275 says: "the results of a recent trial in Glasgow. led to some discussion about the optimum dose of L-tryptophan. This difficulty had arisen because the drug induces the activity of the main degradative enzyme of tryptophan in the liver, tryptophan pyrrolase. Doses of tryptophan over 4 g per day might be self defeating insofar as they result in a more rapid degradation of the amino-acid in the liver". Try as I might, I am unable to see anything in this statement which suggests that tryptophan in doses over 4 g a day seems to provoke depression. What the B.M.J. seems to be saying is that the antidepressive action of L-tryptophan is not enhanced by increasingthe dose beyond the 4 g per day. This statement, which can be justified on theoretical grounds has not, however, been borne out in clinical practice in which a dosage of 6 g of L-tryptophan daily has been shown to be as effective an antidepressant as recommended doses of imipramine and amitriptyline; 1-3 in no case has depression been "provoked".

BM-1. which ...

E. Merck Ltd., Four Marks,

Alton, Hampshire GU34 5HG

ALAN

J. COOPER

*t*We apologise for the misleading reference. In speculating about a possible adverse effect of high doses we had in mind four investigations comparing tryptophan with electroconvulsive therapy. Two of them employed less than 4 g L-tryptophan(or less than 8 g D,L-tryptophan5) daily, and the drug proved at leastaseffective as E.c.T. In the other two the dose of L-tryptophan was over 4 g daily, and the results were inferior to those of E.C.T.;6" a quarter of Carroll’s tryptophan group6 were more depressed at the end of the trial than at the beginning. The editorial suggested a biochemical mechanism whereby a big dose of tryptophan might worsen depression.-ED. L.

ACUTE PERCUTANEOUS PARAQUAT POISONING SIR,-A 44-year-old man using paraquat as a weedkiller did not follow the manufacturer’s instructions and added only eight litres of water to two litres of paraquat. He then used an old sprayer which leaked fluid freely down his neck, back, and legs. After four hours of spraying he complained of a burning feeling on his neck and scrotum. On hospital admission six days later the patient had a cough and respiratory difficulties. X-ray showed no abnormalities but the next day, when his breathing had become worse and he was cyanosed, X-ray showed small speckles with a tendency to coalesce in both lungs. He had a compensated metabolic acidosis and partial respiratory insufficiency with hyposaturation which after an alveocapillary block progressed to a decompensated metabolic and respiratory acidosis and total respiratory insufficiency which required artificial ventilation. Oedema of the lungs appeared and the patient was given corticosteroids, cardiotonics, diuretics, antibiotics, and bicarbonate. The patient’s blood-urea-nitrogen and serum-creatinine raised and protein and red and white blood-cells were found in his urine. He died of renal and respiratory insufficiency three days after admission. At necropsy, there was dry bloody necrosis of the skin at several sites on the neck and scrotum. In the lungs there was oedema and necrotising alveolitis. The kidneys were in a state of shock and showed parenchymal dystrophy. There was steatosis in the liver. This case shows that paraquat can be absorbed by healthy were

1. Jensen, K. and others. Lancet, 1975, ii, 920. 2. Rao, B., Broadhurst, A. D. Br. med. J. 1976, i, 460. 3. Herrington, R. N. and others. Psychol. med. 1976, 6, 673. 4. Coppen, A., Shaw, D. M., Herzberg, B., Maggs, R. Lancet, 1967, ii, 1179. 5. MacSweeney, D. A. ibid. 1975, ii, 510. 6. Carroll, B. J., Mowbray, R. M., Davies, B. ibid. 1970, i, 967. 7. Herrington, J. N., Bruce, A., Johnstone, E. C., Lader, M. H. ibid. 1974, ii,

731.

skin with fatal consequences especially if it is according to the manufacturer’s instructions. Trenčin Hospital, Osvienčimská 1960-II-12, Czechoslovakia

not

diluted

FRANTISEK JAROŠ

ADVERSE REACTIONS TO DRUGS

SIR,-Your editorial referring

to my letter (Jan. 21 issue) concerned with the case for post-marketing surveillance for adverse reactions and with encouraging clinicians to report possible adverse responses to drugs. I support both these concepts, and was disappointed at the indirect inference that I wished to modify your practice and suppress communication about adverse effects. I wrote my letter because I have been concerned about the reactions from individual clinicians to reports in The Lancet of isolated incidents suggesting adverse effects. Clinicians tend to consider the appearance of a letter or other report in The Lancet as firm evidence of an established side-effect of a drug. The real situation is that these reports are usually preliminary, and further inquiry often totally alters the interpretation. I did not intend to suggest that information should be suppressed : on the contrary I would like to encourage disclosure of possible side-effects by exposure in The Lancet and their reporting to the Department of Health and the manufacturing pharmaceutical company’s medical director. However, I would prefer them to be presented in a way which does not unnecessarily alarm or confuse the reader. was

Research Institute, Smith Kline & French Laboratories Ltd, Welwyn Garden City, Hertfordshire

W. L. BURLAND

SiR,-Surely the point at issue on small numbers of individual reports is that they are of suspected adverse reactions? 11 Castle Hill Avenue, Berkhamsted, Herts. HP4 1HJ

S. RUTTLE

ACUTE CHOLANGITIS AFTER ALLOPURINOL TREATMENT

SIR,-A 48-year-old Yugoslavian mason presented with a dragging pain in his groin and hip. His E.S.R. was raised and his erythrocyte count low. Renal insufficiency due to chronic nephritis was diagnosed on biochemical, X-ray, and sonographic findings. His serum-uric-acid was raised. 300 mg allopurinol daily was given and, 3 weeks after admission, amoxycillin was added (250 mg, 3 times daily). 10 days later, the patient had maculous exanthema of the trunk and the adjacent extremities typical of skin sensitivity to ampicillin, with facial oedema and fever. Amoxycillin, but not allopurinol, was stopped and no other antibiotic was given for 10 days. The fever subsided during the following week and blood and urine cultures were sterile. Fever then reappeared, the exanthema began to scale, and eczema appeared on palms and soles and ulcers in the oral mucosa. 12 days after amoxycillin was stopped there was a 10% eosinophilia which, during the next 10 days, increased to 45% and subsequently decreased. At its onset, the serum-bilirubin was normal (1.1 mg/dl) but after 4 days the concentration was 3-35 mg/dl total (direct, 2.97). During the next few days the patient had an acute abdomen. This improved without surgery which was contraindicated because of renal insufficiency (which required dialysis) and sepsis. Laparoscopy was done. Bilirubin was 7.69 mg/dl (direct 6.4). Serum-glutamic-oxaloacetic-transaminase (S.G.O.T.) was 62 units/1 and serum-glutamic-pyruvic transaminase (S.G.P.T.) was 134 units/I, compared wÎ.þ. 27 and 11 units/I, respectively, on admission. Biopsy specimens of the liver showed disseminated parenchymal damage with signs of severe eosinophilic

Acute percutaneous paraquat poisoning.

275 says: "the results of a recent trial in Glasgow. led to some discussion about the optimum dose of L-tryptophan. This difficulty had arisen because...
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