810 thus potentially carcinogenic) viral material. It will also be necessary to search for and identify all the H.s.v.s which can infect the genital area in man (H.S.V.-2, H.s.v.-1, and cytomegalovirus"), all of these viruses possess carcinogenic potential. The male has to be the first 12 target in this investigation.9 Another essential measure has to be the treatment of individuals identified during these investigations irrespective of whether they have complaints or visible symptoms. With males this goal seems to be attainable in view of the superficial location of the infection. 13 These measures may play a crucial role in controlling the spread of H.G. as an acute venereal disease and be an essential step in controlling the development of cancer of the cervix. However, no such programme can solve the problem completely. For example, it cannot eradicate the latent virus in patients who are already infected, and it is also possible that a carcinogenic form of H.S.V. may develop in the female. Thus, further studies of methods for the treatment and eradication Of H.G. are needed.
INTERACTION BETWEEN CARBAMAZEPINE AND
complete (non-multiplying and
’
Leningrad Nuclear Physics Institute, Academy of Sciences of the U.S.S.R., A. YABROV* Leningrad, U.S.S.R. "Present address: Department of Medical Microbiology, Banting Institute, University of Toronto, Toronto, Ontario, Canada.
TRIACETYLOLEANDOMYCIN
SiR,—The only well-known interaction between antibiotic antiepileptic drug is that between isoniazid and phenytoin;’ patients on phenytoin who are given isoniazid get toxic symptoms and their phenytoin blood-levels rise sharply. Chlorand
amphenicol is also said to have been responsible for increasing on the other hand, oxacillin is reported phenytoin blood level;2 3
lower blood-levels. We have seen clinical signs of carbamazepine-induced intoxication in patients on triacetyloleandomycin. Eight regularly to
visited
epileptic patients treated
with carbamazepine were for mild infections, and within given triacetyloleandomycin 24 h all of them had disturbed balance, nausea, vomiting, and pronounced drowsiness. In six cases these symptoms were reported shortly after recovery, but in two we were able to examine the patient during the toxic period and obtained evidence of a cerebellolabyrinthic syndrome with nystagmus and electroencephalographic slowing of rhythms like that in drug overdosage. We measured antiepileptic-drug blood levels for both patients.
LACTOSE-HYDROLYSED MILK
SIR,-Dr Mitchell and his colleagues (March 5, p. 500)
underweight infants with diarrhoea gained signifiweight if fed a lactose-hydrolysed milk (containing cantly glucose and galactose) rather than full-cream milk powder.2 They thus confirm our observations in Apache children 1 given glucose-containing milk or electrolyte formulas or more complex sugar-milk formulas, and in Filipino children3 whom we treated with food and a glucose-electrolyte oral solution or showed that more
,
with food and clear fluids alone. In both studies children getting glucose-containing solutions gained significantly more weight after the diarrhoea stopped. Since actively transported sugar monomers improve salt and water absorption in the intestine even during diarrhrea,4 we believe these children’s appetites were restored by the quick replacement of lost fluid volume and electrolytes.
Cambridge,
NORBERT HIRSCHHORN
ŒSOPHAGEAL ULCERATION DUE TO EMEPRONIUM BROMIDE
SIR,-Dr Kavin (Feb. 19, p. 424) will be happy to know that emepronium bromide already is on "the list of drugs which cause odynophagia and resophageal ulceration", at least as far as readers of The Lancet are concerned.Since our original report we have seen three other patients with oesophageal ulceration from emepronium bromide tablets, and are engaged in correspondence with the Committee on Safety of Medicines on this subject. Gastro-intestinal unit, Hull Royal Infirmary, Hull HU3 2JZ
plasma levels of phenobarbitone (o) and carbamazepine (*) during administration of triacetyloleandomycin.
Daily oral doses: phenobarbitone 150 mg; carbamazepine 400 mg Sept. 28 and 800 mg thereafter; triacetyloleandomycin 2 g Oct.
before 9-12.
sharp increase in carbamazepine once triacetyloleandomycin was withdrawn (see figure). The decrease in phenobarbitone plasma level coincided with the rise in carbamazepine. In the first
Management
Sciences for Health, Massachusetts 02142, U.S.A.
Variation in
JOHN R. BENNETT
case
there
was a
concentration, and a rapid fall
In the second case the measurements were done 48 h after withdrawal of the antibiotic while the clinical signs were disappearing. At that time the carbamazepine concentration was 10 2 [xg/ml; it then fell to 6.9p.glml, the daily dose being unaltered. We did not study carbamazepine metabolites m blood, urine, or fxces so we can only speculate about the mechanism of this drug interaction. All we know about hepatic metabolism of triacetyloleandomycin and carbamazepine leads us to think that an enzymatic interaction responsible for a slowing of carbamazepine metabolism may occur in the hepatic cetl. The rapid appearance of symptoms of toxicity (only a few hours after antibiotic treatment began) supports such a mechanism. The possibility of interaction must be thought of every time a 1.
Kutt, H.
Antiepileptic Drugs (edited by D. M. Woodbury, J. K. Penry, Schmidt); p. 169. New York, 1972. Christensen, L. K., Skousted, L. Lancet, 1969, ii, 1397. Fincham, R. W., Wiley, D. E., Scholttelius, D. D. Neurology, 1976, 26, in
and R. P.
11. 12.
Sabin, A. B. Adv. Pathobiol. 1976, 5, 53. Rawls, W., Laurel, D., Melmck, J., Gliresman, J., Kaufman, R. Am. J. Epidemiol. 1968, 87, 647. 13. Alford, C., Whitley, R. J. infect. Dis. 1976, 133, suppl. P, A101. 1. Hirschhorn, N., Cash, R. A., Woodward, W. E., Spivey, G. H. Lancet, 1972, ii, 15. 2. Hirschhorn, N., Denny, K. M. Am. J. clin Nutr. 1975, 28, 189. 3. International Study Group Bull. Wld Hlth Org. (in the press). 4. Lancet, 1975, i, 79. 5. Habeshaw, T., Bennett, J. R. Lancet, 1972, ii, 1422.
2. 3.
879-81. 4
Frigerio, A., Morselli, P. L. in Complex ment; p. 294. New York, 1975.
Partial Seizures and Their Treat-
5. Garaci, E., Djaczenko, W., Genazzani, E. Ann. Sclavo. 1973, 15, 281. 6. Garaci, E., Djaczenko, W., Genazzani, E. ibid. p. 299. 7. Genazzani, E. Acta ther. 1975, 1, 115. 8 Morselli, P. L. in Complex Partial Seizures and Their Treatment (edited by J. K. Penry and D. D. Daly); p. 279. New York, 1975.
INTERACTION BETWEEN CARBAMAZEPINE AND
complete (non-multiplying and
’
Leningrad Nuclear Physics Institute, Academy of Sciences of the U.S.S.R., A. YABROV* Leningrad, U.S.S.R. "Present address: Department of Medical Microbiology, Banting Institute, University of Toronto, Toronto, Ontario, Canada.
TRIACETYLOLEANDOMYCIN
SiR,—The only well-known interaction between antibiotic antiepileptic drug is that between isoniazid and phenytoin;’ patients on phenytoin who are given isoniazid get toxic symptoms and their phenytoin blood-levels rise sharply. Chlorand
amphenicol is also said to have been responsible for increasing on the other hand, oxacillin is reported phenytoin blood level;2 3
lower blood-levels. We have seen clinical signs of carbamazepine-induced intoxication in patients on triacetyloleandomycin. Eight regularly to
visited
epileptic patients treated
with carbamazepine were for mild infections, and within given triacetyloleandomycin 24 h all of them had disturbed balance, nausea, vomiting, and pronounced drowsiness. In six cases these symptoms were reported shortly after recovery, but in two we were able to examine the patient during the toxic period and obtained evidence of a cerebellolabyrinthic syndrome with nystagmus and electroencephalographic slowing of rhythms like that in drug overdosage. We measured antiepileptic-drug blood levels for both patients.
LACTOSE-HYDROLYSED MILK
SIR,-Dr Mitchell and his colleagues (March 5, p. 500)
underweight infants with diarrhoea gained signifiweight if fed a lactose-hydrolysed milk (containing cantly glucose and galactose) rather than full-cream milk powder.2 They thus confirm our observations in Apache children 1 given glucose-containing milk or electrolyte formulas or more complex sugar-milk formulas, and in Filipino children3 whom we treated with food and a glucose-electrolyte oral solution or showed that more
,
with food and clear fluids alone. In both studies children getting glucose-containing solutions gained significantly more weight after the diarrhoea stopped. Since actively transported sugar monomers improve salt and water absorption in the intestine even during diarrhrea,4 we believe these children’s appetites were restored by the quick replacement of lost fluid volume and electrolytes.
Cambridge,
NORBERT HIRSCHHORN
ŒSOPHAGEAL ULCERATION DUE TO EMEPRONIUM BROMIDE
SIR,-Dr Kavin (Feb. 19, p. 424) will be happy to know that emepronium bromide already is on "the list of drugs which cause odynophagia and resophageal ulceration", at least as far as readers of The Lancet are concerned.Since our original report we have seen three other patients with oesophageal ulceration from emepronium bromide tablets, and are engaged in correspondence with the Committee on Safety of Medicines on this subject. Gastro-intestinal unit, Hull Royal Infirmary, Hull HU3 2JZ
plasma levels of phenobarbitone (o) and carbamazepine (*) during administration of triacetyloleandomycin.
Daily oral doses: phenobarbitone 150 mg; carbamazepine 400 mg Sept. 28 and 800 mg thereafter; triacetyloleandomycin 2 g Oct.
before 9-12.
sharp increase in carbamazepine once triacetyloleandomycin was withdrawn (see figure). The decrease in phenobarbitone plasma level coincided with the rise in carbamazepine. In the first
Management
Sciences for Health, Massachusetts 02142, U.S.A.
Variation in
JOHN R. BENNETT
case
there
was a
concentration, and a rapid fall
In the second case the measurements were done 48 h after withdrawal of the antibiotic while the clinical signs were disappearing. At that time the carbamazepine concentration was 10 2 [xg/ml; it then fell to 6.9p.glml, the daily dose being unaltered. We did not study carbamazepine metabolites m blood, urine, or fxces so we can only speculate about the mechanism of this drug interaction. All we know about hepatic metabolism of triacetyloleandomycin and carbamazepine leads us to think that an enzymatic interaction responsible for a slowing of carbamazepine metabolism may occur in the hepatic cetl. The rapid appearance of symptoms of toxicity (only a few hours after antibiotic treatment began) supports such a mechanism. The possibility of interaction must be thought of every time a 1.
Kutt, H.
Antiepileptic Drugs (edited by D. M. Woodbury, J. K. Penry, Schmidt); p. 169. New York, 1972. Christensen, L. K., Skousted, L. Lancet, 1969, ii, 1397. Fincham, R. W., Wiley, D. E., Scholttelius, D. D. Neurology, 1976, 26, in
and R. P.
11. 12.
Sabin, A. B. Adv. Pathobiol. 1976, 5, 53. Rawls, W., Laurel, D., Melmck, J., Gliresman, J., Kaufman, R. Am. J. Epidemiol. 1968, 87, 647. 13. Alford, C., Whitley, R. J. infect. Dis. 1976, 133, suppl. P, A101. 1. Hirschhorn, N., Cash, R. A., Woodward, W. E., Spivey, G. H. Lancet, 1972, ii, 15. 2. Hirschhorn, N., Denny, K. M. Am. J. clin Nutr. 1975, 28, 189. 3. International Study Group Bull. Wld Hlth Org. (in the press). 4. Lancet, 1975, i, 79. 5. Habeshaw, T., Bennett, J. R. Lancet, 1972, ii, 1422.
2. 3.
879-81. 4
Frigerio, A., Morselli, P. L. in Complex ment; p. 294. New York, 1975.
Partial Seizures and Their Treat-
5. Garaci, E., Djaczenko, W., Genazzani, E. Ann. Sclavo. 1973, 15, 281. 6. Garaci, E., Djaczenko, W., Genazzani, E. ibid. p. 299. 7. Genazzani, E. Acta ther. 1975, 1, 115. 8 Morselli, P. L. in Complex Partial Seizures and Their Treatment (edited by J. K. Penry and D. D. Daly); p. 279. New York, 1975.
