1082 to

trimethoprim

strains

were

from

eight

selected E. coli and Klebsiella

unsuccessful, though all transferred resistance

to sulphamethoxazole. 16 of the 25 resistant E. coli and Klebsiella species isolated in 1977 were from patients with indwelling catheters who had had prior treatment with co-trimoxazole. C. A. HART M. F. GIBSON Department of Pathology, E. MULVIHILL David Lewis Northern Hospital, H. T. GREEN Liverpool L3 6AU

PLATELET MONAMINE OXIDASE IN SCHIZOPHRENIA

SIR,—Dr Belmaker and his colleagues (Oct. 15, p. 821) report an increase in the Michaelis constant (Km) for benzylamine for monoamine oxidase (M.A.O.) in platelets from drugfree schizophrenic patients, and suggest that this change in Km could explain the discrepant findings’’’ about platelet M.A.o. activity in schizophrenia. This seems unlikely. In their original observations on platelet M.A.O. in schizophrenia Murphy and Wyatt1 used 14C-tryptamine as substrate at a concentration approximately 4 times the Km reported by Robinson et al.8 and Berrettini et al. From the Michaelis equation it can be deduced in these circumstances that a two-fold increase in Km (as suggested by the results of Belmaker et al.) would result in a less than 20% decrease in reaction velocity, rather than the 50% change reported by Murphy and Wyatt.’ Moreover in this study patients were receiving neuroleptic medication and, according to Belmaker et al., this may have the effect of returning Km values towards normal. In our own study3 of platelet M.A.o. activity in chronic unmedicated schizophrenic patients we used 14C-tyramine and 14C-tryptamine as substrates at 1 mmol/1 concentrations (approximately 20 and 55 times the Km values reported by Robinson et aI.8,9). We found no significant differences in platelet M.A.o. between patients and controls. At these substrate concentrations two-fold changes in Km values would have a negligible effect. Nevertheless, with the same substrates at the same concentrations, Meltzer and StahP reported a significant reduction in platelet M.A.o. in drug-treated chronic

For these reasons we feel that a simple molecular aberration of brain M.A.o. in schizophrenia is unlikely. The reasons for the discrepant findings on platelet M.A.o. in this disease remain obscure

F. OWEN

A. J. CROSS T. J. CROW E. C. JOHNSTONE

Division of Psychiatry, Clinical Research Centre, Harrow, Middlesex HA1 3UJ

R. LOFTHOUSE G. J. RILEY

PROPRANOLOL IN CHRONIC SCHIZOPHRENIA

SIR,-We thank your correspondents for their comments about our 12-week controlled study from which we conclude that propranolol helped patients with long-standing, florid schizophrenia (Sept. 17, p. 575). Dr Schiff (Oct. 8, p. 761) asks if the lack of statistical significance between the measures of chronicity in table i nevertheless hides a practical difference that favours the propranolol group who, on average, were ill for less than a decade, while the placebo group were ill for more than a decade. The stUdy1 he cites does not clarify this point for illness lasting over 5 years because the outcome was correlated with chronicity ratings on a scale of 1 week, 1 year, and over 5 years. More relevant evidence may come from an open study of 55 patients given propranolol in which chronicity did not seem to alter the proportion in whom schizophrenic symptoms remitted when the duration of the episode

schizophrenic patients. Belmaker et all. present their findings as further evidence for a molecular aberration of M.A.O. in schizophrenia. We investigated this possibility by assaying the activity of the enzyme in post-mortem brain tissue from 10 schizophrenic patients and 10 controls. We examined 14

areas

of brain and used four sub-

(5-hydroxytryptamine and benzylamine for types A and B of the enzyme according to Johnston;9 tyramine for both types; and dopamine since it has been claimed’O that this amine may be deaminated by a specific form of the enzyme). We were unable to find any significant differences in M.A.o. activity between control and schizophrenic brains with any of the substrates in any brain region. These findings11 are consistent with other reports12,13 of normal M.A.O. activity in postmortem brain in schizophrenia. strates

1. 2.

Murphy, D. L., Wyatt, R. J. Nature, 1973, 239, 225. Meltzer, H. Y., Stahl, S. M. Res. Commun. chem. Path. Pharmac. 1974, 7,

419. 3. Owen, F., Bourne, R., Crow, T. J., Johnstone, E. C., Bailey, A. R., Hershon, H. I. Archs gen. Psychiat. 1976, 33, 1370. 4. Domino, E. F., Khanna, S. S. Am. J. Psychiat. 1976, 133, 323. 5. Berrettini, W. H., Vogel, W. H., Clouse, R. ibid. 1977, 134, 805. 6. Shaskan, E. G., Becker, R. E. Nature, 1975, 253, 659. 7. Zeller, E. A., Boshes, B., Davis, J. M., Thorner, M. Lancet, 1975, i, 1385. 8. Robinson, D. S., Lovenberg, W., Keiser, H., Sjoerdsma, A. Biochem. Pharmac. 1968, 17, 109. Johnston, J. P. ibid. p. 1285. Youdim, M. B. H. Br. med. Bull. 1973, 29, 120. Cross, A. J., Crow, T. J., Glover, V., Lofthouse, R., Owen, F., Riley, G. J. Br. J. clin. Pharmac. (in the press). 12. Domino, E. F., Krause, R. R., Bowers, J. Archs gen. Psychiat. 1973, 29, 195. 13. Schwartz, M. A., Aikens, A. M., Wyatt, R. J. Psychopharmacologia, 1974, 38, 319.

9. 10. 11.

Pulse-rates

(mean±S,D.)

in

patients

on

propranolol or placebo.

treated was more than 5 years.2 These proportions, grouped by the duration of episode in years, were 13/17 (under 1 year) and 6/10 (1-5 years). For episodes of more than 5 years the results were 4/13 (6-10 years), 3/10 (11-20 years), and 2/5 (21-30 years). Further, after our trial, the 5 from the placebo group who then had propranolol also improved as described. Dr Tyrer (Oct. 8, p. 761) wonders if the staff could have worked out who was on propranolol from the pulse and bloodpressure readings and so perhaps watched them more cautiously and rated them more favourably; if the improvement came from reducing unwanted extrapyramidal effects of the major tranquillisers rather than reducing the symptoms of schizophrenia; and if the same results would be achieved by merely reducing the dose of the major tranquillisers. Contrary to what might have been expected, the data in our table III show that throughout the trial the two groups did not 1. Strauss, J. S., Carpenter, W. T. Archs gen. Psychiat. 1974, 31, 37. 2. Yorkston, N. J., Zaki, S. A., Themen, J. F. A., Havard, C. W. H. Adv. clin. Pharmac. 1976, 12, 91.

1083 differ significantly in systolic or diastolic blood-pressure and that the pulse-rate did not consistently distinguish the propranolol group. The accompanying figure shows the mean and standard deviation of the pulse-rates for each patient ranked according to pulse-rate. These varied so widely that the groups overlapped and it was not possible to be sure if a given individual was on propranolol. The most obvious signs of taking propranolol were the items of improvement, given with their statistical significance in the text of our paper. The only patient for whom the code was broken because of suspected side-effects had placebo added to chlorpromazine; it was prudent to keep a close eye on all patients who were given major tranquillisers alone or with propranolol. All patients except 1 in the propranolol group were taking a drug to counter extrapyramidal effects before the trial, and these drugs were continued during the trial. The neuroleptic drugs were also kept at the same dosage; there was not "a considerable increase" in the placebo group. The improvements rated were of the factors we described and not of extrapyramidal signs. Our trial was designed to evaluate propranolol as an adjunct to conventional drug treatment. Dr Tyrer suggests that because the patients were on combined medication propranolol may simply be acting as a phenothiazine antagonist. Several lines of evidence imply that this possibility is remote and that propranolol contributes something new. Case-histories showed that lower doses of phenothiazines had proved ineffective in these patients. A novel central action by propranolol was shown in psychophysiological studies of the arousal reaction of the autonomic nervous system and its rate of habituation.3 Most schizophrenic patients on propranolol, alone or combined with phenothiazines, had normal reactions. This contrasts with the abnormal reactions of most patients having no drugs or phenothiazines alone whether in low or high dosage. These results may be interpreted as indicating that propranolol in schizophrenia has a specific sub-cortical limbic action not shared by conventional treatment. We agree that more studies are needed to define the place of propranolol in the treatment of schizophrenia. N.

J. YORKSTON J. H. GRUZELIER

S. A. ZAKI D. HOLLANDER D. R. PITCHER H. G. S. SERGEANT

Friern Hospital, New Southgate, London N11 3BP

D. W. Fraser, Mr C. C. Shepard, lishing the specific diagnosis.

and Dr T. F. Tsai for

Clinical Department of Infectious Diseases, University Department of Infectious Diseases, and Communicable Diseases (Scotland) Unit, Ruchill Hospital, Glasgow G20 9NB Greater

Glasgow Health Board

help in estab-

J. H. LAWSON N. R. GRIST D. REID T. S. WILSON

MANAGEMENT OF WHOOPING-COUGH is on the increase. During the five 1972-76 we admitted years only 51 cases to this unit. This year we have admitted 47 children, only 1 of whom, a already 9-year-old, had been vaccinated. The greatest benefit we can confer on our young prospective patients is to encourage their parents to have them immunised unless there is a specific contraindication. Meantime we have children to treat, and Dr Ware (Oct. 22, p. 872) performs a useful service by drawing attention to matters of management. The variety of drugs recommended is a clear indication of uncertain action. Antibiotics in the catarrhal stage are unquestionably of value in limiting the duration of illness, and we agree that erythromycin is the drug of choice. We would agree with Dr Hughes-Davies (Nov. 5, p. 981) that ampicillin is a useful alternative. In reply to Dr Easton (Nov. 5, p. 981) we have found no support for salbutamol in 20 cases. Eumydrin and chlorpromazine are most helpful in

SIR,-Whooping-cough

controlling vomiting. Dr Ware asks "what one should actually do when a baby has a severe paroxysm"? We agree that the main danger of whooping-cough lies in apnoeic attacks but cannot agree that the subject is "very poorly dealt with in textbooks". All babies with severe or cyanotic attacks in our unit are "specialled" by staff trained in our method of maintaining respiration should apnoea follow, as has been described. 1.2 Oxygen and suction are always in the cubicle but seldom used. None of our latest 1000 patients has died. 478 were under one year of age, and many of these infants have had prolonged and frightening illnesses. Department of Infectious Diseases, St. Ann’s Hospital, London

G. DONALD W. MCKENDRICK S. C. RAYCHOUDHURY

Dr Barley (Nov. 5, p. 981) for his reference A. B. Christie’s textbook in which Christie says that antitussives will reduce paroxysms only if given in doses that will stop the child eating. Christie is clearly referring to older children, and since babies with severe disease, the subject of my letter (Oct. 22, p. 872), nearly always need tube feeding, the question of eating does not really arise. The question is whether these drugs would reduce the lifethreatening spasms in these babies, and whether they would increase the risk of pneumonia. I suspect that, if given selectively, these drugs might be beneficial.

SIR,-I thank

to

LEGIONNAIRES’ DISEASE

SIR,—We wish

to record the first cases of legionnaires’ disrecognised outside North America. In 1973 holidaymakers returning to Scotland from a package holiday in Spain were afflicted by illness, largely respiratory. Three of several cases of pneumonia were fatal. Serological tests at the Center for Disease Control, Atlanta, Georgia, U.S.A., have shown significant fluorescent antibody titres to the legionnaires’ agent (of;:.1024 in a fatal case) and 256 (in each of two cases of nonfatal pneumonia); a patient with pleurisy showed falling titres (64 in 1973;

Propranolol in chronic schizophrenia.

1082 to trimethoprim strains were from eight selected E. coli and Klebsiella unsuccessful, though all transferred resistance to sulphamethoxaz...
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