution of blood pressure, the situation of medical treatment, the incidence of stroke, and etc. It has been well known that the dealth rate of vascular lesions affecting central nervous system in Japan is remarkably higher than that of other nations. Some of the findings of this survey are as follows: 1) 25% of those who were examined showed 150 mmHg or over In systolic blood pressure (160 mmHg or over in case of the age·group of 60 years and over) ; 2) 13% of 8,600 examinees in electro-cardiography showed abnormal findings of heart; 3) 3596 of 8,400 examinees in ophthalmoscopic observation of ocular fundi showed abnormal changes of retinae (3% of them were in higher grades). 4) It was estimated that the number of those suffering from the vascular lesions affecting central nervous system was about 310,000 persons in the whole country. Cancer Control Activity
1. Equipment of Medical Facilities In order to improve the function of medical facilities, the Government started to facilitate cancer treatment centers in national hospitals in 1954, which was a part of the programme for establishing a network of cancer hospitals throughout the country, and in 1956, the National Cancer Center was established, which consists of three major parts, i.e., hospital, research institute and administrative department, as a central facilities in Tokyo. Following this, the local cancer centers in nine bloc of whole country and cancer departments in other main hospitals at prefectural level are being established. 2. Training of Specialists and Research Training of doctors, nurses and X·ray technicians specialized in cancer, improvement
-
27-
of fundamental and applied research are another important programmes which are being promoted by the Government. 3. Cancer Finding Mass-examination In order to control stomach cancer which is characteristically high in incidence among our nations, the Government started the mass-examination campaign by using stomach cancer mass examination car equipped with indirect photofluorography. During 1966 fiscal year more than one million population who were mostly 40 years old and over were examined by the mass examination for stomach, and 120, 000 women of 35 years old and over were examined for uterus cancer. 4.
Voluntary Activity
The Japanese Foundation for Cancer Research (Gan-Kenkyu-Kai) established in 1908, is serving for the investigation, medical treatment and health education of people for cancer, and the Cancer Control Association (Taigan Kyokai) organized in 1958, is serving for improving the people's defence for cancer by the education, practising mass screening examination and training of specialized personnel, in good cooperation with governmental activity. Activities for Stroke and Heart Disease Hypertension is the widely spread disease among adult population, and the general practitioners play an important part for the prevention of stroke and heart disease. On the other hand, the Government has organized and established the hypertension and heart disease centers in the several national hospitals for improving diagnostic and treatment facilities in the regions. Training of health workers for the purpose of improving ability for the rehabilitation of apoplectic person is another important government programme, which was started in 1965.
16. Communicable Disease Control Communicable Disease Control Programme 1. Legal Aspect The communicable disease control programme is based on the Infectious Disease Prevention Law, Preventive Vaccination Law, Venereal Disease Prevention Law, Trachoma Prevention Law, and Parasitosis Prevention Law. As for tuberculosis and leprosy, they are treated separately. The Infectious Disease Prevention Law provides, in detail, diseases with reporting obligation by the physicians, and those measures such as isolation of patients, disinfection of the infected places, and other specific obligation of the national and local health authorities for the control of the spread of specific communicable disease. At present, the following 12 diseases are specified by this law, i.e., cholera, dysentery, typhoid fever, paratyphoid fever, smallpox, epidemic typhus, scarlet fever, diphtheria, epidemic meningitis, plague, Japanese encephalitis, and acute poliomyelitis. In addition, the following 12 diseases are required to be reported of their occurrence by physicians, i.e.,
-
28 -
influenza, rabies, infectious diarrhea, whooping cough, measles, malaria, tsutsugamushi disease, filariasis, yeJlow fever, anthrax, tetanus, and relapsing fever. The total number of beds available for accommodating those patients with reportable diseases were 33,412 as of the end of 1966. 2. Preventive Vaccination The Preventive Vaccination Law provides enforcing of both regular and emergent immunization. a. Regular immunization: (1) SmaJlpox-3 times; during 2-12 months after birth, during 6 months before entering primary school, and during 6 months before graduating from primary school. (2) Diphtheria-4 times; during 3-6 months after birth, during 12-18 months after the first immunization, during 6 months before entering primary school, and during 6 months before graduating from primary school. (3) Typhoid Fever and Paratyphoid Fever-during 36-48 months after birth, and thereafter, once a year up to 60 years of age. (4) Whooping Cough-twice; during 3 - 6 months after birth, and during 12-18 months after the first vaccination. (5) Poliomyelitis-twice (by attenuated live vaccine); during 3 -18 months after birth. b. Emergent immunization: Besides the regular vaccination programme, the law provides immunization for epi(\emic typhus, cholera, plague, influenza, and Weil's disease in case of their epidemics. Table 16. Number of Persons who received Immunization. (1961~1966)
(in thousand)
r-~-~--·-~···~.-=-----
I Sma~~pox-v-a-c-c-in-a-t-ion I Typhoid & Paratyphoid i Vaccination Diphtheria Vaccination
i
Vaccination
-
Year
------
1961
1962 3 702 20 184
1963
1964 3 321 17 811
1965
3 918
4 130 19 032 2 288 98 3718 3
18 701 2 973 208 3195
1: :~: 2 040
I
'r: ~:: 1 951
1966
2 483 100
2 128 108 3 325 10
I
Pertussis Vaccination Diphtheria·Pertussis Combined Vaccination I Epidemic Typhus Vaccination Poliomyelitis Vaccination (attenuated live vaccine)
76 3 561 11 2
47 3 459 5
3 670 11 23 375
15 _1_27220 I
14 473
~49 I
487
2 519
3, Fcorecastillg of Outbreak of Communicable Diseases It is very important to forecast outbreak of communicable disease to plan essential measures for the successful control of its epidemic. This programme has, therefore, been operated for several diseases in order to forecast the possibility of the iroutbreak by investigating various epidemiological factors such as susceptibility, source of infection, environmental conditions, and etc. The forecasting method for each communicable
-
29-
disease is different with each other, because of its different epidemiological character. The brief account of forecasting method being applied for poliomyelitis, diphtheria, Japanese encephalitis and influenza is as follows: a. Poliomyelitis:
(1) Susceptibility study, neutral antibody titer survey by age·group, for 80 persons in each area (2 or 3 areas each in 19 prefectures). (2) Isolation and identification survey for foci of infection of such entero-viruses as poliovirus in stool for 40 persons in each area (2 or 3 areas each in 19 prefectures). b. Diphtheria: Susceptibility study by age-group. Schick's reaction test for 150 persons in each area (3 areas each in 10 prefectures). c. Japanese encephalitis: (1) Susceptibility study, neutral and HI antibody titer survey in blood by age· group for 180 persons in each area (2 areas each in 6 prefectures). (2) HI antibody titer survey in blood for about 20 pigs collected at. one or two slaughter houses each in 40 prefectures. d. Influenza: HI antibody titer survey in blood for the influenza-like patients and virus isolation in each hospital (2 hospitals each in 10 prefectures). Prevalence of Major Commnnicable Diseases During the period of January 1966-August 1967, Japan was free from the quarantinable diseases. The occurrence of two cholera cases, one is the non-imported (3 August 1964) and the other is the imported case (11 October 1964), was the last incidence. Most of other acute communicable diseases remarkably decreased and were well under control during the same period. The high-lights of some communicable diseases are shown as follows.
1. Poliomyelitis As shown in the following Fig. 8, the incidence of poliomyelitis was dramatically reduced after the successful <:"". oral administration of Sabin ,... \ type virus vaccine since 1962. \ ; We are convinced, howe'" ver, that we should continue ~ surveillance of immunity amo'\ I, 1\ " ng the inhabitants as well as I \ proper immunization and try I \\ ' M. JOVO \
:
1
~,
"
i
/)'-
'0 I,_~"---,_
J'
-I-~l~c,~;~~-1962 269 19€3
~~-I-,'9~ J~6j
1961
"
to make close examination for the differentiation with other similar diseases in character.
2. Influenza Japan suffered, to various extent, from influenza epidemics in the past. Last year, influenza epidemic started to occur from early February and prevailed until latter
- 30-
March all over Japan, which ended in April. The epidemic was mainly due to type B, but type A, in some areas of northern part of Japan. The number of cases was 41,457 in 1966. This year, it started from the end of January and lasted until latter April all over Japan. This time, epidemic was mainly due to type B, but type A, in Tokyo. Estimated number of total cases was about 50,000. It is very difficult for us to set up rational counter·measures for influenza, because of its character of rapid world-wide spread and of many changeable variation of virus strain. However, it is noteworthy that we are carrying out intensive immunization programme on the planned basis through the epidemic forecasting method. 3. Japanese Encephalitis The number of cases, case rate, number of deaths and death rate of Japanese encephalitis since 1955 are shown in the following table, and the number of weekly incidence is shown in Fig. 9. Table 17. Annual Change of No. of Cases, Case Rate, Deaths and Death Rate of Japanese Encephalitis. ~r-
Fig. 9.
I~i Year 1955 56 57
"J
No. of Cases
Case Rate
-···-1 ·-1 No. of Death Deaths 1
Weekly No. of Reported Cases of Japanese Encephalitis for the Last 3 Years.
i I
Rate 1.5 1.8 0.8 ' 1. 5 0.8
Cases
600
4.1
I
3731 744
4 538 1 793
5.0 2.0
1 600
500
Yearly Total _ _ 1966 {2.3011 -----1965 (J,179) ... ·----· .. 1664 (2,596)
58 59
3900 1 979 1 607 2 053 .
4.2 2. 1
1 349 723
400 .
60 61
1.7
650 825 568 566 1365 656
0.7 0.9 0.6 0.6 1.4
I I
aoo
2.2 1.4 1.3
62 63 64
1 363 1 205
200
2 683 1 179 ___2
2.8 1. 21
100
65
0.7 24
~
~~_~ ___1_44_2____ 1_.5..J
t
26
~8
~
32
34
36
38
40
~
44 \\'~ek
~'unluldtl\"~ "umb~r uf fir~t
cases for
24 weeks
The Japanese encephalitis presents peculiar epidemiological characteristics, i.e., seasonal characteristics, regional characteristics and mode of infection, that is by the bite of mosquitoes. The number of persons who received immunization during 1966 is estimated to be about 18 million. 4. Dysentery Althongh the number of cases of dysentery had yearly decreased from 1960 to 1965,
-
31-
,_
•
it increased to 65,228 in 1966. The incidence rate and death rate of dysentery reported during the period of 1966 were 65.8 and 0.3 per 100,000 population, respectively. Almost all of the cases were due to bacillary dysentery and only 23 were amoebic dysentery. Some of the recent trends which should be noted are that the occurrence during summer month has shown a smaller proportion to the total cases compared with those of the previous years, clinical symptoms have become milder and milder, and the number of cases by Shigella sonnei has been incre'lsing; it was ab()ut 90% of the total cases in 1956. Out of 911 epidemics in 1966, 11.0% was classified as water-b()rne, 13.3% as foodborne, 63.5% as direct contact, and the rest 12.2% was not known. More intensive effort is being made for the periodic examination and health education of food-handlers, workers in water-supply work and other people dealing with food for public consumption. 5. Venereal Diseases After the World War II, the reported venereal disease cases reached its highest level in 1948. However, they started to decrease rapidly since 1950. As the recent trend of venereal diseases, the increase of early infectious syphilis has been observed. In 1965, early infectious syphilis represented 24.8% of all syphilis cases, and the number of syphilis cases under 24 years old reached 22.7% of the total cases, and 43.9% of those cases were infectious. The reported cases of gonorrhea have been gradually decreasing. However, it is presumed that there must be a large number of non-reported gonorrhea cases than those which are actually reported. We presume that the change of attitude of the younger-aged for sex is now constituting a very difficult problem for venereal disease control programme. In order to cope with the problem, a partial amendment of the Venereal Disease Prevention Law was made on July 26, 1966. The main points of amendments are 1) to simplify the reporting method and the content of the report on patients to be given by the physician, 2) to make obligatory for any man and woman entering into matrimony to receive STS by a physician, and 3) to make such expense free of charge, in case of above STS and the one for pregnant woman. 6. Parasitosis The parasitosis control programme in Japan is being carried out under the provisions of Parasitosis Prevention Law, and the mass examination and treatment for hookworm disease, filariasis and Japanese Schistosomiasis are particularly being carried out. In the endemic area of filariasis, south-west part of Japan, the blood examination for about 127,000 persons, mass treatment for more than 2,600 carriers, and mosquito control with residual spray were simultaneously carried out during the year 1966. As the control programme for hook-worm disease, the stool examination for 618,000 persons and over, and mass treatment for carriers, were carried out in the 6 endemic prefectures during the same period. As for Japanese Schistosomiasis, the intensive molluscicide operation and construction of cemented irrigation ditches carried out in the 5 endemic prefectures as the special control programme since 1957 has been resulting in the gradual decrease of the cases.
';::;"
l __
Table 18. Annual Change of No. of Cases, Deaths, Case Rate and Death Rate for Communicable Diseases.
(Rate per 100,000 population)
(1920-1966)
w
Typhoid Fever ' Case I Death 1 1Case' Death I I Case. Death' : Case I Death I Cases I Rate, Deaths, Rate Cases Rate I Deaths I Rate I Cases Rate I Deaths i Rate I Cases : Rate Deaths Rate i 9.0 I . 3 417'1 723----z3.()-- 8 148 14.7 53 756 97.0 12 073 21. 8,7697i3~9-1-- 783 ,1~4 1920 4969 1930 2 0.0 29 672 46.5 13 014 20.4 31 367 64.8 8 340 13. 1 4 467 7.0 372 I 0.6 , 29 655 45.7 13 002 20. 1 38 202 58.9 8 163 12.6 4 042 6.2 i 308 0.5 1931 4 0.0 1 0.0 32 249 49.0 13 547 20.6 35 437 53.8 6 936 10.5 4 694 7.1 j 368 0.6 1932 38 040 56.9 14 874 22.3 38 403 57.5 7 632 11. 4 5 279 7.9 333 0.5 1933 42 939 63.4 15 484 22.9 42 420 62.6 8 129 12.0 4 462 6.6 319 0.5 1934 ~I 48 964 71. 3 15 915 23.2 37 980 55.3 7 912 10.5 4 173 6.1 279 0.4 1935 52 053 74.9 16 710 24.0 36 799 52.9 6 847 9.8 4 747 6.8 276 0.4 1936 57 O. 1 11, 0.0 78 283 111. 8 19 712 28.0 38 124 54.4 7 062 10.0 4 439! 6.3 263' 0.4 1937 18 0.0 1938 113. 9 21 955 31. 1 42 074 59.7 10 I 0.0 80 221 1 7 803 11. 1 6 100 1 8.7 295 i 0.4 1939 1 0.0 97 249 ,137.3 24 890 35. 1 37 837 53.4 6 954 9.8 5 227 7.4 293 0.4 1940 5 0.0 83 689 117.3 22 025 30.8 40 706 57.0 7 106 9.9 6 251 8.8 312 0.4 ~I 58 803 82.7 16 295 22.4 40 595 57.1 6 904 9.5 6 233 8.8 308: 0.4 1941 55 785 77. 7 14 268 19.4 35 589 49.6 6 428 8.8 6 218 8.7 281 0.4 1942 1943 501881' 69.4 10 208 13.8 52519 72.6 6925 9.4 12382 17.1 508 0.7 1944 55 196 76.2 11 208 15.2 57 448 79.3 7 844 10.6 14 819 20.4 564 0.8 96 462 134.0 20 107 27.8 57 933 80.5 7 990 11. 0 10 059 14.0, 526' 0.7 1945 1946 1 245 1.7 560 0.7 88 214 120.7 13 409 17.6 44 658 61. 1 5 446 7.2 9 154 12.5 I 466, 0.6 39 219 50.2 9 573 12.3 17 809 22.8 2 926 3.7 4 728 6. 1 316, 0.4 1947 1948 14 665 18. 3 5 157 6. 4 9 486 11. 9 1 443 1. 8 2 917 3. 6 170 I O. 2 1949 23961 29.3 7765 9.5 6391 7.8 936 1.1 2189 2.7 116 0.1 1950 49 780 59. 8 11 968 14. 4 4 883 5. 9 630' 0.8 1 711 2. 1 80: o. 1 1951 93 039 1110.0 14 814 17.5 3 878 4.6 351 I 0.4 1 302 1. 5 I 49 0.1 111 709 130. 1 13 585 15. 8 2 898 3. 4 189' o. 2 835 1. 0 I 32 O. 0 1952 1953 2.9 157 0.2 1 098 1. 3 16, 0.0 108 009 124.1 10 851 12.51 2 521 , 1954 98 810 111. 9 9 341 10.5 2 567 2.9 124 O. 1 760 0.9 24: 0.0 80 654 90.3 6 042 6.8 1 939 2.2 105 o. 1 590 0.7 13 j 0.0 1955 84 437 93.6 5 165 5.7 2 123 2.4 80 0.1 509 0.6 19' 0.0 1956 74780 82.1 3763 4.1 2113 2.3 76 0.1 344 0.4 7 0.0 1957 1958 81577 88.7 3176 3.5 1901 2.1 54 0.1 1149 1.2 8 0.0 1959 , 85 695 92.2 2 457 2.6 1 546 1. 7 37 0.0 411 0.4 i 8 0.0 1960 ~I 93 971 1100.6 2 048 2.2 1 572 1. 7 39 0.0 319 0.3: 6 0.0 91 538 I 97. 1 1 646 1. 7 1 061 1. 1 34 0.0 213 0.2' 3 0.0 1961 ! 1962 ' 73 999 I 77.7 1 109 1. 2 910 1. 0 14 0.0 203 0.2' 10 0.0 0.0 1963 1 69 813 I 72.6 757 0.8 995 1. 0 16 0.0 148 0.2 3 0.0 1964 0.0 52420 53.9 471 0.5 890 0.9 20 0.0 148 0.2 3 0.0 , 2 1 I 1965 48 621 49.5 270 0.31 789 0.8 9 0.0 71 O. 1 1 I 0.0 I -- I 65 131 65. 8 I 265 O. 3 893 O. 9 I 12 O. 0 119 O. 1 6 I O. 0 I I 1966 Year 1--,. --
I
Cholera
I--~·- Dysent~;:-y--·--'
~
I_~_. _ _ _ ~ _ _
Paratyphoid Fever
Smallpox Cases i
'"
' Case-'I Death: Rate: Deaths Rate I 729 4 0.0' 8 0.0 44 O. 1 55 O. 1 35 0.1 16 0.0 I 20 0.0 80.0 6 0.0 33 O. 0 60 O. 1 62 O. 1 61 O. 1 73 O. 1 44 O. 1 0.4 4. 0 O. 1 0.0 O. 0 0.0 0.0 -,
6.2lz
=1
'I
3 166 - 5.7 7 0.0 23 0.0 305 O. 5 375 o. 6 , 0.5 320 113 0.2: 178 0.3 900.1 60 0.1 287 O. 4 575 0.8 654 O. 9 381 O. 5 ' 546 O. 8 311 O. 4 .
1:31
I,
1 614 2.2 I 319 17 954, 24. 6' 3 029 386 O. 5 85 29 0.0 3 124 O. 2 14 5 0.0 2 86 0.1 12 2
~,
~ g:g 0.0 1
~I
1
0.0
=1
=1
I
~-~.
--'.
-
----'-
=1 =1I
Note: One case of cholera in 1963 is the imported case.
One of the 2 cholera cases in 1964 is also the same.
(Con'd to the next page)
\
..
'--
t
•
J
~- I I Scarlet Fever Diphtheria
I
I"
,
'
• (Rate per 100,000 population) :
1- - - 1 - - -Epidemic Typhus
I
Epidemic Meningitis
Year l-c---rcase---CDeath I C I Case; Death, 1 Case -:Deathl-c----Case Death ases , Rate i Deaths I Rate ases , Rate: Deaths, Rate i Cases 'Rate Deaths' Rate ases I Rate Deaths Rate 1920 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942 1943 1944 1945 1946 1947 1948 1949 , 1950 I 1951 1952 1953 1954 1955 1956 1957 1958 1959 66 1 3 3 4 26 18 1 17 0.1 3 1 0.0 1: 0.0 31 0.0 1 0.0 1 0.0 1 5' 0.0 I 1 0.0 3 0.0 1 0.0 2 0.0 3 O. 1 14 O. 1 23 1. 9 129 5.4 622 3.4 260 44.3 i 3351 1. 4 , 135 0.6 47 O. 1 I 18 1. 1 68 0.0 2 0.0 'I
I-
949 I 1. 7] 530 1. 0 I . I • 275 0.41 168 0.3 I • 'I • I 280 0.4 165 0.3 . , 238' 0.4 165 0.3 359 I 0.5 239 0.4 1 186 I 1. 8 i 599 0.9 1 304 1. 9 1 699 1. 0 1 003 1. 41 601 0.9 839 1.2 479 0.7 995 1. 4 580 0.8 5 1 632 2.3: 886 1. 2 \ 3 1 350 1. 9 ! 707 1. 0 1 160' 1. 6 524 0.7 87 100 8231 1. 1 443 0.6 1 374 1 113 1. 5 398 0.5 3 941 1 468, 2.0 396 0.5 2 461 4 384 I 6.1 1 072 1. 5 • 1 32366 1436: 2.0 455 0.61 201 0.31 99 1 106 3 373 I 4.3 1 187 1. 5 263 0.3 228 475 2 052, 2.6 650 0.8 4 757 5.9 I 2 620 111 1 446 i 1. 8 492 0.6 1 284 1. 6 I 1 177 938 1 193 I 1. 4 367 0,4 5 196, 6.2 2 430 3 1 111 1. 3 302 0.4 2 188 I 2.6 1 956 16 912 1. 1, 227 0.3 3 545 4. l ' 1 437 859 1. 0 I 196 0.2 1 729 I 2.0 I 720 676 0.8, 155' 0.2 1 758, 2.0 732 630 0.7 161 0.2 3 699 4.1 1 373 610 0.7 147 0.2 4538 5.0 1600 0.0 760 0.8 155 0.2 1 793 2.0 744 638 0.7 135 0.1 3900 4.2 1349 I 573, 0.6 124 O. 1 \ 1 979 2.1 723 526 1 0.6 1960 ' _ I 8 786 9.41 23 0.0 14 921 16.0 497 0, 5 112 O. 1 ' 1. 7 ' 650' 1961 _ 6 251 6.6 32, 0.0 9 790 10.4 286 O.:J 1 504 0.5 96 O. 1 2.21 825 1962 8 382 8.8 181 0.0 7 451 7.8 206 O. 2 390 0.4 73 O. 1 1. 4 568 1963 _ I 16 034 16.7' 20 0.0 4 866' 5. 1 76 O. 1 320! 0.3 79 O. 1 ' 1. 3 566 1964 - I 12 907 12.3 19 I 0.0, 2 774 2.9 421' 0.0. 249 0.3 591 0.1 2.81' 1 365 1965 10 735 10.9 14 0.0 1 2 159! 2.2 39 0.0 214! 0.2 50 0.1 I 1. 2 658 1966 - , - ! 8 827 i 8. 9 1!5.~0_ 1 520,~.s 16 i O. 0 , 144 i 0.1 , .22 0.0 2.3 1 498 Note: The population used as the basis for computing these rates is the estimated PJPulation excluding Okinawa. The number of deaths for years before 1942 is only for Japan Proper, exclusive of Okinawa, but the number of cases and deaths for 1943~1915 includes Okinawa. The number of cases were taken from the Morbidity Statistics, wbile deaths were from Cause-of·Death Statistics and Vital Statistics. (Number of deaths in 1966 is provisional).
I
0.0 I 1 368 I 2.5 1 0.0 I 6 025, 9.4 I 0.0 6 480 10.0' 0.0. 8 257 ' 12.5 0.0 i 12 631 ' 18.9 0.0 116 688 24.6 0.0' 16 506 24.0 0.0 16 707 24.0 0.0 17602 25.1 19 002 27.0 0.0 19 907 28.1 0.0 19 325 27.1 0.0 14 997 21. 1 0.0 12 688 17.7 0.2 9 891 13.7 0.8 6 354 8.8 0.4 2 405, 3.3 4.4 22081 3.0 0.2 , 2 635 3.4 O. 1 2 982' 3.7 0.0 1 4 602 I 5.6 0.1! 5 149 6.2 , 0.0 " 5 096 i 6.0 -- 1 6 168 I 7.2 1 I ' 12 619 ' 14.5 I 1: 0.0 19 861 , 22.51 13 486115.1 -12172 13.5 14 499 15.91 13734114.9 , 9 882 I 10.6
_I
_I
-I
1020. 21 303 0.5 327 0.5 336 0.5 401 0.6 505 0.7 488 0.7 467 0.7 454 0.6 398 0.6 475 0.7 388 0.5 268 0.4 217 0.3 165 0.2 114 0.2 82 0.1 100 0.1 71 O. 1 42 O. 1 58. O. 1 33 I 0.0 34 0.0 48 I O. 1 56 1 0.1 87, 0.1 621 0.1 63 0.1 44' 0.0 31 I 0.0 38 0.0 I'
15 113
127.3
c-
Japanese I
Encepha~1
ases
Case-,!Death Rate Deaths I Rate
I
18 522 29.0 21 048 32.4 21 811 33. 1 28 500 42.6 29 992 44.3 28 054 40.9 28 117 40.4 28003 40.0 28 323 40.2 35 803150.6 38 303 53.7 40 442 56.9 44 431 1 , 61. 9 63 756188.2 9-1 274 130.1 85 8331119.2 49864 68.2 28 307 36.2 16 377 1 20.5 14 555 I 17.8 12 621 15. 2 10 749 112.7 8 381 9.8 9 589 I 11. 0 10 490 9 , 15 557 17.4 18395 20.4 15 423 : 16.9 15611 117.0 17 936 19.3 1
'Ill. 'I'
I
3 801 I 6.9 I 4 069 6.4 4 582 7.1 4 509 6.9 5 418 8.1 5 215 i 7.7 4 432 I 6.5 4 321 6.2 4236 6.0 4 118 1 5.8 5 255 7.4 4 728 6.6 4 985 6.9 5 134' 7.0 5 419 7.3 6 192 8.4' 7 826 10.8 3825 5.0 3 390 4.3 1 903 2.4 1 635 2.0 1 182 1. 4 895 1. 1 639 0.7 773 0.9 I 795 0.9 913 1. 0 980 1,1 1 887 1. 0 , 619 0.71 706 0.8 I 'I
1
1
I'
I I'
0.1 0.3 3.3 1.4
I
I
2.9 1.1 1.7 0.8 0.8 1.5 1.8 0.8 1.5 0.8 0.7 0.9 0.6 0.6 0.4 0.7 1. 5 w W
,I
i
I
I'
-34Table 19. ------
No. of Cases and Case Rate for Reportable Diseases. --_._-_.
(Other than those in Table 18) I 1965 1966
i Malaria Measles Whooping Cough Influenza
1961
,
1962
,
1963
1
1964
Cases
i
Ratei Cases I Rateic;ses 18 0.0
Ratel-casesR~~~I- Cases 10 0.0,1 52 494154_ 1 167, :
Rete!
case~~Rate 1
-
22 I 0_ 0iI 39 192 4L 6 J
16 I 0.0,1 38 141139_ 7, 4 132 'I
63 809: 67.0, 11 552 12. 11
° I
6 0.01 15 0.0 1 37 789, 38.51 52 991 53.5 2 3d 2.4
, I
5 225
5.5
' III 830118 6 474 723498 8
i
I: " I
4.31 I
L 2,
Poliomyelitis Tetanus Rabies Anthrax Tuberculosis
2 436
I
2.6
. i
774
0.8 llO 204',ll3.41 409 391416.6, 41 437 4L 8" 1, I
I',
3 136,' 3_ 2,
1
I
760
, 0_ 8,
289 0.3j 7071' 0.7
131' O. 667
84' 6411
0.11 0.7 1
0_ 7,
76' O. l' 1 1 542 0.6
331 453,
0_ 0 0.51
' ~I -I 2i 0.0 1
0.0
-II, -I 0.0 27 522 28_ 61 21 0.0, 0.0 1 270i O. 31 126 5761 1 O. I' 6.0 4.31 39
_I 22,
11
0.0 1
0.01
-I --I -I 1 .
Leprosy Trachoma Infectious Diarrhea Tsutsugamushi
420 460445.9 387 767407.4' 380 603 395.8 355 500365.81315 006 320.5 286 563289.3 1 1 235 0_ 2 2111 0.2 175 0_ 2 135 0.1 125 0.1 106: 0.1 29 366 3L 11 471 109: I
23 476 24.7 58j
24 147 24.8 1 19 4461 639! 5326 O. 0 0.0'
21 792 22_ 21 12 994 13.1
0.0
o. 11 O. 4 L 61 6.6 1
3~
0.0: 0.01 O. 2
2 13 211 14 ' 1
0.0 1
Disease Schistosomiasis Japonica Filariasis
o. 1 O. 51 0.11 7.8 6.7,
72, 0.1, 359 1 536 6301 1
8 228
0.0, O. 21 0.0
430 80: 7313 6 364
o. 5 0.7 1
118: 0.1 6000 4 663i
Syphilis Gonorrhea Chancroid Lymphogranulomatosis Inguinale
5.51
6.1110821 1O.9i 4 7' 6 951 7. ~ 1
5 125i 5.4 256 51
4 166 221 6
4 041' 4.2, 169 4 O. 2', O. 01
2071 O. 2 5]
o. 3
o. 2,
o. 0 1
o.
1 0,
1791 0: 21 6! O. 0
2881 O. 3: 11 O. 01
o. 01
17. Port Quarantine Service The port quarantine service in Japan is under the management of the Quarantine Section, Public Health Bureau of the Ministry of Health and Welfare, and is being carried out by the Quarantine Stations (16 main offices, 13 branch offices and 37 detached offices which serve for 62 seaports and 6 airports), in accordance with the Quarantine Law and the Law concerning Special Instances of the Quarantine Law relating to Military Vessels, etc. The set-up of these quarantine stations as of 1 July 1967 is as shown in Table 20, next page. 1. 7 quarantine stations shown in the column (1) a) and 1 branch office in the column (2) a) are equipped with the isolation hospitals, detention quarters and the disinfecting facilities. 2. 15 quarantine stations shown in the column (1), 11 branch offices shown in the column (2) b), and 8 detached offices shown in the column (3) a) are able to issue the deratting certificate.
-
~
-
35-
.
,
3. 1 branch office shown in the column (2) c), and 27 detached offices shown in the column (3) b), are able to issue the deratting exemption certificate. 4. The airport quarantine service is being carried out at 6 shown in the column (4), and the Tokyo International Airport is Sanitary Airport, since the quarantine station located therein is isolation hospital, detention quarters and disinfecting facilities in the station. Table 20. I
quarantine airports designated as the equipped with the attached quarantine
Names of Quarantine Stations at Seaports and Quarantine Airports. a) b)
(1)
I
Hakodate; Kobe; Moji; Nagasaki; Nagoya; Sasebo; Yokohama Hakata; Hiroshima; Kagoshima; Niigata; Osaka; Otaru; Shimizu; Tokyo I
----------------------------------------i a) Izuhara Seaport Stations
(2)
I I
b)
Chiba; Fushiki-Toyama; Iwakuni; Kamaishi; Kure; Muroran; Niihama; Tokuyama-Kudamatsu; Wakayama-Shimotsu; Yokkaichi; Yokosuka
I
':~ b) (3) i
1--
::::yama; Kochi; Mlike; Misaki; Wakamats";-; Yaizu I Aomori; Funakawa; Hachinohe; Hagi; Hososhima; Karatsu; Kushiro; Matsuyama; Misumi; Nanao; Naoetsu; Owase; Onahama; Rumoi; Saganoseki; Sakai; Sakaide; Sakata; Shiogama; Tsukumi; Tsuruga; YO-.I ron; China; Wakkanai; Miyake; Saiki .--.-
Mal~~ru;
Mlz~shima;
I
Quarantine II
I_~lrports
(4) ! Itazuke; Iwakuni; Kagoshima; Osaka; Tokyo Airport; Amami
. ___________JI
Note: These are the names of quarantine stations, their branches or detached offices, and not necessarily bear the names of ports where they are serving.
During the year 1966, (1) 28,117 vessels and 14,657 aircrafts involving 1,156,955 and 1,044,856 persons, respectively, received quarantine inspection, (2) 150,065 persons received preventive vaccination for quarantinable diseases, (3) 1,058 vessels received deratting service, and (4) 5,387 vessels received deratting exemption certificates. Fortunately, we were free from any quarantinable diseases, even imported ones, during the reporting period, but we strengthened the quarantine measures for preven· ting import of cholera because of its wide spread, and of smallpox for its transitiveness and of plague in Vietnam, especially.
18. Sanitation Facilities 1. Water-Works
Environmental Sanitation
According to the latest available information, the population served with water supply systems during the year 1966 was, (1) 1,416 urban systems for 56,421,748 popula· tion, (2) 14,131 rural systems for 9,277,274 population, and (3) 3,283 private systems for 2,542,660 population, totalling 18,845 water supply systems for 68,241,682 population. In average, 69.4% of the total population was served with these water supply systems. Under the provisions of Water-Works Law, the water supply installation can be provided by cities, towns, villages, syndicate, private, provinces, and other communities so as to elevate the standard of public health by improving environmental sanitation
-
36-
and by supplying safe drinking water. As far as finance is concerned, self-supporting system is the main principle in the water-works. However, national loan (interest 6.5%, reimbursement period 30 years) is provided by the National Government for the corresponbing undertakings. Also, the Ministry of Health and Welfare may subsidize for the development of water resources, in the case it is the large scaled one in comparison with its present water supply quantity or its construction unit is more expensive than the average, and also for the area expansion of water supply systems involving development of new water resources. The National Government may subsidize for the establishment of water supply system and so-called small-scale water supply system (covering less than 5,000 population), with one third or one fourth of the total expenses, depending upon the financial conditions of municipalities. 2. Sewage Treatment As of the end of March 1966, there were 108 cities operating sewage treatment plants, and 13,480,000 population was covered by those services. 136 cities have been constructing sewage treatment plants. Under the provisions of Sewerage Law, the sewerage installation can be provided by public expenses of cities, towns and villages, and its construction is limited on public land. In the past, the administrative responsibility for sewage disposal and its facilities had been jointly in the hands of Ministry of Health and Welfare and Ministry of Construction, i. e., construction and operation of sewage treatment plants was under the former's jurisdiction and construction and maintenance of sewerage pipes under the latter's. However, in view of simplification of administration, the Ministry of Construction became the single agency responsible for sewage disposal work as to its budget and operation as from 21 June 1967, although it still requires to obtain the consent of the Minister of Health and Welfare from the standpoint of public health when approving the new construction of sewerage facilities and their extension. 3. Nightsoil Disposal The difficulty for proper nightsoil disposal is still one of the important environmental sanitation problems. According to the result of special survey made in 1962, only 36;>6 was disposed by digestion plants and sewerage systems; 14% was used for fertilizer in rural farm, though this has been decreasing year by year since the chemical fertilizer has been replacing the role of nightsoil, and 22% was dumped into ocean. At the end of March 1966, there were 792 communities operating nightsoil disposal plants. As one of the nightsoil treatment programme, 13,480,000 population was benefited by the sewage disposal plants in 108 cities as mentioned in paragraph 2 above. Nightsoil digestion plant is planned to connect to the sewerage systems in future. This is a special situation in Japan, due to difficulty of constructing sewers in large scale. According to the 5-year national programme, it is planned that 37,440,000 population will be covered by flush-toilet system by the end of March 1972. 4. Garbage and Trash Disposal Incineration is the most basic principle for disposal of garbage and trash. According to the result of special survey in 1963, 42% of garbage and trash in the designated
I'
-
37-
·
/'
public cleaning districts was incinerated. As of the end of March 1967, the number of population benefited through garbage incineration and composting reached 45,322,991. Insect and Rodent Control Under the present provision of Infectious Disease Prevention Law, the Cities, Towns, and Villages are responsible for the control of insects and rodents under the technical guidance of the Prefectural Governments, with financial assistance of the Ministry of Health and Welfare. At present each of the Local Health Centers have full· time staff to perform technical guidance for such operation in his own district. The model districts have been established since 1950 in many parts of the country in order to demonstrate insect and rodent control programme under the active participation of organized community people, and it has been quite successful not only in the control of insects and the prevention of insect-borne diseases but also in popularizing the basic understanding and public consciousness on hygiene, and thus in the general development of community social life. The nation-wide movement of establishing "life free from mosquitoes and flies" initiated by the Government in 1955 lasted for 3 years. This movement was widely supported by positive understanding and cooperation of general public as proper movement for the improvement of people's daily living through eradication of insects. Since the favorable results were obtained by this movement, the movement is still being carried on even at present under the supervision of each Prefectural Government. In view of the fact that this kind of organized community activities is essential for various health and welfare programmes, the Government established the National Council for the Promotion of Community Health & Welfare Programmes (juridical person) in 1959, for the purpose of developing organized projects in the communities. Sanitary Inspection and Supervision There are 4,890 sanitary inspectors (including both full-time and part-time) who are working on 17,219 entertainment facilities, 120,9;;6 hotels and inns, 47,940 public bathhouses, 180,628 barber shops, 151,319 beauty parlors, 82,055 laundries, etc. in addition to those water supply facilities, sewage treatment plants, nights oil disposal plants and garbage disposal plants in order to maintain good sanitary conditions. Administrative Regulation Under the provisions of the Law concerning Improved Management of Business Dealing with Sanitation, the Central Council is provided in the Ministry of Health and Welfare to review the operational and trade standard whether it is satisfactory to maintain good sanitary condition or not, in order to improve management of commercial establishments under the jurisdiction of sanitary regulations. Regulating the tariff of the charges of such business as barber-shop, laundry, public bath-house, etc. is always on the subject for review. The Local Council is also provided in each prefecture to settle local standard which is based on principle of the standard settled by the Central Council. This locally settled standard is required to be approved by the Fair Trade Commission of Prime Minister's Office.
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38-
19. Environmental Pollution Control Along with a rapid industrial development and increase of transportation as well as the heavy concentration of population in the larger cities, a problem of public nuisance or environmental pollution is now a matter of social and public health concern. Smoke and air pollution, noise, and stream pollution are most common problems in Japan. The Smoke Control Law and the Water Pollution Control Law are the national legislations exist in these fields, and the former is administered jointly by the Ministry of Health and Welfare and the Ministry of International Trade and Industry, and the latter is by the Economic Planning Board of the Prime Minister's Office with the participation of the Ministry of Health and Welfare as to the responsibility for protecting the source of public drinking water. So far 16 smoke control areas and 20 stream control basins have been specifically designated. L Air Pollution Under the remarkably rapid growth of industrial production and change of energy policy from coal to petroleum because of heavy industrialization policy, the quality and quantity of air pollution problems have changed their magnitude. Especially, petrochemical combinative development and operation of huge power plants generated by heavy fuel have produced complex air pollution problems, as nuisance or public health hazard in the surrounding community. Throughout the country, there are 614 monitoring spots equipped with deposit gauge, 777 monitoring spots for SO, to be measured by PbO, candle methods, and about 80 automatic monitoring instruments for S0, and particulated matters, run by the Local Governments at present. The amounts of deposit matters in the main area is more or less 20 tons per sq. km. per month in average, and roughly speaking, monthly average of S0" as S0, is in-between, 1.0 mg/100 sq. cm/day to 0.5 mg/sq. cm/day in urban area. The major districts where the air pollution is a big community health problem are Sapporo, Tokyo-Kawasaki-Yokohama, Yokkaichi, Osaka-Amagasaki-Kobe, Ube, and Northern Kyushu districts. Since 1964, active approach to the study on the effect of air pollution to the health has been started by Ministry of Health and Welfare, in Osaka and Yokkaichi as a long-range project; not only the epidemiological studies but also the clinical approaches have been made by the team with various professional research staff. Those Prefectural Governments, having the smoke area under their jurisdiction, are required under the law to operate continuous monitoring survey for air pollution. In certain larger municipalities, those administrative functions are delegated by the prefectural authority to those municipalities. Concerning the control of noxious gases, vapour and fume, the law provides special provision for accident handling procedure, and those substances such as HF, H,S, Seo" HCI, NO" SO" C1 2 , SiF 4 , COC1" CS" HCN, NH" Pel" Pel" P and HelSO, are designated as the specific noxious substances. Recently, auto-exhaust control has been getting social concern in larger urban area, and Ministry of Transportation started to regulate CO in auto-exhaust gas to be less than 3% by volume as for the new cars to be produced since September 1966.
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39-
'/J'
The Environmental Pollution Control Service Corporation was established in 1965 by the government fund in order that the industry obtains the loan with low interest from the Corporation for the purpose of installing necessary facilities required under the Smoke Control Law for enforcing rigid emission standard. Needless to say, prevention is the most important approach in the air pollution control. Since the fiscal year 1955, pre-siting studies have been conducted in 8 districts by Ministry of Health and Welfare and Ministry of International Trade and Industry. During the last few years, scientific research on air pollution has been rapidly expanding year by year. Ministry of Health and Welfare shared the efforts, from the stand-point of environmental analysis and evaluation, on effect study and also source study under its jurisdiction. National Air Monitoring Network project, equipped with high level automatic air monitoring machines in the small stations was started in 1965 in three spots. They will be expanded to 20 spots in a few years. 2. Water Pollution Control The Economic Planning Eoard of the Prime Minister's Office has primary power and responsibilities for execution of the "Water Pollution Control Law," and Ministry of Health and Welfare shares the responsibility from the view-point of protection of public health. 80 public water areas were investigated in these 8 years, and 20 public water areas have been specifically designated by the law. Stardards of the qualities of water of those 20 public water areas have been also provided, and natures and characters of the waste-water to be discharged into these public water areas from the factories are regulated under the "Industrial Wastes Law" which is enforced by Ministry of International Trade and Industry. 3. Others From 1965, investigation of the acoustic problem in large cities has been commenced for the purpose of obtaining actual status of noise problem in order to plan out control method.
20. Food Sanitation
Food and Veterinary Sanitation
1. Food Inspection 5,097 food inspectors (including 4,172 inspectors holding an additional post) were stationed in 829 Health Centers to work on 2,530,519 food-handling establishments includ· ing 1,246,017 establishments which are not required to be licensed). They performed inspection on the establishments and supplies of food and drinks. 2. Food Poisoning or- ____ _
During the year 1966, the reported food poisoning cases were in total 1,400, involving 31,204 patients and 117 deaths (for 1965, 29,018 patients and 139 deaths in a total of 1,208 food poisoning cases). As regards the causes of food poisoning, 484 cases with 15,612 patients, involving 5 deaths, were due to bacterial infection and entero-toxin; 20 cases with 608 patients, were due to chemical poisoning; 247 cases with 872 patients, involving 90 deaths, were due to poisonous plants and animals; and others were unknown.
-
40-
As regards the type of food causing these poisoning, 597 cases with 8,101 patients, involving 95 deaths, were by fish, shellfish and their products; 213 cases with 3,671 patients, involving 5 deaths, were by cereals, vegetables and their products; 52 cases, with 2,731 patients, involving 1 death, were by milk, egg, meat and their products; 139 cases with 5,753 patients, involving 3 deaths, were by other food, and 399 cases with 11,048 patients, involving 12 deaths, were by unknown food. As regards the kind of places where the causative food was taken, 689 cases with 6,286 patients, involving 103 deaths, were at home; 338 cases with 15,990 patients, involv· ing 2 deaths, were at the establishments for mass feeding such as in the business place, school, hospital and, etc.; 100 cases with 2,301 patients were at hotels; 109 cases with 2,151 patients, involving 5 deaths, were at restaurants; 97 cases with 3,736 patients, involving 3 deaths, were at other places and 67 cases with 740 patients, involving 4 deaths, were at other unknown places. 3. Food Additives Chemical synthetics used as food additives are fully controlled by authorization system by the Government, and they are listed in the Enforcement Regulation of Food Sanitation Law. Approximately, 349 chemical synthetic food additives are authorized for use at present. The manufacturers or processors of synthetic food additives or their preparations are required to have a qualified self· inspector by the law. In addition, the additional certification system is applied to coal-tar colours and several other food additives. These specified additives are required to be tested for each lot and to be certified by the Minister of Health and Welfare or the Prefectural Governor concerned before sale. Two coal-tar colours (Ponceau 3R and Ponceau R) in 1965, seven coal-tar colours (Ponceau SX, Oil Red XO, Orange I, Orange SS, Naphthol Yellow S, Oil Yellow AB and Oil Yellow OW) in 1966, and one coal·tar colour (Guinea Green B) in 1967, were deleted from the authori?:ed list· 4. Pesticide Residue in Food Pesticide residues in some fruits and vegetables have been investigated from 1964 to establish the tolerance in food. In 1965, apples, pears, grapes, strawberries, cucumbers, tomatoes, green tea, radishes, cabbages, and rice were examined for pesticide residues. Long·term toxicity test of some pesticides was also carried out for animals. In 1966, pears, strawberries, tangerines, green tea, cabbages, radishes, peaches, potatoes, spinach and rice were investigated. In 1967, mandarin oranges, peaches, potatoes, spinaches, eggplants, Chinese cabbages, Welsh onions, onions, carrots and rice are being investigated. In the near future, several tolerances of pesticide residues will be established by the order under the Law. 5. Inspection of Imported Foodstuff The imported food is inspected by the inspectors of Ministry of Health and Welfare who are placed at the main ports in this country. During the year 1966, 12,142,000 tons of food were imported, and approximately 583,000 tons of food were either rejected or ordered to give additional process to make them safe for human consumption as the result of inspections. These were soyabeans containing morning glory seeds, milk products contaminated with bacteria and mould, confectioneries coloured with unauthorized coal-tar colour, and other food decomposed due to mishandling.
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41-
Veterinary Sanitation About 2,500 veterinarians engaged in the work for meat inspection. There are 804 slaughter· houses ; 19 of them are operated by the prefectural authorities, 325 by cities, 215 by towns or villages, ll3 by associations, and 135 by private individuals. The following table shows the number of food animals slaughtered and of carcasses conde· mned during the year 1966. Table 21. No. of Animals Slaughtered and Carcasses Condemned.
(1965) Cattle I
Calves I
I
she-ep-I-G-~~ts 24 328[
!
Swine
Horses
I
T~
. . . ._[
Total No. Slaughtered Xo. prohibited from slaughtering No. of condemned carcasses
666378,
163 698 1
102 38919 404 6211.
51~~:~~03 042 3 1 35 .. 7 85S 2971
I
35[ -c---I
19 140 6
--1[- -.--~i ··--7~81 12 2 438
337 180 478
9
No. of condemned parts
717:
_.~_207i
,-----"----
2
688_~7~55i
81~14 387 056
The rabies control programme is also under the veterinary sanitation programme in Japan. During the year 1966, under the provisions of Rabies Prevention Law, 2,699,474, dogs were registered, 4,295,503 were immunized, and 597,793 stray dogs were caught. There has been no cases of rabies in dogs after 1956, and in humans after 1955.
21.
Nutrition
Intake of Nutrients Consumption of foods in Japan has been increasing year by year, especially the consumption of animal foods, fat and oil, and fruits. As shown in Table 22, intake of essential nutrients has been satisfactorily increased. Table 22. -------_....
Annual Change of Nutrients (percapita per day)
..- .........- - - - - - c - - - - - - - - , - - - - - - - , - - - - - - - , - - - - - - - - ,
1950 -------'.
1955 2104 69. 7 22.3 20.3 411 338 1 084 1.16 0.67 76
1960 2 096 69. 7 24. 7 24. 7 399 389 1 180 1. 05 O. 72 75
1963 2 085 70.6 27. 7 29.2 382 409 1 452 1.03 O. 79 79
1965 2 184 71. 3 28.5 36.0 384 465 1 324 0.97 0.83 78
Calories Proteins (g) Animal Protein (g) Fat (g) Carbohydrate (g) Ca. (mg) Vitamin A (W.) B. (mg) B, (mg) C (mg)
2 098 68 17 18 418 270 1. 52 O. 72 107
Nutrition Guidance l. Nutrition Guidance at Health Center The nutrition guidance programmes are prepared by the Ministry of Health and Welfare, and are transmitted to .the prefectural and municipal authorities, which then
-
42-
given instruction to the Health Centers for the actual performance of the services to be rendered directly to the people in the districts. The Health Center usually has one or more qualified nutritionists to run its nutrition consultation office. The main duties of health center nutritionists are: (1) give consultations for those who visit Health Center; (2) hold educational sessions for nutrition improvement in the districts; and, (3) look after the nutritional needs of the institutional people or group of people who are fed by group-feeding programmes. The number of such nutritional guidance given by the nutritionists of the Health Centers in each year between 1960 to 1966 are shown in Table 23, below. 2. Demonstration Kitchen Car
The mobile nutrition demonstration services have been continuously being operated. They are called "Demonstration Kitchen Cars," which are the bus-type mobile kitchen cars, completely equipped with necessary cooking utensils, supply of water and gas fuel, for nutrition demonstration, and the trained nutritionists are using them for lecture demonstration on preparation and cooking method for the balanced diet for the house-wives and women's group. At present each prefecture has at least one such car for that purpose.
Table 23.
Annual Change of Number of Guidance given by Health Center Nutritionist. (l960~1966)
-
Total No. of-~-Total NO:O£ I Persons received Sessions held Individual I in Group Guidance Guidance Programme I
1960 61 62 63 64 65 66
1 269 0-59 1 1 1 1 1 1 363 397 400 431 378 361 043 642 954 074 229 396
- I- -
-71 709 69 445 74671 77 591 81 494 80 467 85 702 ,
Mass Feeding Many mass feeding facilities in those places such as hospitals, schools, working places, etc. have been organized after thelast World War frem the view-point of nutrition improvement. Particularly, the schcol feeding has spread throughout the country, and at present over a half of the children of primary schools benefit from complete school lunch programme. National Nutrition Survey Since 1946, the national nutrition survey has been conducted four times every year in order to determine the condition of nutrition of the entire population. In the survey, intake of nutrients, physical measurements, physical symptoms probably due to nutritional deficiency, and also blood pressure are surveyed. However, in 1964, the procedure of nutrition survey was revised for the purpose of preparing more clear information on the actual nutrition status of people which has been remarkably changed due to the improvement of mode of living. Nutritionist The license of nutritionist is given to those graduating from the training school of 2 to 4 years authorized by the Minister of Health and Welfare or to those successfully passing the national examination for nutritionist. There are 167 authorized nutritionists training schools and about 105,000 licensed nutritionists at the end of March 1967.
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43-
Cook The Cooks Law stipulates the authorization of training institutions for cooks and their supervision, and examination for qualifying cooks. There are 71 authorized training schools and approximately 500,000 licensed cooks at the end of March 1967. Enriched Food The taking of enriched food has been strongly advocated by the Ministry of Health and Welfare, and at the end of March 1966, the number of enriched food permitted by the Ministry in accordance with the provisions of Nutrition Improvement Law amounted to 1,541. Those food such as the rice, flour, bread, noodle, bean ·paste, jam, soft drinks, canned fruit, biscuit, etc. are enriched with vitamin A, thiamine (vitamin B,), riboflavin (vitamin B2), vitamin C, calcium, iron, lisin, etc. Particularly, the enriched rice has been encouraged. When enriching rice, 1 gram of rice containing 1.2-1.5 mg. thiamine and a bit of riboflavin will be mixed in the polished rice at the ratio of 1 to 200. H?alth Promotion In the recent years, the necessity of promoting positive health which is not merely directed to the prevention of any particular disease or disorder but rather to serve for further improvement of general health and well·being of the people has been emphasized. Through various information media and active participation of civic and voluntary organizations, health promotion campaign and movement are actively carried out to disseminate idea on healthy living with good standard of nutrition, exercise, rest and recreation. Because of having high temperature and high humidity in summer season, we have particularly an active campaign during summer, called "health promtion in summer time."
22.
Dental Health
Prevalence of Dental Caries The latest dental survey in our country is the one made in 1963, which revealed that existence of high percentage of prevalence of dental caries in all age-groups; it was 69.196 in male and 73.696 in female, 71.696 in average. The survey also revealed that the number of DMF permanent teeth per capita was those as shown in Table 24.
Table 24.
Number of DMF Teeth
(Per capita, permanent teeth)
·-~ A.gel 'Male
I
§ex_----. ___ . _;_. __,_
6
I.
10 15 __+-3. 5 5. 0 I
20 6. 3
i
O. 8 I
~emale I~J~=5.91~
Preventive Programme At 121 Health Centers out of a total of 829 Health Centers, 93 dentists and 79 dental hygienists are engaged in dental health work, and the schools are playing important role in carrying out preventive programme on dental health among school children through dental examination and health guidance. Each school has the school dentist in accordance with the School Health Law. Dental examination, health guidance and advice are being given effectively in those facilities, and particularly many schools have been taking
-44-
proper preventive measures in their own facilities. Since 1952, in accordance with the Maternal and Child Health Law, the dental exa· mination and health guidance for pregnant women and infants have been carried out in the Health Centers or by guidance dentists designated by the Law; 215,557 dental health guidance for pregnant women and 1,638,629 for infants were given during the year 1966. During the same year, 3,405 pregnant women received oral prophylactic treatment, and 209,398 infants received topical application of fluoride and oral prophylactic treatment, as the preventive treatment programme. Based on the same law, the programme of dental examination and dental health guidance for 3 year·old children was carried out, and 877,369 infants were covered by the programme during the year 1965 as shown in the following table. Table 25. Results of Examination for 3-year~ld
Children. (1965)
-
3-
Number of Children Total Dental Caries Malocclusion --Diseases of SoffTissues-of Oral Cavity Others 877 369 688 792 33 929 6072 3797
J
Percentage of Children 100.0 78.5 3.9
O. 7 0.4
---
-"
The Department of Dental Health Research of National Institute of Health has been conducting many researches on the prevention and treatment of dental disease and dental health. The information on the number of dental clinics, dentists. etc. can be found in Chapter 27 (pages 51 and 54).
23. Mental Health Legislation The mental health programme has increasingly attracted public and professional attention in these years. Under the Mental Health Law, in addition to the provisions of institutional care for the patients, the community care and the preventive work in mental health services are accelerated. Services for the mentally retarded children and child guidance activities are provided under the Child Welfare Law. In order to extend service for the mentally retarded people in general, the Law for the Welfare of Men· tally Retarded Persons was also enacted. In order to promote the welfare of severelyfeeble-minded children as well as severely physically handicapped children, the special child allowance is granted under the Special Child Allowance Law. ,surveys Since 1954, four special statistical surveys on mental health were carried out by means of stratified sampling on a nation-wide scale, summaries of which are as follows: (1) mental health survey in 1954, the purpose of which was to clarify prevalence of mental disorders, (2) statistical survey in 1956, for hospitalized mental disor-
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..
ders, the purpose of which was to know actual status of hospitalized cases from the medical and social view·points, (3) statistical survey in 1960, for attitudes of the mental disorderd persons or their families toward medical treatment, a part of which cases was placed under observation for follow-up survey in 1961, and (4) mental health survey in 1963, the purpose of which was the same as that of 1954 survey. According to the survey in 1954, the estimated prevalence rates of mental disorders were found to be 1.55% in male, 1.41% in female and 1.48% in total, respectively, and the percentage distribution by sex of cases was 50.7% in male and 49.3% in female, respectively. While the same survey of 1963 revealed that the prevalence rates were 1.41% in male, 1.18% in female, and 1.29% in total, and the percentage distribution by sex of cases was 53.6% in male and 46.4% in female. The followings were, on the other hand, revealed by the survey in 1956. 61.496 of a total was the male patient and remaining 38.6% was female, which showed a comparatively higher proneness of hospitalization of patients as much as the sex distribution of morbid cases in the community is concerned. 70.0% of a total was schizophrenia; while, 15.5% of a total was schizophrenia, according to the percentage distribution by diagnosis of mental disorders in the prevalence survey in 1954. Percentage distribution by duration of stay in hospital at the time of survey of the hospitalized mental disorders was broken down as follows; less than 3 months 20.9%, 3-6 months 13.5%, 6 months-1 year 13.6%, 1-2 years 16.5%, 2-5 years 22.4%, over 5 years 13.0%. According to the survey in 1960, the estimated number of newly attending cases to the mental hospital in a year was approximately 254,000_ The percentage distribution by diagnosis of cases in 4 surveys are shown in the following table.
Table 26.
Percentage Distribution by Diagnosis of Mental Cases.
'-. -- --'--1 , 1954 !
! M;rb-id Cases in the , Community in General
i Cases to Mental Hospital (survey in 1960)
i
Newl; attending
1956
Inpatients in Mental Hospital (survey in 1956) , I
- - - - -.. - . - - - - -
----
-
-----
Total Schizophrenia Manic Depressive Psychosis Epilepsia Mental Disorder due to Intoxication Other Psychoses such as those due to Brain Injuries Mental Deficiency Other types of Mental Disorder :~c1ud~_ng ne~~osis)
100.0 15.5 1.1 9.6 7.0 8. 7 44.5 13.5
100.0 17.8 1.6 8.1 5.5 18.6 32.3 21. 6
100.0 24.1 8.4 9.9 4.3 10.8 3.5 38.0
10'0-:0-70.0 3. 7 3.8 2. 3 12.6 3.0
I
4.8
,
.-
-
Hospitalization Expense
Since 1961, the hospitalization expenses for mental cases to be paid by Prefectural Government for compulsory hospitalization has been subsidized by the National Government with the ratio of eight tenth. Since 1965, one half of the total expenses to be born by the Prefectural Government for daily clinic attendance by patient has been .subsidized by the National Government. The hospitalization expense for mental cases is
~
46
~
paid out from the public fund obtainable under Mental Health Law, Daily Life Security Law, Social and Medical Insurance, or self-payment. Mental Hospitals The latest figures of hospital accommodation for mental patients are shown in Table 27, below. The latest figures of mental hospitals (excluding the psychiatric units in the general hospitals), their beds, hospitalized patients, bed occupancy, and monthly outpatients, are shown in Table 28. Table 27. , , ,
••
Psychiatric Beds. Private, Juridical Persons and Others , 1
Year
Beds
-
I
~
National, Prefectural and Municipal
Total 0' Q
q6 1955 56 57 58 59 60 61 62 63 64 65 66 Note: (1)
--
~~-~~
I
10 982 12 14 15 16 18 502 542 658 953 354
20 182 22 075 23 492 25 842 27 760 30769
27.3 25. 7 24.1 22.5 21. 2 20.5 20.3 19.6 18.2 17.8 16.9 16.9
29 254 36106 45 840 53 814 62 831 70 960 79 150 90 674 105 357 118 981 136 150 150940
72.3 74.3 75.8 77.5 78.8 79. 5 79. 7 80.4 81. 8 82.2 83.1 83. I
40 236 48608 60 382 69 472 79 784 89 314 99 332 112 749 128 849 144 823 163 910 181 709
100 100 100 100 100 100 100 100 100 100 100 100
(2)
All psychiatric beds include beds in the mental hospitals and general hospitals. Data are as of the end of June. Table 28. Mental Hospitals, their Beds and Patients. (end of December) 1960
1 '1 _
------
I
1961 -,
1962
1~~3 I 1
1964
I
1965
I
1966
I
~~-
Mental Hospitals Mental Beds Inpatients Bed Occupancy Monthly Out-patients Monthly Out-patients per 1 Hospital Note: Figures for 1966 are provisonal.
-5061 543 583, 629 676: 725, 769' 73 839 , 81 960 92 3171105 0461117 758 130 119, 142 938 75 669 83 728 95 592 110 050 124 191 136 708' 151 956, 108.1' 108.4' 110.6 110.5, 111.1 109.8 110.8 1 1 1
i 1
-------'---
116 1721135 0021157 219 ' 185 520 209 307, 230 0881 261 4951 230 249 , 270 295 310 317, 340j 1 1
Health Centers and Mental Health Centers
The service for consultation, counselling and home visit guidance on mental health are being given at 829 Health Centers under the provisions of Mental Health Law, while the research and study, dissemination of correct information of knowledge on mental health, counselling and guidance, and technical guidance to the health center staff, etc. are being done at 14 local Mental Health Centers, the number of which will be increased to 22 by the end of March 1968, and it is expected to be increased to 46 by the end of March 1969 so that we could have at least one Mental Health Center in each prefecture.
- 47-
Child Guidance Centers Under the provisions of Child Welfare Law, each prefectural and larger municipal authorities are required to establish the Child Guidance Centers which provide the child guidance and counselling service, and at present a total of 136 centers is functioning. The main work of the center includes: 1) such administrative service on placement and accommodating those children with problems into various types of child welfare institutions (now, 14 types), like homes for dependent, neglected and abused children, etc., and 2) such guidance service for the children with problems as diagnosis, counselling and guidance from medical, psychological, pedagogical, sociological and psychiatrical standpoints. The yearly number of cases handled at the center reaches almost 3~J,OJO, and in particular, many cases require counselling relating to sound development of children, such as problem of aptitude, adaptability, breeding, long absence from school, school phobia, etc. Table 29. Intake Case Load in Child Guidance Centers.
(1 May 1966 and 1967)
I~ FigUEeS~.I_n_ta~k~e~._c_as_e_ - _.. , - - - Total
96 1957 100.0 35.0 16.5 12.5 15.8 12.4 7.8 -----,-
.
1966 271 98 36 32
'1967 265 92 43 33 41 32 21 277 605 ! 774 . 089 925 816 068
1966 100.0 36.4 13,4 12.1 17.9 12.6 7.6
-------,
Problem of aptitude, breeding or character Mentally retarded Health, physical handicap, speech, visual or hearing disorder Delinquency and pre·delinquency Protective measures Others
705 I 926 i 402 829 , ! I
48 611 34 252 20 687
Care for the Mentally Retarded The number of those mentally retarded children who were under the care of Homes for Mentally Retarded Children (246 homes in all) reached 15,663 as of the first of March 1967, and the number of those children who were attending Mentally Retarded Children Day Care Centers (62 centers in all) reached 2,298. The National Home for Mentally Retarded Children has been operating particulary for the severe cases of mentally retarded children. All of them are now operated under the Child Welfare Law. Under the provisions of the Law for the Welfare of Mentally Retarded Persons, each prefecture has the Prefectural Mentally Retarded Persons ConsuItatian Center, and besides, 6,035 persons were under the care of 85 Homes for Mentally Retarded Persons as of the first of March 1967. Training and Education of Juvenile Delinquents The children commiting or liable to commit delinquent acts are admitted to the Home for Training and Education of Juvenile Delinquents where they are given training and education under the Child Welfare Law. As of the first of March 1967, there were 4,499 juvenile delinquents who were accommodated in 56 homes, two national homes, one for boys and the other for girls.
, 48-
24. Medical and Social Rehabilitation Service Statutory Provisions and Organization for the Service As for the rehabilitation services for the physically handicapped persons, it is provided under the Law for the Welfare of Disabled persons that it is the duty of the Prefectural Governors to establish and operate the Con"sultation Centers (52 centers in 1966), where the blind, deaf and crippled adults could be examined and receive the guidance from the medical, psychological and vocational standpoints, and to provide the Pre fectural and Municipal Social Welfare Offices (1,039 offices in 1966) with the staff specialized in the services for the welfare of physically handicapped persons. The provisions of the services for physically handicapped children under 18 years of age are included in the Child Welfare Law. In this case, Consultation Clinics are provided at the Health Centers. PT and OT-New Rehabilitation Staff In June 1964, the Law for Physical Therapists and Occupational Therapists was enacted in order to establish legal system for qualification and licensing for physical therapist and occupational therapist in order to develop and strengthen the medical rehabilitation programme. The license of those profession can be given to those who successfully pass the national examination for physical therapists or occupational therapists. Those who are eligible for receiving examination are those who finished the 3·year course of the school designated by the Minister of Education or such training school designated by the Minister of Health and Welfare. As of July 1967, there were 5 physical therapist training schools and 2 occupational therapist training schools. Out of those schools, the School of Rehabilitation attached to the Tokyo National Chest Hospital established in 1963 for training both professional workers has been receiving WHO assistance in the form of fellowships and experts from 1964 to strengthen the education programme for PT and OT. There are now a total of 493 physical therapists and 72 occupational therapists who have passed the national examination for their respective professions under the above·mentioned Law. Blind Persons Blind persons and persons with defective vision are provided under the laws with walking-sticks, artificial eyes, pairs of glasses, etc., and if necessary, with the medical treatment for the recovery of vision. There are 4 national, 3 prefectural and 1 private Homes for Blind Adults where the blind a dults are given vocational guidance and medico-psychological treatments they require. The blind and partially sighted children are received in 31 Homes for Blind Children and are educated at 77 Schools for Blind Children. There are several publishers who are publishing books in braille points, and also several li braries for the use of the blind. Deaf Persons
J
-49-
Persons with deafness or defective hearing are provided with various hearing aids and medical treatments for the recovery of hearing. The National Rehabilitation Center for the Deaf and Mute is giving the comprehensive medico-psychological treatments and vocational guidance to the persons with deafness or defective hearing. There are 2 Homes for Deaf Adults, 37 Homes for Deaf Children and 107 Schools for Deaf Children. Crippled Persons The crippled adults and children are provided under the law with prosthetic appliances, wheel·chairs, etc., and, in case of need, medical treatments. The National Rehabilitation Center for the Physically Handicapped in Tokyo and 45 Prefectural and one private Rehabilitation Centers provide the crippled adults with medical treatments, physiotherapy and vocational guidance. In addition, there are 2 National and 7 Prefectural Rehabilitation Centers for the Severely Crippled Adults. The Hospital· Homes for Crippled Children provide integrated services of medical care and rehabilitation for the seriously crippled children. As of the first of April 1967, there were 7,587 accommodations for children at 68 Hospital·Homes for Crippled Children all over Japan. As of the first of May 1966, in addition to the hospital·homes, there were 59 special schools and 186 special classes for the crippled children for their school education. There are 23 Hospital-Homes which provide medical care for severely multiplehandicapped children.
25_
Radioactive Isotope and Peaceful Use of Atomic Energy
The use of radioactive isotope CRr.) commenced from 1950 is now extended to more than 1,400 institutions in Japan. It is mostly used in medicine in the field of research, diagnosis, and treatment, which is about 36% of the total institutions. The government organizations responsible for the development of peaceful use of atomic energy in Japan are the Atomic Energy Commission and the Atomic Energy Bureau, Science and Technology Agency of the Prime Minister's Office. While the Promotion Section of the said Bureau is the main body among national government agencies dealing with the production of RI., planning, and execution of its use, the prevention of hazard that may occur through the use of RI. is in the hand of Radiation Safety Section of the same Bureau. The necessary measures for radioactive fall· out are to be carried out by the Environmental Radioactivity Section of above Bureau under the decision of the Headquarters of Counter· Measures for Radioactive Fall-Out established within the Cabinet. The various Ministries are sharing the respective responsibilities in the research work and the use of RI. in the field of their own concern. Various research work on the use of RI. in the field of public health is being carried out at various research institutes attached to the Ministry of Health and Welfare, and particularly, the Department of Radiological Health of the Institute of Public Health is the main one. The
-
50-
laboratory facilities for R.I. at those institutions are being strengthened and expanded under the current year to carry out more intensive research work. The use of RI. in the field of medicine for diagnosis and treatment is also being done at the National Cancer Center and some of the National Hospitals. The National Institute of Radiological Sciences established in 1957 under the jurisdiction of the Science and Technology Agency is dealing with coordination of research work on the medical use of RI. and prevention of radiological hazard. For the purpose of preventing possible health hazards from radiation that may occur along the development of peaceful use of RI., the Law concerning Prevention of Radiation Hazards due to Radioactive Isotopes and Others has been enforced. While, in order to prevent possibie hazard that may occur at the medical institutions and drug manufacturing factories, the neccessary requirments have been provided in the Enforcement Regulations for Medical Service Law and the Enforcement Regulations for Pharmaceutical Affairs Law. Those law and regulations related to radiation hazard are in conformity with almost all the principles of the Recommendations of the International Commissions on Radiological Protection, for which acceptance was advised to the Prime Minister after study made by the Radiation Council. As to atomic reactors in Japan, there are now 20 reactors, 10 of them are for physical research purpose in some of the universities and the private research institutions, and 2 of them are the power reactors. The Atomic Energy Commission worked out a Long-Range Programme on Development and Utilization of Atomic Energy in April 1967. The new programme aims at an effective stepup effort for the development of power reactors, an efficient use and stable supply of nuclear fuels, the development of a nuclear ship and the utilization of radiation which includes radiation chemistry and food irradiation. In accordance with the utilization and development of atomic energy, the greater efforts for such safety measures as safety standard in and around the institute sites, counter-measures for radiation hazards and treatment or disposal of radioactive wastes, are required.
26. Occupational Health The occupational health programme in Japan, where the term "industrial hygiene" is used, is based on Labor Standards Law, Pneumoconiosis Law, Ordinance on Protection of Ionizing Radiation Injuries and other concerned regulations, and is carried out by the Ministry of Labor. As of the end of December 1966, there were 2,668 labor standard inspectors, who made inspection of 210,376 factories out of a total of 2,264,118 factories including inspection of the health condition of the facilities for the period of 1 April 1965-31 March 1966. Pneumoconiosis, organic solvent poisoning, caisson diseases, and ionizing radiation injury are the major occupational disease problems, and neccessary preventive measures have been taken. The patients are given benefits out of workmen's compensation scheme for their treatment. Under the Labor Safety and Hygiene Regulations, the enterprise engaging in manufacturing business which have more than 50
-
51-
workers and those non-manufacturing enterprise having more than 100 workers are required to appoint the health supervisors duly licensed by the Government.
27. Medical Service Hospitals and Clinics
Medical Service Law provides the detailed qualification for hospitals (medical care facilities having 20 or more beds), while the law does not provide such detailed requirements in case of clinics (medical care facilities having no bed or with less than 19 beds) and the administrator of such clinic is required not to keep their patients for more than 48 hours except when inevitable circumstances occur. The hospitals are inspected yearly by the medical inspectors as to their physical facilities, professional staff, and hospital management. This inspection system contributes greatly for the improvement of hospital services to the patients. 1t is true that the number of hospitals and their beds has increased rapidly in the recent years as far as ratio per population is concerned. However, we had confronted with the problem of inadequate hospital planning and distribution which resulted in receiving complaints of scarcity of medical facilities in rural or mountainous districts. In order to relieve the problem, the Medical Service Law was amended, and since 1963 it became possible for the Government to exercise its authority in controlling planning and distribution of public and non-profit hospitals. Because of the progress of medical science, it is necessary to improve the service of medical insitution as well as to increase the number of hospitals and clinics in order to meet the increasing demand for medical care followed after expansion of health insurance system. For that purpose, in addition to the specific suhsidy or financial aid given to the national and public hospital by the National Government, since 1960 the provisions have been made by the Law for Medical Care Facilities Finance Corporation to enable the private hospitals and clinics to receive low-interest and long-term loan for their facilities. Because of the increase of road traffic accidents in these years, the system for emergency medical care was revised in Februrary 1964, and the network of emergency medical care was established. At the end of March 1966, the number of those facilities, either public or private, reached about 3,532. During the same year, a nation-wide survey on the actual condition of ambulance medical care facilities and their services was carried out under joint sponsorship of Japan Medical Association for the purpose of obtaining data which are necessary to make further improvement of the system. The following tables show the number of hospitals and their beds. Table 30. Annual Change of Number of Hospitals, General Clinics and Dental Clinics. (as of the end of Dec.) Year
Hospitals 6 6 6 6 7 7 229 428 621 838 047 308
I I
General Clinics 60 61 62 63 64 301 366 363 296 524
Dental Clinics 27 27 27 28 28 263 488 869 150 602
1961 1962 1963 1964 1965 1966
-
52Table 31. Number of Hospitals by Type and Kind. (1964 and 1965)
~~~_ I
~I I I
Mental Hospital 1964 1 1965 I I
Icommunica. I Tub erc~loslS_ Leprosarium ble Disease SanatorIUm I Hospital 1964 I
G I enera Hospital I
1964 1 1965 I
1965, 1964 11965 i 1964 1 1965 -1964 1 1965 1 I I 1
N ation-a-l------c1---:<4-50 . --448 1 (268) (268) ccr=a"l-ca Prefec·tu =-=n"d"'-'M"uc-·--'-1'-1-55 '1 154 nicip"-a=:I'---_ _ __
3 1 (3) 39
31 ib~1971 (3) (90), (86)
I
I
(11),
11
(11)
11
-
I
332-1 -337(164) (168)
391541501
! Semi.~u~ic
3-1-6~1-31-2---,--1
I 4- 41-' l7T l76 _374 l_340
-I
Social Insurance --,-1-661 I
16-2-------i- 131 1 privat-e-----4-764-14-97-1-1~6-33-1 6821esf 1 ,6
-I 3 1 14 1 3 14
-I 1
-I -I I
47145:1015'1020 311
I 307
-'::'T149 149
li
3 919 4 109
I_Grand Total Note: 1) 2)
-S38
17 047
i
676
I
725
48 1
46 1572615 922
Those figures in the brackets are those directly under the jurisdiction of the Ministry of Health and Welfare. Those semi·public facilities include hospitals operated by the Japan Red Cross Society, etc. Table 32. Number of Hospitals, Beds, and Bed Occupancy Rate. (1965 and 1966) (as of the end of Dec.)
a.
Number of Hospitals. ---Kind of I Hospital,-- Total ... _.... 1 Year I 1
T~b;r~~I~siSI ;
Sanatoria 340 I 283 sS9-1 9241
Mental I Le r . Communicable General p osana Hospitals I Disease Hospitals I Hospitals I'
I'
-----=:11965 -7-0-4-7-'---' Number of Hospitals! ! 1966 7 308 '-19-65-- 873 652 56 Number of Bed --,----''--_ _ _ .. _. _ _ _ 233 45 .. - - - - - - . - - - - - -.- '1' 1
7251 769 130 119 I
1 4 - - - 4 6 - 1 - - - 5922 _ _ -.24
I
13 230
'I
3 444
_~ 1 __ 6 I 670 i
~1_1_96_6J918
142938'
13230 I
2968
201 170 . I 713173
Note: Those mental, TB, leprosy and communicable disease beds at general hospitals are counted as the beds of general hospitals. b. Number of Beds and Bed Occupancy Rate. Kind of' Bed , Year Number of Bed I
Total !
1965 I 873 652 1966 I
TB Bed \ Mental Bed 1 220 757 172 950 211 527 I
1-~:~roSY i I
Bed I
Communicable Disease Bed
I General Bed i
i
13 230 24 179 _. __ .~_~ ___ ~_i__ .. _ 13 230 I 75.3 74.2 I
----442 536 '
918 233
I
191 597 108.0
23 872 1 478 007 16.61 20.0 80.6 79.8 ,
1965 Bed Occupancy Rate •___ 1 ! 1966 1
82.61 ,
--.- 75.41 73.81
82.6
I
.,-------
lORsl
Note: "Bed Occupancy rate" refers to the number of in-patients per 100 beds of the official rated capacity.
Medical Care Personnel Better standard of qualification for medical care personnel and their number have always been the matter of great concern for the Government. Table 33, next page, illust· rates the educational qualification requirements for various personnel as of August 1967. Table 34 shows the number of training institutions for personnel and students entering annually.
,
,
, I
._,---1
Table 33. Standard of Qualification Requirements for Medical Care Personnel. General Education
------1 ------I' I xxxx
Ii lnthern. ',' Examination , S Ip I' ,I i , 1 --11- -N'
' - --h , P' nmary sc 001
I · 1d Med lca octor
(6 years)
I J . h' 1 I sem '. h' 1 unlOr 19l or Igl ! scbaoln years), schoolr3 years)
Professional Education University ---Pre·medC2 yrs.)! Professional(4 yrs.)
License by
-
Dentist
__ Pharmacist _ _ _ Veterinary doctor --P.UbliC health _n~rse_ (a)_ Pubhc .h.e.alth
I ,I -------'1I_~~XX '- - --XXXX xxxx 1' __
J
XXXX
I'
I
-XXX' X
I
.
XXXX XXXX XXXX
I Bre- Pharm(2 ~::'l.~ersity" I're-pharm(2 Pre-vet (2
XXXX ___ XXXX
__ ' 1
-- --~r~~~ers\~y 0__ _
-'~-
I'
xxxx ."..
y~sntiersi,~Y (2 yrs.) i- -~-(4 yrs.) PHN
(2 yrs.) __
I'~' -~' " -I_ ----1(4 yrs.)
Yl':...,_
atlOnal
-or Minister of 'Healt.!:>~_Wel!"re
.~------) --1-
)
I" _
--'.'. "
:t~~!~~T~u~!-
-XXX X XXXX
xxxi- -, XXXX 1 - --U~;versity ______ I I
-~ sCh'I' -.
____
n~rse..cbL
XXXX
--
I
1-
XXX X XXXX
__ J3yrs.1.., __
Nur.slO g sch.
Midwif,,--Ca) Midwife (by _ --- --Clinical nurse(a) i
xxxx! XXXX.. I - - --. xxxx I xxxx--1 xxxx XXXX ----. 1
xxxx _ __ __
g XXXX X, XXX .1 NurslO. ... sCh. I ~!Jdw,fe ,II. '. - - . , -----_ _. _______@.Jlrs.) ___ ,s.c~yr:l___ x x x x i . xxx x , University (4yrs, ,-- XX_X_X_ XXXX XXXX -- --
Uni.v~sity (4 yrs.).-
(1--".':,)
--
'I l
1_ •• _ _
.-.'--'--cl "-=1-----_-----1I " ) __ !
=-
"
,1- -- Minis ..t.er of-'I !Health & _Welfare ' I I
.
_C_lini,,~I_~~rSe(b)1 I Clinical nursec~1 Clinical nurseC d) Assistant nurse(a)
J~_--xxxx __ Nursing Sch.-(3;r.;:):--'=c:------ ~ \1!tr!~1~~~~~~~:S) __pr~ctice(3 yr:_.)_ NUr2s;~.)SCh.; I'
.
-,,--- ---------
I , I'
Health nurse NurslOg sch. ' -'-. course (3y rs.) I (2 yrs.) '!Assistant nurse-I=-----
--=r ...,-,--" Pref. Exam 1
';--'/-
N
" Prefectural Governor
Assistant nurse(b) X~ray
::::
----::::-
technician
xxxx-)--.· xxxx. xxXX--IXXXX xxxx XXXx' XXXX
-1--I I
It""~~iil~~c~~~:ers·)II-==-=_ -~~=-~~= -~~=_~_-----.-- -- -- -:1 course (3 yrs.) - -- _ -xxxx. - - School or train-) mg sch (2yrs.) --Cd'tt) I 1 0 I -___
, Health laboratory) techmCIan
- I --
Physical
the~apist
oC~h~~i~;~i . I-D-ental
1'_' .
=J-= xxxi--= 1
xxxi -
""
---.1, -----. ____
)1
N t' 1 a IOna /I
--- . " " _
-==_xxxx - _ xxxx
i_SCh~~~.0(3~:~Siiig I
--1-I
!l~alth:.§z:_.'Velfare
Minister of
.'.,
xxxx
Cditto)
Dental l;ygienist - I
INutri~ioni;t---I-xXxX --1--
te~hn-ic-ia~1
-I
xxxx-)x-x-xX--.! xxxx----I-
XXXX,-~~~: ({~~a~~~~g,-xxxx xxxx
"-x-x-XX
····-·1-
Jse~~~r(~r:~-~.-\n-g-I--
"- ---
--.
1-- Training seh. (2,3,4 yrs.) 1- --------------_____ 1- Nat~IHea!t~n%tw~iare
----=_!
" Pref.
Prefectural Gov~rnur N
Exa~
I:J
-54Table 34. Number of Training Institutions for Medical Care Personnel and of Students Entering Annually. (as of July 1967) Number of Training Institrtions ---------
Physician Dentist Pharmacist Public Health Nurse University Junior College Others Mid·wife Junior College Others Clinical Nurse University Junior College Others Assistant Nurse High School (Nursing Course) Others X-ray Technician Laboratory Technician Dental Hygienist Dental Technician Ph) si.cal Therapist Ouccpational Therapist
46 15 34 41 3 1
r-------1
Number of Students Entering Annually
37 33 1
3 820 1 220 5 929 1 175 100 20 1 055 710
32 311 3 7
301 752 76 676 21 52 41 24 5 2
20 690 26 781 100 300 22 781 61 191 11 910
49 281 965 2 020 1
306 840 80 40
Under the requirement of various Japanese laws, such as Medical Practitioner's Law etc., the person holding a license to practice as the respective medical care personnel in a foreign country is allowed to practice in such capacity of the respective medical care personnel in Japan only whenl he obtains the Japanese license concerned after passing successfully the national or prefectural examination. Also, the law does not allow any reciprocal arrangement between the countries concerned as regards qualification for practicing referred to above. The followiing tables show the number of medical personnel. Although statistically speaking, the number of physicians, dentists and pharmacists is about the same as Table 35. Number of Medical Care Personnel.
1952 53 54 55 56 57 58 59 60 61 62 63 64 65 Note:
Physician ,-------:O;;;;tist--lPharmacist (PUbl~~~:aIth! Mid;;'ife ,Clinical Nursel i Per -i--,-pef" Per - - I - P e r l --I-Per --,---Per 1 T~tal: 10,000 T~tal, 10,000 Total 10,000 ;Total: 10,000 ITotal 1 10,000 T~tal. 10,000: No. Pop. No. Pop., No. Pop. I No. ! Pop. I No. Pop., No. Pop. j ThoU:------Thou. Thou· ThOU.( IThou. Thou'l sand sand sand sand sand sand I 1
85 90 92 95 96 98: 100 101 103 104 105 107! lOS'
109 1) 2)
1
9.9 10.3 10.5 10.6 10.7, 10.8 10.9 10.9 11.0 11.0 11. l' 11.11 11. 1 11. 1
29 30 31 31 32 32 321 33' 33, 33 34 34 35 351 1
3.4 3.5 3.5 3.5 3.5 3.51 3.5( 3.5 3.6, 3.5 3.6' 3.61 3.6 3.6 I
50( 51 51, 52 53 55, 57 58 60 , 62 62 1
5.8 5.9; 5.8 5.9 1 5.91 6.0 6. 1 6.3 6.5
12 121 12 12
d 121 121 13 13 13
~~I 69
6.51 6.6 6.8 6.9 7.0 1
14 14' 141 15 1
1. 4 1.4 1.4 1.4 1.4 1.3 1.3 1. 3, 1.4 1.4 1.4 1.5 1.4 1.5
55 56 56 55 54 52, 52' 52! 52 51 50 46 44 42
6.4 105 6.5 1121 6.3 119 130 6.2 6.0 137, 5.7, 145 5.71 160' 5.61 1701 5.6, 186' 5.4 195: 2041 4.8 4.8 216 1 4.5 230 245 4.3 I 1 1
1
12.21 12.91 13.5 14.6 15.2 15.9 17.4 18.3 19.9, I 20.7' 21. 5 22.5 23.8 24.9
The number of clinical nurses include assistant clinical nurses. Data for 1966 are not available yet.
, Table 36. Number of Physicians and Dentists by Type of Work. 1
-
55-
those in European countries on a per'population basis, the Government has been confronted with the difficulties of excessive concentration of those personnel in the urban areas and of lack of qualified personnel in the field of public health work.
(1964 and 1965) (as of the end of Dec.)
No. of Physicians & Dentists
-
Physician Dentist - - - . _ - - - -I .. _-- - ---
Number ---'.
Number
---
-~---
1964 54277 36801 9 943 2 006 2 251 2 824 108 102 I
1965 55 217 37 049 9749 2 165 2 260 2 929
I
1964 26 534 I 6249 973 I 169 168 986 1
1965 26 918 6 263 946 183 163 1 085 35 558 --
Owner of hospital or clinic Employed in hospital or clinic Teacher and research worker of clinical med icine Teacher and research worker of medicine ot her than clinical medicine Engaged in other pubic health service Others --
1
i
Total ------
109 369 I
35 079
I
..- - -
,Table 37. Number of Nurses and Midwives Actually Engaged in the Work . .- Public Health M'd . N urs:e==-s_ _ _ _ _ _ _ I ,w_I_v_es_ 1965 Nursing School Hospitals and Clinics Health Cen ters Industries Schools Cities, Towns and Villages Private Duty Others Total 79 502 6926 952 1966 90 544
(1965 and 1966) Cll'nl'cal Nurses I
Type of Work
1965 36 5 415 , 166 i 1
1966
Il%s 2
I
1966_ 1 341 254 423 312 2 534
6012 911 6171 I
371 1 036 7 310 204 999 156 I 314
-I
I
5 664 450 14 -'---
4~
I
35 946 447 -~-
35843 364
5622; I
5386 1234 265 230 1
I
313 41 876
l068i 215 528
573f14 1751
43710
Note: The number of clinical nurses include assistant clinical nurses.
Medical Care Statistical Survey
1. National Health Survey The Government has been conducting National Health Survey (Family Sickness Survey) and Patient Survey since 1948, on a nation·wide scale based on the sampling method. In this survey, about 11,171 households or 41,950 people in 200 areas are sampled, and the incidence and prevalence of diseases and injuries among the people are enumerated by the type of diseases or injury, geographical area, occupation, economic status, sex, age, etc" and also by the mode of treatment of those diseases and injuries, and by amount of payment by the patients for the treatment.
- 56-
2. Patient Survey In the Patient Survey, 678 hospitals C'/10 of the total hospitals), 614 general clinics ('/'00 of the total general clinics) and 216 dental clinics ('/'00 of the total dental clinics), are sampled, and to enumerate the number of in-and-out patients who visit those institutions, by type of diseases or injury, sex, age, and by the method of paying the charge for treatment, together with the length of hospital in·patients. Table 38. How the Diseases and Injuries are Treated. (Based on the National Health Survey in Oct.)
1 9 6 4
--% Total Number of Diseases and Injuries Treated Not Treated Consulted Physician Consulted Dentist C It d {Acupuncturist, Moxa·cauterist onsu e Massagist or J udo.orthopaedist Treated by Home Drug Others
- _ ...
_-
1 9 6 5 --;?6---
100.0 98.2 1.8 51. 2 7.1 3.5 41. 8 0.8
100.0 97.8 2.2 53.3 8. 4 3. 7 33.2 0.9
Note: When disease or injury is treated by two or more kinds of treatments, each of them is counted as one.
Table 39.
Incidence of Diseases and Injuries, and Sick Days among the People. (per 100 population a year) Disease and Injury Total ---I-I-ncidence-'-I S~D-Rate lC ays --"-----
I.
II. Ill.
IV. VI.
V.
VII. VIII. Diseases of the respiratory system Acute nasopharyngitis (common cold) (s.m.) IX. Diseases of the digestive system (s.m.) Diseases of teeth amd teeth·supporting structure X. Diseases of the genito-urinary system XI. Deliveries and complications of pregnancy, child-birth and XII. XIII. XIV. XV. XVI. XVII. YI. Note: puerperium Diseases of the skin and cellular tissue Diseases of the bones and organs of movement Congenital malformations Certain diseases of earl)' infancy Symptoms, senility and ill·defined conditions Accidents, poisoning and violence Convalescent care, plastic treatment and fittting of prosthetic devices _._._--
(s.m.) Neoplasms Allergic endocrine system, metabolic and nutritional diseases Diseases of the blood and blood· forming organs Mental, psychoneurotic and personality disorders Diseases of the nervous system and sense organs (s.m.) Diseases of eye (s.m.) Diseases of ear Diseases of the circulatory system
Infective and parasitic diseases Tuberculosis
239.4 3.3 0.2 0.3 3.0 O. 6 O. 1 15.8 7.2 2. 1 5.4 95. 3 87. 2 44. 9 25.3 2.0 0.4 8.4 15.8 0.0 O. 2 19. 3 23.6 1.2
3 443. 7 158.2 106. 1 34. 0 113.1 23. 8 40.8 450. 1 20. 9 22. 1 444.2 621. 7 483. 1 774. 0 323. 8 72.0 II. 0 105.0 209. 1 6.2 5.5 92.6 260.9 21. 1
- .......
.
- - - - - -.-_.
I ------
i
The Incidence Rate and Sick Days are derived from the National Health Survey in Oct.
1965.
Table 40. Number of Patients visited Hospitals and Clinics.
57-
.._ - _ . .
(per 100,000 population a day) I Total I In· I O~ Patients Patients Patients
Disease and Injury ._-----
.-'
.-
5910 I Total 828 5 082 Infective and parasitic diseases 510 221 289 Tuberculosis (s.m.) 204 97 301 Venereal diseases (s.m.) 20 I 8 12 II. Neoplasms 63 34 29 Malignant neoplasms 22 (s.m.) 38 16 200 ' III. Allergic endocrine system, metabolic and nutritional diseases 15 184 25 4 IV. Diseases of the blood-forming organs 21 V. Mental, psychoneurotic and personality disorders 207 169 38 VI. Diseases of the nervous system and sense organs 801 51 750 Diseases of eye (s.m.) 309 6 304 Diseases of ear (s.m.) 193 3 190 VII. Diseases of the circulatory system 400 44 356 696 17 VIII. Diseases of the respiratory system 679 Acute nasopharyngitis (common cold) (s.m.) 186 0 185 IX. Diseases of the digestive system 1 571 103 1468 Diarrhea and enteritis (s.m.) 127 2 125 899 , Diseases of teeth and teeth·supporting structure (s.m.) 0 899 28 X. Diseases of the genita-urinary system 156 184 I 80 ' Diseases of the female genital organs (s.m.) 4 76 35 48 Xl. Deliveries and complications of pregnancy, child·birth and 83 I puerperium 3 XII. Diseases of the skin and the cellular tissue 360 i 357 24 XIII. Diseases of the bones and organs of movement 236 260 I 27 ' 7 XIV. Congenital malformations 19 16 3 XV. Certain diseases of early infancy 12 4 38 33 : XVI. Symptoms, senility and ill·defined conditions 357 63 XVII. Accidents, poisoning and violence 294 1 34 YO. Special conditions and examinations without sickness 33 1 Prenatal care and postpartum observations (s.m.) 34 33 79 79 YI. Convalescent care, plastic treatment and fitting of prosthetic devices Fitting of dental devices 79 (s.m.) 79 I - - - - - - - - - - - , .. _ - - _ - - - - - - Note: The number of patients are derived from the Patient Survey of July 14. 1965 (Wednesday).
I.
..
1
28.
Pharmaceutical Affairs
Inspection of Drugs. Devices and Cosmetics Under the Pharmaceutical Affairs Law, the licensing system is adopted for all manufacturers of drugs, quasi· drugs, cosmetics and devices for the sake of quality control. Besides, the facilities of every manufacturing factory have been improved in accordance with the standards established by the Law. During the calendar year 1966, the Ministry of Health and Welfare provided 1956 inspectors all over the country, who made a total of 202,980 inspections (including 23,112 for manufacturers, 30,383 pharmacies and others) for a total of 261,993 places (24,159 manufacturers, 21,870 pharmacies and others) in order to prevent adulterated, misbran· ded or exaggeratedly advertised, pharmaceutical merchandises to be sold to the public. Japanese Pharmacopoeia and Others The latest edition of Japanese Pharmacopoeia is its 7th edition, which is composed of Parts I and II. The 8th edition is now in progress for publication on 1 April 1970. The Minimum Requirements for Biological and Antibiotic Preparations and Radio·active Preparations have been revised annually. The first Edition of Official Book on Japanese
-58-
Standard of Cosmetic Ingredient was published in Japanese in August 1967. This Official Book includes the specification for identity and purity of 114 chemicals used to produce cosmetics. Poisonous and Deleterious Substances Control
Because of the increase of accidents through poisonous or deleterious substances particularly those liquid wastes discharged from metal plating factories where cyanic compounds are used, the Government felt necessity of imposing rigid obligations on the part of the above-mentioned establishments, and the Poisonous and Deleterious Substances Control Law was partially revised on 10 July 1964, which came into effect on 9 January 1965. Monitoring Adverse Drug Reaction
, ,
A programme for mcnitoring and studying on adverse reaction of drug commenced from 1 March 1967. In order to develop this programme, a special sub-committee on adverse drug reaction composed of the respective specialists was established by the Minister of Health and Welfare. Under this programme the information on adverse drug reaction is to be collected from 40 university hospitals and 88 national hospitals for evaluation by the sub-committee in request of the Minister of Health and Welfare. Control of Awakening Drugs
There has been no violation of Awakening Drug Control Law by the authorized dealers. However, 722 persons were arrested because of illicit manufacturing, sale or possession of those amphetamine preparations and the like, in 1966 (736 persons for 1965). By this law, the raw materials (l-phenyl-2-methylaminopropanol-l, 1-phenyl-2-dimethyl-aminopropanol-l, phenylacetic acid, and etc.) are controlled as nearly the same as the awakening drugs. Narcotic Control
During the period from Apri 1966 to March 1967, the first year programme of USJapan Cooperative Research on Drug Abuse was successfully carried out under US-Japan Scientific Cooperative Programme. For exchange of information in this research programme, the American principal researcher met with the Japanese research group in Tokyo in October 1966. During the year 1966, the narcotic control conducted by the law enforcement agencies resulted in sending 1,973 cases (2,052 persons) of violations to the Public Prosecutor's Offices, which included 899 cases (974 persons) of violation of the Narcotic Control Law; 917 cases (920 persons) of violation of the Opium Law; and 157 cases (158 persons) of violation of the Cannabis Control Law. The following item was newly designated as a narcotic drug under the Cabinet Order No. 229 of 2 July 1966; 1-(3-cyano-3, 3-diphenylpropyl)-4-(I-piperidino) piperidine-4-carboxylic acid amide and its salts. Blood Transfusion Service
•
-
59-
Blood collection services in Japan are being rigidly controlled by two laws, one of them is the Pharmaceutical Affairs Law aiming at the maintenance of the quality of human blood and its derivatives and of the standard structure of its premises, and the other is the Bleeding and Blood Doner Supply Service Control Law aiming at the prevention of health hazard which may accompany with bleeding intended to manufacture human blood and its derivatives. On this basis, our blood supply service programme has been remarkably developed because of the increased demand for human blood and its derivatives along with progress of modern medicine. However, because of undue dependence on "professional blood donors" and commercial blood banks, our blood service programme has been recently faced with the serious critical situation, such as the risk of the remarkably increasing number of "professional donors" with anemia, the risk of serum hepatitis, etc. which have constituted a great threat to the public health. Therefore, the Government, recognizing the seriousness of the blood supply situation, made a decision on 21 August 1964 to develop voluntary blood donations further to normalize the of blood supply service programme. The table below indicates the good result obtained by the nation-wide campaign for voluntary blood collection carried out to increase the number of voluntary blood donors and quantity of blood collected.
Year
~-I Number:~olu:;:-T.·Ratio .of Donations ~~-~ ---~ --,~
Voluntaryy I Donahons to Total : DonatlOn (96)
----i1963
---
64 65 66
55 166 425 983
950 660 930 460
---1. 9
7. 7 19.6 48. 5
There are 58 organizations engaged in the collection of blood by voluntary bleeding donors. Of the 58 organizations, 49 are the Japan Red Cross and 9 are prefectural ones. 80 mobile blood collection units are operated by these organizations.
,-
Production of Drugs and Devices The production amount of medical supplies such as drugs, quasi· drugs, sanitary materials, medical apparatus and devices have been increasing yearly, as shown in Table 41, next page. While, as for export of those medical supplies, it has been increasing m parallel with the increase of their production. In particular, those vitamin drugs such as vitamin B" vitamin C., other vitamin preparations, amino acids and their salts, and those antibiotics of our originality such as kanamycin, leucomycin, colistin, and dental apparatus, and those medical apparatus as detailed diagnostic instruments and measuring apparatus, have been widely exported to the countries in Southeast Asia, Europe and USA.
-
60-
Table 41.
(a). Production of Main Drugs and Medical Devices. (in thousand dollars) Kinds
i 1965 1966 ~ _ _ _ _ _ '(~an.~-:--Dec.) (Jan.~ Dec.' 'I
i !
Drugs
Vitamin preparations
!
Agents affecting central nervous system Antibiotic preparations
Miscellaneous agents affecting metabolism Agents affecting digestive organs Cardiovascular agents Agents for epidermis Nutrients. tonics and alteratives Hormone preparations
232 170 162 104 103 69 81 71
875 889 650 783 394 722 578 125
Agents affecting peripheral nervous system Chemotherapeutics Biological preparations Agents for public health Agents affecting respiratory organs Agents affecting sensory organs Others Total Quasi· Drugs Agents for epidermis Agents for public health Agents affecting digestive organs Total
37 153 i 29 772 , 37 958 i 27 381 , 22 531 25 861 1 24 869 68 678 I 1 271 219 i 47 983 28 306 13 156 i 89 447 35 631 ' ~----
251 422 180 842 179 180 125 190 121 534 94 222 88 942 62 940 41 420 37081 32544 32 042 31 763 27 601 21960 79 948 1 408 634 5433 105
" .
774
1
Sanitary Materials Medical Devices
I Medical instruments and apparatus Dental instruments, apparatus and materials
20 5341 108 413 , 32 262 , 90 27 42 160 833 117 408 357
Medical supplies Total ~------~---.--.---
88 057 25 732 42 021
i
155 811 I -
!
---
• CJan.~Dec.)
(b). Export 1965 38 375
Export and Import of Drugs.
(in thousand dollars) Import
1966 40 652
--I
J=---~-
I
1965 63 383
1---
------, 84 159
1966
1
--
.
~
.
,
29.
Major Research and Training Institutes in Public Health Programmes
For the purpose of performing research work on technical problems as well as training and educating public health technicians of various categories which are necessary for promoting public health programme in Japan, those major research or training institutes illustrated in the table, next page, are established and are functioning as the affiliated institutes of the Ministry of Health and Welfare. National Institute of Hygienic Sciences This institute is performing test and assay of drugs (excluding biologics and anti· biotics for which the tests are given at the National Institute of Health), food, food
Table 42. Kind and Organization of Public Health Research and Training Institutes.
61-
Cas of 1 Apr. 1967) --I ---
Name of the Institute Date of No. of _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _'---E_s_ta_b_l_is~h~ment! Staff: National Institute of Hygienic Sciences
' Organization I Locality I
1 Mar. 1~~II' -
National Institute of Nutrition Institute of Public Health National Institute of Health
, 17 Sept. 1920 29 Mar. 1938 21 May 1947
311'" 15 departments,:' I 1 library, 1 branch v 5 exprerimental I I stations I 62 7 departments, Tokyo 1 section I 219 16 departments, Tokyo 1 library I 560 17 departments,' Tokyo 1 library, 2 branches 2 ) 1 ' 1
TO~'
National Institute of Hospital Administration Institute of Population Problems National Institute of Mental Health National Institute of Leprosy Research National Cancer Center
1 June 1949 14 Aug. 1950 1 Jan. 1952 1 July 1955 1 Feb. 1962
17 47
,
1
421 34 605 1
3 departments,' Tokyo 1 section 3 departments, Tokyo 2 sections 7 departments,l Chiba 1 section I 2 departments,' Tokyo 1 section I 1 hospital, I Tokyo 1 institnte (12 I depart men ts, I 2 sections)
I _I i _ _
1 department, 1 library 1) 2) The branch is in Osaka. One branch is in Nagasaki and the other in Hiroshima.
1
Note:
additives, cosmetics and devices. It also performs cultivation and research of medici· nal plants, and research on drug manufacturing, and other test, investigation and research on those which are necessary from the standpoint of hygiene and sanitation. National Institute of Nutrition This institute is performing survey and re~earch on peeple's nutrition condition, eating ha bit, physiological and other assay en nutrients of food, and analysis of certain specified food and enriched food based on the :t\utrition Improvement Law. Institute of Public Health This institute is performing training of public health personnel as well as study .and research on the application of basic theory in medicine and public health which is necessary for such training prcgn;mme. The training programmes consist of 5 regular courses, 2 prelimicary ccurses and 12 short ccurses. The course for envircnrr:ental poll uticn centrol w"s nEwly created frem this year. The graduates of those courses totaled 13,017 up to March 1£67; the ma~ority of them ceing in gGvernment service, both nati onal and lecal, actively participating in the health programme in the different fields. It is to be mentioned that the Rcckefeller Foundation of U.S.A. had rendered a great deal of financial contribution particulary in its foundation. The institute has also ·extended its service to the foreign trainees in the recent years, who have been sent under WHO fellowship programme, Colcmbo Plan training programme, or others,
,
t-<.
-
62-
National Institute of Health This institute is performing study and research on the infectious diseases and other specified diseases, and food sanitation. It is also giving training course, performing national assay of antibiotics and biological preparations and their experimental produc· tion. Because of the particular work of the institute, it is designated as the various WHO Western Pacific Regional Centers and Reference Laboratories, i.e., for influenza, entero.virus diseases, leptospira, Shigella, respiratory virus diseases, arthropod·borne virus diseases and Salmonella. National Institute of Hospital Administration This institute is performing study and research on hospital administration and giving training for hospital administration. Institute of Population Probems This institute is performing research and survey on demography and population problem. National Institute of Mental Health This institute is performing study and research on mental health as well as rendering consultation service on mental health by its mental health clinics and training of mental health workers as a national training center in mental health programme. It has been closely associated with the Koonodai National Hospital. National Institute of Leprosy Research This institute is performing study and research on the prevention and treatment of leprosy. It is closely associated with the National Leprosarium "Tama Zensho-en." National Cancer Center This center consists of hospital, research institute, and administration department. The hospital is giving the best diagnosis and treatment to the cancer patients by using the equipments of the highest quality and efficiency. The major projects of the research institute are to make original research in the biochemical, chemotherapeutic and pathological aspects of cancer. The function of administrative department is not only to administer general services of whole center but is to perform the fundamental anti-cancer programme throughout the country.
30. International Cooperation on Health Programmes Health and Medical Technical Cooperation The Ministry of Health and Welfare participated in the international technical cooperation in the health, medical and social service fields under the various schemes through the service of Overseas Technical Cooperation Agency. As far as our Ministry is concerned, the emphasis was placed on the medical technical cooperation for the countries in South-east Asia, Middle and Near East and Africa. During the calendar year 1966, the Government received and trained 64 WHO fellows, (number was trebled from 1965), 42 Colombo Plan trainees and 6 trainees under other scheme, and also, arranged for 9 short-term consultants to work with WHO, 38 with the Colombo Plan, and 1 with other scheme in medical and public health
-
63-
fields. A total of 76 experts from Japan selected from their technical competence in the various fields, such as public health, environmental sanitation, etc. have been serving for a total of 34 panels out of a total of 44 WHO Expert Advisory Panels. In order to disseminate correct information on the medical and public health situation in our country to the neighboring countries and other interested countries, the Ministry prepared sound movie films in technicolor entitled "Medical Training in Japan" in 1966. This is a sequence of those previously prepared films, i.e., "A Report of Medical Services in Japan," "TB Control in Japan," "Maternal and Child Health Programme in Japan," "Communicable Disease Control in Japan," and "Cancer Control in Japan." These films have been already circulated among the countries concerned through the overseas Japanese legations. WHO Assistance Under 1966 year WHO fellowship programme, a total of 29 WHO fellowships were awarded for our country and WHO expert on physical therapy continued training programme from previous year, and one for occupational therapy joind here from December 1966. Special International Studies 1. Joint Japan-Philippines-WHO Cholera El Tor Study In view of terrific spread of Cholera El Tor in the Western Pacific Area and urgency of finding out many unknown factors on this new cholera in order to obtain best weapon to tackle with this disease, the authorized representatives from Japan, Philippines and WHO agreed, in February 1964 to undertake collaborative studies on the efficacy of different cholera vaccines, the role of cholera carrier in disease transmission and the viability of cholera El Tor vibrio. This excellent sample of what can be accomplished when different people work together in harmony and understanding to achieve their common objective showed fruiteful results in the interim reports. At the time of the third technical conference held in Tokyo in May 1967, the parties agreed that the project be expanded to study and practice the measures to control the invasion of diseases. 2. Japan-US Cooperative Medical Science Programme In January 1965, the summits of Japan and the United States, mindful of many areas of human health which are of great concern to all the people of Asia, agreed to undertake the expanded programme of cooperation in medical science. Under the Joint Committee which was established by the two Governments, Cholera-, Tuberculosis-, Leprosy-, Certain Virus Diseases- and Parasitic Diseases (Schistosomiasis and Filariasis) Panels and Malnutrition group are developing unique researches jointly. The Joint Committee so far has met thrice, first in Hawaii in October 1965, the second in Tokyo in August 1966, and third in San Francisco in August 1967 to report the progress of reseasch in each field and to plan out future programme.
,-
31. Public Assistance, Child Welfare and Social Insurances For the reference of readers, some of the informations on the programme of public
-
64~-
assistance, child welfare, and social insurances are given below. Public assistance is provided under the Daily Life Security Law to all persons under certified cases of need after means test. Programmes consist of 1) livelihood aid, 2) educational aid, 3) housing aid, 4) medical aid, 5) maternity aid, 6) occupational aid and 7) funeral aid. Assistance is provided in principle as an out· door care, while some cases may be institutional. All aids except medical care are provided by cash. There are 1,046 Welfare Offices in Japan (approximately one per 100,000 population), and their Welfare Officials as case workers are providing services assisted by 129,793 volunteer workers, who are called Welfare Commissioners. The aids are financed 805'6 by the National Government and 2096 by the Local Governments. The following tables show some of the statistical data on public assistance. Table 43. Fiscal Year 1956 57 58 59 60 61 62 63 64 65 66 Note: Number of Recipients and Amount of Payments. Amount oCPaymenr(Monthly Average) Thousand Yen--3 647 312 3 728 648 4 089 055 4 645 422 5 101 038 6 227 962 7 075 142 8 322 346 9 618 312 11 335 692 13 061 064 No. oCReClpients -1-Ral:l00fReci p ients to (Monthly Average) the Total Population 1 775 ~~~'~~r-~---1.~7% 1 623 744 1 627 571 1 669 180 1 627 508 1 643 445 1 674 001 1 744639 1 674 661 1598786 1 570 054 I
1.79 1. 77 1.80 1.74 1.74 1.74 1.81 1. 75 1.63 1. 57
•I
1) Figures for 1966 are provisional. Table 44. Number of Recipients and Amount of Payments by Type of Aids. (Monthly average, fiscal year 1966) Item Liveliho()d . EducaHonal1 Housing-I-Medical IMaternity· Occupational! Funeral Aid I Aid Aid Aid Aid Aid I Aid , 1402 730 399 658 0.4 7 2 4 836 357 545 7 152 3 I I
Recipients (in thousand) Amount (in million yen)
51
19
-.--------~----
Child Welfare Child Welfare Law provides for a comprehensive programme of care for children aged up to 18 years, and welfare of mothers. Programmes consist of 1) a net-work of Child Guidance Centers, 2) foster parents, 3) vocational foster parents, 4) homes for dependent, neglected and abused children, 5) homes for training and education of juvenile delinquents (aged up to 14 years), 6) homes for mentally retarded children, 7) homes for physically weak children, 8) hospital-homes for crippled children, 9) hospital-homes for severely multiple-handicapped children, 10) homes for blind, deaf and dumb children, 11) homes for mothers with children, 12) baby homes, 13) day nurseries, 14) children'S recreation centers, 15) maternity homes, 16) mentally retarded children's day care centers, and 17) residential treatment centers for emotionally disturbed children.
-'
Social Insurance Japan is the first Asian country to have introduced social insurance measures and
-- 65--
it has developed them steadily during the last few decades. The first social insurance law was passed in 1922, dealing with workers' health insurance in general. Thereafter, it was succeeded by many branches of social insurance as shown in Table 45, below, which illustrates a bird's-eye view of all kinds of social insurances, giving some informations about the pertinent laws with their dates of promulgation, responsible government agencies, the coverage of insurer and the insured people, etc. Table 45. Law Health Insurance Law , /
Classification of Social Insurances. Responsible Ministry Insurer Insured 1
! Date I 1
I Government, and He';'lth Insurance , Umon I
1922
1
Health.& Welfare Mlmstry
! Employee's Pension Insurance , Law I 1941 I I ,
--
-
--
-~
" Ministry of Labor -
I Government I I I
Unemployment Insurance Lawl 1947
•
I I
" "
Employees in the working places (compulsory or voluntary)
Workmen's Accident Compen· 1947 sation Insurance Law 1 I ----,------Seamen's Insurance Law 1939
" 1
Heal.th & Welfare Mmlstry 0
Seamen Mutual Aid Association 1
National Public Service Mutual Aid Association Law , National Health Insurance Law
. t 1948 1M' , llllS ry 1938 1
f F'
Inance
I I
Government employees .
I I'
; Health & Welfare I City-Town-Villa- Other persons besides ge Government, I Ministry and Union those msured 1
I Health Insurance Law for j
I
, Daily workers ; Government 1953 Daily Workers ~utual Aid A-S--So-c~i~a~ti~o-n-'L-a-w~I---'1--------·,---------.I·T"e~a~c~h~e~r~s-a~n~d~w~o~r~--of . Mutual Aid k f' t 1953 Ministry EducatlOn Association ers 0 prtva e for the Teachers and Workers of Private Schools ,schools --Mutual Aid AssoCiati:"o"n~L-a-w-I---~1--------~I--------I-E-m.:cp-Io-y-e~-s-in-t-h-e-for the Employees in the 19561' Ministry of Finance " public enterprises Public Enterpris~e_:s~-~-..-L--.L---------'-----------------Mutual Aid Association Law Ministry of Employees in the for the Employees in the 1958 Agriculture & " agriculture & fishAgriculture & Fishery F t ery organization __QTgan_i_za_tio .. n___________~__ o_r_e_s_r_y_ _ __.-------_,~"'-_'-~''-__ Whole population I those 20--59 years Health & Welfare Notional Pension Law 1959 Government old, except those Ministry covered by other pension schemes I-------------~I- - - ' - - - - - - - - - - ' - - ---------'cj-Offidals oCcitie-s,- towns and villages, Local Public Service Mutual i119621' Ministry of Home Mutual Aid teachers and workers Aid Association Law Affairs Association of public school, '_______________- '_ _--'--_ _ _ _ _ _ _ _ _ _ _ _ _ _ _-'--. and police officials I,
1-
l_
Following is the summary of those social insurance schemes operated under the direct jurisdiction of the Ministy of Health and Welfare. 1. Health Insurance (compulsory for employed persons) Established by Basic Law No. 70 of April 1922, the scheme is covering approximately 19 million insured persons as of the end of the year 1966. The insurance carriers are the Government and the Health Insurance Societies (approved societies). Benefits in kind include all types of medical care, hospitalization, dental care and pharmaceutical
-
66-
medicine in respect of the non·occupational risks of the insured person and their depen· dents. Cash benefits include sickness and injury allowance, delivery expense, mater· nity allowance, child nursing allowance and funeral expense. The scheme is financed from contributions paid by the insured person and the employer in equal proportion. 2. National Health Insurance Established by Basic Law No. 60 of April 1938, the scheme applies to persons not covered under the Health Insurance Scheme. It now covers approximately 43 million insured person including householders and their dependents. The insurance carrier is City, Town or Village, and the National Health Insurance Organization. Benefits include medical care in kind, maternity, funeral and other expenses. The scheme is financed from contributions paid by the insured person and the national subsidies. This law has been wholly amended by the Law No. 192 of December 1958, whereby every city, town and village were given the responsibility to enforce the National Health Insurance. Consequently, "Sickness Insurance for Whole National Programme" has been achieved. 3. Seamen's Insurance (compulsory for seamen) Establi.shed by Basic Law No. 73 of April 1939, the scheme covers approximately 240,000 seamen. The insurance carrier is the Government. The scheme is a comprehen· sive insurance scheme for seamen, covering occupational as well as non·occupational risks of sickness and injury, unemployment, invalidity, old age and death. 4. Daily Worker's Health Insurance (compulsory for daily workers) Established by Basic Law No. 207 of August 1953, the scheme covers 957,000 insured persons. The insurance carrier is the Government. Benefits in kind are almost the same as those under the Health Insurance Scheme, and there are various benefits in cash, too. The scheme is financed from contributions paid by the insured persons and employers, and national subsidy. 5. ~~ployee's Pension Insurance (compulsory for employed persons) Established by Basic Law No. 60 of March 1941, the scheme covers approximately 19 million insured persons. The insurance carrier is the Government. Benefits include old age pension, co·ordination old age pension, invalidity pension, survivor's pension and withdrawal allowance. The scheme is financed from contributions paid by the insured person, the employer and national subsidy. 6. National Pension Established by the Law No. 141 of April 1959, the scheme applies to persons not covered under any other public pension system. The insurance carrier is the Ggovern· ment. This scheme includes the contributory programme and the non-contributory programme. Benefit includes old age pension, co-ordination old age pension, invalidity pension, widowed mother's pension, guardians pension, orphan's pension, widow's pen· sion and lump·sum death grant. The contributory programme is financed from contributions paid by the insured person (approximately 20 million) and national subsidy, while the non·contributory programma is financed by the government contribution.
_....
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67-
"The health of all peoples is fundamental to the a ttainmen t of peace and security"
"Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity" (From the Preamble of the Constitution of the World Health Organization)
-_._ ... - .. -----........ --_. - - .- . . Compiled by the Office of the Counsellor for Liaison in International Affairs,
-~
Minister's Secretariat, Ministry of Health & Welfare Japanese Government Tokyo, Japan
• ,. -
• ORIGINAL: )
ENGLISH
BRIEF REPORT ON THE PROGRESS OF HEALTH ACTIVITIES IN MALAYSIA 1 WES.l' MALAYSIA
J.
:;
1.
INI'RODUCTION
or
.
West Malaysia comprises the eleven states of the former Federation ofoMalaya. It is 51 000 square miles and the temperature ranges from 70 Fto 90°F. The relative humidity is generally high. The average annual rainfall is between 120 inches and 160 inches. In 1966 the estimated mid-year population was 8 297 849, of which, about 60% is under 19 years old • 2. PUBLIC HEALTH ADMINISl'RATION
At the turn of the centruy, almost all the medicSl and health services were provided by the Government. This accidental monopoly was, however, . diluted by tr ~ setting up of estate hospitals by the rubber and mining . industries and in recent years a number of private hospitals were established by missionaI'y·bodies ·and other organizations. until 1932, the Government Health Services were divided into two departments, one being maintained by the Federated Malay States (Perak, Selangor, Negri Sembilan, Pahang) and the Unfederated Malay States (Johore, Kedah, Perlis, Kelantan, Trengganu) and the other by the Straits Settlements (Penang, Malacca). In 1932 the two services merged with a common professional head acting executively as tlDirector lt in the Strait.s Settlements and in an advisory capacity as "Adviser tl to the various Federated and Unfederated States. In 1948, the Federation of Malaya Agreement decentralised control to an extent where, except for some federal institutions, such as mental asylums and leprosy institutions, the executive control over the service became fundamentally a State matter. In 1957, with the declaration of Independence, Health became a Federal matter, except for certain preventive measures in Municipalities and other Local Authority Areas. On the formation of ~Blaysia in 1963, Health in Sarawak became a Federal matter whilst in the State of Sabah it remained a State matter. (Annex I - Organization Chart).
lSubmltted by the Ministry of Health, Kuala Lumpur, 1 September 1967.
t
- 2 -
3.
GENERAL HFALlrH SITUATION
The general health of the population continues to improve and.no epidemic of any quarantinable or communicable disease occurred durLng 1966. Table 1 - Population, Annual Population Growth, Crude Birth Rate, Crude Death Rate, and Crude Mortality Rates Crude Crude Population Birth Death Growth Rate Rate . 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 6 278 6 498 6 ffJ7 6909 ·7 136 7 377 7 610 7 813 8 039 8 297 758 758 827 009 804 280 843 7($ 030 849 3.5 3.0 3.3 3.0 3.3 3.4 2.8 2.8 3.0 N.A. 46.2 43.2 42.2 40.9 41.9 40.4 39.4 39.1 36.7 N.A. 12.4 11.0 9.7 9.5 9.2 9.4 9.0 8.1 7.9 N.A. N.A. 4.
Crude Mortality Rates Neo~Natal
Year Population (mid-year)
Infant Toddler 75 80 66 ($ 60 59 57 48 50 N.A. 11
Maternal 2.8 2.8 2.1 2.4 2.0 2.3 2.2 2.1 2.0) N.A.
30 32 29 30 29
31 29 25 26 N.A.
9 8 8 8 8 7 6 6 N.A.
= Not
yet available
DEVELOPMENT PLAN
December, 1965 marked the end of the Second Five-Year Development Plan (1961-1965) and in January 1966, the First Malaysia Plan (1966-1970) commenced. A total sum of M$108.8 million was spent during the Second Five-Year Development Plan period for improvement and expansion of the medical and health services. In the First Malaysia Plan the estimated. expenditure for Health and Family Planning is M$l89.4 million (Malaya M$l50.4 million, Sabah M$l8.0 million; Sarawak M$2l.0 million) or 4.2% of the total Public Development Expenditure. The broad objectives of the medical and health programme are as follows: .
(i) (ii)
to expand and improve medical and health faCilities, espeCially in rural areas; to provide facilities for the training of personnel to man these services;
- 3 (iii)
to promote the general health of the population by systematic control of communicable diseases. improvement of environmental sanitation and nutritional standards and provision of more and better specialised service; and
(iv) to establish a programme of family plarming.
The main features of the programme designed to meet these objectives are reflected in the breakdown of total cost shown in the table below: Table 2 - Malaysia: Development Expenditure for Health and Family Plarming. 1966-1970. (M$ in Millions)
I
~. r
Malaya I.
Sabah
PREVENI'IVE SERVICES: Control of Communicable Diseases Tuberculosis Control Leprosy Control ~~laria Eradication Sub-total Promotion of Health & Sanitation Rural Health Service Dental Health Service Urban Health Service Municipal Clinics Sub-total 20.0 l.} 1.0 0.4 22.7 6.1
.
Sarawak Malaysia
- 0.6 ---------1------- --------4.0 0.2 0.8 0.9 0.7
3.0 1.0
0.2
0.2
--------_. 5.0 27.0 2.0 1.0 0.4 30.4
3.4 1.0 0.6
- --------_. 1----------------------6.1 1.6 98.0 12.0 1.0 2.8 5.6 2.4 17.6 0.3 0.1 118.4 17.9 3.5
-
-
II.
CURATIVE SERVICES: New Hospitals Extension/Equipment Other Hospitals/ Institutions Sub-total
--------- 1------- --------- --------_. 111.0 10.8 18.0 139.8 3.0 5.0 2.7
III.
OTHER PROJECTS/PROGRAMMES: Training Programmes Institutional Quarters and Hostels Miscellaneous Sub-total
0.4 0.5
0.3
3.3 5.4 3.5
IV.
FAMILY PLANNING
-------_. ------- --------- --------12.2 0.6 10.7 0.9 2.0 2.0 150.4 18.0 21.0 189.4
0.3
TOTAL
- 4·r
5. (i) Rural Health Service
PUBLIC HEALTH
About 6Q% of the population are to be found in the rural areas of the country.. On Independence more than 70,/; of the medical and health services were concentrated in the urban or semi-urban areas. The highest priority, therefore, had to be given to expansion of the health services to the rural areas to correct this imbalance in distribution. The main programme in the promotion of health and sanitation in the rural areas was the Rural Health Service, which involved the building of health centres, sub-centres and midwives clinics. These facilities provide both preventive and curative services, including two specialised services - dental health care and maternal and child health care. The following table shows the progress made in the implementation of the Rural Health Service: . : "Table 3 - Progress in the building programme of Main Health Centres, Sub-Centres and Midwives Clinics 1957 1958 1959 1960 1961 1962 1963 1964 1965 1966 Total Units at end of 1966 8
'.
'.
Category
Main Health Centre Health Sub-Centre Midwife ClinicS .
-
-
7 26
1
12 ?J)
15 52
2 5
1 15 81
- 1 - -
-
13 21
?J)
3
135
29 318
67 ~22
664
#
•
More than 3 million rural people now enjoy the benefits of a basic preventive and curative service. The capital cost of these units is some M$36.47 million. In addition there are 164 mobile dispensaries operating in areas not yet covered by this scheme. Increased care for the rural people is reflected by the !ncreasing work-load of these units as shown below: Table 4 - Attendance at Health Centres, etc., Home Visits and Home Deliveries 1960 Total Anendanees At Health Centres Home Visits Home Deliveries , 5136336 843 073 44 759
1961 5114419 941 BIll 50119
1962 5682426 961360 53246
1963 6661 069 1 73'1037 59436
1964 6721261 1 292164 62561
1965 6969894 1 484 767 64555
1966 6771716 1 480360 68105
- 5 (11) Public Health Programmes (a) Quarantinable Diseases No case of quarantinable disease was reported during 1966. (b) Tuberculosis
The National Tuberculosis Control Campaign is now fully operational. More than 1.2 million people have been X-rayed and some 1.36 million persons including new borns given B.C.G. sinoe the commencement of the campaign in 1961. A special study is being undertaken to resolve the problem of defaulters among ambulatory patients under treatment and those recalled for further investigation where X-ray abnormalities indicate. (c) Malaria Following the successful malaria eradioation pilot project and the subsequent malaria pre-eradication survey, a National Malaria Eradioation Plan has been drawn up. The programme is spread over a period of ten years and is expected to cost about M$llB million. A provisional eradication programme starting from the north has been launched early this year.
Cd) Yaws The eradication of this disease in the oountry is now in sight. The incidence of this disease in local infected areas 1s well below "consolidation level". (e) Filariasis
This control programme has suffered set-backs in personnel and materials and every effort is being made to strengthen the programme. (f) Other Communicable Diseases The incidence of common communicable diseases does not pose a public health problem. (See Annex II). (iii) Immunization Programme Immunization against Smallpox, Diphtheria, Tetanus and Pertussisis routinely performed by health centres and clinicS. A total of 239 205 primary vaccination against Smallpox were performed in 1966; 56 471 children completed their course of Triple Antigen and 22 505 children were given Diptheria Toxoid.
- 6 (iv) Environmental Sanitation This subject is part of the health programme and is being given the importance it deserves. Sanitation Pilot Projects, one in each State, are being implemented. Three point six million people or 43.4% of the population is provided with potable water. I
(v)
Nutrition Protein malnutrition and avitaminosis are still problems to be resolved, particularly in the rural areas. A joint Nutrition Pilot Project with various Ministries and Departments is now being planned.
6.
MEDICAL CARE
All existing hospitals in the country have been renovated and expanded and ancillary departments have been enlarged to cope with the ever-increasing demand for medical care. This demand has increased not only because of the increasing population but also more and more people are taking to modern medical treatment. In the Second Five-Year Development Plan a sum of M$35.6 million has been spent on hospital improvement. Besides this, five new hospitals are being built at an estimated cost of M$120 million. Of these the District Hospitals at Dungun and Tanjong Karang have been completed and the Teaching Hospital at the University of Malaya has started giving service. The overall bed capacity of Government hospitals has increased from 20 337 in 1957 to 26 535 by the end of 1966. Demand for medical attention is still on the increase and has almost doubled since 1957 as shown in Table 5. Table 5 - Hospital admissions and attendances at Out-Patient Departments 19~I
1.)100
Hospital AdmiSSions Hospital out-patient Treatment
271 490 3 281 966
432 955
6 056 718
Beside Government hospitals, there are industrial and private hospitals and maternity homes with a total bed-complement of 5 819 which handled 110 912 in-patients and 1.1 million out-patients during 1966.
- 7 7. DENl'AL SERVICE
Like the medical and health service, the dental services are being expanded primarily into the rural areas. Of the 395 dental clinics 60 per cent. are in the rural areas. Consequent to the increase in the number of dental clinics, attendances have also increased as follows: Table 6 - Number of Dental Clinics and Clinic Attendances
No. of Clinics ~otal Attendances
1960 llI-o
1961
.23<J
19E2 20'(
1963 209
1964 2b7
1965 322
1966 395
655 140 754 896
851
l~
849 670 928 118 1 0)2040 1 131
68;
8.
TRAINING PROGRAMME
Training programmes have been expanded pari pasu with the expansion of the medical and health service. The staffing position of auxiliary medical and health workers has improved considerably but the country still faces an acute shortage of doctors, dental surgeons and pharmaceutical chemists. The Public Health Institute was oficially opened on 1st July, 1967 to house the Public Health Inspectors' Training School and the Public Health Visitors' Training School. In addition the Institute will review public health training needs and plan for the expansion and co-ordination of training programmes. It will also conduct studies and action research in Public Health and Community Development. A training course for Junior Laboratory Technicians has been established and plans are being finalised for the setting up of a School in Medical Laboratory Technology. The Board of Studies, University of t-lalaya, is considering the establishment of a Dental Faculty. It is hoped that a School in Tropical Medicine will be started in the very near future under the auspices of "South-East Asian Ministers of Education Secretariat".
9 • ACKNOWLEDGEMENT The Government of Malaysia wishes to place on record its appreciation of the many and varied technical assistance by way of consultants, equipment and scholarships made available by WHO, UNICEF and friendly foreign governments for the various public health programmes and in the training of local officers.
- 8 SABAH (EAST MALAYSIA )
1. GENERAL During 1966 the emphasis placed on public health was continued as in previous years. Training of staff to fill posts required as a result of development, was also accelerated. As in previous years the main public health problems continued to be Malaria. Tuberculosis. Enteric diseases, Helminthiasis and a low sta.~dard of environmental sanitation in the rural areas. In the curative field,development of the health infrastructure was continued and integration of all aspects of medical work in the various areas was encouraged.
At the end of 1966 there were two general hospitals. seven cottage hospitals and twenty-three static dispensaries (with beds) run by the Government. In addition there were thirty-eight Estate dispensaries under non-government control. There were also six Mission dispensaries. In 1966 in order to further integration, a second area health unit was set up covering the West Coast areas. 2. TRAINING
(i) Following the recognition of the NurSing School in Queen Elizabeth Hospital by the General Nursing Council of England and Wales, the syllabus of the School was maintained at the .approved atandard and of the first group of twenty-nine General Nurses trained under the syllabus, twenty-two qualified in September 1966. The girls are offered further training in midwifery following qualification and the midwifery section can train up to twelve nurses per year. (ii) Training of Rural Health Nurses was carried out based on a twoyear rotating course comprising eight months in general orientation, eight months in maternity and eight months in field training under superviSion of a qualified Rural Health Nurse. This is in the National Language medium.
(iii) The Department also runs training courses for _
Ca) (b) (c) (d) (e)
ASSistant Nurses. General 2 years Assistant Nurses, Psychiatric 2 years Laboratory Technicians 3 years Male Environmental Health Workers 6 months Health Inspectors In-Service Training 18-24 months
- 9 -
3. BUILDING AND DEVELOPMENI' Three more static dispensaries (with beds) were put into operation during the year. The new General Hospital at Tawau and the new Outpatients Department in the Queen Elizabeth Hospital, Jesselton, are nearing completion. Thirteen new Village Group Sub-centres were put into operation and various minor projects to improve existing buildings were carried out.
4.
PUBLIC HEALTH
(i) Tuberculosis Control Scheme The Tuberculosis Control Scheme continued its basic policy of mass miniature radiography, Hear testing of schoolchildren (with B.C.G. where indicated) and follow-up of contacts, cases and defaulters. More emphasis was placed on out-patient treatment. (ii) Maternal and Child Health Services Due to the full commission of the two-year rotating scheme for Rural Health Nurses, Maternal and Child Health services underwent considerable expansion during the period. The importance of these services was emphasized by bearing in mind the broad-based pyramid population of the State. Special attention was given to provision of clinics in rural areas, immunization of expectant mothers with tetanus toxoid to prevent neo-natal tetanus and administration of immunization against smallpox, diptheria, tetanus and poliomyelitis for infants and children. (iii) Malaria Eradication During 1966 consolidation areas were expanded to cover half the population of the State. For various reasons, mostly operational, setbacks occurred and several local epidemic flare-ups were seen. The importance of rapid corrective action was recognised and appropriate steps were taken during the year. (iv) Environmental Health A school for re-orientation of junior specialist health workers was started in the Interior in 1966. The main emphasis being placed on training men in rural sanitation and water supply.
- 10 SARAWAK (EA...CJl:' MALAYSIA)
1. During the year considerable progress was achieved in the field of health activities in the state of Sarawak. under the First Malaysian Development Plan. This plan may be conveniently divided into three main sections, namely: (i) The Building Programme for new medical buildings including hospitals. dispensaries. clinics. medical stores and a variety of other medical buildings and institutions. (11) The state-wide Public Health Projects such as the Sarawak Malaria Eradication Project. the Tuberculosis Control Project, the Rural Health Improvement Scheme and the School Dental Service. (iii) The training of staff to keep pace with the expansion of medical and health facilities in the state. 2. BUILDING PROGRAMME
(i) The State Hospital The main item is the construction of a new State Hospital. the Sarawak General Hospital. for which the sum of M$16.l million has been allocated under the First Malaysian Development Plan, to complete the first phase of the project. This new hospital which will oontain 567 beds when oompleted. will serve as a base hospital with specialist facilities for the Whole State. Considerable progress was made on this project during the year. after the signing of a formal contraot for its construction in January. The hospital has been designed by a firm of Australian hospital architects. whose servioes were provided partly under Colombo Plan Aid by the Australian Government. and the same firm has been retained as consultants to supervise the oonstruotion of the building. The first phase of the building programme is soheduled to take 33 months. so that the main block should be ready for ocoupation by the end of 1968. or early 191$. (ii) Local Hospitals In addition to the new State Hospital, work commenoed on the construction of two new 25-bed local hospitals at Bintulu in the Fourth Division and Lawas in the Fifth Division. These hospitals are being built to serve the needs of the people living in the rural areas. where access to a divisional hospital is difficult. It is antiCipated that these two local hospitals (at Bintulu and Lawas) will be completed during 1967.
- 11 -
(ii1) Dispensaries During the year, three static dispensaries were completed at Roban in the Second Division, Pulau Bruit in the Third Division and Tatau in the Fourth Division. In addition to these dispensaries, a travelling road dispensary was established at Bau in the First Division. Work on two more static dispensaries at Bantu Niah and Long Lama in the Fourth Division commenced during the year, and it is anticipated that these two new dispensaries will be completed during 1967. (iv) Dental Clinics One new dental clinic was under construction during the year at Sibu in the Third Division, and Should be completed during 1967. This clinic will add to the number of dental clinics throughout the State which form part of the expansion of the School Dental Service in Sarawak. ~e School Dental Service has been considerably expanded as a result of the return of a number of new dental nurses after training in Penang, West Malaysia. (v) Miscellanous buildings other building projects were the completion of the Central Medical Store in Kuching. the completion of an extension to the Maternity Section of the General Hospital in Sibu in the Third Division, and the completion of a new Mental Health Unit at Miri in the Fourth Division. In addition to these building projects, plans were being finalised for the construction of a new Mental Health Unit in Sibu in the Third Division, and a combined Medical Store and Salt Iodisation Plant also at Sibu in the Third Division.
3. PUBLIC HEALTH PROJEC1l'S (i) Malaria Eradication With regard to the Public Health Projects, the main one is the Sarawak Malaria Eradication Project, which commenced as a control project in 1954. This project has now reached the stage where malaria has been eradicated completely from areas containing about 50% of the population of the State. Another 38% of the population live in areas where malaria is now an uncommon disease. The remaining 12% of the population live in areas mainly situated along the borders of Sarawak where the risk of infection is still high. The project has had a
12 remarkable effect on the economy of the state having reduced the overall incidence of malaria in Sarawak from the previous figure of 10 to 15% to the present figure of 0.2 to O.~. Malaria is a disease which is now seldom seen in the hospital wards of Sarawak. The project receives assistance from WHO and UNICEF. (ii) Tuberculosis Control The Tuberculosis Control Project is a more recent programme than the Malaria Project having started in 1960 with Colombo Plan Aid from Australia. Originally it operated only in the urban areas of Kuching and Sibu. However, during the period 1964 - 1966, the Project was extended to cover all five Divisions in the State, and during 1966 much of the work done was in the rural areas. (iii) Rural Health Improvement The Rural Health Improvement Scheme commenced in 1963 and has expanded a great deal since then. The main object of the scheme is to train suitable personnel to carry out environmental sanitation work and health education in the rural areas of Sarawak. Such personnel also work in areas closely associated with land development and re-settlement schemes. During 1966 another 9 Rural Health Supervisors were trained making a total of 33 (Rural Health Supervisors) working (under this scheme at the end of the year) in all 5 Divisions of the State. The scheme receives assistance from WHO and UNICEF. 4. TRAINING
All medical development projects need to be staffed by trained personnel of various categories. This aspect of development has not been neglected in Sarawak and every effort has been made to ensure that the training of all categories of staff is based on the general expansion of medical and health activities in the urban and rural areas of the state.
ANNEX I
MINISTRY OF HEALTH
[ I Pengarah j
Minister of Health
t-
Parliamentary
y Secretar~
I Permanent Secretary and Director of Medical Services Dy.sectetary
Political Secretary
"t
Dy • Director
Dy. D lrect or
J
I Hospitals Divison Administration and Finance
I Dental Division
Dy.Di~ector j . Health Division
T.E.Spe cialist
J
I Natic >nal T.E. Cc >ntrol
Institute for Medical Research Principal Marron
NurSing Division
. .1 Phar~e,ut'oal Division Chief Medical Malacca Kelantan
Chit f
Asst .Director
Asst.D,rector
i ~-
Senior Records ofycer
Development Division (Offices 'in states) I
I Officers Penang Perak ,I
Training Division
I
Medie.' R,eord, and Statistics
and Negeri Sembilan
Health Pahang
Officerin-charge Selangor Trengganu Perlis
Directors Medical Services
Johore
I
-
Kedah
Sabah ~---.-
Sarawak
,
)
ANNE:: II
INCIDENCE OF COt-iMON COMMUNICABLE DISEASES IN WEST MALAYSIA 1961 - 19S6
YEAR
1S61
1S62
1963
1964 J:J.. 0
1965
W66 C) C)
~ Cholera Cerebro-Spinal Feve Chickenpox Diptheria
., ., ., u
..
Q)
" c <'J
g.. ... 8' OJ 0 0..
'" u ,~
.Ei
0 0 0
., <lJ .,
12 4027
-
-
t3
U C <lJ "0 ,~
&0 0 u 0 .Ei
g.. " . . g-
., ., ., U
C)
9
-
-
..
8' @ &,8
U C
~
s a 512 "
.,
.,
U
<lJ Q)
C
"0
OJ
"" ... 8' 0
.Ei 6,56
'0
0..
0 0 0 0
., ., ., U
-
.. 1
Q.,
0
<lJ r:: ... 0 '" @ :(j ~ &8 u $ 8
.,
u c
<'J
"0
<lJ
,~
~
"'8 &0 0
e
,;c ,;-
153
2.01
0.01
- 1 0.01 1765 21.27
-
0.17
0.12
4
0.05
,
0.05
4
0.05
56.43
4270
57.89
4780
62.96
36·17
46.70
5690 70.8S
1683
20,58
1335
18,10
1160
15.25
1139
14.58
439
17,91
968
ll.67
Dysentery (all forms)
3121
,13.73
2850
38.64
2888
37.98
2!)22
37,41
2427
30,20
2011
24.24
Enteric Fever
877
12.29
942
12.77
854
11.23
874
ll,W
1216
15.13
950
11,45
Erysipelas
314
'1.<10
243
3,29 0.46
1 1 0.01 8 0.01 2 0.01 5 0.06
Leprosy
256
3.37
632
8.09
331
4,12
216
2,60
I
I
Paratyphoid
61
0,85
3'1
37
0.49
33
0.42
72
0.90
42
0.51
Poliomyeli!is
160
2,24
56
0,76
8S
1,17
175
2.24
399
4.97
97
1.17
P. Tuberculosis
9889
138.56
10322
139.94
10706 140.7S
11463
146,77
11089
138.10
9467
ll4.09
Pueperal Fever
III
1.56
70
0,95
29
0,38
1'15
1.86
150
1.87
146
1.75
Scrub Typhus
52
0.68
111
1.42
ll4
1,42
120
1.45
Urban Typhus v
16
0.22
12
0.16
22
0,29
20
0,26
29
0,36
15
0.18
Yaws
3523
4S,36
2043
27,70
1455
19.13
825
10,56
560
6.97
420
5.06
Source of information: Monthly Return of communicable Diseases.
ORIGINAL: ENGLISH PROORESS
m HE:Al['H 1.
ACTIVITIES 1966/671
m NEW
ZEAI/lND
POLIOMYELITIS c~aign
using the Sabin vaccine in 1961/62 no confirmed case of poliomyelitis has been recorded since April 1962. In order to maintain at the highest possible level community-wide iImmmity to this dise~se, the Depc.rtment of He<.:..lth has continued to .offer, through Departmental clinics, the Sabin v<.:.ccine to all new~ born infants and permanent settlers arriving in New Zealand. The complacency engendered by the continuing freedom from poliomyelitis resulted, hOvrever, in a number of parents failing to have their children immunised. In order, therefore, to save mothers the inconvenience of attending these special clinics, general practitioners now give the Subin vaccine at the same time as the triple vaccine against diphtheria, tetanus and pertussis. Departmental clinics ure, hOlrever, still available for those who .dsh to use them. 2. PHENYI.KE!TONURIA
Following the mass immunisation
The Guthrie Blood Test for phenylketonuri.:.. ;;as introduced throughout New Zealand in 1966. It is c...rried out before the baby leaves hospit.:..l and between 1 April 1lIlcl 31 December 1966, 89.1% of those born during this period (40 305 babies) were tested. Three babies lrere found 1-lith ruised phenylalanine blood levels and c.re being further investigated. 3. HEAIlrH CURRICUUJM: FOR PRIMARY SCHOOLS
A handbook on he<:.clth educc.tion in the prilnD.ry schools, ready for publication ear~ in 1968, is the resUlt of close co-operation and careful planning by Health and Educo.tion Departments' staff throughout the country. The handbook includes suggestions for the teaching of health topics throughout all the grc.des in the primary schools <..llld methods of integrating health llith other subjects in the curriculum. A large section gives buck.. ground material for the teacher.;ith a uidely representative bibliography. and classified visual aids. Publication of this work is one of the most important forward steps in child health that has talcen place for some years. It is expected that the introduction of the bool( into primary schools \Till ensure a better standard of health teaching uhich, it is hoped, mll improve community health attitudes and ImolTledge. 1
Submitted by the Department of Health, Wellington, 16 August 1967
- 2 -
4.
NARCOTICS
By Order in Council the Schedule to the N~rcotics Act was extended by adding, in lILrch 1967, Acetorphine, Etorphine and Nicodicodine, and in July 1967, !usergide, ~sc.::.line and Peyotl. !usergide l-ras also placed in the cluss of' narcotics (with heroin) f'or action against which Police have the right of' entry <md search lrithout wa.rrant. !usergide remains under the control of the Poisons Act (effective from May 1964) restricting its distribution to and use solely by medical practitioners specialist in psychiatry. Peyotl (Iophophora willi.:.u:nsii and Iophophora leminii) have been made prohibited plants, possession and cultivation of ,rhich may be only under license. (Note: Resolution WHA20.42 adopted by the Twentieth ~lorld Health Assenibly on the subject of' "Control ~asures for I.'ID and Related Substances II is germane. )
5.
HHO TECHNICAL REPORTS
In order to ensure tlkl.t lmO Technical Reports &re adequately studied and, where appropriate, acted on, the Board of Health instituted the practice of having all these reports reviewed und reported on by the appropriate New Zealand expert.
6.
NATIONAL POISONS INFORMATION CENTRE
During the second year of' its operation, the National Poisons Information Centre received 556 culls as against 330 in the previous year. Household commodities were the subject of most calls (202) followed by drugs (J92) and plants at 42 showed ..J. sharp increase. Among the household commodities featuring ,rith particular frequence ,rere detergents (35), disinf'ect--nts (20), petroleum distillates (16), paint and paint products (12), polishes (15) and rat pOisons (10). The risk posed to children in particular of accidental poisoning (highlighted by the statistics produced by the Natio~ POisons Information Centre) is the theme of' a national health education programme for 1967.
·
.
ORIGINAL: BRIEF REPORT ON WHo-AssrsrED PR~S
ENGLISH
m THE PHILIPPINES·m 1966
1.
MALARIA
ERADICATION PROORAM
Activities in the first semester: Congressional legislation centralized the services. The malarious areas have been re-delimited and geographical reconnaissance brought up to date. Pre-service and in-service training of all malaria personnel categories was intensified. A review of all available sources was made with a view to tapping them for future activities. In the second semester: There was a reorganization of the malaria· eradication services. Baseline data were established for entomological and epidemiological activities. For thiS, indicator districts were established at selected sites to measure the impact of the spraying campaign; 86 983 blood smears were examined with 11 625 positive giving a slight positivity rate of 13.4%.
2.
TUBERCULOSIS
Tuberculosis continues to be a major disease problem. It accounts for 12% of deaths from all causes, and 28% of deaths among the economically productive ages 50-65 years. (1) BCG vaccination is now integrated into the regular function of the Rural Health Units and 13 million vaccinations have been performed. (2) The ambulatory chemotherapy program provides free medicines to about 40 000 active cases a year and more than 200 000 patients have been benefited by the program. (3) The demonstration training center conducted studies on control methods under local conditions. (4) Case-finding by direct microscopy was started involving 19 Rural Health Units and 4 City Health Offices. 3. LEPROSY CONl'ROL PROJECI'
There has been a substantial reduction (32.5%) of patients in the sanitaria and a corresponding increase (50.9%) in those under home treatment. This is a result of the new law (R.A. 4073) which revised the national approach to leprosy control. In view of this, two travelling clinics, 2 statio units, 20 para-medical personnel were added to the program with also intensification of the health education program. It is hoped to integrate the program eventually into the rural health services.
lSubmitted by the Department of Health, Manila, 30 August 1967
- 2 -
4.
CANCER CONl'ROL
Of the 8 envisioned regional diagnostic centers, 3 have been programmed namely: Health Region 1 - Baguio General Hospital; Health Region 3 - Jose R. Reyes Memorial Hospital. and Health Region 6 Southern Island Hospital. A pilot project for cancer clinical services was established at the Rizal Provincial Hospital and another at Andres Bonifacio Hospital in Cavite. Under the research phase of the cancer program, the national tumor registry has been activated.
5.
MENl'AL HYGIENE
A three-year epidemiological survey in a pilot area is almost complete bringing about meaningful materials to strengthen the long-range expansion program in the prevention and control of mental disorders. A study of the status of undergraduate teaching in psychiatric and mental hygiene nursing is being undertaken with a WHO nurse consultant. An increasing awareness of government and civic entities has been progressively generated to enhance the application of preventive concepts and a network of activities amidst the limited ability of the national government for program financing.
6.
PEDIATRIC NURSING
(1) New services developed: Play area of polio ward. San Lazaro Hospital. pediatrics, Maternity and Children's Hospital and center formula room at National Children's Hospital. (2) Training programs - Training programs conducted: Maternal and New Born Care - 15 trainees; Pediatric Nursing - 31 trainees, Care of LowBirth Weight Infant - 21 trainees. Assistance to private schools of nursing and strengthening maternal and pediatric nursing curriculum. (3)
(4) Formulation of standards and recommendations for pediatrics and pediatric nursing - the manual is nearly completed. (5) Assistance to graduate nurses pursuing the Master t s degree in and preparation of studies for maternal and child health.
• - 3 7. SOCIAL PEDIATRICS
(1) Schools of midwifery assisted: . 10 private schools in Luzon, 1 private school in Visayas, 2 private schools in Mindanao, 1 government school in Manila. Assistance given in the form of technical services, teaching aid equipment, assistance in regional curriculum, development of maternal services manual and legislation. (2) Health training - The program ended in 1966 with 7000 "hilots" trained. Six hundred and thirty-four nurses and midwives "hilot" teachers were trained. The project is being implemented in 27 provinces and 91 centers. Its activities give encouraging results as evidenced by increased attendance at prenatal and well-baby clinics in areas where it is implemented.
8.
DENl'AL PUBLIC HEALTH
Two WHO short-term consultants provided technical guidance in the development of a national program. Technical advice was given to the Director of the Department so that the objective of the national program was changed from a purely remedial approach to one of prevention.
9. -~
CHOLERA EL TOR
In 1966, continuation of the vaccine trials was pursued among the
inmates of Muntinglupa. Encouraging results were obtained and later on tried in Negros Occidental with the support of the WHO-Japan-Philippines cholera project. Parallel to this vaccine trial are the carrier studies to determine the real epidemiological picture of cholera. The results of of this project will soon be released. The experiment consists of using a single dose and double dose comparison. The bacterial content per ml of three types of vaccines is as follows: 8000 million were given to 90 000 people; 16 000 million to 90 000 people and the others were given typhoid vaccine as a control. Staff members were recipients of WHO fellowships and attended seminars on cholera in the United States of America and in Calcutta, India, respectively in 1964, 1965 and 1967. These fellowships aim to promote staff development towards better services to health consumers. In case of emergency it will be easy to create a surveillance and epidemiological team in the v!estern Pacific Region.
- 4 10. ENVIRONMENl'AL SANITATION
(1) The Division of Environmental Sanitation has submitted 272 surveys for UNICEF-assisted water supply projects for health centers and schools which have received approval from the WHO engineering staff. The materials for 147proJeo:ts have already been delivered by UNICEF and another 125 projects are under procurement. The engineering staff of WHO has also given approval to water supply projects for two small communities barrio Cayanga, San Fabian, Pangasinan and Pook, Talisay, Cebu and water supply projects for seven government hospitals. All the materials have arrived in the country and many of these projects have recently started their initial construction. (2) The Environmental Sanitation Project assisted by UNICEF has received various dollar commodities to assist the four Sanitarian Training Centers in the countr;r - Manila, Dagupan, Cebu and Davao, in the form of motor transport for sanitary engineers and motor bikes for trained sanitary inspectors, kits for sanitary engineers and sanitary inspectors, tools, books, manuals and other laboratory equipment through the favorable recommendation of the WHO engineers. (3) WHO has also continuously sponsored fellowships for studies and travel grants to sanitary engineers and sanitarians of the Department of Health and has committed itself to continue supporting these activities in the years to come.
(4) The Division of Environmental Sanitation is now almost ready with the submission of another 100 projects for small water supplies for health centers and schools, one small water supply project for a selected community in Davao province, and for ten government hospitals, which will have to be reviewed again and favorably recommended by WHO to UNICEF for their approval.
BRlEF RErom ON HFMIrH S:frUATION IN
~966 -
m:Ptr.3LIC OF 1roREAJ.
1.
GENImAL
S~UATION
-, .~
Under the national policies of the Second Five-Year Economic Development Plan (1967-1971)., .the Government has made every_possible effort to build a foundation for expanded health activities based on the strategy of: (1) prevention and control of communicable diseases to protect the productivity of human resources; (2) developing m:.:lternal and child health services linked 'With family planning, and. (3) 1D.ying the basis for an expanded health center network by giving particular attention to the local health services, using qualified and trained health' workers as well as the valuable assistance provided by HHO, UNICEF and other international agencies. Information on the general progre~s of the heal~h and medical services in 1966 is given below:
The number of health and medical personnel and of educational institutes registered is as follows: (a) Health and medical personnel licensed Rlysicians ." ... """" . """ .. ",, ...... ,, ............ .. Dentists "" .................. ,,"""""""""""""""" Nurses """"""""""""""""""""""""""""""
11 456 1 810
9 851 5 8ll 10 750 2 838 42 516
14idvr.l.ves """"""" .. ,,"""""""""""""""""""
Herb Medical Practitioners •••••••••• Total """"""".' .. '" """""". """"""""""""""
l?b.arm.acists """""""""",,""""""""""""""
(b)
Educational !nstitutes Schools Medical schools " . " " " ........ " " Dental schools •••••••••••• Rlarmaceutical schools •••• Nursing schools •••••••••••. Herb medical school .••••••• Total No. of Schools 9 2 1
Annual Graduates
767
14 35 61
41
1 416 950 80 3254
lsubmitted by the Ministry of :a:ealth and Social Affairs, Seoul, 8 September 1967
- 2 -
1.2 Health and medical facilities The total number of medical facilities was 7251, consisting of 212 general hospitals (including 64 national and provincial hospitals), 4264 clinics, 877 dental clinics, 1709 herb-clinics and 189 health centers. The health center net-vork vith 189 health centers has been extended on the basis of one center for each Gun (County) and Ku (District). Number of facilities Hospitals •••••.•••• Clinics .••.•.•.•.•. Dental clinics ••••• Herb-clinics •••••.• Health centers ••••. Total ................. .. 2.
Number of beds 212
4 264 1
877 709
189
General Hospitals and hospitals •••••••• Mental hospitals ••••••• Tuberculosis hospitals •• Leprosy hospitals •••••• Others ......................... . Total .................. .
20 ;06 1 174 ; 400 9 762
405 35047
7 251
MAJOR PUBLIC HEALTH PROBLEMS
2.1 Acute communicable disease control The Government concentrated its main efforts on the control and prevention of cholera and encePhalitiS, While health education and sanitation measures 'Were enforced. The folioving figures 'Were reported in 1966: TyPhoid Japanese Fever us J'liphtheria Encephalitis
Tw 2 1
Cases Deaths
3 680 77
1 283
8;
3 595 957
The following vaccination-programmes were carried out: Smallpm: ••••••••••••••••••••••••••.• TYPhoid and ParatYPhOid, A & B •••..•. Typhus ......................................... . Cholera ................................................... ..
D.P.T.
.. ............................................. .
Pol1anyeli tis ................................. ..
2 465 876 17 792 499 49 76; 6 216 064 486 300 1001 655
2.2 Chronic communicable disease control (a) Tuberculosis
It has been shown by the nation-wide prevalence survey in 1965, undertaken by the Government with the cooperation of WHO and UNICEF } that the prevalence rate vas 5.1'1> in the population over 5 years of
~
3-
age (2 800 000). This accounts for 1 250 000 patients of whom 230 000 bacteriologically positive; 465 nell cases :per 100 000 pa,pulation are estimated annually. The prevalence rate ill t he urban areas was 5.3%, in the rural areas 5%, and in Cholla-Namdo and Seoul City it was over 6%. This indicates that 940 000 persons among the 'Working population over 15 years of age can be assumed to be tuberc'J.losis patients. Thus the Government has inter~ified both preventive and cU~l'ative measu.~s with mass case-finding, based on X-ray er.amination and sputum tests J and ECG vaccination, which has been carried out by 25 mobile teams and through the health centers r netwo:~k" with a vaccination target figure of 2 000000 children. About 70 000 of the registered cases are under constant medical care. The pilot project established in 1963 is being carried out jointly with villO and tT.NICEF. Tuberculosis workers will be assigned to 1334 health sub-centers in 1967.
are
;:
No. Uo. No. No. (b )
of of of of
cases cases cases cases
registered tuberculin tested ......... X-rayed .. .......................... BeG vaccinated ...............
..................
73 058 1 964 590 1 058 030 1 313 529
Leprosy
The number of leprosy patients in our cotu~try was estimated to be about 80 000 and they were forceably segregated from the COt:mnL.~ ty • Thus the Government had to undertake measures to provide ~or the medical care and resettlemenT. of 10 000 patients. A total of 500 non-infectious pa.tierrt:.s with potential labour power were discharged from national and private leprosaria and resettled. .An active case-finding programme is being carried out by nine mobile teams. 2.3 Local health services
The Government has carried out a local health services project (K- 2 5) with the technical and material al$sistance of 'l-lHO and UNICJI:F in Chungchong :Uamdo Province. Eighteen national hospitais·, 46 prc\v1Ilcial hospitals, 189 health centers and 1334 health sub- celrters, lIorldng closely together to ensure nation-wide cov.eJ;age, contributed greatly to the inrprovement o:f' the health and medical services.
all
2.4 Training of health workers The five-year training :programme for health workers 1 which is receiving assistance from }lHO and um:CEF, has been continued at the liational Ir~titute o:f' Health. TarGets :f'or Training Over 5 ·Year Period Physicians •••••••• Nurse_Midwives ••••• "tari ana ...•..... Sanl. Laboratorians •••••• 900 800 400 300 Actually Trained so far 475
666 462
213
- 4 -
The training programme for heal.th workers "WaS al.so carried out in cooperation ;nth the School of Public Health, Seoul ~rational Ul'I.iversity. 2.5 Environmental Sanitation (a) Water supp1l
Twenty new water plants ~e constructed mostly in medium or smallsized urban communities. At the end of 1966 the total out-put of water pl.aJ1l;s in Korea amounted to 879 413 tons per day. The construction of 2334 new public wells and the renovation of 5328 existing ones were completed in an effort to improve the "Water supply for the rural population. Piped water supply systems for four primary schools in the rural areas have been completed with material assistance from UNICEF. I.b} Food sanitation
A total of 159 food additives 'Were standardized in 1966. An average of 7 inspections were carried out on each restaurant and 4 on each food manufacturing or food processing plant by food inspectors. During the same period 86 482 food samples 'Were collected for laboratory analysis; this is equivalent to one food analysis per 660 population. Food har~lers I training courses 'Were carried out by 189 health centers. The participants consisted of food handlers in food services as ,lell as house'Wives. Under the three-year plan, 5000 sanitary inspectors will be secured. 2.0 Maternal and ~il<Lhel:!J.:tp, -E.ery!c_~_~_and
family plan.'1ing
The maternal and child health services are closely associated 'With family planning programme. The major programme of family planning had been scheduled for the second Five-Year Economic Development Plan 'With the target goal of reducing the population increase rate from 2.7 in 1966 to 2.0 in 1971. The population growth control programme ;nll go hand in hand 'With the maternal and child health services in order to assure the sucecss of the family planning programme. The family project was originally planned to be linked 'With the maternal and child health services including pre-natal and post-natal care and birth attendance services. The maternal and child health services 'Will be developed in close coordination 'With the ministries concerned as part of rural development programmes. Thus the Government is planning to assign maternal and child health 'WOrkers to 1334 ~ealth sub-centers by the end of 1967 ~o 'Will be integrated 'With the family p1 ann:! ng prognmme. Loops inserted ..................................... .. Vasectomies performed ••••••••••••••• Persons freely supplied 'With • contraceptives ••.•.•••.•.•.••.•.•• Couples registered for FP services ., Number of filed staff increased ...•• Mobile clinics (care) in each local area ............................................ ..
391 827
19 923 168
758
344 553 2 297 12
ORIGINAL:
ENGLISH
SINGAPORE 1 REPORl' ON THE PROGRESS OF HEAmH ACTIV-rrIF.S, 1966 1. GENERAL BACKGROUND
Singapore is a tropical island-city Republic of 225 sq. miles with a cosmopolitan population of over 1.9 million consisting mainly of three Asian racial groups (Chinese, Malay and Indian). More than half the population is below the age of 20 and the sex ratio is 93 females to every 100 males. Singapore occupies a geographically strategic position in South East Asia and enjoys the second highest per capita income in Asia (00$555 or 8$1666). Government is based on the parliamentary democratic system with full adult suffrage. 2. 2.1 ORGANIZATION AND RF.SOURCES FOR HEAIJI'H ACTIVJ!rIES
The Ministry of Health
The Ministry of Health has overall responsibility for the administration of health in the Republic. However, the subjects of sewerage and water supplies are dealt with by the Ministry of National Development and Public utilities Board respectively. 2.2 Financial resources
Expenditure for health services in 1967 is S$78 million (over U8$25 million) which represents 15% of the national budget and ranks second only to education. 2.3 Manpower resources Singapore' s overall medical manpower position is as follows: category Number Registered 1 071 344 148 4 884 Ratio to !ypulation (1. 9 million) 1 1 : 1 1 1921 5 523 12 830 389
"'
Doctors Dentists Fharmacists Nurses
lSubmitted by the l~nistry of Health, Government of the Republic of Singapore, 14 August 1967.
I - 2 The Government-employed heal.th manpower totals 19 764, inclusive of medical. manpower totalling 5342 (comprising 569 doctors, 66 dentists, 4625 nurses and 82 pharmacists). The medical. and dental schools of the University of Singapore graduate over 100 doctors and 30 dental. surgeons per annum.
2.4
Physical resources
Singapore has 17 hospitals (ll government and 6 private) l-lhich provide 7618 beds (6851 and 761, respectively) or a ratio of 3.9 beds per thousand of population. There are 31 outpatient dispensaries, 65 dental. cllnics, and 51 maternal. and child health centres. An Institute of l-1edical. Special.ties is being built jointly by the Government and the Univers.ity of Singapore. The Institute will cater for various specia1ties such as radiotherapy, cardiac surgery, neurology, . neurosurgery, renal. diseases, dermatology and endocrinology.
3. C<H4UNICABLE DISEASES COMMUNICABLE DISEASES are reasonably under control. Malaria has been eradicated but a vigilant watch is still kept. Haemorrhagic fever is increasing and to meet the menace of mosquito-borne diseases, the former .Anti-Me.l.aria Department has been re-vamped into an Anti-Mosquito Department working side by side with a new Vector Control Unit to co-ordinate the. attack on the mosquito problem. Tubercu].osis which was Singapore I s No. 1 killer-diseaSe ten years ago, has now gone down to sixth place as a result of the mass X-ray campaigns I mass BeG inoculation of new-born infants and schoolchildren. Leprosy cases have decllned and the Leprosy Home is now only half :f'ul.l. .An intensive case-find:lng and hea1th education programme has been launched to seek out the remaining cases. Diphtheria and.pollomyelltis have shown a welcome drop in incidence to nearly one quarter of their levels of five years ago, mainly due to the good we;rk of the maternal. and child heal.th centres and the mass diphtheria iDmunization and pollo vaccination campaigns. Cancer and cardio-vascular diseases command greater attention with the eradication of infectious diseases. A Cancer Society has been formed and the new Institute of Medical Special.ties will be equipped with up-to-date radiotherapy equipment to increase the effectiveness of the continued fight against that disease. :
\
3 4. 4.1 HIGHLIGlfrS IN ~966/l967
Marked progress in family planning and population contro~ Since the inauguration of the Government-sponsored Family Planning
and Population Board in January 1966 to implement the Government's F1 ve-
, ~ I
-
i
Year Mass Family Planning Programme, family planning clinics services have expanded. The Board now operates 33 clinics in collaboration with the maternal and child health services. By the end of June 1967, more than 45 000 women have obtained family planning assistance (12-5'~ above the target f'igure for the period). In 1966 (the first year under the Five-Year Mass Family Planning Programme) the rate of natural increase was 23 per thousand (crude birth rate at 28.6 and death rate at 5.5 per thousand). Preliminary figures for the first half of 1967 give cause for hope that the rate of natural increase for 1967 may register a 10'1- drop. If' this rate of progress can be maintained, then the target under the Five-Year Mass Family Planning Programme that "Singapore I s future annual net increase in population in the 1910s be brought down to around 15 per thousand" may well be in sight.
Legislation will soon be introduced to legalise abortion in Singapore. 4.2 Tightening of environmental health control
Under this programme a new hawkers code is now in force and more unlicensed hawkers are being licensed and controlled. Public cleansing services have been reorganized and the average daily tonnage of refuse cleared is around 850 tons as against 640 tons in 1965. The straying cattle nuisance has also been effectively dealt with through strict enforcement after passing special legislation.
5.
APPENDIXES
More detailed figures are given in the appendixes as follows: (i) (11) Appendix A - Selected Vital Statistics; Appendix B - Principal Causes of Death 1966; Appendix C - Notification of Infectious Diseases, 1962-1966 •
•
(iii)
I
- 4 Selected Vital statistics
Appendix A
Births. Deaths, Drl'ant and Maternal Mortality, etc. I
, ~ I j ! I
.,
Vital statistics Mean Population Number of live births Birth rate per 1000 of population Number of deaths Death rate per 1000 of population Natural increase (~) Number of infant deaths Drl'ant mortality rate per 1000 live births Number of maternal deaths Maternal mortality rate per 1000 live births
~ ~ 732 800
!2§l
1
~
~
1775 200 59 530 33·5 10 l38 5.7 2·78 1674
1820 000 58 217 32.0 10 434 5.7 2.63 1 738
1 864 900 1 913 500 55 725 I 29·9 10263
58 cn7 34.0 10 178 5.9 2.81 1843
54 680 28·6 10 444
I
i 5.5 2.44 1464
5.5 2.3l 1410
31.2 23
28.1 2l
29·9 24
26.2 22
25·8 16
0.4
0·3
0·4
0·4
I
0·3 --
•
) I
- 5Ap;pendu B
Princi;pal Causes of Deaths 1966 Number of Deaths Rates per 1 000 000 of Mean PgPulation 279
Causes of Deaths Tuberculosis (all forms) Syphilis and its sequelae Acute poliomyelitis All other infective and parasitic diseases ~ialignant
533 II NIL
6
116
61
neoplasms
1279 85
678 44
Diabetes mellitus Vascular lesions affecting the central nervous system (cerebral haemorrhage, thrombosis, etc.) Rheumatic fever and chronic rheumatic heart disease other diseases of the heart and hypertension Influenza Pneumonia Bronchitis Ul.cer of stomach and duodenum Nephritis and nephrosiS Motor-vehicle accidents other accidents All other causes Total:
644 49 1060 24 607 145 45 126
337 26
554 12
317 76 23 66 136 285 2616 5516
260 546 5004 10 552
... 6 -' Awendix C Noti1'ication of Infectious Diseases! 1962-1966
~! Smal.lpox
~l 0 27 187 5 400 2511
•
W!!. 0 24 123 6 206 1270 li4 0 0 0 0 136 17 1 4532
~ 0 0 278
~ 0 0 124 1
0 0 liO 2 353 2 024 47 0 0 0 0 ll2
Cholera Typhoid Para-Typhoid Diphtheria Chickenpox Puerperal fever Erysipelas Cerebro spinal fever Scarlet fever Anthrax
t
2 230 3 782 647 0 0 1 0 242 40 4 4 711 201
I I
I
216 925 529 1 0 1 0 198 10 1 4 163
I
18 0 0 3 0 108 68 4 4654
I I I , I
Leprosy Poliomyelitis Typhus (endemic) Tuberculosis Malaria
14 2 5 773
No Record
f i
177
216 .
(Footnote:
These 1'igures include imported cases.)
ORIGINAL: ENGLISH COUNTRY REPORT
on
HJ!'.AI.[rH
FOR 1966, TAIHAN, REPUBLIC
(F
CK[NAl
In the Country :Report on Health tor 1965, ve concluded that our next to illUlrove the qu.c.lity of people's health, to help build a people he~lthy in the more positive sense, not only free from dangerous cmmro1ni_ cable diseases, but also with Co view to sustaining industrial growth and increasing the value of people's property. step Vcl.S
Some work has been done in the past year to c.chieve this purpose but not ...11 that vre bud hoped. The m;..in reasons irere too low a budget for health needs and not enough cOllUletent vork.ers in the health field. The following is an account of the major llork done in the past year. 1. CHECKING THE RAPID POPUIMION GROWTH
-~-
Both the Committee on F~ Planning and the T~i\Tan Population Studies Center under the Provincial Department of Health lave further expanded their family planning ;fork with fin.c.ncial aid trom the PopuL::.tion Council of New York, the Committee tor Internutional Economic Cooperation ;:nd Development (CIECD) mid the Joint Commission on Rural :Reconstruction. The aid from these agencies amounted to NT$18.5 million in FY-1966 ~d to NT$25 million in FY-1967 'lThich have gre..;.tly contributed to the
exp:msion of the fTork. In 1966, 350 nurses ;:nd family plD.nning vTOrlrers vrere worIdng in 217 townships for family planning, III 242 women L.ccepted the IUD and by the end of 1966 the number of IUD ~cceptors had accumulcted to 261 000. This meiJIlS that one out of every six 'Tomen aged 20-44 in T!;.iwan had accepted a loop. Birth rates have been continuously decreusing; 36.), 34.5, 32.7 Olld 32.4 in 1963, 1964, 1965 and 1966, respectively. To accelerate the decrease, un or;,:,.l pill project hz.s been .c..dded for women who discontinued the IUD, and applicution of vasectomy or tub~l ligation, as ~ tri~, on a voluntaryb!;.sis this year. 2. CHOLERA. PREVENTION AND MAIARIA ERADICATION
The threat of a cholera inVasion of Taiwan still persisted. Through our concerted efforts, no indigenous cuse has occurred since 1962. In 1966, 10.8 million out of the 12.8 million pop~tion were vaccinated ~gainst cholera; 27 561 pussengers and crews from infected areas vrere rOlloved up at their residences as part ot the surveillance programme. No illUlorted cases were detected during this period.
lsubmitted by the Dep.c..rtment ot Health Administration, August 1967
- 2 The Shihlin Serum. and Vaccine I.e.boratory, the H;ygienic I.e.boratory o.nd the Entomol.ogy Section of the Malaria Institute moved into the nev
building in Nanl~. Equipment, vaccine production, as well as the quality of the technic1ans,h~ve been considerably improved as a result of the technical and financiu1 support of WHO, UNICEF end the CIECD this year. The maintenance phase of the malaria progro.m. was well performed. There vrere .30 m:tlaria cases including 14 imported, 7 relapsing, 6 indigenous, 2 cryptic and 1 induced, but they were put under immediate control after detection. .3. INTENSIVE DMJNIZATION FOR POLIOmELITIS AND CONTROL OF JAPANESE B ENCEPHALITIS
The five-year intensive immunization progrum against poliomyelitis started in November 1966. By the end of 1966, 975 000 children under .3 yeurs old had been vacciIw.ted "\lith the first dose of Sabin vaccine donated by UNICEF. By the end of March 1967, these children had completed their second dose of the vaccine; 400 000 newborns llill be vacciniited annuc.lly therecf'ter. iI. total of 819 CiJ.ses of Jo.panese B encephalitis Wi;.S reported in 1966, cOIlq)ared .lith 377 in 1965 and 444 in 1964. To control this problem, epidemio10gic~1 studies were cc.rried out in the four northern counties ilith pre-epidemic spraying of insecticides in the c.reas previously infected. In addition, as mouse-brain vaccine \Tas proved to be 8C1f, effective in our field trial, the policy Wi.J.S adopted that this vaccine should be used as a preventive measure in the future control program.
As a preparatory step to start mouse-brain vc.ccine production, a Ji.J.pe.nese expert on Japanese B encephalitis was invited to Taiwan, and a trial production of the vaccine v1th nel'T eCluipment has been carried out. Ml.ss production of this vaccine 'Irill be started in 1967. 4. TUBERCULOSIS CONTROL
In 1966, 912 000 infants "ere BeG vaccinated simultaneously with sme.l.lpox vaccination; 541 000 persons were X-rayed and 155 000 sputumexamined, exceeding the target numbers of 700 000, 500 000 and 150 000 respectively. In addition, 5200 open tuberculosis cases lTere ne,Tly detected and received free treatment. Although great strides rove been made in recent years in Our tuberculosis control work, to find and to take cc.re of all the estimated 290 000 cases in Taiwan, inc1uding.38 000 open cases, is still far to reach. Therefore, a four-yec.r tuberculosis control program started this year, with the assistance of lmO, UNICEF, CIECD c.nd the Social llelfare Special Funds, with the aim of accelerating the program.
.~
- 3 -
5.
REHABILITATION AND IMPROVEMEN'r CF GOVERNMENl' HOOPITALS
Rehabilitation of governmentoJ. hospitals is progressing. The construction of TaitWlg Hospital and Yul.1 MentoJ. Hospital was completed in the middle of this year. In Q.ddition, the construction of new" buildings for the Taipei Homen and Children's Hospital, Taichung Hospital, Changhua Hospital and Tainan Hospitc.l has been approved. Among them, Taichung, Changhua and Tainan Hospitals are under construction. The :NT::;63 million required for the construction of the latter four hospitals have been raised mostly from the sale of portiOns of hospital-owned land.
An increase of 156 positions in the staff of hospitals has been approved and nelr staff ,rere recruited in the second lw.l.f' of this year. The procedures related to consultation and hospitalization for the patients were simplified .md the 1fOrking morale of the hospital staff tre.s ilqproved.
The occupancy rate of beds for all provincial hospitals bas been kept ;::.s high as 850;" and the aIllluul income has oJ.so increased from 81+.7 million in 1963 to 103.4 million in 1965, and l~.l million in 1966, due lOOstly to improvements in hospital services.
6.
IMPROVEMENT OF ENVIRONMENTAL SANITATION
As a result of the aid from UNICEF and the efforts of both the Government and the cOmmunity, ~ great deal of improvement has been made this year. Ho-wever, much remains to be done .::nd continuoUs efforts are needed.
In the rural areas, eJl :.:.dditional 56 simple 1mter supply systems and 1532 public wells were constructed. Another 44 simple water supply ~d
systems are under construction. A total of 180 public latrines in the cities 2433 latrines in the rural areas have been constructed.
The three-year Community Development Plan to accelerate rural sanitation imJ::I:r:ovement \las approved by the Uorld Food Programme of the United Nations. The agreement 'I1ill be signed early in 1967. As a step in the finalization of this plan, 23 comnnmities out of the planned 330 communities have started constructing public vells, latrines, public baths, draiDages and village roads in accordance lrith the original plan.
For the control of air pollution in large Cities, a strict interdiction against burning coal in Taipei, Keelung and Kaohsiung Cities has been promulgated by the Government. This measure has brought good results by reducing pollution of the air in these cities. To improve the shortage of vehicles to collect garbage and nightsoil in the big cities, particularly in Taipei and KeelWlg, a loan of NT$23.92 million from CIECD to buy 27 closed motor garbage cars and 38 nightsoil cars 1rith vacuum pumps ,ras approved.
- 4 1. DROO AND FOOD CONTROL
Drugs for domestic saJ.e and export have recently increased remarlcably. For domestic sal.e, there were Us$15.1 million in 1964, 11.6 million in 1965 and 20.6 million in 1966. Exports increased from US$0.21 million in 1964 to 0.28 million in 1966. To ensure and iIlq)rove ClWllity, not only to safeguard the people's health but also to promote exports, periodic supervision of drug factories and the inspection of unlicensed and low-quality drugs in the market have been strengthened. On the other hand, to intensify drug control, existing lavlS or regulations have been revised and neil ones have been drafted. These will be enacted early next year. Attention has also been paid to food control, especially to lowquality food and residual insecticide in vegetables and fruits.
8.
STRENGTHENING OF RURAL MIDHIFERY SERVICES
A plan to encourage theprivate mid.dves to practice in rural areas 1lhere there are no midwives started in July 1966 with UNICEF assistance. By the end of this year, 15 rurul mid.nfery homes had been established in 16 counties. They have attended 1033 deliveries and provided 1520 ante-natal health examinations und 10 901 home visits. To integrate M::H services into the public hospitals, following the establishment of MeH clinics in 12 prOvincial hospit~s and 3 county/cit~ hospitals in 1965, 9 more 10I clinics (2 in the former, 1 in the latter) have been established.
9.
CARE OF PSYCHIATRIC PATIENTS
To meet the urgent needs of the psychiatric patients, the l'uli Mental Hospital of 600 beds "..;.s established this year. As the capacity of the present mental beds is far from actual needs, it was decided to set up psychiatric clinics in the provincial general hospitals to improve this situation.
ORIGINAL:
ENGLISH
TRUS!' TERRn'ORY OF THE PACIFIC ISLANDS REPORT OF DEVELOPMENI'S IN HEAIJI'H ACTIVITIESl
1.
MEDICAL CARE
There is a district hospital in each of the six districts of the Trust Territory (less than 100 beds); there are three sub-district hospitals (10 to 20 beds), and 130 dispensaries. None of the hospitals can approach standards of accreditation in staffing, organization nor physical plant; in fact, they are of the order of African bush hospitals. Characteristically, dispensaries are cramped, ramshackle affairs constructed of traditional island materials or cast-off metal sheeting from World War II quonsets. CONSTRUCTION PROORAM Construction
2.
Truk District Hospital - apprOXimate cost of $3 000 000. to begin in Fiscal Year 1969.
Ponape Teaching-Referral Hospital - approximate cost of $5 000 000. Construction to begin in Fiscal Year 1969. Yap District Hospital - approximate cost of $2 000 000. to begin Fiscal Year 1970. Construction
Six sub-district hospitals of the order of $200 000 construction costs are planned for out-lying islands (Kusaie, Ponape; Ebeye, Marshalls; Rota, Marianas; and unannounced sites in Yap, Truk and Marshalls) are planned for construction over next five years. It is planned to rebuild seventy-five of the present dispensaries, utilizing local self-help means and grants-in-aid over the next three years. New dispensaries will be added as impact of domiciliary-care methods indicate their need. Communities are eager to develop new dispensaries and the problem becomes one of exercising judgment and restraint.
lSubmitted by the Office of International Health, Department of Health, Education and Welfare, Public Health Service, Washington, D.C., 24 August 1967.
•
- 2 -
So much for improvement in physical plant - - essential. no doubt. but of less consequence than the quality of professional and ancillary staff. These things are being done to improve quality and quantity of staff:
(a)
Active recruitment of doctors ,of medicine (promisingly successful at this initial stage) for one in .each district hospital this fiscal year, and'for two next fiscal year~ Aocompanying letter indicates just one method of recruitment. Reinstitution of medical training for medioal officers at Fiji School of Medicine, Suva. Fiji. began February 1967. There are now eleven students attending medioal and paramedical oourses there and at least twenty new students will be admitted to the next class which starts in February 1968. Courses are offered in medicine, dentistry. sanitary "inspection. pharmacy. laboratory and X-ray technique. Extensive use of East-West-Center for in-service training for upgrading Micronesian staff in all medical and paramedical categories will be continued and accelerated. Candidates for nurSing degrees (R.N.) are sent to College of Guam School of Nursing (there are three Trust Territory students now enrolled in this program and five more nave been accepted for the September class. 1967). The Trust Territory maintains a nursing school of two years for which a diploma in nursing (recognized locally only) is given. The school was begun in 1953 and the classes were down to six in 1963. but enrollment has been increased and will reach a total of sixty by fall, 1967. The length of the course will be increased to two and one-half years by 1969. The new Vocational School proposes a nine-month course of training to upgrade the dispensary health aides to that of practical nurse and to maintain continuous in-service training of these practical nurses thereafter, depending on program requirements.
(b)
(c)
(d)
(e)
Essential premise for medical care: By far the greatest quantity of medical care is delivered at the dispensary level. To materially influence the quality of care this most neglected and despise4 level must be the essential target for change. Upgrading the training of health aides to that of practical nurse is a start. But a good practical nurse left to his or her own devices on a lonely atoll will lapse to health aide status very rapidly. A hierarchy of supervision. descending from the most responsible clinical level, is essential. start with the teaching-referral hospital which is to be built at Ponape! Its medical staff, representing the major specialties, will have as their responsibility the health of all persons 11 ving in the Truk. Ponape and Marshall Islands
- 3 Districts. The hospital, though planned to have the facilities of a comparable 168-bed hospital in the United states, should be regarded only as a base for their field activities and as a teaching device. Their principal job will be to create a system of comprehensive care utilizing all available modalities (central teaching-referral hospital, district and sub-district hospitals, dispensaries, domiciliary program), with final convergence of effort on the dispensary and domiciliary programs. A surgeon, for instance, will rotate Micronesian physicians through his service for teaching new techniques, and will visit them in their own districts, where, across the operating table, will assist them in surgery under conditions that actually exist. By radio-voice he will conduct daily, if necessary, consultation with the Micronesian physicians. His aims will be to make the district hospitals safe for most surgery and to develop with the local physicians the idea of flow of similar supervisory methods and attitudes on to the dispensary and domiciliary programs. A similar central system, though utilizing fewer of the specialties (one orthopedic surgeon or urologist, for instance, might be shared) can be set up at a district hospital or at Guam for the western tier of districts. These plans have not been formulated; the policy that will determine action: facilities for care must be equivalent in all districts.
..
3.
PREVENl'IVE MEDICAL PROORAMS
As in most developing areas. curative programs have sapped energies and resources from preventive programs: though one can point to several achievements. Imrmmizations have been carried out rather extensively by the district immunization teams for smallpox, DPl', poliomyelitis, diphtheria, pertussis, tetanus and typhoid and by special limited programs for measles, influenza, and cholera. Documentation is insufficient and often over-estimated, but it does appear that in some areas the level of immunity is higher than in the United states. An attempt is being made to improve the record keeping. Most district hospitals conduct prenatal and well-baby clinics; however, their availability decreases very rapidly as one leaves the district center. OVerall organization, know-how and availability are lacking. Funds for Crippled Children are now available through the Children's Bureau and are administered through a Guam-Trust Territory state Plan.' So far t.wenty-eight children have utilized-these new services which are limited to hareiip, cleft palate. strabismus and cardiac cases. Plans are (1) to add one qualified public health n~se to each district. (2) to assign crippled children responsibility to one 1>1.D. physician, and (3) to develop within the next few months a demonstration domiciliary care program in Saipan and to add to this structure,
- 4a full-scale preventive program in an attempt to show how preventive methods can most readily be introduced and fused into a total system. If feasibility is shown, preventive methods should be similarly adapted to the structure of comprehensive care described above. Work in sanitation is more extensive than meets the eye. There are fifty-one sanitarians (five with formal training) and one qualified sanitary engineer. They are active in spreading the gospel of water-· sealed latrines, mosquito control (an extensive predatory-fish project is being experimented within the Truk District). rat control (a rat-control expert is being added to the staff - - just in time, perhaps, for neighboring Guam has just demonstrated rabies in a shrew and is pondering the possibility of these animals constituting a reservoir of rabies) and, to everyone's dismay, especially their own, venereal disease contact followup. However, it is village sanitation that presents us with the most immediate and glaring defects in our total programs. Crowding of villages has resulted in failure of traditional methods of hygiene, and pollution of lagoons has progressed to the point of scandal in some areas. Drinking water is usually of questionable purity. We plan to introduce laboratory facilities for water examinations in all districts. Data processing, utilizing computer, will become available within several months. However, it is data collection itself that invalidates our documentation. A qualified record librarian has been assigned to supervise the hospitals. A record committee has been formed consisting of headquarters and district staffs.
4.
PEACE CORPS ACI'IVlTmS
Many of the new activities in preventive methods are being spearheaded by the Peace Corps. The Peace Corps has just completed the first reliable census of the Trust Territory, and is now engaged in making a health survey of tuberculosis, leprosy and filariaSis. When this is completed, the resulting load of patients will require treatment; accordingly, a domiciliary program developed about dispensaries will be formulated. The next group of volunteers, whose training will start in February 1968. will be trained specifically in the methods of domiciliary care.
•
•
Sample letter to hospitals having residencies in general practice Dear Sir: I am writing to you because it seems possible that we may have positions in our district hospitals which will be attractive to physicians who complete your residency program in general practice. Let me explain our situation. The Trust Territory of the Pacific Islands operates hospitals of 100 beds or less in each of its six Districts: Marshalls, Ponape, Truk, Marianas, Yap and Palau. These hospitals are staffed by Micronesian physicians who have had five years training (M.O.) at the Central Medical School at Fiji. These men are praotically trained and delight in the technical aspects of medical work especially in surgical procedures. For the most part, they have considerable competence. At each hospital one of these phySicians is designated as the District Director,and the resulting relations may be demonstrated in the follo~ng manner: Micronesian District Director of Public Health Chief of Clinical Staff
-
--. Chief of Preventive Medicine (M.O. )
Staff Physicians
, -....
Our idea is that an M.D. should occupy the slot of chief of Clinical Staff and that such a physician should have the abilities and special skills of a general practitioner who has sufficient competence in surgery and obstetrics to be the supervisor and mentor of the Micronesian phySicians. But there are other less easily defined qualities that this person must have if there is to be mutual satisfaction. He must be able to endure the excitement, almost of an astronaut, in first condng on the strangeness and perplexities of exotic medical and human problems in this farflung island paradise; and then he must possess the durability to face up to the frustrations that are an almost immediate sequel as he must innovate, improvise. compromise and worry himself almost to despair in finding solutions. Up to now the sheer lack of material resources and, what has been interpreted as indifference, have been the greatest bugbears to the young enthusiast. But this is changing.
A mandate from our own government that standards for health and medical care must conform to those in the United States sets a new pace and a new kind of headiness to the planning. There is a new and aggressive administration. The operating budget is expanding realistically. A
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hospital building program will replace the present ramshackle structures with the necessary physical requirements for modern medical practice-- ' one hospital being designated as a central referral-teaching hospital, and is budgeted at $5,000,000.00. Close and harmonious working relationships are developing with the University of Hawaii and the East-West Center, the South Pacific Conunission, the WHO and the Unit~d Nations. the Children's Bureau. The Peace Corps is now spearheading, extensive field work in public health, as it evolves this will include a program in hospital-based domiciliary care. • • • Those of us who are here feel that we are at the start of an authentic crusade--though a crusade in blue print at this stage. Our job--and here is where I am asking your help-is to translate these new resources of budget and bricks and mortar and general enthusiasm into a program which, after all, can be no better than the physicians who are in it. If you know of physicians who might be suitable and who could be interested in coming with us, I will appreciate being put in contact with them so that we can discuss the work, living conditions, salary (which would start at $15,000 to $18,500 depending on experience), the magnificence of the three million square miles of wild ocean we are dealing with, the kinds of disease that one sees here. I hope that my
writing to you has not been an imposition. Sincerely yours,
(Sgd.) William M. Peck, M.D., M.P.H. Director of Public Health
vVESTERN SAMOA
Rl':PORT ON PROGRESS OF HEALTH ACTIVITIES 1966 - 1967 Introduction: The Independent State of' Western Samoa lies in the mid Pacif'ic, south of the equato!" between 13') and 15 0
and west of the date line between 171
0
and
-'
173 • At the time of the last census (November 1966) the population of Western Samoa had increased to 131,379 which is 15.~ more ~an the previous
o
-
census in 1961.
About SOC}'; of the population is under 15 years of age.
The appropriate expenditure of the Health Department f'or 1967 is £305,855 or 611 ,710 Tala sinos t he introduction ct: the decimal system on 10 July 1967 which is General Review: The hurricane which struck the Samoan Islands on 28th and 29th January 1966 brought in a sharp economic decline. The primary reason for this
1o.i3fo
of the total Government expenditure.
has been a reduction in export income mainly through the decrease of banana and copra production. The sho!"tage of food as a result of the hurricane has been
overcome by increased planting of staple food mainly of taro. The Rural Health Development Plan: The need to improve the rural health serviQe has been recognised and therefore the Rural RaaUh Project has been inclmed in the 1966 - 1970 Development Plan Budget of the Government of Western Samoa. The first step of
the plan the establishment of a principal medic al officer in Savaii which is the larger but less developed and populated island scheduled to be implemented in 1966 has been delayed. completed in Savaii. Only the quarters for a medical
ct: ficer has been
In the meantime the Faasaleleaga District, which is the
most populated area of Savaii, has erected a hospital structure at their own expense at Tuasivi in tm hope that the main hospital fer Savaii will be located there. As the Health Department was satisfied that the hospital
building at Tuasivi was adequate adjustments have been made in the Rural Health Plan to suit , .~lOspi tal
this development promoting the Tuasivi Hospital as the main
for Savaii,
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Community Water Supply and School Sanitation Project: The Western Samoa Community Ilater Supply and School Sanitation Project is a joint effort by the Government, W.H.O. and UNEEF to provide piped water for ten villages in the ~afata District and sanitary facilities for schools of those ten villages, The intakes have been completed and ille Sofata East
or Mulivai Yvuter Supply has reached six villages while the Safata west Nu'usuatia River has not been compJe ted because of shortage of pipes. HaW6ver,
it is hoped tr..a t t be end of the ye ar the Safata District Community Wat er Supply rill be completed together with the smool sanitation project. Community 'uater Supply &ld
A new
School Sanitation Project has been planned for 1968
for an area north west of Apia, the capital of Western Samoa. Filari~sis
Control
P~ect:
The Government cf Western Samoa requested assistance from W.H.O. for the control of filariasis. As a result of this request financial assistance
has been provided by W.H.Oo; UNICEF, the New Zealand Medical Research Council (Phillips Bequest) and 111 e Government. The W.H.O. under this Egreement The aim of the
provides a short term consultant to supervise the project.
project was to reduce 'lhe microfilarial infection as to no longer contribute a major health problem. The method employed was to admin:ister diethylcarba18
myciril to the whole population to dEJstroy the circulat ing microfila ria.
doses of diethylcarbamacirll 5 mgm/kg was given for the f:ir st six doses at r/ookly
.a..' .,
intervals, the last 12 in monthly do ses.
Before the commencement r:£ the mass
drug treatment the percentage of microfilarial carriers ranged from 25.6% to 38.1% in various districts.
An independent blood survey after the mass drug
treatment has been made in 21 villages, selected at random fram each district at the first quarter of 1967. A total of 9,734 persons were examined revealing
83 (47 males and 36 females) positive for microfilaria (0.8%), the maximum microfilarial density per 20 cmm being 84-. The microfilarial rate (
%) When
was
highest in the village Malie (2.~) and lowest at Salelesi (0.37%).
cases are discovered i~ the course of the blood survey, an intensive retreatment with diethylcarbamacine daily for 14 days has been adopted.
Tuberculosis Control Project: J!'ollowing the first tuberculosis campa gn conducted in Western Samoa (1960-63) with assistance from W.H.O. and UNICEF, an agreement for the operation
- 3of a second e,ampaign ,laS
drawn up and incorporated in the First Addendum to the In
Plan of Operation for a National T.B. Control Project in 'Western Samoa.
termf of the agreemenb W.H.O. undertook to provide the services of the Regional :::-.B, Advisory Team during 1 966, and a short term consultant fo r thr ee months 1
ate in 1967, in addition to a sum of US$300 for equipment and supplies urgently
needed fer 1S57. The Regional T.B. Team arrived in June 1966 and commenced immediately ~he second p}1ase of
tm
Tuberculosis Control Project with the introduction of
beG vaccination.
As tuberculosis ixf' ection aCten takes place during adult life
in Western Samoa, 1he BeG vaccimtion campaign will cover all the age groups. 'l.o.e rJ
ase finding and BeG vaccination has been nearly completed on the islmd The tUberculosis ,"ontro1 team moved over to Savaii in July 1967 and
of Upolu.
i t is e:xp ected that beg inning of 1968 the case finding and BCG vaccination
will be finished.
The MCH Advisory Team which is sponsored by the W.H.O. and S.P.C. ~ sited ff9stern Samoa from 2nd September 1966 to 6 Janm ry 1 967. The team assisted th e
~
'.
Governnent ,.ith the organising of
0.
new M.C.H. Section at the Health Depariment.
In tho ~eginni,:g of December 1966 the section was establ ished and the IV!edi cal CfPicer-in-charge of t:1e paediatric department was appointed as head aC this s3ction. .At the same time he will continue to work in the paediatric department The main efforts are towards improvement of the District
of the Apia Hospital.
Nur ses' Well Clinics, which are held monthly in ne ar1y all villages and 1h e supervision of tre District Nurses' work by planned visits to all nurses, by the Public Health Sister, her Assistant and the Paediatrician. Bow He~lth Logi~lation:
The Legislativo Assembly passed on the 7th July 1966 1he Medical and Den tal Practitioners Act 1966 which sets up a Medical and Dent a1 Council md p:c'escri bes the qualifications required for tlE practice d' me dicine, surgery Q~d
dentistry in Western Samoa.
A new Food
,Wlet Drug Act 1967 was assented
to by the Head of State on 24 July 1967 and the Narcotic Act 1967 c/:1!lle into lo::-ce on 1 August 1967.