- Email: [email protected]
TOXICITY OF TETRACYCLINES
840 is known to cause strong contractions of the Moreover, there is very obvious remission in many myasthenic patients during pregnancy. The well-known obstetric preparationThymophysin’ contains oxytocin and thymus extract, which has been observed to potentiate the effect of the hypophyseal hormone.
neostigmine uterus.
This
hypothesis calls for experimental investigation.
Vammala, Finland.
LAURI KANTELE.
HÆMAGGLUTINATION-INHIBITION TESTS IN THE DIAGNOSIS OF PREGNANCY SIR,-I was interested in the article of Dr. Shuttleworth’ (Oct. 5), describing her experience with thePrepuerin ’ pregnancy test, since I have been recently trying out a similar form of haemagglutination-inhibition test.1 In the few months since the test became available commercially, we have performed 250 tests by thePregnosticon’ technique, with an overall accuracy of 98-8%, of these 159 have been positive and 91 negative. There has been 1 negative result in a woman who was later shown to be pregnant and only 2 positives in cases where pregnancy was not confirmed. In one of these cases there was the possibility of recent abortion, the Hogben test being also weakly positive; and in the other patient a presumptive diagnosis of Stein-Leventhal syndrome with ovarian failure has been made. It is well known that in such cases of primary ovarian failure a high level of pituitary gonadotrophin may be present in the urine. For a similar reason it is advised that the urine should be diluted with an equal volume of water in menopausal cases. In a small series of 24 tests performed in parallel with the Hogben method, 14 cases gave positive results by both tests; in 6 (25%) cases the pregnosticon test was positive, while the Hogben was negative, and in these pregnancy was subsequently confirmed; in 4 instances both tests were negative, and these cases were found subsequently to be not pregnant. The test has been found positive at a urinary dilution of 1 in 40 in a patient who was suspected of hydatidiform mole, but who proved to have a tubal pregnancy; it was also found positive in a man with chorio-carcinoma of the testis. My experience with the prepuerin test agrees with that of Dr. Shuttleworth in that occasional false positive results may arise; these have been less common with the pregnosticon test, and since the latter is performed on undiluted urine in the ampoules provided, without the need of additional glassware, I have found it preferable because of its simplicity. Mayday Hospital, R. A. M. OLIVER. Croydon, Surrey. TOXICITY OF TETRACYCLINES
SiR,ňWe have refrained from commenting on your Aug. 10, which, in our view, presents an exaggerated picture of the risks of using this group of antibiotics, until the completion of some fresh work by our scientists on one aspect of this subject to which you refer.2 This is the production by a degradation product of tetracycline of a condition resembling the Fanconi syndrome. In the few cases of this recorded,3-5 the capsules responsible editorial of
had been exposed to heat and moisture by improper storage. These conditions have been imitated and exaggerated experimentally in our laboratories; and the degradation products have been examined, both chemically and toxicologically. Of several products formed, the only one possessing toxicity and producing the renal lesion evidently responsible for the human Fanconi syndrome is epianhydrotetracycline. This is not, as stated in your editorial, formed from chlortetracycline, the 1. The ’ Pregnosticon ’ Pregnancy Test, Organon Laboratories Ltd. 2. Benitz, K.-F., Diermeier, H. F. Unpublished. 3. Gross, J. M. Ann. intern. Med. 1963, 58, 523. 4. Frimpter, G. W., Timpanelli, A. E., Eisenmenger, W. J., Stein, H. S. Ehrlich, L. I. J. Amer. med. Ass. 1963, 184, 111. 5. Frimpter, G. W., Timpanelli, A. E., Eisenmenger, W. J., Stein, H. S. Ehrlich, L. I. ibid. 1963, 185, 414.
degradation products of which are of a different nature and innocuous. Studies of the tetracycline degraded in our laboratories show that the rate of formation of epianhydrotetracycline is greatly accelerated by the combination of heat, high humidity, and low pH. The low pH required can be achieved by any acid or acid-yielding substance. ’Achromycin’ tetracycline hydrochloride with ordinary non-acidic excipients such as lactose and starch does not degrade to epianhydrotetracycline to any significant extent when exposed to high temperature and heat. Achromycin V (tetracycline base with sodium hexametaphosphate) is non-acidic and therefore does not degrade to epianhydrotetracycline even under severe experimental conditions. The serious side-effects which your article warns about have never been reported in Great Britain and cannot, in fact, occur because of the absence of acidic excipients in our capsules. There was no reason, therefore, to anticipate the dangers to which you refer, and the precautions you suggestthe dispensing of " small supplies " and " a system of routine inspection or even assay "-are superfluous. ’
Clinical Research Department, Lederle Laboratories, Bush House, Aldwych, London, W.C.2.
A. T. MENNIE.
PERSUASIVE RESEARCH SIR,-It is difficult to see how The Lancet (Aug. 17, p. 342) makes so many critical comments, when your last paragraph quotes and accepts the Institute of Economic Affairs’ own conclusions. The report, the first of its kind, is, if I understand correctly, the first of a series, and if the only result so
far is to " ascertain what kind of questions and the problems of eliciting significant answers ", then this surely is not a bad basis from which to promote further studies?2 Perhaps a clue to your attitude can be found in the annotation immediately following the leader, for here the view that further change in the National Health Service will provide a better service is accepted, This would suggest that change within the present structure is acceptable, but change of the present structure is sinful. To accept this point of views however, is to accept the original assumption on which the N.H.S. was basednamely, that individual freedom is possible within the framework of a nationalised undertaking. This is an unproven postulate that requires repeated efforts at compromise to support. For the G.P.S in particular, the N.H.S. is a house built on sand, and the efforts of the medico/political hierarchy to shovel in more sand has neither reason nor history to support it. Probably the only clear way round this impasse is to get out (private medicine) or get in (full-time salaried service). In any event the whole concept of State Medicine must be given new foundations, and in a democracy where the vote is the instrument of power, 20,000 G.P.S are as nothing compared with the bulk of the voters. Thus, even if the medical profession presented a united front, unless their claims were politically expedient or the cheapest way of doing things (perhaps synonymous terms ?) their voice would be lost in the public outcry. Education of the public is therefore the only hope of any profession; and to educate, we need to know where to start and where to aim. I would have thought that Choice in Welfare was the first, and therefore the best, effort so far to find out what the public knows and would like if it was free to choose. As such I personally welcome it, despite the fact that it does not claim to be all-embracing or in any way final, and should not be judged from that standpoint.
neostigmine uterus.
This
hypothesis calls for experimental investigation.
Vammala, Finland.
LAURI KANTELE.
HÆMAGGLUTINATION-INHIBITION TESTS IN THE DIAGNOSIS OF PREGNANCY SIR,-I was interested in the article of Dr. Shuttleworth’ (Oct. 5), describing her experience with thePrepuerin ’ pregnancy test, since I have been recently trying out a similar form of haemagglutination-inhibition test.1 In the few months since the test became available commercially, we have performed 250 tests by thePregnosticon’ technique, with an overall accuracy of 98-8%, of these 159 have been positive and 91 negative. There has been 1 negative result in a woman who was later shown to be pregnant and only 2 positives in cases where pregnancy was not confirmed. In one of these cases there was the possibility of recent abortion, the Hogben test being also weakly positive; and in the other patient a presumptive diagnosis of Stein-Leventhal syndrome with ovarian failure has been made. It is well known that in such cases of primary ovarian failure a high level of pituitary gonadotrophin may be present in the urine. For a similar reason it is advised that the urine should be diluted with an equal volume of water in menopausal cases. In a small series of 24 tests performed in parallel with the Hogben method, 14 cases gave positive results by both tests; in 6 (25%) cases the pregnosticon test was positive, while the Hogben was negative, and in these pregnancy was subsequently confirmed; in 4 instances both tests were negative, and these cases were found subsequently to be not pregnant. The test has been found positive at a urinary dilution of 1 in 40 in a patient who was suspected of hydatidiform mole, but who proved to have a tubal pregnancy; it was also found positive in a man with chorio-carcinoma of the testis. My experience with the prepuerin test agrees with that of Dr. Shuttleworth in that occasional false positive results may arise; these have been less common with the pregnosticon test, and since the latter is performed on undiluted urine in the ampoules provided, without the need of additional glassware, I have found it preferable because of its simplicity. Mayday Hospital, R. A. M. OLIVER. Croydon, Surrey. TOXICITY OF TETRACYCLINES
SiR,ňWe have refrained from commenting on your Aug. 10, which, in our view, presents an exaggerated picture of the risks of using this group of antibiotics, until the completion of some fresh work by our scientists on one aspect of this subject to which you refer.2 This is the production by a degradation product of tetracycline of a condition resembling the Fanconi syndrome. In the few cases of this recorded,3-5 the capsules responsible editorial of
had been exposed to heat and moisture by improper storage. These conditions have been imitated and exaggerated experimentally in our laboratories; and the degradation products have been examined, both chemically and toxicologically. Of several products formed, the only one possessing toxicity and producing the renal lesion evidently responsible for the human Fanconi syndrome is epianhydrotetracycline. This is not, as stated in your editorial, formed from chlortetracycline, the 1. The ’ Pregnosticon ’ Pregnancy Test, Organon Laboratories Ltd. 2. Benitz, K.-F., Diermeier, H. F. Unpublished. 3. Gross, J. M. Ann. intern. Med. 1963, 58, 523. 4. Frimpter, G. W., Timpanelli, A. E., Eisenmenger, W. J., Stein, H. S. Ehrlich, L. I. J. Amer. med. Ass. 1963, 184, 111. 5. Frimpter, G. W., Timpanelli, A. E., Eisenmenger, W. J., Stein, H. S. Ehrlich, L. I. ibid. 1963, 185, 414.
degradation products of which are of a different nature and innocuous. Studies of the tetracycline degraded in our laboratories show that the rate of formation of epianhydrotetracycline is greatly accelerated by the combination of heat, high humidity, and low pH. The low pH required can be achieved by any acid or acid-yielding substance. ’Achromycin’ tetracycline hydrochloride with ordinary non-acidic excipients such as lactose and starch does not degrade to epianhydrotetracycline to any significant extent when exposed to high temperature and heat. Achromycin V (tetracycline base with sodium hexametaphosphate) is non-acidic and therefore does not degrade to epianhydrotetracycline even under severe experimental conditions. The serious side-effects which your article warns about have never been reported in Great Britain and cannot, in fact, occur because of the absence of acidic excipients in our capsules. There was no reason, therefore, to anticipate the dangers to which you refer, and the precautions you suggestthe dispensing of " small supplies " and " a system of routine inspection or even assay "-are superfluous. ’
Clinical Research Department, Lederle Laboratories, Bush House, Aldwych, London, W.C.2.
A. T. MENNIE.
PERSUASIVE RESEARCH SIR,-It is difficult to see how The Lancet (Aug. 17, p. 342) makes so many critical comments, when your last paragraph quotes and accepts the Institute of Economic Affairs’ own conclusions. The report, the first of its kind, is, if I understand correctly, the first of a series, and if the only result so
far is to " ascertain what kind of questions and the problems of eliciting significant answers ", then this surely is not a bad basis from which to promote further studies?2 Perhaps a clue to your attitude can be found in the annotation immediately following the leader, for here the view that further change in the National Health Service will provide a better service is accepted, This would suggest that change within the present structure is acceptable, but change of the present structure is sinful. To accept this point of views however, is to accept the original assumption on which the N.H.S. was basednamely, that individual freedom is possible within the framework of a nationalised undertaking. This is an unproven postulate that requires repeated efforts at compromise to support. For the G.P.S in particular, the N.H.S. is a house built on sand, and the efforts of the medico/political hierarchy to shovel in more sand has neither reason nor history to support it. Probably the only clear way round this impasse is to get out (private medicine) or get in (full-time salaried service). In any event the whole concept of State Medicine must be given new foundations, and in a democracy where the vote is the instrument of power, 20,000 G.P.S are as nothing compared with the bulk of the voters. Thus, even if the medical profession presented a united front, unless their claims were politically expedient or the cheapest way of doing things (perhaps synonymous terms ?) their voice would be lost in the public outcry. Education of the public is therefore the only hope of any profession; and to educate, we need to know where to start and where to aim. I would have thought that Choice in Welfare was the first, and therefore the best, effort so far to find out what the public knows and would like if it was free to choose. As such I personally welcome it, despite the fact that it does not claim to be all-embracing or in any way final, and should not be judged from that standpoint.