BRITISH MEDICAL JOURNAL
25 MARCH 1978
Ambulance personnel and casualty staff in 62 London casualty departments were asked in a questionnaire survey for their recommendations for the management of cases of deliberate self-poisoning. From the 1350 questionnaires distributed, 1248 (92 %) were returned, of which 858 were completed by doctors and nurses. Among this group 88% believed that these patients should never be discharged without full psychiatric evaluation, 850% thought that there should be a resident psychiatrist in the hospital to advise patients, and 80 °'? thought that patients with deliberate self-poisoning should always be admitted, at least overnight. Although 73% thought that doctors and nurses should be given additional training to deal with these patients, 57 % believed that they should be taken to special emergency centres and not brought to hospital casualty departments at all. The opinions of these doctors and nurses cannot be lightly dismissed as their experience of all drug-related problems, including that of deliberate self-poisoning, is considerable.' In some London casualty departments, for example, there is a daily average of three drug overdose patients compared with 13 at Addenbrooke's. It is against this background that the recommendation of Dr Gardner and his colleagues is set; before it is generally adopted the opinions of those who would have to assume greater responsibility for this very large group of patients should be sought most carefully. If, as has been reported,2 their attitude to deliberate self-poisoning patients is an unsympathetic one the care of these patients might well be affected adverselyparticularly if staff in other hospitals are less fortunate and lack the support and instruction of an interested and involved psychiatrist. In any case, the aim of any amendment to the recommendations of the Hill Report should surely be that the treatment of the patients is improved, not merely shifted from one group of doctors to another. A HAMID GHODSE
785
and in the clinical trial they did so in five out of 133 instances. Since they requested psychiatric opinions for only 16 % of their patients it is unlikely that in other hospitals physicians would require psychiatrists to see every self-poisoned patient. Sir Denis Hill (11 February, p 362) has done much to improve the whole standard of undergraduate education in psychiatry. But most student psychiatric attachments are for only 8-12 weeks. Is this sufficient training for the future doctor? In general medicine and surgery further training is considered essential during the preregistration year. It is this aspect of medical education which has been neglected by psychiatrists and to which they might contribute with their colleagues in other specialties. I share Sir Denis Hill's concern lest psychiatrists should now leave physicians to undertake the initial psychiatric assessment of self-poisoned patients without first ensuring that junior doctors and nurses are adequately taught and that both psychiatric treatment and help from social workers are available once such patients have been discharged. What should be taught and how consultation liaison can be achieved might best be discussed at a joint meeting between the Royal Colleges of Physicians and Psychiatrists. A decade has now elapsed since the Hill report.' Is it not time that the standing medical advisory committees reviewed the arrangements for the treatment and after-care of self-poisoned patients and initiated a detailed study of the prevention of poisoning ? R GARDNER Self-poisoning Unit,
Addenbrooke's Hospital, Cambridge Central and Scottish Health Services Councils, Hospital Treatment of Acute Poisoning. London, HMSO, 1968.
Institute of Psychiatry, London SE5
Drug treatment of chronic stable angina pectoris
Ghodse, A H, British Journal of Preventive and Social Medicine, 1976, 30, 251. Patel, A R, British Medical Journal, 1975, 2, 426. 3 Ghodse, A H, Social Science and Medicine. In press.
SIR,-Your leading article on the above subject (25 February, p 462) states that studies on prenylamine have generally shown it to be no more effective than placebo. This statement is contrary to the facts and indeed misquotes one of the references.' The reference concerned actually states: "Prenylamine (SynadrinHoechst) depletes catecholamines in a similar way to reserpine, and acts in angina probably by reducing the sympathetic stimulation to the heart. In several adequately controlled doubleblind trials, prenylamine in a dose of 180-300 mg daily was significantly better than placebo in preventing anginal attacks." However, both this paper and another cited2 are review articles. We agree with your statement that "new drug preparations for the treatment of angina invariably have a strong placebo effect, and double-blind trials are essential for their evaluation." Since 1965 there have been a number of double-blind controlled studies published3-14 in the world literature definitely reporting the superiority of prenylamine over placebo in reducing the number of attacks and the consumption of short-acting nitrites in patients with angina pectoris. One study"5 reported no difference between prenylamine and placebo in reducing either anginal episodes or nitroglycerin consumption, but even this
2
SIR,-Dr M D Enoch and Professor J R M Copeland (4 February, p 300) have touched on the issue of clinical responsibility. When we stated (17 December, p 1567) that "physicians should decide for each of their patients if specialist psychiatric advice is necessary" we were, of course, referring to consultant
physicians.
The Department of Health's recommendation' does have implications which extend far beyond the management of self-poisoned patients in the general hospital. What if other expert committees were to recommend, say, that in all cases of head injury patients must be clinically evaluated by neurosurgeons, or that all men with chest pain should be referred to cardiologists, or that every patient with abdominal pain must be examined by a general surgeon? Such clinical decisions are usually left to the discretion of the medical practitioner. We decided at Addenbrooke's that physicians must have ultimate clinical responsibility for the self-poisoned patients admitted under their care. It followed that they could overrule psychiatrists' assessments,
investigation, while never reaching statistical significance, shows a trend in favour of prenylamine over placebo. While there are doubtless criticisms which can be levelled at some of the above studies either on the basis of design or statistical interpretation, the overall weight of evidence demonstrates, in contrast to your leading article, that prenylamine is more effective than placebo as an antianginal agent. R H ROUSEL GERALDINE DODD Hoechst UK Ltd, Pharmaceuticals Division, Hounslow, Middx ' Drug and Therapeutics Bulletin, 1974, 12, 1. 2Aronow, W S, American Heart Journal, 1973, 85, 132. Kappert, A, Zeitschrift fiur Therapie, 1965, 2, 82. Donat, K, and Schlosser, G A, Medizinische Klinik, 1966, 61, 352. Cloarec, M, Proceedings of symposium on "Prenylamine in therapy," Monaco, 1 March 1968, p 52. Cardoe, N, British Jrournal of Clinical Practice, 1968, 22, 299. Stoker, J B, British Journal of Clinical Practice, 1968, 22, 384. O Cardoe, N, Postgraduate Medical J7ournal, 1970, 46,
708. Mikkelsen, E, Ugeskrift for Laeger, 1971, 133, 873. 1 Sepatia, G C, Jain, S R, and Prakash, J, Clinical Trials Jfournal, 1971, 8, 43. Winsor, T, et al, American Heart_Journal, 1971, 82, 43. 1 Arora, R, Indian Heart Journal, 1973, 25, 62. 13 Tucker, H, et al, British Heart_Journal, 1974, 36, 1001. Kotia, K C, et al, Medikon, 1977, 6, 33. 5 Bjorum, N, Christensen, M, and Rathsach, P, Ugeskrift for Laeger, 1967, 129, 47.
Ectopic pregnancy rates in IUD users SIR,-In a recent review of ectopic pregnancy and contraceptive use Tatum and Schmidt' suggested that "there may be a causal relationship between the use of an intrauterine device (IUD) and the occurrence of an extrauterine pregnancy." This review, in addition, suggested that the Progestasert IUD may carry a higher risk of ectopic pregnancy than other IUDs. In a recent letter (17 December, p 1600) Dr Robert Snowden has also proposed that the Progestasert IUD may carry a selectively greater risk of extrauterine pregnancy. At a meeting in Geneva from 27 February to 1 March 1978 of the steering committee of the Task Force on Intrauterine Devices for Fertility Regulation of the World Health Special Programme of Organisation's Research, Development and Research Training in Human Reproduction the available published and unpublished data on the occurrence of ectopic pregnancy in IUD users was reviewed, and the committee had the following reservations about the interpretation of these data by the above authors: (1) It has long been argued on the basis of the mechanism of action that an IUD protects more against intra- than against extrauterine pregnancy. It would therefore be anticipated that there should be a higher ratio of extra- to intrauterine pregnancies in IUD users, a difference in incidence which has in fact been found in many studies. The steering committee believes that the available data indicate a real increase in the risk of ectopic pregnancy among IUD users when compared with non-users. However, the magnitude of this risk is difficult to quantitate with the existing data as there are no studies in which adequate comparisons of risk have been made. (2) The methods used to present ectopic pregnancies in published studies may give misleading information, especially when ectopic pregnancy rates are presented as a percentage of total pregnancies; such percentages may be affected by the contraception-dependent reduction in intrauterine pregnancy rate. Accordingly ectopic pregnancy rates should be expressed as a
786
life table rate per 100 woman-years, in which this problem of interpretation does not arise. (3) The risk factors which predispose to ectopic pregnancy vary from population to population and may vary between users of different contraceptive methods. Unless this variability is taken into account bias may be introduced. Future studies should be designed to ensure that such bias is excluded. (4) All published studies of ectopic pregnancy rates have, so far as can be determined, failed to state the criteria for the diagnosis of ectopic pregnancy, leading perhaps to an overestimate of its incidence. If ectopic pregnancy is thought to have occurred in test or control patients in any clinical trial of an IUD all material removed from the peritoneal cavity should be examined. Fluid, blood clots, and curettings, if taken, should be studied macroscopically. Clots should be sieved or fixed and sliced for gross examination and all suspicious areas examined microscopically. The aim of the verification of the diagnosis of ectopic pregnancy is to improve the accuracy of incidence data in IUD studies. For this purpose it is considered essential for the diagnosis that fetal parts (identified grossly or microscopically) and/or trophoblast are identified. Decidual reaction and/or blood in the Fallopian tube is not sufficient to establish the diagnosis. This definition does not preclude a presumptive diagnosis made for clinical purposes, based for example on tubal disruption, decidual change in Fallopian tube or endometrium, gross blood in the peritoneal cavity, or other suggestive operative findings. (5) Because of the limited data available and the difficulties of comparisons between studies it is not possible to state that the Progestasert IUD users are at higher risk of ectopic pregnancy than other IUD users. Ectopic pregnancy rates for Lippes Loop and copper-carrying IUD users quoted by Dr Snowden, 0 06 and 0-05/100 woman-years respectively, are much lower than those cited by Vessey et al,2 0121/100 woman-years for a variety of IUDs. Dr Snowden compares UK data with world-wide data for the Progestasert IUD, a comparison which is felt to be invalid. At the present time it is not possible to make a valid comparison of the ectopic pregnancy
BRITISH MEDICAL JOURNAL
made the effort to read each of them, it became clear that several of the applicants were of high quality. It is regrettable, therefore, that partly out of a poor knowledge of English and partly out of ignorance of the high value (perhaps much too high a value) placed in our culture upon neatness and etiquette in matters of this kind many doctors do not do themselves justice and risk repeated disappointments over not being short-listed. I would like to suggest that those whom overseas graduates request to be a referee might offer their help over composing letters of application and curricula vitae. Since nearly all overseas graduates spend some time in hospital appointments, should not the consultants for whom they work make sure that their proteges have mastered the rules of this procedure, which is one of such importance to them in their future career ? IAN GREGG Department of Clinical Epidemiology in General Practice, Cardiothoracic Institute, London SW3
"Baby and Child"
SIR,-When I read Dr Penelope Leach's letter (25 February, p 506) I felt some initial anxiety lest I had misread certain sections of her book. However, your readers will find if they will refer to the book that I have nowhere misquoted it. D P ADDY Dudley Road Hospital,
a significant increase in perinatal mortality in hypertensive patients with a plasma urate concentration above this value. Their recent paper, however, makes use of incremental changes in plasma urate concentration without reference to this critical value. We are not shown the epidemiological justification for this new method of defining disease severity. Our own data would suggest that the rise of 30 ,umol/l (0 5 mg/100 ml) used by the authors to categorise "borderline" preeclampsia may be physiological in normotensive pregnancy, during which a gradual increase in plasma urate concentration is to be anticipated.4 We have found that (1) between 16 and 36 weeks' gestation in normal pregnancy an increase in plasma urate concentration of 30 cmol/l or more occurred in 13 out of 24 healthy patients,5 while eight patients in fact showed a rise of more than 60 ftmol/l (1 mg/ 100 ml); and (2) throughout the course of a single 24-h period in the third trimester of normal pregnancy a diurnal variation of 30 Lmol/l or more occurred in 10 out of 14 healthy patients.6 (One subject showed a maximum variation of 61 Vmol/l.) In the recent study by Dr Redman and his colleagues, the groups of patients showing a "borderline increase" and "no increase" in plasma urate did not differ appreciably in terms of mean blood pressure, proteinuria, gestational age at delivery, mean birth weight, and perinatal mortality. This seems to strengthen our suggestion that an increase in plasma urate concentration of 30 ,umol/l should not be regarded as abnormal.
Birmingham
W DUNLOP J M DAVISON
Stiff-neck syndrome
SIR,-I was most interested to read the letter from Dr J Shafar describing a stiff-neck rates for different IUDs. syndrome (25 February, p 511). About four years ago I witnessed a similar incident. Three J R NEWTON R AZNAR nurses working in the theatres at one hospital E PIZARRO C L BERRY where I worked and one auxiliary working in P J ROWE I D COOKE the theatres of another all complained of stiff S T SHAW, jun A CUADROS neck at about the same time. I was also affected T WAGATSUMA R GRAY as was my sister with whom I lived. G P McNICOL F WEBB E WILSON Although I was not concerned with treating any of the nursing staff, the clinical picture Geneva relating to my sister and myself was as des' Tatum, H J, ahd Schmidt, F H, Fertility and Sterility, cribed by Dr Shafar. The close association of 407. 1977, 28, 2 Vessey, M P, et al, Journal of Biosocial Science, 1976, cases in time seemed to be more than coinciSuppi 11. dence and an infective origin the most likely explanation. M DUCROW How not to apply for an appointment Solihull Hospital, Solihull, W Midlands
SIR,-Among the large number of applications received in response to a recent advertisement in the BMJ for a vacancy in this department many were from overseas graduates. Most were handwritten and several were scarcely legible. One spelt the addressee's rlame incorrectly. In other cases the carbon copy of a standard letter of application was sent with amendments and additional information in ballpoint. Typed curricula vitae, when these were sent, were generally set out badly and often contained spelling mistakes. One applicant requested the return of his curriculum vitae after "we had finished with it." The immediate reaction on receiving applications such as these is to dismiss them as being so carelessly prepared that they indicate little real desire to be considered seriously for the vacancy. However, having
25 MARCH 1978
Plasma urate changes in pre-eclampsia
SIR,-Dr C W G Redman and his colleagues (25 February, p 467) are to be commended for attempting to establish the sequence of events leading to pre-eclampsia. However, in using plasma urate concentration to define incipient pre-eclampsia they may have underestimated the variations which occur in normal pregnancy. Previous publications' 2 from Oxford have made use of a critical value (350 ,umol/l (6 mg/100 ml)) above which patients might be classified as having significant preeclampsia. The justification for such a classification is to be found in an epidemiological study3 in which the same authors demonstrated
Department of Obstetrics and Gynaecology, and MRC Reproduction and Growth Unit, Princess Mary Maternity Hospital, Newcastle upon Tyne
Redman, C W G, et al, Britishyournal of Obstetrics and Gynaecology, 1977, 84, 904. Redman, C W G, et al, Lancet, 1977, 2, 1249. 3Redman, C W G, et al, Lancet, 1976, 1, 1370. 4 Boyle, J A, et al, Journal of Clinical Pathology, 1966, 19, 501. Dunlop, W, and Davison, J M, British Journal of Obstetrics and Gynaecology, 1977, 84, 13. 'Hill, L M, Furness, C, and Dunlop, W, British Medical3Journal, 1977, 2, 1520. 2
Osteoporosis and osteomalacia SIR,-Dr T C B Stamp (25 February, p 511), discussing a paper by Dr R G Long and others on the treatment of hepatic osteomalacia (14 January, p 75), comments that the x-rays in the latter study "indicated osteoporosis and not osteomalacia." Apart from numerous fractures the radiological skeletal survey in all four patients showed bone thinning but no evidence of osteitis fibrosa cystica or periosteal reactions. In 56 consecutive cases of thinning of the upper cortex of the clavicle in adults aged 42-91 idiopathic osteoporosis was present in 44, but osteomalacia was present in 4.2 In elderly patients it is uncertain whether cortical thinning is due to osteomalacia, as there may be a concomitant osteoporosis due to aging. For this reason I followed up all cases of clavicular cortical thinning (1 5 mm or less) in adults over 45. There were 18 such patients in a 10-year period. Chronic renal failure accounted for eight, coeliac disease seven, steroid therapy two, and Cushing's syndrome one. All the patients with coeliac disease had biochemical osteomalacia. Pseudofractures were common but were absent in one case,
25 MARCH 1978
Ambulance personnel and casualty staff in 62 London casualty departments were asked in a questionnaire survey for their recommendations for the management of cases of deliberate self-poisoning. From the 1350 questionnaires distributed, 1248 (92 %) were returned, of which 858 were completed by doctors and nurses. Among this group 88% believed that these patients should never be discharged without full psychiatric evaluation, 850% thought that there should be a resident psychiatrist in the hospital to advise patients, and 80 °'? thought that patients with deliberate self-poisoning should always be admitted, at least overnight. Although 73% thought that doctors and nurses should be given additional training to deal with these patients, 57 % believed that they should be taken to special emergency centres and not brought to hospital casualty departments at all. The opinions of these doctors and nurses cannot be lightly dismissed as their experience of all drug-related problems, including that of deliberate self-poisoning, is considerable.' In some London casualty departments, for example, there is a daily average of three drug overdose patients compared with 13 at Addenbrooke's. It is against this background that the recommendation of Dr Gardner and his colleagues is set; before it is generally adopted the opinions of those who would have to assume greater responsibility for this very large group of patients should be sought most carefully. If, as has been reported,2 their attitude to deliberate self-poisoning patients is an unsympathetic one the care of these patients might well be affected adverselyparticularly if staff in other hospitals are less fortunate and lack the support and instruction of an interested and involved psychiatrist. In any case, the aim of any amendment to the recommendations of the Hill Report should surely be that the treatment of the patients is improved, not merely shifted from one group of doctors to another. A HAMID GHODSE
785
and in the clinical trial they did so in five out of 133 instances. Since they requested psychiatric opinions for only 16 % of their patients it is unlikely that in other hospitals physicians would require psychiatrists to see every self-poisoned patient. Sir Denis Hill (11 February, p 362) has done much to improve the whole standard of undergraduate education in psychiatry. But most student psychiatric attachments are for only 8-12 weeks. Is this sufficient training for the future doctor? In general medicine and surgery further training is considered essential during the preregistration year. It is this aspect of medical education which has been neglected by psychiatrists and to which they might contribute with their colleagues in other specialties. I share Sir Denis Hill's concern lest psychiatrists should now leave physicians to undertake the initial psychiatric assessment of self-poisoned patients without first ensuring that junior doctors and nurses are adequately taught and that both psychiatric treatment and help from social workers are available once such patients have been discharged. What should be taught and how consultation liaison can be achieved might best be discussed at a joint meeting between the Royal Colleges of Physicians and Psychiatrists. A decade has now elapsed since the Hill report.' Is it not time that the standing medical advisory committees reviewed the arrangements for the treatment and after-care of self-poisoned patients and initiated a detailed study of the prevention of poisoning ? R GARDNER Self-poisoning Unit,
Addenbrooke's Hospital, Cambridge Central and Scottish Health Services Councils, Hospital Treatment of Acute Poisoning. London, HMSO, 1968.
Institute of Psychiatry, London SE5
Drug treatment of chronic stable angina pectoris
Ghodse, A H, British Journal of Preventive and Social Medicine, 1976, 30, 251. Patel, A R, British Medical Journal, 1975, 2, 426. 3 Ghodse, A H, Social Science and Medicine. In press.
SIR,-Your leading article on the above subject (25 February, p 462) states that studies on prenylamine have generally shown it to be no more effective than placebo. This statement is contrary to the facts and indeed misquotes one of the references.' The reference concerned actually states: "Prenylamine (SynadrinHoechst) depletes catecholamines in a similar way to reserpine, and acts in angina probably by reducing the sympathetic stimulation to the heart. In several adequately controlled doubleblind trials, prenylamine in a dose of 180-300 mg daily was significantly better than placebo in preventing anginal attacks." However, both this paper and another cited2 are review articles. We agree with your statement that "new drug preparations for the treatment of angina invariably have a strong placebo effect, and double-blind trials are essential for their evaluation." Since 1965 there have been a number of double-blind controlled studies published3-14 in the world literature definitely reporting the superiority of prenylamine over placebo in reducing the number of attacks and the consumption of short-acting nitrites in patients with angina pectoris. One study"5 reported no difference between prenylamine and placebo in reducing either anginal episodes or nitroglycerin consumption, but even this
2
SIR,-Dr M D Enoch and Professor J R M Copeland (4 February, p 300) have touched on the issue of clinical responsibility. When we stated (17 December, p 1567) that "physicians should decide for each of their patients if specialist psychiatric advice is necessary" we were, of course, referring to consultant
physicians.
The Department of Health's recommendation' does have implications which extend far beyond the management of self-poisoned patients in the general hospital. What if other expert committees were to recommend, say, that in all cases of head injury patients must be clinically evaluated by neurosurgeons, or that all men with chest pain should be referred to cardiologists, or that every patient with abdominal pain must be examined by a general surgeon? Such clinical decisions are usually left to the discretion of the medical practitioner. We decided at Addenbrooke's that physicians must have ultimate clinical responsibility for the self-poisoned patients admitted under their care. It followed that they could overrule psychiatrists' assessments,
investigation, while never reaching statistical significance, shows a trend in favour of prenylamine over placebo. While there are doubtless criticisms which can be levelled at some of the above studies either on the basis of design or statistical interpretation, the overall weight of evidence demonstrates, in contrast to your leading article, that prenylamine is more effective than placebo as an antianginal agent. R H ROUSEL GERALDINE DODD Hoechst UK Ltd, Pharmaceuticals Division, Hounslow, Middx ' Drug and Therapeutics Bulletin, 1974, 12, 1. 2Aronow, W S, American Heart Journal, 1973, 85, 132. Kappert, A, Zeitschrift fiur Therapie, 1965, 2, 82. Donat, K, and Schlosser, G A, Medizinische Klinik, 1966, 61, 352. Cloarec, M, Proceedings of symposium on "Prenylamine in therapy," Monaco, 1 March 1968, p 52. Cardoe, N, British Jrournal of Clinical Practice, 1968, 22, 299. Stoker, J B, British Journal of Clinical Practice, 1968, 22, 384. O Cardoe, N, Postgraduate Medical J7ournal, 1970, 46,
708. Mikkelsen, E, Ugeskrift for Laeger, 1971, 133, 873. 1 Sepatia, G C, Jain, S R, and Prakash, J, Clinical Trials Jfournal, 1971, 8, 43. Winsor, T, et al, American Heart_Journal, 1971, 82, 43. 1 Arora, R, Indian Heart Journal, 1973, 25, 62. 13 Tucker, H, et al, British Heart_Journal, 1974, 36, 1001. Kotia, K C, et al, Medikon, 1977, 6, 33. 5 Bjorum, N, Christensen, M, and Rathsach, P, Ugeskrift for Laeger, 1967, 129, 47.
Ectopic pregnancy rates in IUD users SIR,-In a recent review of ectopic pregnancy and contraceptive use Tatum and Schmidt' suggested that "there may be a causal relationship between the use of an intrauterine device (IUD) and the occurrence of an extrauterine pregnancy." This review, in addition, suggested that the Progestasert IUD may carry a higher risk of ectopic pregnancy than other IUDs. In a recent letter (17 December, p 1600) Dr Robert Snowden has also proposed that the Progestasert IUD may carry a selectively greater risk of extrauterine pregnancy. At a meeting in Geneva from 27 February to 1 March 1978 of the steering committee of the Task Force on Intrauterine Devices for Fertility Regulation of the World Health Special Programme of Organisation's Research, Development and Research Training in Human Reproduction the available published and unpublished data on the occurrence of ectopic pregnancy in IUD users was reviewed, and the committee had the following reservations about the interpretation of these data by the above authors: (1) It has long been argued on the basis of the mechanism of action that an IUD protects more against intra- than against extrauterine pregnancy. It would therefore be anticipated that there should be a higher ratio of extra- to intrauterine pregnancies in IUD users, a difference in incidence which has in fact been found in many studies. The steering committee believes that the available data indicate a real increase in the risk of ectopic pregnancy among IUD users when compared with non-users. However, the magnitude of this risk is difficult to quantitate with the existing data as there are no studies in which adequate comparisons of risk have been made. (2) The methods used to present ectopic pregnancies in published studies may give misleading information, especially when ectopic pregnancy rates are presented as a percentage of total pregnancies; such percentages may be affected by the contraception-dependent reduction in intrauterine pregnancy rate. Accordingly ectopic pregnancy rates should be expressed as a
786
life table rate per 100 woman-years, in which this problem of interpretation does not arise. (3) The risk factors which predispose to ectopic pregnancy vary from population to population and may vary between users of different contraceptive methods. Unless this variability is taken into account bias may be introduced. Future studies should be designed to ensure that such bias is excluded. (4) All published studies of ectopic pregnancy rates have, so far as can be determined, failed to state the criteria for the diagnosis of ectopic pregnancy, leading perhaps to an overestimate of its incidence. If ectopic pregnancy is thought to have occurred in test or control patients in any clinical trial of an IUD all material removed from the peritoneal cavity should be examined. Fluid, blood clots, and curettings, if taken, should be studied macroscopically. Clots should be sieved or fixed and sliced for gross examination and all suspicious areas examined microscopically. The aim of the verification of the diagnosis of ectopic pregnancy is to improve the accuracy of incidence data in IUD studies. For this purpose it is considered essential for the diagnosis that fetal parts (identified grossly or microscopically) and/or trophoblast are identified. Decidual reaction and/or blood in the Fallopian tube is not sufficient to establish the diagnosis. This definition does not preclude a presumptive diagnosis made for clinical purposes, based for example on tubal disruption, decidual change in Fallopian tube or endometrium, gross blood in the peritoneal cavity, or other suggestive operative findings. (5) Because of the limited data available and the difficulties of comparisons between studies it is not possible to state that the Progestasert IUD users are at higher risk of ectopic pregnancy than other IUD users. Ectopic pregnancy rates for Lippes Loop and copper-carrying IUD users quoted by Dr Snowden, 0 06 and 0-05/100 woman-years respectively, are much lower than those cited by Vessey et al,2 0121/100 woman-years for a variety of IUDs. Dr Snowden compares UK data with world-wide data for the Progestasert IUD, a comparison which is felt to be invalid. At the present time it is not possible to make a valid comparison of the ectopic pregnancy
BRITISH MEDICAL JOURNAL
made the effort to read each of them, it became clear that several of the applicants were of high quality. It is regrettable, therefore, that partly out of a poor knowledge of English and partly out of ignorance of the high value (perhaps much too high a value) placed in our culture upon neatness and etiquette in matters of this kind many doctors do not do themselves justice and risk repeated disappointments over not being short-listed. I would like to suggest that those whom overseas graduates request to be a referee might offer their help over composing letters of application and curricula vitae. Since nearly all overseas graduates spend some time in hospital appointments, should not the consultants for whom they work make sure that their proteges have mastered the rules of this procedure, which is one of such importance to them in their future career ? IAN GREGG Department of Clinical Epidemiology in General Practice, Cardiothoracic Institute, London SW3
"Baby and Child"
SIR,-When I read Dr Penelope Leach's letter (25 February, p 506) I felt some initial anxiety lest I had misread certain sections of her book. However, your readers will find if they will refer to the book that I have nowhere misquoted it. D P ADDY Dudley Road Hospital,
a significant increase in perinatal mortality in hypertensive patients with a plasma urate concentration above this value. Their recent paper, however, makes use of incremental changes in plasma urate concentration without reference to this critical value. We are not shown the epidemiological justification for this new method of defining disease severity. Our own data would suggest that the rise of 30 ,umol/l (0 5 mg/100 ml) used by the authors to categorise "borderline" preeclampsia may be physiological in normotensive pregnancy, during which a gradual increase in plasma urate concentration is to be anticipated.4 We have found that (1) between 16 and 36 weeks' gestation in normal pregnancy an increase in plasma urate concentration of 30 cmol/l or more occurred in 13 out of 24 healthy patients,5 while eight patients in fact showed a rise of more than 60 ftmol/l (1 mg/ 100 ml); and (2) throughout the course of a single 24-h period in the third trimester of normal pregnancy a diurnal variation of 30 Lmol/l or more occurred in 10 out of 14 healthy patients.6 (One subject showed a maximum variation of 61 Vmol/l.) In the recent study by Dr Redman and his colleagues, the groups of patients showing a "borderline increase" and "no increase" in plasma urate did not differ appreciably in terms of mean blood pressure, proteinuria, gestational age at delivery, mean birth weight, and perinatal mortality. This seems to strengthen our suggestion that an increase in plasma urate concentration of 30 ,umol/l should not be regarded as abnormal.
Birmingham
W DUNLOP J M DAVISON
Stiff-neck syndrome
SIR,-I was most interested to read the letter from Dr J Shafar describing a stiff-neck rates for different IUDs. syndrome (25 February, p 511). About four years ago I witnessed a similar incident. Three J R NEWTON R AZNAR nurses working in the theatres at one hospital E PIZARRO C L BERRY where I worked and one auxiliary working in P J ROWE I D COOKE the theatres of another all complained of stiff S T SHAW, jun A CUADROS neck at about the same time. I was also affected T WAGATSUMA R GRAY as was my sister with whom I lived. G P McNICOL F WEBB E WILSON Although I was not concerned with treating any of the nursing staff, the clinical picture Geneva relating to my sister and myself was as des' Tatum, H J, ahd Schmidt, F H, Fertility and Sterility, cribed by Dr Shafar. The close association of 407. 1977, 28, 2 Vessey, M P, et al, Journal of Biosocial Science, 1976, cases in time seemed to be more than coinciSuppi 11. dence and an infective origin the most likely explanation. M DUCROW How not to apply for an appointment Solihull Hospital, Solihull, W Midlands
SIR,-Among the large number of applications received in response to a recent advertisement in the BMJ for a vacancy in this department many were from overseas graduates. Most were handwritten and several were scarcely legible. One spelt the addressee's rlame incorrectly. In other cases the carbon copy of a standard letter of application was sent with amendments and additional information in ballpoint. Typed curricula vitae, when these were sent, were generally set out badly and often contained spelling mistakes. One applicant requested the return of his curriculum vitae after "we had finished with it." The immediate reaction on receiving applications such as these is to dismiss them as being so carelessly prepared that they indicate little real desire to be considered seriously for the vacancy. However, having
25 MARCH 1978
Plasma urate changes in pre-eclampsia
SIR,-Dr C W G Redman and his colleagues (25 February, p 467) are to be commended for attempting to establish the sequence of events leading to pre-eclampsia. However, in using plasma urate concentration to define incipient pre-eclampsia they may have underestimated the variations which occur in normal pregnancy. Previous publications' 2 from Oxford have made use of a critical value (350 ,umol/l (6 mg/100 ml)) above which patients might be classified as having significant preeclampsia. The justification for such a classification is to be found in an epidemiological study3 in which the same authors demonstrated
Department of Obstetrics and Gynaecology, and MRC Reproduction and Growth Unit, Princess Mary Maternity Hospital, Newcastle upon Tyne
Redman, C W G, et al, Britishyournal of Obstetrics and Gynaecology, 1977, 84, 904. Redman, C W G, et al, Lancet, 1977, 2, 1249. 3Redman, C W G, et al, Lancet, 1976, 1, 1370. 4 Boyle, J A, et al, Journal of Clinical Pathology, 1966, 19, 501. Dunlop, W, and Davison, J M, British Journal of Obstetrics and Gynaecology, 1977, 84, 13. 'Hill, L M, Furness, C, and Dunlop, W, British Medical3Journal, 1977, 2, 1520. 2
Osteoporosis and osteomalacia SIR,-Dr T C B Stamp (25 February, p 511), discussing a paper by Dr R G Long and others on the treatment of hepatic osteomalacia (14 January, p 75), comments that the x-rays in the latter study "indicated osteoporosis and not osteomalacia." Apart from numerous fractures the radiological skeletal survey in all four patients showed bone thinning but no evidence of osteitis fibrosa cystica or periosteal reactions. In 56 consecutive cases of thinning of the upper cortex of the clavicle in adults aged 42-91 idiopathic osteoporosis was present in 44, but osteomalacia was present in 4.2 In elderly patients it is uncertain whether cortical thinning is due to osteomalacia, as there may be a concomitant osteoporosis due to aging. For this reason I followed up all cases of clavicular cortical thinning (1 5 mm or less) in adults over 45. There were 18 such patients in a 10-year period. Chronic renal failure accounted for eight, coeliac disease seven, steroid therapy two, and Cushing's syndrome one. All the patients with coeliac disease had biochemical osteomalacia. Pseudofractures were common but were absent in one case,
