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ANTIDIABETIC DRUGS AND TERATOGENICITY
1264 "
(2) The higher frequency of X-ray examinations in the M series is a consequence of the lower ’pre-leuksemic fitness ’ of this group. For example, genetic carriers for M-type leukaemias could also be more susceptible to certain infectious diseases, and more accident-prone than the general population. (3) By a combination of (1) and (2). "
"
The last possibility is favoured here I further indicated that it is difficult to assess the relative contributions from (1) and (2). Dr. MacMahon and Dr. Stewart (March 30) evidently share some of my agnosticism, although Dr. Wise wishes to explain all the
evidence by
hypothesis (1).
The argument regarding the latent period is best illustrated from the accompanying figure. It will be seen that the interval between irradiation and the onset of leukxmia is generally shorter in the (mainly heavily irradiated) ankylosing-spondylitis series (curve 2) than in the (less heavily irradiated) survivors at Hiroshima and Nagasaki (curve 1). I pointed out that a difference of this kind is to be expected on the basis of animal experiments where large doses of radiation are associated with a relatively short latent period. For some reason Dr. Wise mistakenly regards this observation as a criticism of his calculations.3 Although the difference in latent period distribution between the ankylosing-spondylitis series and the nuclear bomb survivors is understandable, it is impossible to account for all the diagnostic X-ray (low dose) evidence (curve 3) in the same way. A special explanation is called for and the preleukaemic unfitness hypothesis (2) has the advantage of harmonising a wide range of other epidemiowith thatunder logical evidence (quoted in footnote discussion. Dr. Wise’s contention that the leukaemic response in the ankylosing-spondylitis series was not well correlated with the mean dose to spinal marrow needs to be considered in relation to the extreme complexity of the dose-response relationship described elsewhere."6 For small doses of radiation to the adult, however, I conclude that the average dose to cells at risk "-which for myeloid leukaemias can probably be regarded as the average dose to active bone-marrow-should be a good guide to the leukaemogenic effect. The apparent ineffectiveness of digestive " as compared with " respiratory " X-rays (table 15 4) is very difficult to account for on the radiogenic "
"
5)
"
"
hypothesis (1). To decide whether any of the excess of diagnostic X-rays in the M series was due to an excess of illnesses or accidents in that group, it is important that the age structure and sexratio of the M series and any control group should be identical. The table (compiled from table 5 4) reveals big discrepancies between the M series and any other group:
It will be surprising if the younger and more feminine composition of the M series does not affect some of the conclusions (table 14 ) regarding the relative frequency of illnesses and accidents.
Further discussion of the possible leukxmogenic role of infection should perhaps be deferred until Dr. Stewart and her colleagues have completed their analysis. Medical Research Council, Environmental Radiation Research Unit, Department of Medical Physics,
University of Leeds, The General Infirmary, Leeds. 5. 6.
P. R.
J. BURCH.
Burch, P. R. J. Nature, Lond. 1963, 197, 1042, 1145. Burch, P. R. J. Discovery 1963, 24, 2, 16.
ANTIDIABETIC DRUGS AND TERATOGENICITY SIR,-Dr. Sterne’s statement (May 25) that " Insulin is the most suitable drug for the treatment of pregnant diabetic women " should be corrected to read that insulin is the only suitable drug for the treatment of pregnant diabetic women. There is as yet far too little information available about the effects of oral hypoglycxmic agents in pregnancy and it seems prudent therefore to avoid the use of these drugs in any woman likely to conceive. Finally, our experience would not support his contention that " diabetic women, even if the disease is well controlled, are not very fertile ". M. I. DRURY. National Maternity Hospital, Dublin. WHOLE-TIME CONSULTANTS AND DOMICILIARY VISITS
SIR,-Dr. Smith (May 18) takes for granted that pathologists do domiciliary consultations, and he may infei (but does not specifically state) that they form part of his
continuing education and are good for his patients, as is so obviously true for consultants, physicians, and surgeons, In my opinion a pathologist should not do domiciliary work unless he has full charge of hospital beds. If he has not such charge he will find himself providing no more than a blood-taking service. This is a function at which he certainly becomes expert, but no more expert than: say, an ansesthetist, or an enthusiastic medical student, or a houseman, or a 17-year-old laboratory technician, or a nurse who has been enabled to practise this technique. The pathologist can be fully occupied in attending to the accuracy of the tests performed in his laboratory, and in the discussion of the relevance of their results, as his main duties. For example the control of anticoagulant therapy is the duty of the man who initiates it, and who has full clinical charge of the case and of the hospital bed which may be necessary to deal with complications of the therapy. In avoiding the diversions of private practice and domiciliary consultations the whole-time non-physician pathologist would also do better to have coroners’ postmortems as part of his duties (not paid for, as at present, as overtime work "). The solution to the problem of who does coroners’ work which the forensic pathologists recently have put forward (intended to avoid missing the small numbers of murders, mainly by poisoning, which they feel go undetected when unforensically trained pathologists perform postmortem examinations) is a logical solution only if all postmortem examinations (including hospital ones) are carried out by the same trained group of morbid anatomists (with their central forensic affiliation). This solution is at present excessive, and would be a wasteful loss of the experience of and experience given to the ordinary hospital pathologist, since the sudden-death problems he has to face contribute much to his clinical-pathologist acumen, and certainly assist him in applying the maximum " suspicion index " (in the best scientific interpretation of this concept) to his hospital cases. "
At present it is this " coroners’ overtime work " (and domiciliary consultations) that contributes to the continuing education of the pathologist, and thus to the good of the patients whom he serves in the ratio of more than one hundred of the living to one dead (ratio of patientrequests per annum to postmortems per annum). He cannot fail to profit from the analysis of symptoms in all types of common disease which he hears described by both clinicians and policemen (from relatives) and he is thus helped in maintaining and increasing his awareness of the clinical aspect of his work. not
County Hospital, York.
G. A. C. SUMMERS.
(2) The higher frequency of X-ray examinations in the M series is a consequence of the lower ’pre-leuksemic fitness ’ of this group. For example, genetic carriers for M-type leukaemias could also be more susceptible to certain infectious diseases, and more accident-prone than the general population. (3) By a combination of (1) and (2). "
"
The last possibility is favoured here I further indicated that it is difficult to assess the relative contributions from (1) and (2). Dr. MacMahon and Dr. Stewart (March 30) evidently share some of my agnosticism, although Dr. Wise wishes to explain all the
evidence by
hypothesis (1).
The argument regarding the latent period is best illustrated from the accompanying figure. It will be seen that the interval between irradiation and the onset of leukxmia is generally shorter in the (mainly heavily irradiated) ankylosing-spondylitis series (curve 2) than in the (less heavily irradiated) survivors at Hiroshima and Nagasaki (curve 1). I pointed out that a difference of this kind is to be expected on the basis of animal experiments where large doses of radiation are associated with a relatively short latent period. For some reason Dr. Wise mistakenly regards this observation as a criticism of his calculations.3 Although the difference in latent period distribution between the ankylosing-spondylitis series and the nuclear bomb survivors is understandable, it is impossible to account for all the diagnostic X-ray (low dose) evidence (curve 3) in the same way. A special explanation is called for and the preleukaemic unfitness hypothesis (2) has the advantage of harmonising a wide range of other epidemiowith thatunder logical evidence (quoted in footnote discussion. Dr. Wise’s contention that the leukaemic response in the ankylosing-spondylitis series was not well correlated with the mean dose to spinal marrow needs to be considered in relation to the extreme complexity of the dose-response relationship described elsewhere."6 For small doses of radiation to the adult, however, I conclude that the average dose to cells at risk "-which for myeloid leukaemias can probably be regarded as the average dose to active bone-marrow-should be a good guide to the leukaemogenic effect. The apparent ineffectiveness of digestive " as compared with " respiratory " X-rays (table 15 4) is very difficult to account for on the radiogenic "
"
5)
"
"
hypothesis (1). To decide whether any of the excess of diagnostic X-rays in the M series was due to an excess of illnesses or accidents in that group, it is important that the age structure and sexratio of the M series and any control group should be identical. The table (compiled from table 5 4) reveals big discrepancies between the M series and any other group:
It will be surprising if the younger and more feminine composition of the M series does not affect some of the conclusions (table 14 ) regarding the relative frequency of illnesses and accidents.
Further discussion of the possible leukxmogenic role of infection should perhaps be deferred until Dr. Stewart and her colleagues have completed their analysis. Medical Research Council, Environmental Radiation Research Unit, Department of Medical Physics,
University of Leeds, The General Infirmary, Leeds. 5. 6.
P. R.
J. BURCH.
Burch, P. R. J. Nature, Lond. 1963, 197, 1042, 1145. Burch, P. R. J. Discovery 1963, 24, 2, 16.
ANTIDIABETIC DRUGS AND TERATOGENICITY SIR,-Dr. Sterne’s statement (May 25) that " Insulin is the most suitable drug for the treatment of pregnant diabetic women " should be corrected to read that insulin is the only suitable drug for the treatment of pregnant diabetic women. There is as yet far too little information available about the effects of oral hypoglycxmic agents in pregnancy and it seems prudent therefore to avoid the use of these drugs in any woman likely to conceive. Finally, our experience would not support his contention that " diabetic women, even if the disease is well controlled, are not very fertile ". M. I. DRURY. National Maternity Hospital, Dublin. WHOLE-TIME CONSULTANTS AND DOMICILIARY VISITS
SIR,-Dr. Smith (May 18) takes for granted that pathologists do domiciliary consultations, and he may infei (but does not specifically state) that they form part of his
continuing education and are good for his patients, as is so obviously true for consultants, physicians, and surgeons, In my opinion a pathologist should not do domiciliary work unless he has full charge of hospital beds. If he has not such charge he will find himself providing no more than a blood-taking service. This is a function at which he certainly becomes expert, but no more expert than: say, an ansesthetist, or an enthusiastic medical student, or a houseman, or a 17-year-old laboratory technician, or a nurse who has been enabled to practise this technique. The pathologist can be fully occupied in attending to the accuracy of the tests performed in his laboratory, and in the discussion of the relevance of their results, as his main duties. For example the control of anticoagulant therapy is the duty of the man who initiates it, and who has full clinical charge of the case and of the hospital bed which may be necessary to deal with complications of the therapy. In avoiding the diversions of private practice and domiciliary consultations the whole-time non-physician pathologist would also do better to have coroners’ postmortems as part of his duties (not paid for, as at present, as overtime work "). The solution to the problem of who does coroners’ work which the forensic pathologists recently have put forward (intended to avoid missing the small numbers of murders, mainly by poisoning, which they feel go undetected when unforensically trained pathologists perform postmortem examinations) is a logical solution only if all postmortem examinations (including hospital ones) are carried out by the same trained group of morbid anatomists (with their central forensic affiliation). This solution is at present excessive, and would be a wasteful loss of the experience of and experience given to the ordinary hospital pathologist, since the sudden-death problems he has to face contribute much to his clinical-pathologist acumen, and certainly assist him in applying the maximum " suspicion index " (in the best scientific interpretation of this concept) to his hospital cases. "
At present it is this " coroners’ overtime work " (and domiciliary consultations) that contributes to the continuing education of the pathologist, and thus to the good of the patients whom he serves in the ratio of more than one hundred of the living to one dead (ratio of patientrequests per annum to postmortems per annum). He cannot fail to profit from the analysis of symptoms in all types of common disease which he hears described by both clinicians and policemen (from relatives) and he is thus helped in maintaining and increasing his awareness of the clinical aspect of his work. not
County Hospital, York.
G. A. C. SUMMERS.