1175 Africa under the principalship of one of the foremost medical educators in Southern Africa can only be seen as a great advance in the training facilities for Black doctors in Southern Africa and can only be to the advantage of everyone. The Medical Association of South Africa was, however, still of the opinion that the phasing-out of Black medical students from the University of Natal Medical School was contrary to the interests of Black medical education and expressed itself on this matter in no uncertain terms. I am happy to be able to report that this phasing-out will no longer be implemented and I have every reason to believe that this matter will be settled to everyone’s satisfaction. Those of us in this part of the world who are concerned with the wellbeing of our fellow men, be they White or Black, find articles such as Dr Gude’s not only crassly ignorant of the true facts but also I believe, contrary to the interests of the very profession which he presumes to serve. Medical Association of South Africa,
N. DE KLERK, Chairman, Federal Council
J.
P.O. Box 20272 Pretoria 0005, South Africa
PATHOGENICITY OF AND &bgr;-LACTAMASE PRODUCTION BY BRANHAMELLA (NEISSERIA) CATARRHALIS
SIR,-We
agree with Ninane
et
al.l and others2 that Bran-
(Neisseria) catarrhalis is a respiratory-tract pathogen and that a minority of isolates produce &bgr;-lactamase. The organism was isolated, as single pathogen, from 4% of infected sputa from patients in this hospital,3 and we have lately confirmed this finding; and it is more frequent in mixed infections together with Hcemophilus influenzce and pneumococci. All the infected patients observed by us were chronic bronchitics or had bronchiectasis but, even in such patients, infection by other gram-negative cocci (Neisseria) is rare. hamella
SUBSTRATE PROFILES OF
&bgr;-LACTAMASES
FROM B. CATARRHALIS
AND N. GONORRHCEA
* Expressed as % of hydrolysis of benzylpenicillin (=100).
During the past six months, we have isolated p-lactamaseproducing B. catarrhalis from seven patients, all having received broad-spectrum penicillins. Five were given further treatment with these agents but failed to respond, although cotrimoxazole was then successful. Because these organisms could be a potential source of &bgr;-Iactamase transferable to other more pathogenic bacteria found in the upper respiratory, tract, it is important to establish that the &bgr;-Iactamase from all seven isolates of B. catarrhalis is different from the plasmid mediated and transferable enzymes described in gonococci4 and H. influenzae.5 As with both these organisms, p-lactamase-producing B. catarrhalis show profound inoculum effects in minimum inhibitory concentration determinations (M.i.c.s of benzyl1. Ninane, G., Joly, J., Piot, P., Kraytman, M. Lancet, 1977, ii, 149. 2. Malmvall, B. E., Brorsson, J. E., Johnson, J. J. antimicrob. Chemother. 1977, 3, 374. 3. Percival, A. in Current Antibiotic Therapy (edited by A. M. Geddes and J. D. Williams); p. 151. Edinburgh, 1973. 4. Percival, A., Corkill, J. E., Arya, O. P., Rowlands, J., E., Annels, E. H. Lancet, 1976, ii, 1379. 5. Madeiros, A. A., O’Brien, T. F. ibid. 1975, i, 716.
Alergant,
C. D.,
Rees,
8 and >250 g/mt, with’inocula of 104 and 106 organisms/ml). However, the substrate profile of the B. catarrhalis j3-lactamases, (see table) is different. Isoelectric focusing shows three bands of -lactamase activity distinct from those produced by adjacent gonococcal p-lactamase, and attempts to transfer -lactamase activity from B. catarrhalis to other organisms have, so far, been unsuccessful.
penicillin, respectively,
Department of Medical Microbiology, University of Liverpool, Liverpool L69 3BX, and Royal Infirmary, Liverpool
A. PERCIVAL J. E. CORKILL J. ROWLANDS
Squibb Institute for Medical Research, Princetown, New Jersey 08540, U.S.A.
R. B. SYKES
PROPRANOLOL AND PROLACTIN
SIR,-There have been several reports of therapeutic effects
beta-adrenergic-receptor blocking agent propranolol in schizophrenia,’-3 and Dr Yorkston and his colleagues (Sept. 17, p. 575) have lately confirmed their earlier findings.4 Most of these reports claim that very high doses of propranolol (up to 6000 mg/day) are needed to obtain antipsychotic effects; of the
there seems to be little effect at low doses. All antipsychotic agents that have been tested raise plasmaprolactin concentrations,5 suggesting a blockade of the dopamine-mediated tonic inhibition of prolactin release.6 If propranolol is an effective antipsychotic agent in high but not low doses, then it should increase plasma-prolactin concentrations differentially at high and low doses. We administered D,L-propranolol hydrochloride by intraperitoneal injection to male Sprague-Dawley rats at doses of 1, 10, 50, or 100 mg/kg. Groups of five rats were decapitated after 15, 30, and 60 min; the blood was put on ice and the plasma separated, coded, and stored at -70°C. Prolactin was measured by radioimmunoassay.’ Our preliminary data showed a 2.6-fold increase in plasma prolactin at 15 min with the 50 mg/kg dose (P=0-028, onetailed Mann-Whitney U test) and a 3 - 0-fold increase with the 100 mg/kg dose (P=0.008) as compared with vehicle-injected controls. Prolactin concentrations in the 50 mg/kg group had returned to control levels by 60 min. 1 and 10 mg/kg doses had no effect on prolactin concentration at any time. While our hypothesis predicted this result, the pharmacological interpretation of the finding is not clear. Does propranolol at high doses become a non-specific receptor blocker, thus blocking dopaminergic, in addition to adrenergic receptors, or are there entirely different mechanisms of action for propranolol at high and low doses? Thus, there is need for further clinical and basic research in this area, especially to elucidate the differential effect of propranolol on psychosis at different dose levels. HENRY A. NASRALLAH* Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, WILLIAM J. FREED Intramural Research Program, ALAN ROGOL† Saint Elizabeth’s Hospital, RICHARD JED WYATT Washington, D.C. 20032, U.S.A. *Present address: Department of Psychiatry, University of California, San Diego. tPresent address: Department of Pediatrics, University of Virginia, Medical Center, Charlottesville.
1. Atsmon, A., Blum, I., Maoz, B., Sterner, M., Wijsenbeck, H. Harefuah, 1970, 79, 20. 2. Atsmon, A., Blum, I., Steiner, M., Latz, A., Wijsenbeck, H. Psychopharma-
cologia, 1972, 27, 249. 3. Sterner, M., Latz, A., Blum, I., Atsmon, A., Wijsenbeck, H. Psychiat. Neurol. Neurochir 1973, 76, 421. 4 Yorkston, N., Zaki, S., Malik, M., Morrison, R., Harard, C. Br. med. J. 1974, iv, 633. 5. Meltzer, H., Fang, V. Arch. gen. Psychiat. 1976, 33, 279. 6. Macleod, R., Lehmeyer, J. Endocrinology. 1974, 94, 1077. 7. Rogol, A., Chrambach, A. ibid. 1975, 97, 406.
N. DE KLERK, Chairman, Federal Council
J.
P.O. Box 20272 Pretoria 0005, South Africa
PATHOGENICITY OF AND &bgr;-LACTAMASE PRODUCTION BY BRANHAMELLA (NEISSERIA) CATARRHALIS
SIR,-We
agree with Ninane
et
al.l and others2 that Bran-
(Neisseria) catarrhalis is a respiratory-tract pathogen and that a minority of isolates produce &bgr;-lactamase. The organism was isolated, as single pathogen, from 4% of infected sputa from patients in this hospital,3 and we have lately confirmed this finding; and it is more frequent in mixed infections together with Hcemophilus influenzce and pneumococci. All the infected patients observed by us were chronic bronchitics or had bronchiectasis but, even in such patients, infection by other gram-negative cocci (Neisseria) is rare. hamella
SUBSTRATE PROFILES OF
&bgr;-LACTAMASES
FROM B. CATARRHALIS
AND N. GONORRHCEA
* Expressed as % of hydrolysis of benzylpenicillin (=100).
During the past six months, we have isolated p-lactamaseproducing B. catarrhalis from seven patients, all having received broad-spectrum penicillins. Five were given further treatment with these agents but failed to respond, although cotrimoxazole was then successful. Because these organisms could be a potential source of &bgr;-Iactamase transferable to other more pathogenic bacteria found in the upper respiratory, tract, it is important to establish that the &bgr;-Iactamase from all seven isolates of B. catarrhalis is different from the plasmid mediated and transferable enzymes described in gonococci4 and H. influenzae.5 As with both these organisms, p-lactamase-producing B. catarrhalis show profound inoculum effects in minimum inhibitory concentration determinations (M.i.c.s of benzyl1. Ninane, G., Joly, J., Piot, P., Kraytman, M. Lancet, 1977, ii, 149. 2. Malmvall, B. E., Brorsson, J. E., Johnson, J. J. antimicrob. Chemother. 1977, 3, 374. 3. Percival, A. in Current Antibiotic Therapy (edited by A. M. Geddes and J. D. Williams); p. 151. Edinburgh, 1973. 4. Percival, A., Corkill, J. E., Arya, O. P., Rowlands, J., E., Annels, E. H. Lancet, 1976, ii, 1379. 5. Madeiros, A. A., O’Brien, T. F. ibid. 1975, i, 716.
Alergant,
C. D.,
Rees,
8 and >250 g/mt, with’inocula of 104 and 106 organisms/ml). However, the substrate profile of the B. catarrhalis j3-lactamases, (see table) is different. Isoelectric focusing shows three bands of -lactamase activity distinct from those produced by adjacent gonococcal p-lactamase, and attempts to transfer -lactamase activity from B. catarrhalis to other organisms have, so far, been unsuccessful.
penicillin, respectively,
Department of Medical Microbiology, University of Liverpool, Liverpool L69 3BX, and Royal Infirmary, Liverpool
A. PERCIVAL J. E. CORKILL J. ROWLANDS
Squibb Institute for Medical Research, Princetown, New Jersey 08540, U.S.A.
R. B. SYKES
PROPRANOLOL AND PROLACTIN
SIR,-There have been several reports of therapeutic effects
beta-adrenergic-receptor blocking agent propranolol in schizophrenia,’-3 and Dr Yorkston and his colleagues (Sept. 17, p. 575) have lately confirmed their earlier findings.4 Most of these reports claim that very high doses of propranolol (up to 6000 mg/day) are needed to obtain antipsychotic effects; of the
there seems to be little effect at low doses. All antipsychotic agents that have been tested raise plasmaprolactin concentrations,5 suggesting a blockade of the dopamine-mediated tonic inhibition of prolactin release.6 If propranolol is an effective antipsychotic agent in high but not low doses, then it should increase plasma-prolactin concentrations differentially at high and low doses. We administered D,L-propranolol hydrochloride by intraperitoneal injection to male Sprague-Dawley rats at doses of 1, 10, 50, or 100 mg/kg. Groups of five rats were decapitated after 15, 30, and 60 min; the blood was put on ice and the plasma separated, coded, and stored at -70°C. Prolactin was measured by radioimmunoassay.’ Our preliminary data showed a 2.6-fold increase in plasma prolactin at 15 min with the 50 mg/kg dose (P=0-028, onetailed Mann-Whitney U test) and a 3 - 0-fold increase with the 100 mg/kg dose (P=0.008) as compared with vehicle-injected controls. Prolactin concentrations in the 50 mg/kg group had returned to control levels by 60 min. 1 and 10 mg/kg doses had no effect on prolactin concentration at any time. While our hypothesis predicted this result, the pharmacological interpretation of the finding is not clear. Does propranolol at high doses become a non-specific receptor blocker, thus blocking dopaminergic, in addition to adrenergic receptors, or are there entirely different mechanisms of action for propranolol at high and low doses? Thus, there is need for further clinical and basic research in this area, especially to elucidate the differential effect of propranolol on psychosis at different dose levels. HENRY A. NASRALLAH* Laboratory of Clinical Psychopharmacology, Division of Special Mental Health Research, WILLIAM J. FREED Intramural Research Program, ALAN ROGOL† Saint Elizabeth’s Hospital, RICHARD JED WYATT Washington, D.C. 20032, U.S.A. *Present address: Department of Psychiatry, University of California, San Diego. tPresent address: Department of Pediatrics, University of Virginia, Medical Center, Charlottesville.
1. Atsmon, A., Blum, I., Maoz, B., Sterner, M., Wijsenbeck, H. Harefuah, 1970, 79, 20. 2. Atsmon, A., Blum, I., Steiner, M., Latz, A., Wijsenbeck, H. Psychopharma-
cologia, 1972, 27, 249. 3. Sterner, M., Latz, A., Blum, I., Atsmon, A., Wijsenbeck, H. Psychiat. Neurol. Neurochir 1973, 76, 421. 4 Yorkston, N., Zaki, S., Malik, M., Morrison, R., Harard, C. Br. med. J. 1974, iv, 633. 5. Meltzer, H., Fang, V. Arch. gen. Psychiat. 1976, 33, 279. 6. Macleod, R., Lehmeyer, J. Endocrinology. 1974, 94, 1077. 7. Rogol, A., Chrambach, A. ibid. 1975, 97, 406.
