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menon which has been more striking in adult diabetes.5 6 A survey among children under 16 years in Erie County, New York,7 found a similar sex distribution, but again the differences were very small. On the other hand, a recent British report8 showed the reverse, the male prevalence up to age 26 being 3-2 per 1000 and the female prevalence 2-8. The most accurate information about diabetic children in Great Britain and Ireland is to be found in a register sponsored by the British Diabetic Association. Notifications between 1972 and 1974 showed an excess of boys from 0 to 4 years and from 11 to 15 years and of girls from 5 to 10 years.9 Overall there were more boys (1279) than girls (1145), and the minimum annual incidence for both sexes combined was 8 cases per 100 000. Added weight is lent to these figures by the very close similarity of sex ratios in diabetic Israeli children of equivalent age groups.'0 Can these sex differences be satisfactorily explained ? Both genetic" and environmental factors are thought to be important in juvenile diabetes. There is mounting evidence, mostly circumstantial, that viruses may initiate the pathogenetic process in some cases of insulin-dependent diabetes.'2 Coxsackie B,'3-15 mumps,'6 and rubellal7 viruses have each been implicated. Now sex differences are known to occur in the incidence of childhood viral infections. In both Britain'8 I"' and the United -States2" Coxsackie B infections are twice as common in boys as in girls, and a similar male preponderance has been described in outbreaks of Coxsackie A virus,21

echovirus,2: and poliovirus24 infections. Boys may come into closer contact with each other during play than girls, but this seems unlikely to be the whole explanation. The newly described Y-linked histocompatibility locus25 raises the possibility of hereditary sexual differences in susceptibility to adenovirus,22

infections. An investigation of schoolchildren aged 9-12 years found higher mean serum insulin concentrations in girls than in boys one hour after a 50-g oral glucose load.26 The antagonistic action on insulin of higher serum concentrations of oestrogen and growth hormone in the prepubertal girls was suggested as a possible cause. There is substantial evidence that female hormones may influence the onset and clinical course of diabetes in later life: pregnancy may unmask latent diabetes or aggravate pre-existing disease, and multiparous women are much more likely to develop diabetes than women with no children.27 Surprisingly, the effect of parity is delayed for many years. Oral oestrogens may cause deterioration of glucose tolerance,28 and some women experience changes in diabetic control related to the menstrual cycle. Diabetic coma,2" urinary tract infections,3" and skin conditions such as necrobiosis lipoidica diabeticorum31 and lipoatrophy32 are all commoner in women than in men, and the normal life expectation advantage of women over men is abolished in female diabetics by the susceptibility to coronary disease.33 Microangiopathic complications affect the sexes equally. Juvenile diabetes may lend itself to subdivision into separate entities with different aetiologies.34 : One suggestion is that individuals may vary in their genetic susceptibility to diabetogenic viruses.36 37 The excess of males with childhood diabetes may be explained by the tendency for enterovirus infections to be commoner in boys than girls.' 8- 2() Furthermore, the prevalence of infections with different virus types varies from year to year and country to country; this might explain temporal and geographical variations in sex incidence. Beardmore, M, and Reid, J J A, British Medical Journal, 1966, 2, 1383. Jarrett, R J, British J'ournal of Hospital Medicine, 1976, 16, 200. 3 Tattersall, R B, Quarterly J7ournal of Medicine, 1974, 43, 339.

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Jloslin's Diabetes Mellituts,

11th edn, ed Marble A, et al, p 13. Philadelphia, Lea and Febiger, 1971. 5 Malins, J M, FitzGerald, M G, and Wall, M, Diabetologia, 1965, 1, 121. 6 Nicholson, W A, British Medical3Journal, 1971, 4, 465. 7Sultz, H A, Schlesinger, E R, and Mosher, W E, American Journal of Public Health, 1968, 58, 491. Wadsworth, M E J, and Jarrett, R J, Lancet, 1974, 2, 1172. 9 Bloom, A, Hayes, T M, and Gamble, D R, British Medical Journal, 1975, 3, 580. '"Cohen, T, Nelken, L, and Wolfsohn, H, Diabetes, 1970, 19, 585. Penrose, L S, and Watson, E M, Proceedings of the American Diabetes Association, 1945, 5, 165. 12 Steinke, J, and Taylor, K W, Diabetes, 1974, 23, 631. 13 Gamble, D R, and Taylor, K W, British 1969, 3, 631. 14 Gamble, D R, et al, British Medical3Journal, 1969, 3, 627. 5 Gamble, D R, Taylor, K W, and Cumming, H, British Medical3Journal, 1973, 4, 260. 6 Sultz, H A, et al, J7ournal of Pediatrics, 1975, 86, 654. 17 Forrest, J M, Menser, M A, and Burgess, J A, Lancet, 1971, 2, 332. 18 British Medical Journal, 1971, 2, 178. 19 British 1972, 1, 453. 211 Lennette, E H, Magoffin, R L, and Knouf, E G,3Journal of the American Medical Association, 1962, 179, 687. 21 Connolly, J H, and O'Neill, H J, Ulster 1971, 40, 146. 22 Sutton, R N P, et al, Lancet, 1976, 2, 987. 23 Connolly, J H, and O'Neill, H J, Ulster Medical Journal, 1972, 41, 155. 24 Hall, W J, Nathanson, N, and Langmuir, A D, American Journal of Hygiene, 1957, 66, 214. 25 Lancet, 1976, 2, 1008. 2t; Florey, C du V, Lowy, C, and Uppal, S, Diabetologia, 1976, 12, 313. 27 Pyke, D A, Lancet, 1956, 1, 818. 28 Spellacy, W N, American Journal of Obstetrics and Gynecology, 1969, 104, 448. 29 Hockaday, T D R, and Alberti, K G M M, British Journal of Hospital Medicine, 1972, 7, 183. 30 Thornton, G F, Medical Clinics of North America, 1971, 55, 931. 31 Braverman, I M, Medical Clinics of North America, 1971, 55, 1019. 32 Pyke, D A, Postgraduate Medical3Journal, 1971, 47, January suppl, p 54. 33 Pyke, D A, Postgraduate Medical Journal, 1968, 44, 966. 34 Cudworth, A G, British Journal of Hospital Medicine, 1976, 16, 207. 35 Bottazzo, G F, and Doniach, D, Lancet, 1976, 2, 800. 36 Nelson, P G, et al, Lancet, 1975, 2, 193. 37 Nelson, P G, Pyke, D A, and Gamble, D R. British Medical Journal, 1975, 4, 249.

Medical_Journal,

Medical_Journal,

Medical_Journal,

Breast conservation in mammary carcinoma In recent years publications on the management of primary carcinoma of the breast have been dominated by the radicalversus-conservative controversy, complicated recently by a superimposed debate on the place of adjuvant systemic chemotherapy. Perhaps of more interest to the average woman than whether or not her axilla should be entered is the place for breast conservation in the treatment of primary carcinoma. Contrary to the stereotype image, today's breed of surgeon is in fact well aware of the psychological insult that may result from mastectomy. This gives a compassionate motive for preserving the breast, but there is also a widely held view that should the public be aware that a lump in the breast need not necessarily imply a mastectomy women would present themselves earlier in the development of the disease. A recent study by Watts' was started with these motives in mind. He described a series of 200 cases spread over seven years in which subcutaneous mastectomy was followed by reconstruction using a silicone implant. Selection of favourable cases presenting with small carcinomata made comparison with conventional treatment of little value. Nevertheless, the local recurrence rate of 60 and the fact that there were only four deaths from carcinoma suggest that this method of treatment warrants serious consideration. Watts's conclusions, however, were couched in emotive language and should not go without challenge. "Perhaps most important of all," he wrote, "is the ,

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fact that patients are now less afraid of mastectomy and the mutilation which it has previously entailed. This means less emotional distress and also encourages them to seek help earlier than they might otherwise have done." Though at first glance these assumptions may seem simple common sense, they have no firm foundation in fact. There are hardly any reliable data on the attitudes of women to breast lumps and the threat of mastectomy, and there have been few worthwhile studies on the psychological sequelae of mastectomy.2 3 A recent survey conducted in the Cardiff Breast Clinic4 showed that 20O1 of women with breast lumps delayed in getting medical advicenot through ignorance or the threat of mastectomy but the fear of being told that they had cancer. Possibly, therefore, at least some women would be concerned that anything less than a mastectomy would leave cancer behind; and indeed a further study5 on healthy women by the same group found that 6000 believed that should they develop breast cancer they would be more concerned about the adequacy of complete clearance than the extent of any deformity. Surgeons need to collaborate with psychiatrists and psychologists in further research of this kind. We need proper coniparisons of the reactions and quality of life in women with mammary carcinoma treated by methods that conserve the breast and those having a mastectomy and a good prosthesis.6 It would not necessarily be surprising if the second group of women believed they had been treated more adequately and that their self-confidence had been sufficiently restored by the provision of an appropriate prosthesis. Apart from subcutaneous mastectomy followed by silicone implant, there are other methods of treatment for carcinoma aimed at conserving the breast: radical radiotherapy after diagnosis by cytology or needle biopsy,7 wide local excision without radiotherapy,8 wide local excision plus postoperative radiotherapy,9 wide local excision plus radiotherapy after an axillarv clearance through a counter incision,10 and, finally, staged reconstruction of the breast after total mastectomy.1' All face theoretical objections. Local excision alone leaves the worrying possibility that one or more microscopic foci of cancer will be left behind.'2 Radical radiotherapy with 6000 or 7000 rads might in itself induce new cancers in the residual breast tissue over the following 10-20 years-and women treated this way are in the subgroup with small tumours and a favourable prognosis who could well be expected to survive that period of time. Recent doubts about the radiation risk of mammographic screening" have been based on doses of 1-2 rads."4 One of the most important considerations in breast surgery today is the use of the nodes in the axilla as a prognostic indicator which may determine whether the patient is prescribed adjuvant chemotherapy.'5 Methods of breast conservation which preclude sampling of the axilla should not be encouraged. Finally, silicone implants may cause anxiety since they themselves may induce malignancy, though the evidence for such an effect comes only from animal studies." No policy of conservation should be advocated without the evidence of prospective controlled trials. To date only one such study has been published, that of Atkins et (il at Guy's Hospital," in which wide local excision plus radiotherapy was compared with radical mastectomy plus radiotherapy. The results at a maximum follow-up period of 10 years showed that the conservatively treated group who were clinically nodepositive had a reduced survival compared with the more radically treated group. That trial was criticised for using what would now be considered inadequate doses of postoperative radiotherapy; but it produced useful information, including its finding that only a very few women presenting with carcinoma are suitable for local excision.

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At present surgeons and patients alike would probably agree that cure is more important than contour. It would be quite wrong to suggest to women at large that breast conservation is generally feasible, for that would lead inevitably to a bitter disappointment for most women presenting with breast cancer. Surgeons should therefore be encouraged to concentrate on entering their patient into trials of systemic therapy, leaving a minority of specialist groups to develop techniques of breast conservation and then to compare these in controlled studies with more conventional treatment. IWatts, G T, British Journal of Surgery, 1976, 63, 823. 2 Greer, S, Proceedings of the Royal Society of Medicine, 1974, 67, 470. 3Cameron, A, and Hinton, J, Cancer, 1968, 21, 1121. 1 Williams, E M, Baum, M, and Hughes, L E, Clini:al Oncology, 1976, 2, 327. Bennett, G C J, and Baum, M, personal communication, 1976. 6Winick, L, and Robbins, G F, Americat Jouirnal of Surgery, 1976, 132, 599. 7 Calle, R, Fletcher, G H, and Pierquin, B,J7ournal de Radiologie, d'Electrologie et de Medecine Nuecll'aire, 1973, 54, 929. Crile, C, jun, Lancet, 1972, 1, 549. 9 Atkins, H, et al, British Medical Journal, 1972, 2, 423. 10 Poisson, R, et al, Clinical Oncology, 1976, 2, 55. Millard, D R, Devine, J, and Warren, W D, American Journal of Suirgery, 1971, 122, 763. 12 Morgenstern, L, Kaufman, P A, and Friedman, N B, Americanyournal of Suirgery, 1975, 130, 251. 13 British Medical Journial, 1977, 1, 191. 14 Bailar, J C, Breast Catncer: A Report to the Professioni. Washington Hilton, National Cancer Institute, 1976. 15 Forrest, A P M, Clinical Oncology, 1976, 2, 313. 6 Brand, K G, in Scientific Founldations of Oncology, eds T Symington and R L Carter, p 490. London, Heinemann Medical, 1976. 5

Screening for cystic fibrosis Cystic fibrosis (mucoviscidosis) is the most common potentially lethal autosomal recessive disease in Caucasian peoples. Recent surveys' give a mean birth frequency of 1 in 2000. There are some odd variations,2 even in ethnically similar groups, from 1 in 500 to 1 in 10 000-and this is one area in which European co-operation could provide more accurate data. In the member countries of the European Community some 1500 infants are born each year with cystic fibrosis and about 10 million people (4-5", of the population) are apparently normal, healthy heterozygote carriers of the CF gene. Despite much research and several promising leads there is no completely reliable test for detecting heterozygotes, nor a test for the identification of the affected homozygous fetus in utero,3 which would permit selective abortion. Ciliary dyskinesia factors, metachromasia in cultured cells, serum factors affecting membrane transport studies-all have so far led to inconclusive or overlapping results.4 The solution of any one of these problems might well lead to a clarification of the whole picture. Again, European collaboration in a planned programme of research could lead to great social, medical, economic, and humanitarian benefits. Meanwhile, attention is being focused on the value and the means of screening newborn infants. Pilot studies carried out in the past six years have indicated two main possibilities. Firstly, the examination of meconium for excess albumin,4 6 refined to include immunoelectrophoretic estimation of the albumin xl antitrypsin ratio, disaccharidases, and lysosomal enzymes.7 A central meconium bank would greatly aid research here. A second approach is based on the work with a chloride-sensitive electrode,8 9 which has been modified recently to give greater precision in measurement of neonatal

Breast conservation in mammary carcinoma.

BRITISH MEDICAL JOURNAL 5 MARCH 1977 menon which has been more striking in adult diabetes.5 6 A survey among children under 16 years in Erie County,...
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