29 "
grounds of the " inoperability of the fetal lesion. Indeed, mere size alone is of little impor-
justified simply
on
the
in connection with the ease of surgery in these cases. I should add that lesions in the sacral area are not " probably operable "-they all are. One must not confuse the objective fact that nearly all lesions in spina bifida are treatable and operable with one’s subjective judgment as to whether or not the results of such surgery are acceptable or worthwhile. The Children’s Hospital, Western Bank, R. J. BRERETON. Sheffield S10 2TH. tance
COXSACKIE B4 VIRUS INFECTION AND DIABETES
SIR,-The interesting report by Dr Dippe and his colleagues (June 14, p. 1314) has highlighted a difficult but important question concerning the aetiology of juvenileonset diabetes. Although a negative correlation was found between a severe epidemic of CB4 infection and the develop-. of diabetes, notably in the 5-20-year age-group in the community on the Pribilof Islands, this does not exclude viral infection and in particular CB4 as a cause of islet-cell injury in genetically susceptible individuals. It has been shown that individuals possessing HL-A8 or W15 antigens have an approximate 2-3-fold increased risk of developing insulin-dependent diabetes. 1-4 Furthermore, strong evidence that the major locus producing susceptibility to this type of diabetes is in the HL-A chromosomal region has been obtained by study of siblings with " juvenile " diabetes. The fundamental question is what is the mechanism of action of this HL-A-linked diabetogenic gene(s) ? It is likely that different alleles at this locus are interacting with different environmental factors to precipitate clinical disease. The circumstantial evidence for CB4 infection as a possible triggering environmental factor in the U.K. is well known.ó However, this type of epidemiological evidence, together with current estimates of the population incidence of juvenile onset diabetes, suggest that only a small proportion of individuals are likely to develop diabetes as a result of CB4 infection, and the population studied by Dippe et al. may not be large enough to detect this association. If the concept of viruses interacting with HL-A-linked genes to produce diabetes is a real one, a way of investigating this would be to ascertain whether a positive association exists between evidence for recent infection with a particular virus and HL-A8 or W15, these antigens being in linkage disequilibrium with the diabetogenic genes. Thus, HL-A8 might be linked with a gene which interacts with one virus or group of viruses, and W15 with another. If HL-Alinked genes are present in the Aleuts, they might produce susceptibility to diabetes by interacting with viruses other than CB4. Since the national register for diabetic children was started in 1972 under the segis of the British Diabetic Association, 69 blood-samples have been received for virological analysis from new diabetics under the age of 16 years residing in the Liverpool area. Efforts are being made to trace all these children for HL-A typing. From Oct. 1, 1974, all the new cases of diabetes under the age of 30 years (43 cases so far) have been seen within a week of onset of clinical symptoms in order to obtain blood as early as possible for estimation of virus-antibody titres as well as HL-A typing. It is hoped that these retrospective ment
Nerup, J., et al. Lancet, 1974, ii, 864. Cudworth, A. G., Woodrow, J. C. ibid. p. 1153. Cudworth, A. G., Woodrow, J. C. Diabetes, 1975, 24, 345. Cudworth, A. G., Woodrow, J. C. Br. med. J. (in the press). 5. Gamble, D. R. Postgrad. med. J. 1974, 50, suppl. 3, p. 538. 1. 2. 3. 4.
and prospective studies will throw further light on the relative importance of CB4 and other known virological agents in the pathogenesis of juvenile-onset diabetes. University Department of Medicine, A. G. CUDWORTH P.O. Box 147,
Liverpool L69 3BX. Public Health Laboratory, West Park Hospital, Epsom, Surrey.
J. C. WOODROW. D. R. GAMBLE.
MAGNESIUM AND MYOCARDIAL ISCHÆMIA SIR,-At a symposium held by the E.E.C. in Luxembourg this May, D. G. Clayton described the higher incidence of heart-attacks in the soft-water areas of North-West England and in Scotland in comparison with the hard-water areas of the South-East. The problem is complicated by differences in the social-class structure of the populations, in smoking habits, and in other variables. Nevertheless, many studies have provided evidence that hard water does appear to offer some protection against dying from a heartattack. 2-10 Calcium or magnesium salts seem to be the likeliest factors; for instance, the magnesium in the myocardium has been found to be low after an ischaemic heart-attack." Many thousands of people in Great Britain and Ireland are in the habit of taking effervescent health salts (magnesium sulphate) every morning, and these salts greatly increase their daily intake of magnesium. It would be interesting to find out whether regular takers of salts living in areas of soft water have a lower risk of dying from a heart-attack than the rest of the community. As a previous correspondent pointed out, perhaps those who take " enough to cover a sixpence every morning have been wiser than they realised.12
grounds of the " inoperability of the fetal lesion. Indeed, mere size alone is of little impor-
justified simply
on
the
in connection with the ease of surgery in these cases. I should add that lesions in the sacral area are not " probably operable "-they all are. One must not confuse the objective fact that nearly all lesions in spina bifida are treatable and operable with one’s subjective judgment as to whether or not the results of such surgery are acceptable or worthwhile. The Children’s Hospital, Western Bank, R. J. BRERETON. Sheffield S10 2TH. tance
COXSACKIE B4 VIRUS INFECTION AND DIABETES
SIR,-The interesting report by Dr Dippe and his colleagues (June 14, p. 1314) has highlighted a difficult but important question concerning the aetiology of juvenileonset diabetes. Although a negative correlation was found between a severe epidemic of CB4 infection and the develop-. of diabetes, notably in the 5-20-year age-group in the community on the Pribilof Islands, this does not exclude viral infection and in particular CB4 as a cause of islet-cell injury in genetically susceptible individuals. It has been shown that individuals possessing HL-A8 or W15 antigens have an approximate 2-3-fold increased risk of developing insulin-dependent diabetes. 1-4 Furthermore, strong evidence that the major locus producing susceptibility to this type of diabetes is in the HL-A chromosomal region has been obtained by study of siblings with " juvenile " diabetes. The fundamental question is what is the mechanism of action of this HL-A-linked diabetogenic gene(s) ? It is likely that different alleles at this locus are interacting with different environmental factors to precipitate clinical disease. The circumstantial evidence for CB4 infection as a possible triggering environmental factor in the U.K. is well known.ó However, this type of epidemiological evidence, together with current estimates of the population incidence of juvenile onset diabetes, suggest that only a small proportion of individuals are likely to develop diabetes as a result of CB4 infection, and the population studied by Dippe et al. may not be large enough to detect this association. If the concept of viruses interacting with HL-A-linked genes to produce diabetes is a real one, a way of investigating this would be to ascertain whether a positive association exists between evidence for recent infection with a particular virus and HL-A8 or W15, these antigens being in linkage disequilibrium with the diabetogenic genes. Thus, HL-A8 might be linked with a gene which interacts with one virus or group of viruses, and W15 with another. If HL-Alinked genes are present in the Aleuts, they might produce susceptibility to diabetes by interacting with viruses other than CB4. Since the national register for diabetic children was started in 1972 under the segis of the British Diabetic Association, 69 blood-samples have been received for virological analysis from new diabetics under the age of 16 years residing in the Liverpool area. Efforts are being made to trace all these children for HL-A typing. From Oct. 1, 1974, all the new cases of diabetes under the age of 30 years (43 cases so far) have been seen within a week of onset of clinical symptoms in order to obtain blood as early as possible for estimation of virus-antibody titres as well as HL-A typing. It is hoped that these retrospective ment
Nerup, J., et al. Lancet, 1974, ii, 864. Cudworth, A. G., Woodrow, J. C. ibid. p. 1153. Cudworth, A. G., Woodrow, J. C. Diabetes, 1975, 24, 345. Cudworth, A. G., Woodrow, J. C. Br. med. J. (in the press). 5. Gamble, D. R. Postgrad. med. J. 1974, 50, suppl. 3, p. 538. 1. 2. 3. 4.
and prospective studies will throw further light on the relative importance of CB4 and other known virological agents in the pathogenesis of juvenile-onset diabetes. University Department of Medicine, A. G. CUDWORTH P.O. Box 147,
Liverpool L69 3BX. Public Health Laboratory, West Park Hospital, Epsom, Surrey.
J. C. WOODROW. D. R. GAMBLE.
MAGNESIUM AND MYOCARDIAL ISCHÆMIA SIR,-At a symposium held by the E.E.C. in Luxembourg this May, D. G. Clayton described the higher incidence of heart-attacks in the soft-water areas of North-West England and in Scotland in comparison with the hard-water areas of the South-East. The problem is complicated by differences in the social-class structure of the populations, in smoking habits, and in other variables. Nevertheless, many studies have provided evidence that hard water does appear to offer some protection against dying from a heartattack. 2-10 Calcium or magnesium salts seem to be the likeliest factors; for instance, the magnesium in the myocardium has been found to be low after an ischaemic heart-attack." Many thousands of people in Great Britain and Ireland are in the habit of taking effervescent health salts (magnesium sulphate) every morning, and these salts greatly increase their daily intake of magnesium. It would be interesting to find out whether regular takers of salts living in areas of soft water have a lower risk of dying from a heart-attack than the rest of the community. As a previous correspondent pointed out, perhaps those who take " enough to cover a sixpence every morning have been wiser than they realised.12
