THE PRACTICE OF EPIDEMIOLOGY

1214 before marketing and should consider giving special training to staff in charge of its drug evaluation departments. Department of Pharmacology, Neuropharmacology Section, University of Panama, Panama City, Panama

which are never tested. We might improve our care ifwe small number of surgeons within a region who saw all potential new breast cancers, and who worked together with radiotherapists, chemotherapists, and oncology nurses and had the backup of plastic surgeons and psychiatrists. Many will say that such a goal (appropriate for several tumours) is idealistic in a time of financial constraint. But our present debate should be "how to improve care", and we must aim for the best. We consider that radical changes are necessary: (a) surgeons must be willing to specialise (there are, for instance, a few gynaecological oncology surgeons-we need more); (b) more and earlier cooperation in combined clinics is necessary; (c) dedicated nursing facilities are required for some patients; (d) improved junior staffing and nursing is needed in radiotherapy; (e) a broader experience must be sought treatments

identified

FEDERICO GUERRERO-MUÑOZ

RADIOTHERAPY AND MEDICAL ONCOLOGY

SIR,—The correspondence on radiotherapy and medical oncology illustrates all too well the deplorable state of affairs which has arisen from the multiplicity of Royal Colleges, each representing a different component of medical practice and each bidding in rivalry for the largest stake in any new found territory. Haematology is another conspicuous example. It should be evident that in medicine, as in other walks of life, progress, or at least change, will often occur at the boundaries of disciplines not at their centres so that the origin of a new specialty will have more than one derivation. It will be a pity if any specialty comes to be defined as a result of intercollegiate contest rather than rational need. Indeed the necessity of a definition should be questioned; the correspondence has shown the futility of trying to label and circumscribe oncologists or other specialists, since the demands for particular sorts of doctors will vary so greatly from place to place and from time to time. A retirement or death in any place or region will leave a gap in the services of almost infinite diversity; the requirement will depend on the specialised skills and case-loads of the remaining consultants, on their ages, and on the changes of practice which have occurred in recent years, in this case the innovation of cancer chemotherapy. The solution, which is obvious to any unbiased observer, is the statutory dissolution of the Royal Colleges and the sequestration of their funds in the interests of hard-pressed universities. In the short run the benefits would be enormous, and probably in the long run most of the few useful (e.g., educational) functions of the Royal Colleges could be taken over elsewhere. Meanwhile from the residuum of the Royal Colleges and the Royal Society of Medicine it might be possible to synthesise one unsurpassed medical library for the whole country. The D.H.S.S. and the universities could probably do it through Parliament if they tried but are, I dare say, intimidated by the sheer weight of calf-bound volumes and by apprehension of what the worthies, whose portraits line the walls of the more ancient colleges, might think. At least let them not be deterred by the apparent weight of vested interest represented,for example, by the letters which follow my signature. There must be many who would happily celebrate the event by a bonfire of certificates and bankers orders. Department of Clinical Pathology, Royal Marsden Hospital, London SW3 6JJ

problem, but many large hospitals do not have joint clinics for early and late disease. Most doctors hold strong views on whatis right for patients with breast cancerl but work in isolation, using ment

by chemotherapists. As far as training of radiotherapists and chemotherapists is concerned, of course, there should be joint training. But the training must include subspecialisation in either radiotherapy or chemotherapy which is based on a common core of experience. As more cancers are treated with drugs there is a need for more chemotherapists ; these should be additional to present radiotherapists who carry a large service commitment. If there are to be physicians with an

oncology, we would suggest that they have a

and it is important that cancer services be organised in such a way if make the best use of thin resources. The era when doctors could become familiar with a "half dozen" drugs and then specialise in the medical treatment of cancer is past. Even if a consultant is familiar with these six drugs it is the inexperienced junior staff and nurses who are asked to give the treatment and deal with its complications. This approach has also frequently resulted in inadequate or inappropriate chemotherapy which only serves to reinforce the prejudices of chemotherapeutic nihilists. The specialty of medical oncology is new and this is bound to cause dispute amongst those treating cancer; we must use this opportunity to re-examine the way we organise all cancer services in Britain and not become bogged down by inter-collegiate demarcation disputes of the type that have bedevilled trade unions. we are to

,

CRC Medical Oncology Unit, Southampton General Hospital

CHRISTOPHER J. WILLIAMS

Department of Radiotherapy, Royal South Hants Hospital, Southampton

ROGER B. BUCHANAN

H.E.M.KAY

SIR,—The debate following the articles in your issue of April 18 has largely become a demarcation dispute amongst those who treat cancer patients. If you believe, as we do, that the care of the patients in Britain is variable and on the whole poor, then the main question is how we reorganise cancer care to improve the patient’s lot. Debates on training and division of labour, although important, are secondary to the goal of producing a truly professional service. Surgeons, radiotherapists, and physicians have been too complacent, have accepted second rate facilities, and have been slow to examine their methods of practice. Improvements in cancer care, despite our best efforts, have resulted in increasingly complex and toxic treatments. No one surgeon, radiotherapist, or physician can an

interest in medical

joint appointment between a district general hospitaland a regional cancer centre. Radiotherapy is already organised on a regional basis,

M.D., F R.C P , F.R.C.Path

be

a

expert in the management of all types of cancer, and there is

increasing subspecialisation within radiotherapy and chemotherapy. Optimum care of cancer will only come from the availability of specialised groups of doctors jointly managing different tumour types. This approach results in the radical suggestion of subspecialisation by surgeons. Generality has been a basic tenet of British medicine, but the proposal for more combined specialty clinics must be examined. For instance, breast cancer is a complex and changing manage-

THE PRACTICE OF EPIDEMIOLOGY

SIR,—Sir John Brotherston’s reassurances (April 11) about the training and accreditation of epidemiologists are welcome as far as they go. But they still leave an increasing number of younger doctors in an uncertain position. The traditional uses of epidemiology are in the study of the distribution and causes of disease. Successful inquiries will mostly have health service implications. These implications lead to other studies, often of an epidemiological nature as well. But community medicine and the N.H.S. stand to benefit from those whose interests in aetiology without necessarily extending to practical applications (though if they do, so much the better). Sir John’s comments do not explicitly recognise epidemiologists of this kind, for whom, as for their supervisors, specialist training in community medicine may be distracting and irrelevant. Another group not properly catered for are those in cliiucal specialties who are also interested in the epidemiological approach to their subjects. They include cardiologists, obstetricians, rheumatologists, gastroenterologists, and ophthalmologists. They face a number of career problems. One of them is specialist accreditation, where they fall between two stools. Many give up the are

1. Baum M Breast cancer trials—a

new

initiative Br Med J

1980; 281:

1422.

1215 initiative is stifled and much potential talent goes to waste. epidemiological At least two steps are necessary. The Faculty of Community Medicine must ensure that its flexibility over training programmesIs does extend to those whose interests are exclusively "academic". Secondly, the Faculty and those responsible for Joint Committee on Higher Medical Training accreditation in clinical specialties must encourage training programmes for clinicians with strong epidemiological interests. Could they also jointly review the evidence that specialist accreditation, as currently organised, does lead to improved standards of practice?

unequal struggle;

MRC Epidemiology and Medical Care Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ

T. W. MEADE

HUMAN PARTURITION IS NOT PRECEDED BY A WITHDRAWAL OF PROSTAGLANDIN SYNTHASE INHIBITION

SIR,-The mechanism of the initiation of human parturition

uncertain despite a considerable understanding of the regulation of birth in other mammals.2It is widely accepted, remains

however, that prostaglandins have

central role in the onset of labour in man, as in many other species. The mechanisms controlling uterine prostaglandin synthesis during the3 periparturitional period have not been completely worked out, although availability of free arachidonic acid, the precursor of the 2-series prostaglandins, is thought to be the rate limiting step in There is, however, evidence from studies their with primatesbthat uterine prostaglandin synthesis cannot be increased by administration of arachidonic acid and hence may be tonically inhibited during pregnancy. Our findingof an endogenous circulating inhibitor ofprostaglandin synthesis (originally described by Saeed et al.and termed EIPS) in the plasma of pregnant women has led us to consider the possibility that EIPS plays a part in the control of prostaglandin production during human pregnancy and parturition. We have measured the ability of plasma from 32 healthy women to inhibit prostaglandin synthesis in an assay system designed to detect EIPS activity. The women formed four groups of equal numbers: (a) non-pregnant women, (b), women with uncomplicated pregnancies at term (range 38-42 weeks), (c) women in established labour of spontaneous onset at term who were delivered vaginally of a healthy infant, and (&a cute;) women who were 3-6 days postpartum. None of the women had recently taken steroidal drugs or nonsteroidal anti-inflammatory agents. For EIPS measurements, dilutions of plasma in 50 mmol/1 phosphate buffer (pH 7’ 4) were added to a standard assay mixture of total volume 0 - 5 ml containing 2-55 mg lyophilised microsomal bovine seminal vesicle prostaglandin synthase, 61 mol/1 sodium arachidonate, and 1 - 3 mmol/1 reduced glutathione. This mixture was gently agitated in air at 37°C for 20 min. Prostaglandins were extracted into acidified ethyl acetate, and prostaglandin E2 (the principal synthase product under these conditions) was measured in the extract by radioimmunoassay. The intra-assay and inter-assay coefficients of variation of the EIPS assay are 13% and 15%, a

biosynthesis.I,4,S

1. MacDonald

PC, Porter JC, Schwarz BE, Johnston JM. Initiation of parturition in the human female Sem Perinatol 1978; 2: 273-86. 2. Ellendorf F, Taverne M, Smidt D, eds. Physiology and control of parturition in domestic animals. Amsterdam: Elsevier, 1979. 3. Novy MJ, Liggins GC. Role of prostaglandins, prostacyclin and thromboxanes in the physiologic control of the uterus and in parturition. Sem Perinatol 1980; 4: 45-66. 4 Gustavii B. Labour: a delayed menstruation. Lancet 1972; ii: 1149-50. 5. Batra S, Bengtsson LP. Mechanism for increased production of prostaglandins in labour. Lancet 1976; i: 1164. 6. Robinson JS, Chapman RLK, Challis JRG, Mitchell MD, Thorburn GD. Administration of extra-amniotic arachidonic acid and the suppression of uterine prostaglandm synthesis during pregnancy in the rhesus monkey.J Reprod Fertil 1978; 54: 369-73. 7. Brennecke SP, Collier HOJ, Denning Kendall PA, McDonald Gibson WJ, Mitchell MD, Saeed SA. Inhibition ofprostaglandin biosynthesis by ovine and human blood plasmas in relation to reproductive function. Proc Physiol Soc Jan. 16-17, 1981; 49P. 8 Saeed SA, McDonald Gibson WJ, Cuthbert J, et al. Endogenous inhibitor of prostaglandm synthetase Nature 1977; 270: 32-36.

EIPS activities

(expressed as ICje). (a) non-pregnant women; (b) pregnant women at term; (c) spontaneous labour; and (d) women 3-6 days after delivery.

women

in

respectively. Inhibitory activity of a plasma is expressed as an ICso which is the concentration (% v/v) that inhibits by 50% production

of prostaglandin E2. The EIPS activities of the plasma are presented in the figure. The ICso (mean±SEM) for each group was: (a) non-pregnant, 0-35±0-04; (b) term pregnancy, 0-35±0-03; (c) spontaneous labour, 0 -34:t0’03; (ci7 post partum, 0 -30:t0.03. There were no significant differences between the ICso values for each group (Mann-Whitney rank sum test). The lack of significant differences in EIPS activity between non-

pregnant and pregnant women and women in labour suggests that plasma EIPS activity may not play a major role in the control of

prostaglandin synthesis in human pregnancy and parturition. Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU

S. P. BRENNECKE R. L. BRYCE A. C. TURNBULL M. D. MITCHELL

DEPRESSION AS COMPONENT OF POST-CRANIAL IRRADIATION SOMNOLENCE SYNDROME

SIR,-A group of adults with acute lymphoblastic leukaemiaI (ALL) experienced depression after therapeutic cranial irradiation, the episodes being temporally related to the drowsiness and lassitude well-recognised as the post-irradiation somnolence syndrome seen in children with ALL. The seventeen adult ALL

patients’ had very few behavioural disturbances but four of the first seven were

patients became profoundly depressed so the next ten patients given imipramine 25 mg three times daily starting before

cranial irradiation and continued for not less than 3 months. Mood alteration and somnolence did not occur in the patients so treated. One individual who discontinued the antidepressant because of atropine-like side-effects became depressed. In our experience of 100 cases of childhood ALL 70% developed somnolence 6-8 weeks after 2400 rad given in 10-15 fractions. The older paediatric patients also described additional "hypothalamic" symptoms during the somnolence syndrome. There was marked subjective alteration of temperature appreciation in that they felt continually cold, in addition to experiencing marked reduction of

appetite. 1. Proctor SJ, Finney R, Walker W, Thompson RB. Treatment of adult lymphoblastic leukaemia using cyclical chemotherapy with three combinations of four drugs Postgrad Med J 1981; 57: 19-22. 2. Freeman JE, Johnston PGB, Voke JM. Somnolence after prophylactic cranial irradiation in children with acute lymphoblastic leukaemia Br Med J1973, iv: 523-25