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.
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.
