INSULIN AUTOANTIBODIES—WHICH METHOD?

622

Recognising that the health of a population is primarily influenced by hygiene, sanitation, nutrition, housing, lifestyle, education, and primary health care "MASA seeks the abolition of all discriminatory measures in South Africa to ensure the disappearance of the practice of apartheid, so that the human dignity of all people be acknowledged, affording them equal and just opportunities". Medical Association of South Africa, 428 King’s Highway,

B. B. MANDELL

Lynnwood, Pretoria 0081, South Africa

Chairman, Federal Council, MASA

COMPUTER SOFTWARE IN GENERAL PRACTICE

SIR,-Your July 22 editorial on databases did not mention care. Here, too, there is a remarkable epidemiological opportunity, if suitable software is provided to manage the drug

primary

budget in the practice and at the family practitioner committee. The white-paper and accompanying working paper suggest a choice between PACT (prescription analysis and costing), derived from data held by the Prescription Pricing Authority, and special software and PACT as a temporary expedient, software being provided later. It seems that the choice has fallen on PACT: the Government is not asking for software to be written. PACT tells us how many prescriptions were dispensed and how much they cost. It does not relate to individual patient morbidity. It is a blunt instrument to control the drug bill. The doctor, unless he has voluminous records

or a

computer with effective software,

adequately a charge of overprescribing-but if he can relate prescribing, day after day, to patient and to morbidity his choice of drug can be defended as a clinical judgment. With information on morbidity and prescriptions, as well as cost, data can be analysed in several ways-by patient according to prescription over time, by prescriptions related to episode of illness, by drug or therapeutic group related to morbidity, and all these by cost-a far better way of controlling cost and improving quality. The doctor would learn from his evaluated experience and we would begin to understand the thinking behind his prescribing and choice of drugs. We would be on the way to assessing the comparative efficacy of drugs by learning about treatment outcome. In other areas software can expand epidemiological opportunity--outpatient referrals, laboratory investigation, audit of hospital care as seen in the practice, and post-marketing cannot meet

surveillance. It is not too late to introduce the modest changes that would make possible all these studies. The software envisaged in the white-paper for drug budget and practice budget should be written as a matter of policy. Morbidity should be an essential element of data collection under that software so that the triad, morbidity/item/cost (where "item" is drug, prescription, investigation, outpatient referral, or

operation), becomes the essential quota of information on a patient’s computer record. In this way the epidemiological opportunity to transform the NHS will not be lost. Update Computers Ltd, 19-30 Alfred Place,

ABRAHAM MARCUS

London WC1E 7EA

TIME LIMIT FOR ANTI-SNAKE VENOM

ADMINISTRATION

SiR,—The accepted treatment for snake-bite poisoning is prompt administration of anti-snake venom. But how long after envenomation is antivenom therapy still effective? Antivenom is said to be useful if given within 4 h, of less value if delayed for 8 h, and of doubtful value after 24 h.l Therefore, should antivenom therapy be withheld if a patient with snake bite seeks medical advice after a delay of more than 24 h? We report a patient with a severely bleeding snake bite, admitted 8 days after the bite. A 19-year-old man was admitted with a history of snake bite 8 days previously. He had bleeding from multiple sites (ecchymosis, melaena, and frank haematuria). The patient was apprehensive and restless with pronounced pallor, swelling around the site of bite on the left foot, and multiple ecchymotic patches all over his body. His pulse was 120/min and feeble. Blood pressure was 120/80 mm Hg.

tachycardia and functional haemic murmur all over the precordium. There was diffuse tenderness all over the abdomen, but no mass was palpable. Chest and neurological examinations He had

were

normal. The fundus did not show any evidence of

haemorrhage. Haemoglobin was 5-8 g/dl, total and differential leucocyte counts were normal, and platelets numbered 168 000 cells/J..ll. Erythrocyte sedimentation rate was 150 mm/h. Bleeding time was 4-5 min and clotting time was more than 30 min. Prothrombin time was 23 s. Urine showed macroscopic and microscopic haematuria. Renal indices including blood urea and creatinine were normal. At this stage, 40 ml of polyvalent antivenom diluted in 500 ml of isotonic saline was given by intravenous infusion over 4 h, after which bleeding stopped completely, the urine became clear, clotting time 6 h after admission was normal (8 min), and prothrombin time was 15/10 s. The coagulation profile after 3 days continued to be normal. Even though our patient presented after a delay of 8 days and had haemorrhagic manifestations, his response to antivenom administration was striking. The prolonged bleeding could be attributed to persistence of the venom in the blood. Reid et al2 gave antivenom up to 72 h after Malayan viper bites and found it to be effective. A report from the Jammu region of India showed 1 patient in a series of 232 consecutive snake-bite cases had prolonged bleeding for up to 18 days. The anti-snake venom was started on the 4th day and continued till the cessation of bleeding.3 Antivenom therapy has proved effective in patients still defibrinated weeks after bites by Viperidae.4 These observations indicate that antivenom

therapy has a useful role even after 24 h of snake-bite poisoning. S. DWIVEDI

Department of Medicine, SHUBHA SHESHADRI Kasturba Medical College, C. D’SOUZA India 576119, Manipal 1. Russell FE, Carison RW, Wainschel J, Osbome AH. Snake venom poisoning in the United States. JAMA 1975; 233: 341-44. HA, Chan KE, Thean PC. Prolonged coagulation defect (defibrination syndrome) in Malayan viper bite. Lancet 1963; i: 621-26. 3. Virmani SK, Dutt OP. A profile of a snake bite poisoning in Jammu region. J Indian Med Ass 1987; 85: 132-35. 4. Warrel DA. In: Weatherall DJ, Ledingham JGG, Warrel DA, eds. Oxford text book of medicine, vol 1. 2nd ed. Oxford: Oxford University Press, 1987: 6.75. 2. Reid

INSULIN AUTOANTIBODIES—WHICH METHOD?

SIR,-Dr Betterle and colleagues (July 22, p 223) present four patients in whom insulin autoantibodies (IAA) were retrospectively demonstrated before the onset of insulin dependent diabetes mellitus (IDDM). As organisers of the next International IAA Standardisation Workshop we believe that their conclusion that IAA are markers of potential diabetes (as are islet cell antibodies, ICA) is misleading. An earlier IAA Workshopl has demonstrated that the two IAA detection methods generally used-fluid-phase radiobinding and solid-phase enzyme-linked assay-measure distinct and only partly overlapping populations of IAA. This means that there is no defined IAA entity. Which of the various IAA-assays detects an antibody population most predictive of potential IDDM is the topic of the present IAA-Workshop. Betterle and co-workers used an enzyme-linked immunosorbent assay (ELISA) to measure IAA. Previous experience for a large number of subjects raises serious questions about the predictive value of the positive IAA signal as a marker of potential IDDM:2 IgG-IAA was found in 6 (29%) of 21 ICA-positive first-degree relatives of patients with IDDM and in 25 (22%) of 114 ICA-negative relatives (IgM-IAA 10% and 9%, respectively). Among non-diabetic relatives of IDDM patients IDDM develops mainly in those who are ICA positive; and the risk in ICA-negative relatives is very low.3 Thus, the similarly high percentage of (ELISA-negative) IAA in ICA-positive and ICA-negative relatives suggests a lack of specificity of their IAA results for predicting subsequent IDDM. In our IAA-ELISA assay (B. K. and H. K.) the prevalence of IgG-IAA among 1266 first-degree relatives is 94%. After a mean observation period of 2-4 years, 8 IAA-positive individuals had IDDM (6 of them were ICA positive). Thus, we confirm the occasional presence of IAA in the absence of ICA in prediabetics. Additionally, like Dr Betterle et al, we did not find a significant association of IgG-IAA and ICA."

623 IAA measured by fluid-phase radioimmunoassay have been reported to be associated with ICA and also to be predictive markers for later IDDM.5,6 However, differences in results between several fluid phase assays occurred.Results from the next IAA-Workshop will hopefully settle the dispute on IAA-detection methods and IAA usefulness in diabetes prediction. Diabetes Research Institute,

that immigrants are at risk of paranoid illness, that linguistic and social difficulties contribute, and that the physical illness is a life event are as to

equally applicable to perpetuating a pre-existing psychosis

orecipitatins a psychosis. A. K. SHAH R. TOBIANSKY J. J. BRADLEY

Psychiatric Wing, Whittington Hospital, London N19 5NF

University of Dusseldorf, D-4000 Dusseldorf, FRG

BERND KUGLIN HUBERT KOLB

Division of Endocrinology, VA Medical Center ZB-20, Seattle, USA

JERRY PALMER

TJ, Schoenfeld SL, Diaz J-L, et al. Systemic variation and difference in insulin-antibody measurements. Diabetes 1989; 38: 172-81. 2. Zanchetta R, Ruso V, Presotto F, et al. Detection of insulin autoantibodies using an ELISA technique in first-degree relatives of IDDM patients and in autoimmune patients. Diabetes Res 1987; 6: 189-94. 3. Tarn AC, Thomas JM, Dean BM, et al. Predicting insulin-dependent diabetes. Lancet 1988; i: 845-50. 4. Kuglin B, Bertrams J, Linke C, et al. Prevalence of cytoplasmatic islet cell antibodies and insulin autoantibodies is increased in subjects with genetically defined high risk for insulin-dependent diabetes mellitus. Klin Wochenschr 1989; 67: 66-73. 5. Atkinson AN, Maclaren N, Riley W, et al. Are insulin autoantibodies markers for insulin dependent diabetes? Diabetes 1986; 35: 894-98. 6. Ziegler AG, Ziegler R, Jackson RA, Eisenbarth GS. Testing the linear destruction hypothesis in type 1 diabetes: the Joslin study. In: Andreani D, Kolb H, Pozzilli P, eds. Immunotherapy of type 1 diabetes. Chichester: John Wiley & Sons, 1989:

1. Duncan H, Kerr D. Toxic psychosis due to isoniazid. Br J Dis Chest 1962; 56: 131-38. 2. Pare CMB. The present state of monoamine oxidase inhibitors. Br J Psychiatry 1985; 146: 576-84. 3. Kottegoda SR. Cheese, wine, and isoniazid. Lancet 1985; ii: 1074. 4. Toutoungi M, Carroll RLA, Enrico JF, Perey L. Cheese, wine, and isoniazid. Lancet 1985; ii: 671.

1. Wilkin

155-67.

PSYCHOSIS AND ANTITUBERCULOSIS THERAPY

SIR,-Dr Ball and Professor Rosser (July 8,

105) report two cases of paranoid psychosis during treatment for tuberculosis (TB) in immigrants to the UK. We have treated two Asian patients who had a clear diagnosis of schizophrenia and later developed TB needing treatment. We report some difficulties in managing psychiatric patients on antituberculous drugs. Patient 1.-A 29-year-old Indian man with a 6-year history of paranoid schizophrenia was admitted following exacerbation of psychotic symptoms. He was treated with neuroleptics and showed a slow improvement. Six weeks after admission acute abdominal symptoms developed, and gastrointestinal TB discovered. He was treated with rifampicin, isoniazid, pyrazinamide, and ethambutol. Three days after beginning these drugs his psychosis worsened. The dose of neuroleptics was increased. After six months antituberculous drugs were stopped and he showed some improvement. Patient 2.-A 59-year-old Mauritian woman with a history of schizo-affective illness was admitted following the relapse of her psychosis. She was treated with a depot neuroleptic and a tricyclic antidepressant and the psychotic symptoms improved. During the admission she was found to have hepatomegaly and abnormal liver function, which proved to be due to tuberculous infiltration of the liver. She was treated with rifampicin, isoniazid, ethambutol, and pyrazinamide, and her antidepressant was stopped in view of possible interaction with isoniazid. She was maintained on the same dose of her depot neuroleptic and showed no overt psychotic p

symptoms. In patient 1 there are two possible explanations for the exacerbation of psychosis related to antituberculous treatment. Isoniazid is a monoamine oxidase inhibitor (MAOI) and Ball and Rosser and others1 have reported that it precipitates a psychosis. Hence it may exacerbate a pre-existing psychosis in predisposed patients. Antituberculous drugs like rifampicin and ethambutol induce liver enzymes, which increase the metabolism of neuroleptics and hence reduce their bioavailability and relative efficacy, which in turn makes it difficult to treat the psychosis. In patient 2 both these mechanisms might have operated. Another problem is highlighted. Interactions between MAOIs and tricyclics have been reported/ and isoniazid is an MAOI. Although we are unaware of any specific reports of interaction between isoniazid and a tricyclic, there have been reports of reactions to cheese with isoniazid .3Hence the concomitant prescription of tricyclics has to be cautious. These two cases highlight difficulties with antituberculous treatment in patients with psychosis. Ball and Rosser’s conclusion

SIR,-Dr Ball and Professor Rosser report paranoid psychosis in

immigrants being treated for tuberculosis. Having worked with thousands of tuberculosis cases in Africa I came across several with psychosis, both ambulatory working patients and hospital patients, most of which were associated with isoniazid. We found that treating adults for only 5 days a week (Monday to Friday) completely eradicated this problem and was in no way detrimental to recovery. This timescale had the added advantages of giving patients on streptomycin a rest from injection and reducing other toxic effects, and nurses did not have to arrange weekend treatment. This, together with intensive short-course therapy, is an ideal way to treat tuberculosis patients, especially those wishing to return to work quickly. two

School Health Service, Douglas, Isle of Man

ZOE VERMAAK AIDS AFTER MONTREAL

SiR,—Your May 20 editorial on the Vth International Conference on AIDS in Montreal, refers to 10000 delegates attending the meeting. Given the resources tied up in arranging and in attending such an event it is justifiable to ask whether such expenditure is appropriate. Despite generous allocations of funds to UK regional health authorities for AIDS, sending someone to Montreal was not thought here in East Anglia to be a proper use of that money. The organisers would argue that the conference provided an opportunity to speed the sharing of information: meeting others involved in AIDS control programmes creates networks where the interchange of knowledge and good models of practice can readily take place. But in 1989 is that enough to justify such jamborees? The response to AIDS has covered the whole spectrum from apathy, through denial and stigmatisation, to what may be described as a global panic attack. The good intentions expressed at the World Summit of Ministers of Health in January, 1988, have been largely diluted by the pressures on governments and international and non-governmental organisations to maintain a high profile. Political influences make it impossible for even the best motivated organisations to avoid making appearances their main priorities-and these include being seen at Montreal. In Africa, some surveys of selected population groups, not specifically "high risk", in urban areas have shown that 20% of men and women are HIV positive. The continent’s economic debt is now three times greater than its export earnings. In countries such as Zambia per caput spending on education has fallen by 60% in a decade; and in Africa there is a desperate shortage of basic equipment for managing the AIDS epidemic, such as rubber gloves, drugs, and other supplies, let alone personnel. The pattern of the AID S epidemic in Africa is very different from that in Europe and North America. The cost of sending a delegate to Montreal from the UK would be about ,E 1000: if that were an average cost worldwide, 10 000 delegates would have cost ,E10 million. Your account questions the real commitment to prevention shown by health professionals. The response to AIDS in the UK has been inappropriately dominated by a mass-media campaign which has detracted energy and resources, and eventually credibility, from the development of communiy-based health education programmes. The international response is in danger of similarly going adrift. Instead of espousing the principles of Health