every 5 cigarettes smoked dailv, 95% confidence interval 1 ... relative risk=2 81 for every 3 cigarettes smoked ... are many small machine code lengths built in as.
and health services research. This has necessitated reductions in staff funded by the University Grants Committee in several departments, including occupational health. The school recognises, however, the importance of occupational and environmental health as a vital component of public health and that an academic presence in occupational health to serve the large concentration of industry and commerce in south east England is essential. It will, therefore, retain occupational health at a level that will maintain its Master of Science and other courses in occupational medicine and hygiene. The school has survived the financial problems since the change in overseas student policy by the strenuous efforts and success of its departments in staffing their teaching and research from external funding. Only about 30% of academic and research staff in the school are funded from University Grants Committee sources. Occupational health, unfortunately, has been unable to match this, mainly because of lack of funding from the beneficiaries, industry and commerce. We are grateful to many professional colleagues from industry and commerce for their unstinting help in enhancing the quality of our teaching by their practical contributions, but we urgently need more generous help in promoting research if occupational health is to compete successfully with other subjects for University Grants Committee funding. We look forward to the University Grants Committee's review of occupational health in the hope that it may find ways of reversing the decline in academic occupational health and enhancing its prospects and morale, but the main thrust must come from industry and commerce.
or both parents and partly in the Caribbean, usuallv by other members of their familv. The resulting experiences of separation from key parenting figures, friends, and home must have left their emotional scars. The authors raise the question of whether genetic influences might be at the root of the patterns seen. This seems unlikely as the pattern of a generation at much greater risk, at least in early adult life, than their parents does not fit with the patterns of genetic influence that have been described for the disease. It would be wrong for British psychiatry to regard the pattern "simply as an interesting research possibility." It would be equally wrong, however, if the appearance of this epidemic in the Caribbean community was not investigated with the rigour usually applied to epidemics in the population as a whole. It is ironic that Drs Littlewood and Lipsedge, who so influentially counselled caution in the diagnosis of schizophrenia in Caribbeans, should be so ready apparently to diagnose the cause of the epidemic on such flimsy evidence. GYLES R GLOVER
Charing Cross and Westminster Medical School, ILondon SWI 1l 2AR 1 Torrev lEF. Schzzophretila and cizvilsation. New York: Jason Aronson, 1980. 2 Murray RM, Lewis SW. Is schizophrenia a nieirodevelopmental
disorder? BrAledj 1987;295:681-2. 3 Eagles J, Hunter D, McCance C. Declinc in the diagnosis of schizophrenia among first contacts with psychiatric sersvices in north east Scotland. Br7 Psichiatn, 1988;152:793-8.
P This correspondence is now closed.- ED, BMJ.
C E GORDON SMITH
London School of Hygiene and Tlropical Medicine, London WC I E 7HT
Psychiatric illness among British Afro-Caribbeans Drs Roland Littlewood and Maurice Lipsedge (2 April, p 950) inclined towards an explanation of the recent patterns of schizophrenia in young AfroCaribbeans in terms of their experience of racism and ignored other possible causes. Subsequently (9 July, p 135) they argued that it is justifiable to consider British born and Caribbean born subjects together as their experiences in this respect are similar. This again prejudges the issue. Torrey has drawn attention to epidemiological patterns of the disease that may implicate an infective agent.' If this acted around the time of birth, as has been suggested,2 the epidemic might be seen as analogous to the epidemic of congenital rubella in children born to Caribbean women shortly after their arrival in the United Kingdom. The pattern of a falling incidence of schizophrenia in the United Kingdom in the past two decades, described by Eagles et al,' may suggest that something like host resistance, which can be enhanced by good nutrition and other general health measures, is involved. The children of Caribbeans who had recently arrived in the United Kingdom in the 1950s and 1960s may not have had easy access to the child welfare services. If one wishes to invoke social explanations then experiences of racism and of striving in a climate of limited opportunity are important possible causes. I understand, however (Dr Harrison, personal communication), that anecdotal evidence sufficient to warrant a formal study has emerged that there may have been a similar increase in the incidence of schizophrenia in Caribbeans in New York, where the Caribbean community has enjoyed much more material success. Another important stressor that Drs Littlewood and Lipsedge did not mention is that many of the children of the migrants were brought up partly in the United Kingdom by one BMJ
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Implications of the Cleveland inquiry The events in Cleveland and the resultant ButlerSloss report have shown a need for a better recognition by doctors of "the importance of the forensic element" of their medical practice. It would be easy for us to sav that we told you so. For years the dwindling number of practitioners occupied in various aspects of forensic medicine have been drawing attention to the insufficient resources for the training of young doctors in this discipline. Moreover, anxiety has been expressed by agencies outside medicine over matters as far removed from the present concern as, for instance, the inadequate completion of death certificates. Within the profession the mistaken attitude has developed that forensic medicine is solely concerned with "Home Office pathology." In fact, this forms a comparatively small part of the subject. The relevance of the clinical and legal aspects of forensic medicine to normal medical practice have largely been ignored. It would be foolish to assume that because of this current furore sexual abuse of children is the only medicolegal problem likely to be met by doctors in practice. At the other end of the scale, with an aging population the extent of physical abuse of the elderly could well be the next matter to erupt, or, in another area, the lack of competency of doctors in giving evidence. It is time-indeed, long past time-to improve the training of doctors in all the forensic elements of their work. Many years ago the medicolegal training given was commensurate with the knowledge available and the problems encountered. Currently training has decreased just when the forensic problems facing any doctor have greatly increased in amount and range. When attention is being given to forensic problems it is in areas of less importance, such as the view that all future examiners of children suspected of having been sexually abused or of alleged rape victims should be women. It is much
more important, surely, to consider the examiners' competence rather than their sex. We emphasise the importance of the case for improving the education of doctors in all aspects of forensic medicine before the lessons clearly spelt out in the Butler-Sloss report become submerged by other concerns; so that we can reverse the present trend towards a generation of doctors ill informed in and fearful of the wider legal aspects of their practice. NEVILLE DAVIS Scction ot(Clinical Forensic Medicine, Rosal Societv of Medicine, London W I DAVID GEE
Knaresborough, No-th Vorkshire HG5 OLY
In discussing the Cleveland inquiry Dr Bernard Valman refers to the lack of proper understanding and communication between the main agencies and to the recommendation that specialist assessment teams should be formed in each district (16 July, p 151). This is such an important recommendation that we must ask why attempts by professionals from different disciplines to collaborate often break down. Experience has shown that there are many reasons for this, and they mostly stem from the areas in which professional boundaries overlap. The different professions have many misconceptions of each other's work, and there is often uncertainty about how much to communicate; there are problems stemming from interprofessional rivalry about sharing the care of a patient or client; there may be feelings of status in comparison with members of the other professions; and issues of responsibility and authority are often blurred. Because feelings about these various issues tend to be strong they are difficult to discuss. In particular, in a subject such as child abuse those who are giving care also have to cope with the powerful emotions that this rouses in each of them. The most important conclusion to be borne in mind is the one that is most frequently overlooked-namely, that breakdown in collaboration commonly occurs when the professionals concerned concentrate only on the practical tasks and do not give proper consideration to their own feelings and to the interpersonal aspects of their working relationship. Even with good will it usually take time, often several months, before a working relationship of mutual trust is firmly established. Only then can the team make rational decisions based on a proper sharing of the findings, perceptions, and views of the members of the different
professions. ALEXIS BROOK Tavistock Clinic, 'Tavistock Centre, London NW3 5BA
Cigarette smoking and early neonatal death Dr Sven Cnattingius and colleagues (23 July, p 258) have provided evidence that maternal smoking during pregnancy is a risk factor not only for late fetal death but also for early neonatal death. As a result of an extensive secondary analysis of data from the United Kingdom multicentre study of postneonatal mortality,' funded by the Foundation for the Study of Infant Deaths, we believe that the increased risk associated with maternal smoking during pregnancy may last at least until the eighth week of life. A multiple logistic regression analysis of the multicentre study data on 303 sudden infant deaths and control infants showed that maternal smoking during pregnancy was the largest risk factor for the sudden infant death syndrome in infants under 8 weeks of age (estimated relative risk= 155 for
487
every 5 cigarettes smoked dailv, 95% confidence interval 1 11 to 2 14) but was not a risk factor for sudden infant death syndrome in infants over 24 weeks. On the other hand, when paternal smoking in the absence of maternal smoking was studied there was no significantly increased risk for the young infants with sudden infant death syndrome. The older infants who died were, however, at a significantly increased risk of sudden infant death syndrome if their fathers smoked (estimated relative risk=2 81 for every 3 cigarettes smoked daily, 95% confidence interval 111 to 7 15). There are two types of explanation for how smoking could be causally related to postnatal deaths: smoking during pregnancy may leave the newborn infant more vulnerable, or postnatal passive smoking by the infant may increase the risk of death. These data provide some evidence for the passive smoking mechanism in older infants but not in younger infants, in whom maternal smoking during pregnancy appears to be an important factor lasting well beyond the neonatal period. J P NICHOLL ALICIA O CATHAIN Medical Care Research Unit, Sheffield Medical School. Sheffield S 10 2RX I Knowelden JI Keeling J, Nicholl JP. A multicentre studv of post-neonatal mortlitv. London: HMSO, 1985.
Computer viruses Dr John Asbury points out that "a computer virus is a small piece of computer code which has been maliciously inserted on computer storage media" (23 July, p 246). Although this is true in most cases, there remains the possibility that some of these viruses have "evolved" out of random mutations of computer programs. Some computer viruses are extremely small, consisting of short lengths of machine code. There are many small machine code lengths built in as part of the operating systems of computers to fulfil various tasks, such as reading, writing, and erasing data. Anyone who has ever used a computer will be extremely familiar with computer failures, or "crashes," when all the data in a computer's memory are scrambled and data are lost. This scrambling consists of random substitution of the computer memory locations with tiny fragments of machine code one or two bytes long. It is entirely possible, considering the number of times such events occur and the few substitutions required to mutate an existing length of machine code, into a virus (analogous to base pair substitution in DNA), that such viruses will be thrown up quite regularly. Most will be fatal mutations and will wipe themselves out. Others will be stillborn, stable but nonfunctioning. Even fewer will emerge as infectious viruses. According to Darwinian natural selection, the viruses that are adapted to survive hidden inside computer systems will be the most successful and may proliferate, either as a result of the initial mutation or as a result of subsequent non-fatal mutations. Thus it is that life of a sort may have evolved in the computer systems designed by humans. The worrying thing is, as Dr Asbury suggests, that these new viruses may be very dangerous indeed, much more so than their biological counterparts. The AIDS virus may eventually kill many thousands of people. Yersinia pestis killed many millions in the Black Death. But a lively virus in the control system of an intercontinental ballistic missile may prove a greater human pathogen than any mere biological microbe. JOHN CROALL
Public Health Laboratory, William Harvey Hospital, Willesborough,
Ashford, Kent rN24 OLZ
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Drug Points
Hypomagnesaemia and hypocalcaemia after treatment with mitozantrone Drs K D GRIFFI1Hs and D H PARRY (Ysbvtv Gwvnedd, Bangor, Gwynedd LL57 2PW) write: Hypomagnesaemia hypocalcaemia, and hypoparathyroidism have been reported in patients with acute leukaemia and breast carcinoma after chemotherapy. 2 We describe a patient with metastatic breast carcinoma who was given chemotherapy which included mitozantrone and developed hypomagnesaemia and hvpocalcaemia apparently unrelated to hypoparathyroidism. As far as we are aware these biochemical abnormalities have not been reported with mitozantrone. A 52 year old woman was referred with recurrent breast carcinoma eight years after a left mastectomy and bilateral salpingo-oophorectomy. After surgery she was treated with tamoxifen and aminoglutethimide and had been receiving thyroxine for several vears. Nine months before this referral she had received radiotherapy to the sternum and ribs for painful metastases. Examination showed a mass in the contralateral breast, lymphadenopathy in the neck, and a mass in the left lower abdomen. Routine biochemical investigations gave normal results. One month later, just before cytotoxic treatment was started, the results of biochemical investigations were: normal urea, creatinine, and albumin concentrations; potassium concentration normal at 3-6 mmol/l; calcium concentration 2 09 mmol/l; alkaline phosphatase activity 484 U/I; aspartate transaminase activity 149 U/I; alanine transaminase activity 83 U/I; and y-glutamyltranspeptidase activity 33 U/I. An isotope bone scan confirmed multiple areas of increased uptake consistent with widespread metastases. Chemotherapy with mitozantrone 20 mg (10 mg/ m2), cyclophosphamide 1-2 g (0-6 g/m2), and vincristine 2 mg was given intravenously. Four davs later she was admitted to hospital as an emergency with a grand mal fit having had persistent nausea, vomiting, and diarrhoea. The abnormal biochemical findings were: potassium concentration 2 1 mmol/l, chloride concentration 93 mmol/l, aspartate transaminase activity 73 U/I, alanine transaminase activity 30 U/l, y-glutamyltranspeptidase activity 25 U/l, calcium concentration 1-54 mmol/d (with a normal albumin concentration), and phosphate concentration 0-91 mmol/l. Magnesium concentration measured a dav later was 0 19 mmol/l. Parathyroid concentration was 0 7 ng/ml (reference range less than 0-2 ng/ml),. and vitamin D concentration was normal. A random measurement of urinary calcium did not show a significantly increased excretion. No brain metastases were evident on computed tomography. She was treated with intravenous and oral calcium supplements, vitamin D (as alfacalcidol), and intermittent intravenous magnesium sulphate infusions. The calcium concentration fell to 1 20 mmol/l after admission in spite of replacement treatment, and magnesium concentrations fell rapidly when infusions were stopped, rarely rising above 0 5 mmol/l. The serum albumin concentration was always within normal limits. Initially there was considerable clinical improvement, but continuous replacement treatment with calcium and vitamin D was required to maintain normal serum calcium concentrations. The initial response to the cytotoxic drugs was complete disappearance of soft tissue disease. Because of the metabolic complications, however, no further chemotherapy was given, and she died of progressive metastatic disease five months later. The grand mal fit was probably caused bv rapid onset of hypocalcaemia and hypomagnesaemia. This rapid onset, occurring within four days, was much faster than has been reported with other drugs having this effect. The probable explanation is that the chemotherapy induced proximal renal tubular damage causing severe loss of magnesium with a concurrent reduction in serum calcium concentration. This wvould be supported by the low concentrations of potassium and phosphate. The vomiting and diarrhoea may also have been contributorv. Similar observations have been made with different cytotoxic drugs,3 but, unlike Freedman et al,' we found no evidence of hypoparathyroidism. The side effects of the cytotoxic drugs may have been enhanced by pre-existing
impaired liver function relatcd to hepatic metastases. The doses were related to bodv surface area, and, because the patient was grosslv overweight, the dose of drug given may also have been important. We consider that these profound metabolic abnormalities were probably caused by the cvtotoxic chemotherapy, perhaps by inducing renal tubular damage. The case was unusual in that although the patient received continuous calcium, vitamin 1), and magnesium replacement until the time of hcr dcath satisfactory control was never achieved. As far as we know this has not been reported previouslv in association with mitozantrone. Frccdman DB, Shannon M, Dandona 1', P'renticc HG. Hoffbrand AV. Hvpoparahvro,idism and hvpocalcacmia during treatmcnt I-or acuite leukaeinia. Br fed7 1982;284:700-2. 2 (Gmoez-(amphera 11, (ionzalcz 1P, Camillo A, Estellcs MC, Rengcl M. Cisplatin nephrotoxicity: symptomatic hypomnagnesaemia and renal f-ailurc. InternaoionaluJounal o .Vephrolokv 1986:7:151-2. 3 Womer RB, Pritchard J, Barrart 'IM. Renal toxicity of cisplatin in children. 7 Pcdilatr 1985;106:659-63.
Small bowel perforation associated with an excessive dose of slow release diclofenac sodium Mr M DEAKIN and others (Queen Elizabeth Hospital, Birmingham B15 2TH) write: Intestinal perforation associated with the ingestion of indomethacin is a well documented but uncommon side effect with a high risk of death. There have been seven deaths among the 18 cases reported to the Committee on Safety of Medicines (personal communication). Osmosin, a long acting preparation of indomethacin, was withdrawn because of a number of reported perforations, possibly due to increased local toxicity associated with the formulation and drug delivery system. 'The risk of perforation is also present with other non-steroidal anti-inflammatory drugs thought to have a lower incidence of side effects.2 A 70 year old man was referred with a 24 hour history of pain in the left iliac fossa. He had a fever and signs of localised peritonism in his left iliac fossa. Twenty seven years previously he had had a laminectomy for a prolapsed intervertebral disc. He had suffered with continuous low back pain for many years and had been taking a combination of dipipanone hydrochloride and cyclizine hydrochloride (Diconal) twice daily for two years. Two weeks before admission he had been prescribed the recommended dose of diclofenac sodium, 100 mg daily, in a sustained release preparation (Voltarol Retard). During the week before admission he had increased the dose to 100 mg four times daily. An initial diagnosis of acute diverticulitis was made, and he was treated with parenteral antibiotics. His fever and abdominal tenderness resolved over 48 hours. Six days after admission he developed increasing abdominal distension and then had a sudden onset of generalised pain and tenderness. A laparotomy was performed, and he was found to have two perforations in the terminal ileum, each about 3 mm in diameter. The terminal ileum otherwise seemed to be normal. A biopsy specimen from the edge of a perforation showed no specific features. The perforations had sealed initially and had remained confined within a small abscess cavity beside the sigmoid colon in the left iliac fossa, thus accounting for his localised signs at presentation. The abscess had ruptured subsequentlv into the peritoneal cavity. The two holes were oversewn with cat gut, and he made an uneventful recovery. Blood cultures and faecal samples were negative for salmonella. To our knowledge this is the first reported case of small bowel perforation associated with the ingestion of slow release diclofenac sodium (a phenylalkanoic derivative). Non-steroidal anti-inflammatory drugs, including indomethacin and fenamic acid derivatives, given orally or parenterally to rats cause small bowel perforation within three or four days. This effect is dose dependent, is believed to be caused by reduced prostaglandin synthesis by the small bowel mucosa, and can be prevented by giving prostaglandin E2. Our patient was suffering from pain that had been difficult to control over a long time, and he had increased his dose of diclofenac sodium to four times the recommended dose. The perforation could have been caused by high local drug concentrations, a factor that might have been exacerbated by taking the combination of dipipanone hydrochloride and
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