SIDE-EFFECT OF THIOCARBAMIDES

231

standard deviation and standard

summarisation is

to

of the mean for data all make an effort to convey and then present them unerror

continue, that

understand what they

we

ambiguously. Community Medicine, University of Southampton, Southampton General Hospital, Southampton S09 4XY.

M.

J. GARDNER.

steroids or anticoagulants. Although we treated the patient with azathioprine, treatment was started when the renal function was already improving. Successful treatment of non-responders by anticoagulants2 and large doses of steroids3 has been reported. We suspect that in our patient, return to normal renal function was spontaneous and independent of the treatment given. We doubt whether azathioprine was of any benefit to our patient. Medical

ACUTE OLIGURIC GLOMERULONEPHRITIS SIR,-Brown et al.l assessed the value of immuno-

suppression and anticoagulants in the treatment of rapidly They claimed that progressive glomerulonephritis. oliguric or anuric patients with a renal-biopsy specimen showing more than 62% crescents, and in whom poststreptococcal glomerulonephritis can be excluded, do not respond to chemotherapy and invariably-if they surviverequire regular dialysis treatment or transplantation. Lately we have treated a patient of the type that Brown et al. regard as a non-responder to treatment. A man, aged 53, was admitted to hospital on Nov. 8, 1973, with general malaise, back pain, and dyspepsia. We found that he was in acute renal failure with oliguria (diuresis less than 400 ml. per 24 hours), and hsmodialysis was started immediately because his blood-urea was 295 mg. per 100 ml. Urine output was less than 300 ml. per 24 hours for the first 4 days. Bloodpressure was 170/90 mm. Hg. Renal biopsy performed Nov..13 showed extracapillary glomerulonephritis (30 glomeruli with over 80% crescents), and, although the urinary output was increasing, azathioprine was started. At this time steroids were not given, since a duodenal ulcer was suspected. After a week the patient had a creatinine clearance of over 5 ml. per minute and hoemodialysis became unnecessary. Although renal function improved steadily, his condition remained critical because of severe gastrointestinal bleeding. The patient underwent an exploratory laparotomy, but the bleeding site was not found. A barium enema showed signs compatible with ulcerative colitis and a course of steroid treatment was begun on Nov. 26, 1973, for 10 days. His condition improved and creatinine clearance was 51 ml. per minute 3 weeks after admission. The patient was discharged, but treatment with azathioprine (150 mg. per day) was continued. During the next 6 months renal function improved (creatinine clearance 85 ml. per minute). In June 6, 1974, a new renal biopsy was performed. 50% of the glomeruli were totally sclerosed and the rest showed minor alterations with thickening of the basement membranes

(15 glomeruli were examined).

Laboratory values at the time of admission were: erythrocyte sedimentation-rate 74 mm. per hour, haemoglobin 12-7 g. per 100 ml.,

per ,1., thrombocytes 308,000 per 295 mg. per 100 ml., serum-creatinine 13-1 mg. per 100 ml., serum-potassium 6-6 meq. per litre, serum-sodium 138 meq. per litre, standard bicarbonate 10-4 meq. per litre, serum-protein 70 g. per 100 ml., plasma-albumin 32 g. per litre, complement C3 0-51 g. per litre (range 0-5-1-2), plasmafibrinogen 47 g. per litre (range 2-4-4-9), IgG 9-4 g. per litre (range 58-143), IgA 1-4 g. per litre (0-6-3-4), IgM 0-5 g. per

nl.,

leucocytes 18,800

serum-urea

litre (range 0-3-1-5), prothrombin-time 125%, antistreptolysin titre 30 E per ml., antinuclear factor none, R.A.T. negative, Wasserman reaction negative, Yersinia enterocolitica titre 0, bone-marrow normal. A renal-biopsy specimen taken on Nov. 13, 1973, consisted of 30 glomeruli with more than 80% crescents and no signs of arteritis. Immunofluorescence showed deposition of small amounts of IgG, IgM, IgA, and complement C3 in the glomeruli. The fluorescence was of fine granular type.

Our patient presented with oliguria and renal insufficiency enough to require five hsemodialyses in the first week. The criteria for extracapillary glomerulonephritis were fulfilled. Since the antistreptolysin 0 titre was normal and remained so, poststreptococcal glomerulonephritis can be excluded. This case shows that such patients can regain almost normal renal function even without treatment with

severe

Kommunehospitalet, Copenhagen, Denmark.

Brown, C. B., Wilson, D., Turner, D., Cameron, J. S., Ogg, C. S., Chantler, C., Gill, D. Lancet, 1974, ii, 1167.

BIRGER BROCH MØLLER

HENNING JANS.

FETO-FETAL TRANSFUSION AND SINGLE UMBILICAL ARTERY SIR,—This year I have seen two examples of the fetofetal transfusion syndrome in which the recipient twin had only one umbilical artery, whereas the donor had the normal complement of vessels in the umbilical cord. There is still some doubt as to the incidence of single umbilical artery in multiple pregnancy,4 but most authors agree that it is more common for the lighter of the two infants to be affected,4whereas in these cases both recipient twins were considerably heavier than their respective donors. As the feto-fetal transfusion syndrome is comparatively rare, it is possible that a real association with single umbilical artery has not been recognised and I should be very interested to hear of any further cases. The exact mechanism of the twin-to-twin transfusion is still uncertain, and no clue to its aetiology should be missed. Department of Pædiatrics and Neonatal Medicine Hammersmith Hospital, Du Cane Road, London W12.

ELIZABETH BRYAN.

SIDE-EFFECT OF THIOCARBAMIDES

SIR,—Two females, aged 28 and 52 years, experienced loss of taste (one also of smell) during treatment with thiamazole and carbamizole, respectively. No other drug could be blamed. In one of the patients, withdrawal of the treatment was followed by complete return to normal taste (i.e., ability to taste sour, salt, sweet, and bitter) while in the other patient taste and smell disturbances still persist one year after the treatment was stopped. The thyroid gland is the first endocrine gland to appear during phylogenesis. It has a close anatomical and phylogenetic relationship to the salivary glands and the taste apparatus in the oropharynx. We suggest that taste cells may have the same reactions towards enzyme blockers as .do thyroid cells, and that taste disturbances, albeit very mild, may be quite common in patients treated with This side-effect has previously been thiocarbamides. reported but is poorly appreciated. The bitter-tasting chemical phenylthiocarbamide (P.T.C.) is tasted strongly by 70% of Europeans and not at all by 30%. There is an increased frequency of tasters in thyrotoxicosis ; in atoxic goitre (especially in males) there is a reverse relationship as there is in endemic athyroid cretinism (as well as in the parents of these individuals). The active thiocarbamide is thiamazole, which contains an -SHgroup. -SH groups combine with heavy-metal ions of which Zn++ may be of importance in this connection. Removal of zinc from the organism may cause loss of Kincaid-Smith, P., Saker, B. M., Fairley, K. F. ibid. 1968, ii, 1360. Nakamoto, S., Dunea, G., Kolff, W. J., McCormack, L. J. Ann. intern. Med. 1965, 63, 359. 4. Bryan, E. M., Kohler, H. G. Archs Dis. Childh. 1974, 49, 844. 2. 3.

1.

Department III,

Renal Unit,

232 taste and treatment

smell ability. Loss of taste is also seen during with penicillamine, a chelating agent with an active -SH group. On treatment with zinc, taste returns. We suggest that thiocarbamides act on taste cells as well as the thyroid, inhibiting related enzymes. The active -SH group may remove zinc. This would explain the taste disturbances during treatment with thiocarbamides. Subtle taste disturbances may be quite common in individuals treated with thiocarbamides. Medical Department B,

JAN ERIKSSEN

Rikshospitalet, Oslo, Norway. Pharmacological Department, University of Oslo.

ERIK SEEGAARD. KNUT NAESS.

When nerve section is proved to be complete on the oesophagus in proximal gastric (highly selective) vagotomy, ulceration does not occur, and there is no need to define the junction of the gastric antrum and body. Johnston in Leeds and I in London have evidence of this in at least recurrent

600 cases over 5 or 6 years. There is, therefore, no evidence that G-cell antral hypertrophy is the cause of recurrent ulceration. We must not forget that at least 50% of all vagotomies in England and in other countries are incomplete on the oesophagus. It was indeed sad for me to have to operate recently on a 26-yearold man with severe recurrent duodenal ulceration and

hxmorrhage following

a

grossly incomplete vagotomy peran important university centre. was easily completed using the

formed without a test in His incomplete vagotomy test.

PARVOVIRUS-LIKE PARTICLES IN HUMAN SERA SIR Following the communication by Dr Cossart and her colleagues1 describing 23 nm. parvovirus-like particles in serum, we should like to comment on the relationship between these particles and the 22 nm. particles which we found in fxces from patients with gastroenteritis and normal subjects in 1973,2 and subsequently compared with known animal parvoviruses.3 Particles similar in size and morphology have since been detected in human fxcal extracts by Dr Flewett and his colleagues4 and Dr Almeida and her 5

colleagues. Dr Cossart has

shall, I am sure, enjoy Professor Allgower’s work proving the importance and simplicity of the electrical stimulation test when he publishes his results soon. I am sure you will agree that a test at operation is We

essential. As you say, proximal gastric vagotomy without drainage is the best operation for gastric ulcer; although there are To use proximal gastric vagotomy difficult problems. without drainage both for duodenal ulcer and for gastric ulcer is one of the greatest advances in the whole history of

gastric

surgery. Charing Cross Hospital, London W6 8RF.

kindly supplied

us

with

some

virus-containing serum, and we have compared her particles with our faecal virus particles by immunoelectron microscopy with a panel of 50 sera from children between the ages of 10 and 15 years. Preliminary results show that these two antigens are identical in size, morphology, and buoyant density, but are serologically distinct. A more detailed analysis of our results will be published shortly. W. K. PAVER Public Health Laboratory, E. O. CAUL Myrtle Road, Kingsdown, S. K. R. CLARKE. Bristol BS2 8EL.

FEBRILE CONVULSIONS AND PINK DRUMHEADS SIR The finding of a pink tympanic membrane at the initial hospital examination in a child admitted following a febrile convulsion is often taken as an indication for antibiotic therapy. The policy of withholding such treatment in the absence of definite evidence of pyogenic infection has been adopted at the Royal Alexandra Hospital,

Brighton, in VAGOTOMY was surprised that you should have written the article (Jan. 18, p. 149) without dealing adequately leading with the problem of incomplete nerve section on the cesophagus. I am surprised, too, that you should not have stressed the importance of a test for completeness during

SIR,-I

operation. My studies of the results of vagotomy with the electrical stimulation test in some 1500 cases over 17 years have shown that recurrent duodenal ulceration does not occur if nerve section on the oesophagus is proved complete with the test to a sensitivity of 1 mm. of water pressure-except, of course, in patients with the Zollinger-Ellison syndrome. Professor Allgower and his colleagues in their important work on the Burge electrical stimulation test in Basle have confirmed that it must be used to this sensitivity. They have found, as I have, that surgeons greatly experienced in vagotomy fail without a test to achieve completeness of nerve section on the oesophagus in some 30% of their cases. They have found, as I have, that less experienced surgeons fail in perhaps 70%. Cossart, Y. E., Cant, B., Field, A. M., Widdows, D. Lancet, Jan. 11, 1975, p. 72. 2. Paver, W. K., Caul, E. O., Ashley, C. R., Clarke, S. K. R. ibid. 1973, i, 237. 3. Paver, W. K., Caul, E. O., Clarke, S. K. R. J. gen. Virol. 1974, 22, 1.

447. 4. 5.

Flewett, T. H., Bryden, A. S., Davies, H. J. clin. Path. 1974, 27, 603. Almeida, J. D., Deinhardt, F., Zuckerman, A. J. Lancet, 1974, ii, 1083.

HAROLD BURGE.

of her

recent years.

135 -admissions for febrile convulsions twelve months. The appearance of the child’s drumheads was noted and recorded on admission, and this was repeated daily thereafter using one of the following descriptive categories: normal; pink; abnormal -i.e., clear evidence of otitis media. When there was doubt about the abnormality either a second opinion was sought or appropriate treatment for otitis , media was begun without delay. In 30 children the tympanic membranes were " pink " on admission (sometimes only one side affected). However, 8 of these had clear evidence of pyogenic infection elsewhere (e.g., exudative tonsillitis, pneumonia, urinary-tract infection), and accordingly they were started on an antibiotic. Such treatment was withheld in the remaining 22. 16 of these 22 had associated flushing of the fauces. The clinical progress of the 22 children was uneventful. 19 were afebrile and back to normal within forty-eight hours of admission and the remaining 3 by the fifth hospital day. The slight ear changes quickly resolved without antibiotic therapy and none developed otitis media. The redness of the fauces also quickly receded in the 16 affected children. In all, antibiotic therapy was introduced, or a course begun by a general practitioner maintained, in only 46 (34%) of 135 admissions. These observations suggest that pink drumheads in a child shortly after a febrile convulsion should not be uncritically labelled otitis media and an antibiotic prescribed. The ear changes may possibly be related in some way to the recent convulsion or result from hyperæmia of There

during

were

a recent