371
(e.g., the serum-creatinine levels in the hypertensives and normotensives). There is a need for more data on the relation between cadmium and hypertension in man, and the work of Glauser et al. would be of great value if they were to give uents
complete data.
Environmental Hygiene,
Department of Karolinska Institute,
MAGNUS PISCATOR
S-104 01 Stockholm 60, Sweden
It
This letter lows.-ED. L.
was
shown
to
Dr
Glauser, whose reply fol-
SIR,-Dr Piscator’s letter is welcome since it presents
an
opportunity define more precisely our patient population. This patient selection is crucial. Hypertensives whose disease was due to renovascular disease, phxochromocytoma, and aldosteronism were excluded from our study. Also excluded were patients with retinopathy, azot2emia, or left ventricular hypertrophy. Our patient population was thus comprised of patients that were hypertensive, had no demonstrable endorgan changes, had no detectable classical organic aetiology for their hypertension, and had received no previous therapy. This group is known from previous haemodynamic studies to have a high cardiac output and a normal total peripheral resistance. Once end-organ changes supervene there are many other processes that are not necessarily cadmium-related and the haemodynamic picture changes to that of high total peripheral resistance and at best normal cardiac output. Thus, we have chosen a population that is as close as possible to the initiating events of the hypertensive process. This patient selection might well account for any discrepancy between this study and previous studies. The control and hypertensive groups, as noted in the paper, had no significant difference with respect to age by the Student t-test on a group comparison of these two populations. Using a 2 x 2 contingency table we found no significant difference in distribution between males and females in the two groups. As noted above, neither controls nor hypertensives were azotaemic, the hypertensives being selected from that group which still had normal renal function. Urinary cadmium levels were not as discriminating in our hands as blood cadmium levels in differentiating normotensives from early essential hypertensives. The matter of urinary cadmium levels is unresolved: Wester’ did not find differences between normotensives and hypertensives whereas Perry and Schroeder2did find differences, We feel the blood cadmium level is biologically more significant and at least as good a discriminator as the urinary cadmium level. It is true and unfortunate that Lener and Bibr4 did not present data on the liver level of cadmium in human hypertensives, but concomitantly raised cadmium in the liver and kidney have been found in dogs, rats,6 and rabbits.7 One would hope ’. that in the near future the World Health Organisation8 will be ! able to rectify this deficit. In the discussion of the relation between cadmium levels and hypertension, the dose-dependent biphasic response of the mammalian organism to cadmium levels should be borne in mind. The results of Perry3 indicate that with chronic exposure to slightly raised cadmium levels one sees a hypertensive response due to an increase in cardiac output. Chronic expoto
i
1 Wester, P. O. Acta med. scand. 1973, 194, 505. 2 Perry, H. M., Schroeder, H. A. J. Lab. clin. Med. 1955, 46, 936. 3 Perry, H. M. in Trace Substances in Environmental Health-II (edited by D D. Hemphill); p. 101. Columbia, Missouri, 1968. 4 Lener. J. Bibr, B. Lancet, 1971, i, 970. 5 Byerrum, R. U., Anwar, R. A., Hoppert, C. A. J. Am. Water Works Ass. 1960, 52, 651. 6 Decker, L. E., Byerrum, R. U., Decker, C. F., Hoppert, C. A. Langham, R F Archs. ind. Hlth, 1958, 18, 228. 7 Fischer, G. M., Thind, G. S. Archs environ, Hlth, 1971, 23, 107. 8 Masironi, R. Trace Elements in Relation to Cardiovascular Disease. W.H.O. Offset Publication no. 5, Geneva, 1974.
high levels of cadmium does not produce hypertension. The same phenomena are seen in human beings, in whom modest elevation of cadmium leads to hypertension while severe cadmium toxicity is not associated with hypertension.9 Thus the dose of the cadmium and the duration of exposure are both crucial in determining what type of disease results from exposure to cadmium. In a set of experiments with previously untreated hypertensive patients, we have demonstrated a very significant drop in the blood cadmium levels into the normal range concomitant with a drop in the blood-pressure, systolic and diastolic, into the normal range for those hypertensive patients treated with a thiazide diuretic.’° These patients had no change in their smoking habits. sure to
Department of Pharmacology, Temple University Medical School,
Philadelphia, Pennsylvania 19140, S. C. GLAUSER
U.S.A.
PRESCRIBING IN GENERAL PRACTICE
SIR,-I found Dr Bliss’s article (July 31, p. 248) irritating, because her criticism of repeat prescriptions was invalid,
not
but because, like most G.P.s, I have heard it all before. For years I have been told in the medical Press that I do not know enough aoout, nor do enough for, mental illness, deafness, arthritis, or wife-beaters. I have been told one year that I must have an appointments system and the next that I must scrap it because it interferes with the patient’s access to medical care. Criticism of repeat prescriptions is at least twenty years old and has generated an excellent monograph" which would give Dr Bliss an insight into the reason for the repeat prescription and might temper her criticism of the way in which it is issued. The fact is that few people seem prepared to take the view, or at least investigate it rationally, that the general-practitioner service in its present form is a luxury that the ailing N.H.S. can no longer afford. One half of my workload is concerned with self-limiting minor illness for which the available treatments do not alter the natural history of the disease. Theorists of general practice advise us to refuse to deal with the "common cold", whereas the patient knows he has the right to see his doctor almost when and where he chooses. If he is denied this, the doctor can easily find himself the subject of an unpleasant complaint. Another quarter, perhaps, is spent diagnosing conditions that will have to be treated by other doctors, Why, for instance, does the unfortunate patient with a hernia have to come through me to be sent to a surgeon who will carry out an identical history and examination? The other quarter of the work may represent a real contribution to the welfare of the individual, providing that the G.P. is not so demoralised by the pressure of trivia that he no longer has the application to tackle the minority of his practice whom he can
really help. It must be apparent by now, after all the soul-searching that has been done on behalf of general practice, that the way the service is run is wasteful both of money and of men. Those who would reform it might find it profitable to ask first whether it is necessary to have general practitioners at all, rather than nibble at their more obvious shortcomings. And if the answer is that we are required, then it should be decided exactly what contribution we should be making to the public’s health and this part of the N.H.S. reformed in order to enable us to make it. The Surgery, Newport, Pembs. SA42 0TS 9. 10. 11.
J. C. BIGNALL
Tsuchiya, K. Keto J. Med. 1969, 18, 181. Glauser, E. M., Glauser, S. C., Bello, C. T. Pharmacologist, 1976, 18, 188. Balint, M., and others. Treatment or Diagnosis: a Study of Repeat Prescriptions in General Practice. London, 1970.
372
SiR,—Iam
that many of your readers could add their Dr Bliss. As a G.P. I feel that I can be less charitable and more forthright in my condemnation of these doctors. There can be no justification or excuse for lack of control over the prescription of potentially harmful medicines. Doctors who fail to give proper consideration to each prescription they sign are either totally ignorant of drugs’ potential for harm or, worse still, know the dangers of their prescriptions but are prepared to ignore them out of pure laziness. In either case, their conduct is far more reprehensible than that of the doctor guilty of the kind of misdemeanour with which the G.M.C. seems eternally preoccupied. It is all very well for our profession to throw up its hands in horror when an M.P. threatens to curb our freedom to prescribe, but how on earth can we claim this freedom when so many of our number are abusing it so flagrantly? The answer to the bad doctor is not more complicated prescribing rules-Dr Bliss herself describes one situation in which the present regulations are flouted. Bad doctors only survive in the shadows where they do not have to justify their bad habits: once they emerge into the light of day and have to justify themselves to their peers, the quality of their medicine must rise sufficiently to keep their self-respect afloat.
own
SIR,-Lack of any quantitative data makes Dr Bliss’s argufor change impossible to evaluate, but I would suggest
sure
hair-raising anecdotes to those of
The answer to bad medicine is audit, and if our profession does not organise peer review on a large scale in the very near future, we may find punitive audit imposed from the dizzy heights of the D.H.S.S. After all, if we abdicate responsibility for standards of care, who can blame the Minister for stepping in? 112A Dib Lane, Leeds LS8 3AY
ARNOLD G. ZERMANSKY
SIR,-Dr Bliss draws attention to the ubiquitous but real problem of repeat prescribing in general practice. She is perhaps less than fair to the experienced doctor in continuing practice, having drawn her conclusions from findings during locum posts, presumably of relatively short duration. Each practice evolves its own "system" for the safe issue of inevitable repeat prescriptions without consultation. Firstly, a receptionist, if employed, must be trained to handle telephone requests reliably. I agree that the supply of signed blank prescription forms to anyone is to be strongly deprecated. Secondly, adequate record-keeping is essential for the benefit of one’s patients, one’s colleagues, and oneself. Thirdly, the apparent confusion over hospital-prescribed drugs could be dispelled by better recording in notes. The delegation of repeat prescribing to trained pharmacists would in practice lead to legal and administrative difficulties, and is not, for practical purposes, feasible. The issue of a prescription for whatever substance places certain legal and ethical responsibilities on the prescriber which cannot be shirked. No system is foolproof, and Dr Bliss may have acted for practitioners whose arrangements may require revision, or her experiences may have been singularly unfortunate. As an example, we use a coloured small proforma, not of our own basic design, kept by the patient, bearing the basic information of drugs prescribed, dates of repeats, and of the next consultation clearly recorded. These intervals are strictly monitored by ourselves and our staff. This may be only one way of solving some of the potentially dangerous situations to which Dr Bliss has rightly drawn attention. I hope that both she and I will sometime reach the ideal of seeing every patient personally every time a "repeat" is requested. Under present conditions of practice workload, this sort of Utopia is regrettably unattainable. 131 Dartmouth Road, London NW2 4ES
D. S. NACHSHEN
ments
that most repeat prescriptions are not for short-term therapy but for conditions such as diabetes, hypertension, epilepsy, &c. If anything, these patients should be made more responsible for their own treatment, not hedged around with more legislation. 32
Raphael Drive, Elburton,
G. M. WAKLEY
Plymouth
PRENATAL SEX-HORMONE EXPOSURE AND CONGENITAL LIMB-REDUCTION DEFECTS
SiR,—Nora and Nora’ recorded exposure
period of embryogenesis
to a
at a vulnerable progestagen-oestrogen compound
progestagen alone in 8 of 10 patients with multiple congenital anomalies, mainly of the VACTEL type (vertebral, anal, cardiac, tracheal, cesophageal, limb). A similar exposure was found in 20 of 224 patients with congential heart-disease. A or a
connection between malformations and hormone exposure was, however, not supported by Oakley et al. who interviewed more than 400 mothers with malformed children.2 More than 10% of these had had a hormone pregnancy test during the first trimester, but it seemed unlikely that this was the cause of the malformations because there was no difference in such exposure between the chromosomal and non-chromosomal malformations. Studies on the relation between prenatal sexhormone exposure and cardiac defects, especially transposition of the great vessels, have been conflicting.34 Janerich et al.’ investigated the exposure to exogenous sex steroids during pregnancy for 108 mothers of patients with congenital limb-reduction defects and 108 mothers of normal controls. Exposure resulted from pregnancy tests, supporting hormone therapy early in pregnancy, and breakthrough pregnancies in women using oral contraceptives. Among mothers with malformed children 14% had a history of exposure; 4% of the control mothers were exposed. Affected children with a history of exposure to orally administered hormones were all males. In a parallel study oral-contraceptive failure was reported among approximately 300 mothers of children with spina bifida. The rate of such a failure was almost the same as in a similar number of control mothers. The rate was slightly lower in both groups than in that of the controls from the limb-reduction study. Nora and Nora6 gave additional data supporting the possible connection between progestagen-cestrogen exposure and VACTERL malformations (R
=
renal). We have been following up 35patients with congenital limb deformities born during 1965-74. We contacted 32 of these families and asked parents to report on exposure to a hormone pregnancy test, oral-contraceptive failure, and hormone treatment for threatened abortion during the first 3 months of pregnancy. As a control group 30 mothers of children with spina bifida born during the same period were asked the same questions. The groups did not differ with regard to age or parity of the mothers. In the group with the limb-reduction defects 3 mothers had had a hormone pregnancy test and 4 had been treated with hormone: no instance of oral-contraceptive failure was recorded. 1 control mother had had a hormone pregnant test and she had also been on hormone treatment for threatened abortion. In the limb-reduction group all the 3 malformed children whose mothers had had hormone pregnancy tests were males. 1. Nora, J. J., Nora, A. H. Lancet, 1973, i, 941. 2. Oakley, G. P., Jr, Flynt, W. J., Jr, Falek, A. ibid. 1973, ii, 256. 3. Levy, E. P., Cohen, A., Fraser, F. C. ibid. 1973, i, 611. 4. Mulvihill, J. J., Mulvihill, C. G., Oneill, C. A. Teratology, 1974, 9, A30. 5. Janerich, D. T., Joyce, M. P. H., Piper, M. S., Glebatis, D. M. New Engl. J. Med. 1974, 291, 697. 6. Nora, J. J., Nora, A. H. ibid. p. 731.
(e.g., the serum-creatinine levels in the hypertensives and normotensives). There is a need for more data on the relation between cadmium and hypertension in man, and the work of Glauser et al. would be of great value if they were to give uents
complete data.
Environmental Hygiene,
Department of Karolinska Institute,
MAGNUS PISCATOR
S-104 01 Stockholm 60, Sweden
It
This letter lows.-ED. L.
was
shown
to
Dr
Glauser, whose reply fol-
SIR,-Dr Piscator’s letter is welcome since it presents
an
opportunity define more precisely our patient population. This patient selection is crucial. Hypertensives whose disease was due to renovascular disease, phxochromocytoma, and aldosteronism were excluded from our study. Also excluded were patients with retinopathy, azot2emia, or left ventricular hypertrophy. Our patient population was thus comprised of patients that were hypertensive, had no demonstrable endorgan changes, had no detectable classical organic aetiology for their hypertension, and had received no previous therapy. This group is known from previous haemodynamic studies to have a high cardiac output and a normal total peripheral resistance. Once end-organ changes supervene there are many other processes that are not necessarily cadmium-related and the haemodynamic picture changes to that of high total peripheral resistance and at best normal cardiac output. Thus, we have chosen a population that is as close as possible to the initiating events of the hypertensive process. This patient selection might well account for any discrepancy between this study and previous studies. The control and hypertensive groups, as noted in the paper, had no significant difference with respect to age by the Student t-test on a group comparison of these two populations. Using a 2 x 2 contingency table we found no significant difference in distribution between males and females in the two groups. As noted above, neither controls nor hypertensives were azotaemic, the hypertensives being selected from that group which still had normal renal function. Urinary cadmium levels were not as discriminating in our hands as blood cadmium levels in differentiating normotensives from early essential hypertensives. The matter of urinary cadmium levels is unresolved: Wester’ did not find differences between normotensives and hypertensives whereas Perry and Schroeder2did find differences, We feel the blood cadmium level is biologically more significant and at least as good a discriminator as the urinary cadmium level. It is true and unfortunate that Lener and Bibr4 did not present data on the liver level of cadmium in human hypertensives, but concomitantly raised cadmium in the liver and kidney have been found in dogs, rats,6 and rabbits.7 One would hope ’. that in the near future the World Health Organisation8 will be ! able to rectify this deficit. In the discussion of the relation between cadmium levels and hypertension, the dose-dependent biphasic response of the mammalian organism to cadmium levels should be borne in mind. The results of Perry3 indicate that with chronic exposure to slightly raised cadmium levels one sees a hypertensive response due to an increase in cardiac output. Chronic expoto
i
1 Wester, P. O. Acta med. scand. 1973, 194, 505. 2 Perry, H. M., Schroeder, H. A. J. Lab. clin. Med. 1955, 46, 936. 3 Perry, H. M. in Trace Substances in Environmental Health-II (edited by D D. Hemphill); p. 101. Columbia, Missouri, 1968. 4 Lener. J. Bibr, B. Lancet, 1971, i, 970. 5 Byerrum, R. U., Anwar, R. A., Hoppert, C. A. J. Am. Water Works Ass. 1960, 52, 651. 6 Decker, L. E., Byerrum, R. U., Decker, C. F., Hoppert, C. A. Langham, R F Archs. ind. Hlth, 1958, 18, 228. 7 Fischer, G. M., Thind, G. S. Archs environ, Hlth, 1971, 23, 107. 8 Masironi, R. Trace Elements in Relation to Cardiovascular Disease. W.H.O. Offset Publication no. 5, Geneva, 1974.
high levels of cadmium does not produce hypertension. The same phenomena are seen in human beings, in whom modest elevation of cadmium leads to hypertension while severe cadmium toxicity is not associated with hypertension.9 Thus the dose of the cadmium and the duration of exposure are both crucial in determining what type of disease results from exposure to cadmium. In a set of experiments with previously untreated hypertensive patients, we have demonstrated a very significant drop in the blood cadmium levels into the normal range concomitant with a drop in the blood-pressure, systolic and diastolic, into the normal range for those hypertensive patients treated with a thiazide diuretic.’° These patients had no change in their smoking habits. sure to
Department of Pharmacology, Temple University Medical School,
Philadelphia, Pennsylvania 19140, S. C. GLAUSER
U.S.A.
PRESCRIBING IN GENERAL PRACTICE
SIR,-I found Dr Bliss’s article (July 31, p. 248) irritating, because her criticism of repeat prescriptions was invalid,
not
but because, like most G.P.s, I have heard it all before. For years I have been told in the medical Press that I do not know enough aoout, nor do enough for, mental illness, deafness, arthritis, or wife-beaters. I have been told one year that I must have an appointments system and the next that I must scrap it because it interferes with the patient’s access to medical care. Criticism of repeat prescriptions is at least twenty years old and has generated an excellent monograph" which would give Dr Bliss an insight into the reason for the repeat prescription and might temper her criticism of the way in which it is issued. The fact is that few people seem prepared to take the view, or at least investigate it rationally, that the general-practitioner service in its present form is a luxury that the ailing N.H.S. can no longer afford. One half of my workload is concerned with self-limiting minor illness for which the available treatments do not alter the natural history of the disease. Theorists of general practice advise us to refuse to deal with the "common cold", whereas the patient knows he has the right to see his doctor almost when and where he chooses. If he is denied this, the doctor can easily find himself the subject of an unpleasant complaint. Another quarter, perhaps, is spent diagnosing conditions that will have to be treated by other doctors, Why, for instance, does the unfortunate patient with a hernia have to come through me to be sent to a surgeon who will carry out an identical history and examination? The other quarter of the work may represent a real contribution to the welfare of the individual, providing that the G.P. is not so demoralised by the pressure of trivia that he no longer has the application to tackle the minority of his practice whom he can
really help. It must be apparent by now, after all the soul-searching that has been done on behalf of general practice, that the way the service is run is wasteful both of money and of men. Those who would reform it might find it profitable to ask first whether it is necessary to have general practitioners at all, rather than nibble at their more obvious shortcomings. And if the answer is that we are required, then it should be decided exactly what contribution we should be making to the public’s health and this part of the N.H.S. reformed in order to enable us to make it. The Surgery, Newport, Pembs. SA42 0TS 9. 10. 11.
J. C. BIGNALL
Tsuchiya, K. Keto J. Med. 1969, 18, 181. Glauser, E. M., Glauser, S. C., Bello, C. T. Pharmacologist, 1976, 18, 188. Balint, M., and others. Treatment or Diagnosis: a Study of Repeat Prescriptions in General Practice. London, 1970.
372
SiR,—Iam
that many of your readers could add their Dr Bliss. As a G.P. I feel that I can be less charitable and more forthright in my condemnation of these doctors. There can be no justification or excuse for lack of control over the prescription of potentially harmful medicines. Doctors who fail to give proper consideration to each prescription they sign are either totally ignorant of drugs’ potential for harm or, worse still, know the dangers of their prescriptions but are prepared to ignore them out of pure laziness. In either case, their conduct is far more reprehensible than that of the doctor guilty of the kind of misdemeanour with which the G.M.C. seems eternally preoccupied. It is all very well for our profession to throw up its hands in horror when an M.P. threatens to curb our freedom to prescribe, but how on earth can we claim this freedom when so many of our number are abusing it so flagrantly? The answer to the bad doctor is not more complicated prescribing rules-Dr Bliss herself describes one situation in which the present regulations are flouted. Bad doctors only survive in the shadows where they do not have to justify their bad habits: once they emerge into the light of day and have to justify themselves to their peers, the quality of their medicine must rise sufficiently to keep their self-respect afloat.
own
SIR,-Lack of any quantitative data makes Dr Bliss’s argufor change impossible to evaluate, but I would suggest
sure
hair-raising anecdotes to those of
The answer to bad medicine is audit, and if our profession does not organise peer review on a large scale in the very near future, we may find punitive audit imposed from the dizzy heights of the D.H.S.S. After all, if we abdicate responsibility for standards of care, who can blame the Minister for stepping in? 112A Dib Lane, Leeds LS8 3AY
ARNOLD G. ZERMANSKY
SIR,-Dr Bliss draws attention to the ubiquitous but real problem of repeat prescribing in general practice. She is perhaps less than fair to the experienced doctor in continuing practice, having drawn her conclusions from findings during locum posts, presumably of relatively short duration. Each practice evolves its own "system" for the safe issue of inevitable repeat prescriptions without consultation. Firstly, a receptionist, if employed, must be trained to handle telephone requests reliably. I agree that the supply of signed blank prescription forms to anyone is to be strongly deprecated. Secondly, adequate record-keeping is essential for the benefit of one’s patients, one’s colleagues, and oneself. Thirdly, the apparent confusion over hospital-prescribed drugs could be dispelled by better recording in notes. The delegation of repeat prescribing to trained pharmacists would in practice lead to legal and administrative difficulties, and is not, for practical purposes, feasible. The issue of a prescription for whatever substance places certain legal and ethical responsibilities on the prescriber which cannot be shirked. No system is foolproof, and Dr Bliss may have acted for practitioners whose arrangements may require revision, or her experiences may have been singularly unfortunate. As an example, we use a coloured small proforma, not of our own basic design, kept by the patient, bearing the basic information of drugs prescribed, dates of repeats, and of the next consultation clearly recorded. These intervals are strictly monitored by ourselves and our staff. This may be only one way of solving some of the potentially dangerous situations to which Dr Bliss has rightly drawn attention. I hope that both she and I will sometime reach the ideal of seeing every patient personally every time a "repeat" is requested. Under present conditions of practice workload, this sort of Utopia is regrettably unattainable. 131 Dartmouth Road, London NW2 4ES
D. S. NACHSHEN
ments
that most repeat prescriptions are not for short-term therapy but for conditions such as diabetes, hypertension, epilepsy, &c. If anything, these patients should be made more responsible for their own treatment, not hedged around with more legislation. 32
Raphael Drive, Elburton,
G. M. WAKLEY
Plymouth
PRENATAL SEX-HORMONE EXPOSURE AND CONGENITAL LIMB-REDUCTION DEFECTS
SiR,—Nora and Nora’ recorded exposure
period of embryogenesis
to a
at a vulnerable progestagen-oestrogen compound
progestagen alone in 8 of 10 patients with multiple congenital anomalies, mainly of the VACTEL type (vertebral, anal, cardiac, tracheal, cesophageal, limb). A similar exposure was found in 20 of 224 patients with congential heart-disease. A or a
connection between malformations and hormone exposure was, however, not supported by Oakley et al. who interviewed more than 400 mothers with malformed children.2 More than 10% of these had had a hormone pregnancy test during the first trimester, but it seemed unlikely that this was the cause of the malformations because there was no difference in such exposure between the chromosomal and non-chromosomal malformations. Studies on the relation between prenatal sexhormone exposure and cardiac defects, especially transposition of the great vessels, have been conflicting.34 Janerich et al.’ investigated the exposure to exogenous sex steroids during pregnancy for 108 mothers of patients with congenital limb-reduction defects and 108 mothers of normal controls. Exposure resulted from pregnancy tests, supporting hormone therapy early in pregnancy, and breakthrough pregnancies in women using oral contraceptives. Among mothers with malformed children 14% had a history of exposure; 4% of the control mothers were exposed. Affected children with a history of exposure to orally administered hormones were all males. In a parallel study oral-contraceptive failure was reported among approximately 300 mothers of children with spina bifida. The rate of such a failure was almost the same as in a similar number of control mothers. The rate was slightly lower in both groups than in that of the controls from the limb-reduction study. Nora and Nora6 gave additional data supporting the possible connection between progestagen-cestrogen exposure and VACTERL malformations (R
=
renal). We have been following up 35patients with congenital limb deformities born during 1965-74. We contacted 32 of these families and asked parents to report on exposure to a hormone pregnancy test, oral-contraceptive failure, and hormone treatment for threatened abortion during the first 3 months of pregnancy. As a control group 30 mothers of children with spina bifida born during the same period were asked the same questions. The groups did not differ with regard to age or parity of the mothers. In the group with the limb-reduction defects 3 mothers had had a hormone pregnancy test and 4 had been treated with hormone: no instance of oral-contraceptive failure was recorded. 1 control mother had had a hormone pregnant test and she had also been on hormone treatment for threatened abortion. In the limb-reduction group all the 3 malformed children whose mothers had had hormone pregnancy tests were males. 1. Nora, J. J., Nora, A. H. Lancet, 1973, i, 941. 2. Oakley, G. P., Jr, Flynt, W. J., Jr, Falek, A. ibid. 1973, ii, 256. 3. Levy, E. P., Cohen, A., Fraser, F. C. ibid. 1973, i, 611. 4. Mulvihill, J. J., Mulvihill, C. G., Oneill, C. A. Teratology, 1974, 9, A30. 5. Janerich, D. T., Joyce, M. P. H., Piper, M. S., Glebatis, D. M. New Engl. J. Med. 1974, 291, 697. 6. Nora, J. J., Nora, A. H. ibid. p. 731.
