- Email: [email protected]
NEW METHOD OF PHENOBARBITONE ADMINISTRATION
1127
Professor McMichael considers that " strong emotional to corn-oil diets or anticoagulant pills will do no medicine ". Prof. Ancel Keys,14 possibly more to good has colourfully, derisively inveighed against those who entertain the view that the coronary-heart problem may be solved without retreating from present high-fat diets merely " by taking a daily swig of linoleic acid and a few Mere We concur with these views. vitamin pills ". favourable " bloodattainment and maintenance of a lipid picture per se need not reduce the chance of dying from coronary-artery disease; we believe that for that " favourable " blood-lipid picture to be effective, directly or indirectly, it may well have to lie within a particular dietary and metabolic context. Although most writers regard it as premature to recommend significant changes in diet to ward off death from coronary occlusion, our belief is that the only certain known way to do this is by adoption of the pattern of diet (with all its concomitant metabolic ramifications) consumed by the Bantu and similar populations. For this viewpoint there is much evidence, published and unpublished, which one of us (A. R. P. W.) hopes to present in the near future. It would be naive, however, not to recognise that the likelihood of any marked change occurring voluntarily in the diets of Western populations, no matter how frightening is the increasing mortality from coronary disease, is so remote as scarcely to merit serious discussion.
devotion
"
C.S.I.R. Human Biochemistry Research Unit, South African Institute for Medical Research,
Johannesburg.
ALEXANDER R. P. WALKER.
Baragwanath Hospital and African Institute for
South Medical
I. W. SIMSON.
Research, Johannesburg.
NEW METHOD OF PHENOBARBITONE ADMINISTRATION
SiR,ŁIthank Dr. O’Connor (May 3) for his reply. (1) I have accepted his facts and have said, giving reasons, that from them no conclusion can be drawn about the value of ’Spansule ’ phenobarbitone. If its value was so great, why had other anti-convulsants to be simultaneously given, sometimes in increasing doses ? (2) The description of the rigid routine for administration of drugs, and the statement that the same nurses had attended the patients for a number of years, are new, though not very precise, data. They do not amount to the required guarantee, especially with patients who were spiteful, cunning, paranoid, hostile, and suspicious. (3) There is a confusion here between improvement of personality, in which we all hope that psychotherapy has a great future, and relief from epilepsy, in which we all agree that it has not. (4) Added interest and stimulation on the one hand, and increased medication on the other, are not mutually exclusive alternatives. I said, and meant, may have helped ". (5) " Either wholly or in part "-there’s the rub. (6) If 18 patients with, say, a hitherto invariably fatal disease were given a certain drug and all recovered, that number would be superfluously great for proof; but where everything is a matter of degree and careful assessment, 20 is nearly always the bare minimum. I did not mention inert substances; the comparison should be with the same dosage of ordinary phenobarbitone, as suggested by Dr. Pearson "
(April 19). (7) Striking " "
does not mean convincing. There is no conflict here. Kurtzke and Berlin’s data were impressive except for two flaws: the control series, having been earlier than the treated series, was studied retrospectively; and in the treated series both patients and doctors knew who was receiving a new treatment. The parallel is close, and instructive 14. Keys, A. ibid. 1956, i, 576.
to anyone
who
sees
the
same
general difficulties
in all thera-
peutic trials. Dr. Levitt (May 10) seems to say that the paper is open to criticism but we ought not to criticise it. I agree with him that the method may be of great value; would he agree with me that equally it may not ? That is what I mean when I say that no conclusion can be drawn from the present data. If I had thought that they should be ignored I should have ignored them instead of writing a letter about them. Perhaps we may now all agree to await the results of a controlled clinical trial.
JOHN PENMAN. THE Y CHROMOSOME IN MAN
SIR,-Both the true hermaphrodite and the man with the uterus referred to in my letter of May 3 have elastic tissue surrounding the hyalinised seminiferous tubules of their testes. This distinguishes them from Dr. Ferguson-Smith’s latest description of chromatin-positive microrchidism (May 3, p. 928). It also alters the premises on which I based my argument on the function of the Y chromosome. Department of Anatomy, The Medical School, King’s College, Newcastle upon Tyne.
JOHN GRAY.
" THESE DYING DISEASES " SIR,-The paper by Mr. Ambrose King (March 29) concerning present-day problems of venereology was timely, especially in regard to gonorrhoea, in which there is the alarming situation of an increasing number of cases and an apparent lessening sensitivity of the gonococcus to
penicillin.
The number of new male cases of gonorrhoea seen in the clinics of England and Wales has increased by approximately 28%during the last two years, and the current figure for both sexes is virtually the same as it was as far back as 1949. At the same time doses of repository penicillins, which were once 95% effective, today produce far less satisfactory results. Indeed, in recent series treated with single doses of 1-2 mega units of procaine penicillin with aluminium monostearate or of benzathine penicillin, failure-rates in the range of 18%-30% have been encountered. While similar experiences have not so far been widely reported in the U.S.A., the situation is certainly not confined to Britain. At the recent World Health Organisation seminar in Tokyo it was evident that the declining powers of penicillin in gonorrhoea had been widely noted in the Far East. Indeed, in a sex store " in Yokohama, where I asked the proprietor what he used for gonorrhoea (drug-store treatment being legal in Japan), I was informed that for some time he had employed the tetracycline antibiotics, because penicillin was no longer "
effective. It is not known for certain whether the gonococcus is alternative metabolic processes or whether, as likely, the apparent lessened sensitivity is arising from repeated selection of the more insensitive strains. Further research is required. In any event it seems that higher doses of
developing
seems more
shorter-acting penicillin preparations are required to provide higher peaks of penicillinaemia than are obtained with repository penicillins which the gonococcus now seems capable of overcoming. This would mean the sacrifice of the so-called epidemiological tail " provided with repository penicillins which act during the time that the consorts are being traced and which reduce the possibilities of reinfection of the original patient, and at the same time help to reduce the reservoir of syphilis. All-purpose penicillins, by providing a higher initial level, and also a prolongation, at present give better results and might provide the answer, but, on the other hand, "
"
"
Professor McMichael considers that " strong emotional to corn-oil diets or anticoagulant pills will do no medicine ". Prof. Ancel Keys,14 possibly more to good has colourfully, derisively inveighed against those who entertain the view that the coronary-heart problem may be solved without retreating from present high-fat diets merely " by taking a daily swig of linoleic acid and a few Mere We concur with these views. vitamin pills ". favourable " bloodattainment and maintenance of a lipid picture per se need not reduce the chance of dying from coronary-artery disease; we believe that for that " favourable " blood-lipid picture to be effective, directly or indirectly, it may well have to lie within a particular dietary and metabolic context. Although most writers regard it as premature to recommend significant changes in diet to ward off death from coronary occlusion, our belief is that the only certain known way to do this is by adoption of the pattern of diet (with all its concomitant metabolic ramifications) consumed by the Bantu and similar populations. For this viewpoint there is much evidence, published and unpublished, which one of us (A. R. P. W.) hopes to present in the near future. It would be naive, however, not to recognise that the likelihood of any marked change occurring voluntarily in the diets of Western populations, no matter how frightening is the increasing mortality from coronary disease, is so remote as scarcely to merit serious discussion.
devotion
"
C.S.I.R. Human Biochemistry Research Unit, South African Institute for Medical Research,
Johannesburg.
ALEXANDER R. P. WALKER.
Baragwanath Hospital and African Institute for
South Medical
I. W. SIMSON.
Research, Johannesburg.
NEW METHOD OF PHENOBARBITONE ADMINISTRATION
SiR,ŁIthank Dr. O’Connor (May 3) for his reply. (1) I have accepted his facts and have said, giving reasons, that from them no conclusion can be drawn about the value of ’Spansule ’ phenobarbitone. If its value was so great, why had other anti-convulsants to be simultaneously given, sometimes in increasing doses ? (2) The description of the rigid routine for administration of drugs, and the statement that the same nurses had attended the patients for a number of years, are new, though not very precise, data. They do not amount to the required guarantee, especially with patients who were spiteful, cunning, paranoid, hostile, and suspicious. (3) There is a confusion here between improvement of personality, in which we all hope that psychotherapy has a great future, and relief from epilepsy, in which we all agree that it has not. (4) Added interest and stimulation on the one hand, and increased medication on the other, are not mutually exclusive alternatives. I said, and meant, may have helped ". (5) " Either wholly or in part "-there’s the rub. (6) If 18 patients with, say, a hitherto invariably fatal disease were given a certain drug and all recovered, that number would be superfluously great for proof; but where everything is a matter of degree and careful assessment, 20 is nearly always the bare minimum. I did not mention inert substances; the comparison should be with the same dosage of ordinary phenobarbitone, as suggested by Dr. Pearson "
(April 19). (7) Striking " "
does not mean convincing. There is no conflict here. Kurtzke and Berlin’s data were impressive except for two flaws: the control series, having been earlier than the treated series, was studied retrospectively; and in the treated series both patients and doctors knew who was receiving a new treatment. The parallel is close, and instructive 14. Keys, A. ibid. 1956, i, 576.
to anyone
who
sees
the
same
general difficulties
in all thera-
peutic trials. Dr. Levitt (May 10) seems to say that the paper is open to criticism but we ought not to criticise it. I agree with him that the method may be of great value; would he agree with me that equally it may not ? That is what I mean when I say that no conclusion can be drawn from the present data. If I had thought that they should be ignored I should have ignored them instead of writing a letter about them. Perhaps we may now all agree to await the results of a controlled clinical trial.
JOHN PENMAN. THE Y CHROMOSOME IN MAN
SIR,-Both the true hermaphrodite and the man with the uterus referred to in my letter of May 3 have elastic tissue surrounding the hyalinised seminiferous tubules of their testes. This distinguishes them from Dr. Ferguson-Smith’s latest description of chromatin-positive microrchidism (May 3, p. 928). It also alters the premises on which I based my argument on the function of the Y chromosome. Department of Anatomy, The Medical School, King’s College, Newcastle upon Tyne.
JOHN GRAY.
" THESE DYING DISEASES " SIR,-The paper by Mr. Ambrose King (March 29) concerning present-day problems of venereology was timely, especially in regard to gonorrhoea, in which there is the alarming situation of an increasing number of cases and an apparent lessening sensitivity of the gonococcus to
penicillin.
The number of new male cases of gonorrhoea seen in the clinics of England and Wales has increased by approximately 28%during the last two years, and the current figure for both sexes is virtually the same as it was as far back as 1949. At the same time doses of repository penicillins, which were once 95% effective, today produce far less satisfactory results. Indeed, in recent series treated with single doses of 1-2 mega units of procaine penicillin with aluminium monostearate or of benzathine penicillin, failure-rates in the range of 18%-30% have been encountered. While similar experiences have not so far been widely reported in the U.S.A., the situation is certainly not confined to Britain. At the recent World Health Organisation seminar in Tokyo it was evident that the declining powers of penicillin in gonorrhoea had been widely noted in the Far East. Indeed, in a sex store " in Yokohama, where I asked the proprietor what he used for gonorrhoea (drug-store treatment being legal in Japan), I was informed that for some time he had employed the tetracycline antibiotics, because penicillin was no longer "
effective. It is not known for certain whether the gonococcus is alternative metabolic processes or whether, as likely, the apparent lessened sensitivity is arising from repeated selection of the more insensitive strains. Further research is required. In any event it seems that higher doses of
developing
seems more
shorter-acting penicillin preparations are required to provide higher peaks of penicillinaemia than are obtained with repository penicillins which the gonococcus now seems capable of overcoming. This would mean the sacrifice of the so-called epidemiological tail " provided with repository penicillins which act during the time that the consorts are being traced and which reduce the possibilities of reinfection of the original patient, and at the same time help to reduce the reservoir of syphilis. All-purpose penicillins, by providing a higher initial level, and also a prolongation, at present give better results and might provide the answer, but, on the other hand, "
"
"