Discussion The only two viral infections presenting problems in these patients receiving long-term immunosuppression were shingles and warts. No increase in the number of colds or cold sores occurred, nor was there any remarkable increase in non-specific febrile illness. Of the six patients who had had shingles, three had had early infections-that is, within the first three months after transplantation-while three had had late infections-that is, over three years after transplantation. In all the course was typical and benign. This bi-peaked incidence may indicate two different mechanisms. In a previous study2 we found that two out of seven cases of shingles appeared within the first three months, while four occurred from one and a half to two and a half years after transplantation. Our findings are the same in patients receiving long-term and short-term immunosuppression with regard to the great prevalence of warts in these patients.2

6 OCTOBER 1979

No late cases of cytomegalovirus disease were seen, and patients who were seronegative three months after transplantation remained so during the whole period of observation (six to 13 years). The high titres seen shortly after immunosuppressive treatment was started remained high for years. Even though titres were high, virus excretion was rare, indicating that chronic cytomegalovirus infection in these patients is immunologically

well controlled.

References 1Andersen, H K, and Spencer, E S, Acta Medica Scandinavica, 1969, 186, 7. 2Spencer, E S, and Andersen, H K, British Medical3Journal, 1970, 3, 251. 3Spencer, E S, Scandinavian Journal of Infectious Diseases, 1974, 6, 315. 4Moller-Larsen, A, et al, Intervirology, 1976, 6, 249. (Accepted 31 July 1979)

SHORT REPORTS Oxamniquine fever-drug-induced or immune-complex reaction?

this immunological event. Further investigation is needed to ascertain the presence of either endogenous pyrogen in such patients' plasma or oxamniquine metabolites that can cause fever.

Oxamniquine, a new schistosomicidal drug, is effective against schistosomiasis mansoni; it is given by mouth in a dose of 20-30 mg/kg/day for three days. The most common side effects are dizziness, drowsiness, and headache.1 We report an additional side effectnamely, a characteristic fever-which occurred in 40 out of 106 patients (3800) given oxamniquine during the past three years. In most cases the temperature rose to 38-39-C 24-72 hours after completing the three-day course and lasted two to five days before defervescence. Six of the 40 patients also developed a typical Lofflerlike syndrome, with fever, pronounced peripheral blood eosinophilia, and scattered pulmonary infiltrates. Thirty-seven of the 106 treated patients were studied immunologically in an attempt to explain this febrile reaction.

This work formed part of research project MRO41.09.01-0153, NMRDC, NNMC, Bethesda, Md 20014.

Methods and results Thirty-seven male patients aged 7-50 years with varying excretion rates of Schistosoma mansoni eggs (100-2560/g faeces) were studied immunologically. Seventeen of the patients had developed the typical febrile reaction after treatment and 20 (serving as controls) had not. Urinary excretion of schistosomal antigens was assayed by a template agar microimmunodiffusion method2 using rabbit antiserum to homologous adult worm extract. All urine specimens were concentrated 30-50-fold by membrane filtration. The presence of serum circulating immune complexes was assessed by a polyethylene glycol precipitation technique.3 All serum samples were assayed at 1/5 dilution in saline, at which dilution normal samples were negative. Specimens of urine and serum were obtained on admission, on days 3 and 14 of treatment, and on discharge. Of the 37 patients, 23 had increased excretion of antigens (up to five immunoprecipitin bands) in the urine and an increase in immune complexes (optical density 280 nm, 0 150-0-275) in the serum but only 12 of the 23 patients developed the febrile reaction; the other 11 (though showing similar increases in antigen excretion and serum immune complexes) did not develop post-treatment fever.

'Omer, A H S, British Medical_Journal, 1978, 2, 163. 2Crowle, A J, Imnrnunodizffusion, 2nd edn, p 289. New York, Academic Press, 1975. 3Digeon, M, et al, ournal of Immnunological Methods, 1977, 16, 165. 4Foster, R, Revista do Instituto de Medicina Tropical de SSo Paulo, 1973, 15, suppl No 1, p 1. 5 Coutinho, A, Domingues, A L C, and Bonfim, J R A, Revista do Instituto de Medicina Tropical de Sro Paulo, 1973, 15, suppl No 1, p 15. (Accepted 6July 1979) Immunology and Tropical Medicine Departments, United States Naval Medical Research Unit No 3, Cairo, AR Egypt G I HIGASHI, MD, SCD, head of immunology department Z FARID, MD, DTM&H, head of tropical medicine department

Gamma-glutamyltransferase activity in ascitic fluid in diagnosis of hepatocellular carcinoma Peters et al reported' that five patients with hepatoma had highly significantly increased activities of gamma-glutamyltransferase (y-GT) in ascitic fluid compared with 26 patients with ascites associated with other diseases. Since there was no overlap in the two ranges of values they suggested this test as a useful adjunct in the diagnosis of primary liver cancer.

Comment The cause of the fever remains uncertain. In normal, uninfected adults oxamniquine does not invoke fever. I In Brazil and East Africa patients with schistosomiasis mansoni have been treated with oxamniquine with varying results on fever as a side effect. Coutinho et al,5 however, reported the occurrence of fever lasting one to three days in 17 out of 74 patients given oxamniquine but did not emphasise its importance. The high incidence in our series suggests that Egyptian patients handle the drug differently metabolically, leading to a pyrogenic metabolite. Alternatively schistosome immune complexes formed during treatment may bind complement and thus invoke fever. People must differ noticeably, however, in their response to

Patients, methods, and results We studied the y-GT activity in ascites from five patients with hepatocellular carcinoma, 22 with alcoholic liver cirrhosis, and six with miscellaneous liver diseases (one chronic active hepatitis, one haemochromatosis, two cryptogenic inactive cirrhosis, one Budd-Chiari syndrome, and one metastatic liver disease). We used the method recommended by the Scandinavian Committee on Enzymes.2 The table shows that the activity did not differ among the groups. The measurements in the patients with hepatocellular carcinoma were similar to those of Peters et al.1 Our patients, like theirs, all had high serum a-fetoprotein concentrations. None of their patients had alcoholic cirrhosis (one had alcoholic hepatitis). Since alcoholic liver disease is generally associated with high serum y-GT activities



6 OCTOBER 1979

Gamma-glutamyltransferase in ascitic fluid in patients with various liver diseases Diagnosis

Hepatocellular carcinoma Alcoholic cirrhosis Miscellaneous

No of patients 5 22 6

Enzyme activity (U/1) Mean ± SD


24 2 ±16 3 581 ± 83 4 40 0±58 5

9-50 5 8-375


the high activity in ascitic fluid from these patients is not surprising. In fact, the activity in seven of the patients with alcoholic liver disease was higher than the highest activity in the hepatoma group, the highest being in one patient with portacaval shunt established one month previously. Nevertheless, our different findings do not seem to be accounted for solely by our alcoholic patients, since both studies comprised patients with inactive cirrhosis, chronic active hepatitis, Budd-Chiari syndrome, and metastatic

liver disease.

Comment In our experience, therefore, measurement of y-GT activity in ascitic fluid cannot be used to detect hepatocellular carcinoma or to differentiate between different liver diseases. a Scandinavian Committee MedicalyJournal, on Enzymes, ScandinavianJournal of Laboratory

Peters, T J, et al, British

1977, 1, 1576.

Investigation, 1976, 36, 119.

(Accepted 13July 1979) Departments of Medicine and Clinical Chemistry, Sahlgren's Hospital, S-413 45 Gothenburg, Sweden ROLF OLSSON, MD, lecturer in medicine JOHAN WALDENSTROM, MD, lecturer in clinical chemistry

Trauma and severe proliferative retinopathy in diabetes mellitus We describe two young men who developed severe proliferative retinopathy within six months of the diagnosis of diabetes mellitus. Both patients had suffered major trauma before this diagnosis, and we speculate that this may have precipitated the development of their retinopathy.

Case histories Case 1-A 21-year-old restaurant manager was in a car accident in October 1972 and sustained multiple fractures. After admission to hospital he remained drowsy, unwell, and dehydrated. Diabetic ketoacidosis was diagnosed, and he was treated appropriately. He had noted some intermittent blurring of vision during the previous few months, but no retinopathy had been seen on examination. In February 1973 his eyes were re-examined because of severe blurring of vision. Proliferative retinopathy was found and he was referred to the diabetic retinopathy clinic at Hammersmith Hospital. Visual acuity was 6/5 on the right and 6/6 on the left. Examination showed that he had bilateral florid diabetic retinopathy. He was advised to have pituitary ablation, but this resulted in only slight diminution of pituitary gland function and there was no real improvement in the retinopathy; hence further yttrium-90 implantation of the pituitary gland was carried out giving a total dose of 600 000 rads. The retinopathy improved considerably but he retained some new vessels, and photocoagulation was therefore performed. Visual acuity remained normal. Case 2-A 34-year-old lorry driver sustained a fractured pelvis, tibia, and fibula in a road traffic accident in September 1975. While in hospital he complained of intermittent blurring of vision. After discharge this became more severe and severe proliferative retinopathy was noted in both eyes. An oral 50-gn glucose tolerance test was performed. The blood concentrations (mmol/l) were as follows: fasting 7 6; 30 min 9-0; 60 min 111; 90 min 11-0; and 120 min 8 8. Diabetes mellitus was diagnosed. He developed a large vitreous haemorrhage in the left eye and was referred to the diabetic retinopathy clinic at Hammersmith Hospital. His visual acuity was 6/9 in both eyes; ophthalmoscopy showed severe proliferative retinopathy of both discs and retinal periphery, while in the left eye there was also a large preretinal haemorrhage. Because of the severity of the retinopathy the right eye was treated immediately with the xenon arc photocoagulator. Further

treatment was given three and seven weeks later and in all 1696 xenon arc burns resulted in regression of the new vessels in this eye and maintenance of visual acuity at 6/9. A massive vitreous haemorrhage developed one day after the right eye was treated and has not cleared since. The visual acuity has remained around 3/60 to counting fingers since.

Comment The striking feature of these two young men was that they both developed severe diabetic retinopathy shortly after the appearance of diabetes and associated with severe trauma. Severe proliferative and florid retinopathy is rare after so short a duration of diabetes, particularly at this age,' 2 being usually seen in diabetes of longstanding and poor control.' In non-diabetics retinopathy is well described after severe trauma, particularly multiple fractures.4 The question posed by these two cases is whether the retinopathy resulted from diabetes, trauma, or both. Many factors, both genetic and acquired, are probably concerned in diabetic retinopathy, one suggested factor being a disturbance of blood viscosity, which is also affected by severe trauma.' We would speculate, therefore, that trauma, possibly by its effect on blood viscosity, may have been the precipitating factor in producing severe proliferative retinopathy in the susceptible fundi of these two young, newly diagnosed diabetic patients. We thank Dr T D R Hockaday, Dr T M Hayes, and Dr J 0 Williams for permission to report these cases and for their helpful comments. 1 Soler, N G, et al, British Medical,Journal, 1969, 3, 567. 2Steel, J M, Skenfield, G M, and Duncan, L F P, British Medical_Journal, 1976, 2, 852. 3Colwell, J A, Diabetes, 1966, 15, 497. Purtsher, 0, Albrech v. Gracfes Archiv fur ophthalomolgie, 1912, 82, 347. 'Dintenfass, L, Rheology of Blood in Diagnostic and Preventive Medicine. London, Butterworth, 1976.

(Accepted 25_July 1979) Queen Mary's Hospital, Sidcup, Kent DA14 6LT WILLIAM D ALEXANDER, MB, MRCP, consultant physician Hammersmith Hospital, London MARGARET KEARNS, FRACS, research fellow, hon senior registrar EVA M KOHNER, MD, FRCP, consultant physician, hon senior lecturer Radcliffe Infirmary, Oxford C M ASPLIN, MB, MRCP, senior registrar

Normal ileostomy output: close relation to body size What determines the normal ileostomy output for an individual is unknown, but we have suspected for some time that it is related to the size of the patient.' Such a finding would be of importance to clinicians who manage patients with ileostomies but would also have important implications in gastrointestinal physiology. For this reason we studied the relation between various anthropomorphic measurements and the output of ileostomy fluid from a group of healthy patients with well-functioning ileostomies.

Patients, methods, and results We studied 18 healthy patients (10 women, 8 men) aged from 27 to 71 years (mean 50 4 years). Each had had total proctocolectomy for histologically proved ulcerative colitis at least one year previously. None had had an ileal resection greater than 10 cm. The patients were studied out of hospital during their usual daily routine and none were taking any medication. They were asked to collect five consecutive full 24-hour samples of ileostomy fluid, each in a separate polyethylene container supplied to them; to eat their normal diet with the exception of cooked cabbage and prune juice2; and not to disturb their usual routine. Containers were collected each day from their homes. The weight of each daily sample was measured on arrival in the laboratory and the daily ileostomy volume was expressed as the mean measurement for the five consecutive daily collections. The physical characteristics and chemistry of the ileostomy fluid were also measured in each sample. In all collections they were within the published normal range.' At the end of the study the height and weight of the patients were measured

Gamma-glutamyltransferase activity in ascitic fluid in diagnosis of hepatocellular carcinoma.

BRITISH MEDICAL JOURNAL 830 Discussion The only two viral infections presenting problems in these patients receiving long-term immunosuppression wer...
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