pregnancy, breast-cancer risk, and maternal-fetal genetics

1
559 CHOLESTEROL AND TRIGLYCERIDE STUDIES IN VASCULAR DISEASE: ALL PATIENTS AGED 50-59 Statistical significance as compared with controls (Student’s t test). between normal and low H.D.L.-cholesterol in the range 20-25%. The findings of Bradby et al. differ from our experi- ence. We measured enzymatically triglyceride and total and H.D.L.-cholesterol (heparin/manganous chloride method) in 96 patients with P.V.D., 80 patients with C.H.D., and 72 controls. P.V.D. was confirmed by angiography and C.H.D. by coronary angiography and/or exercise tests. Controls were free of signs of coronary, cerebral or peripheral vascular disease. The data are shown for the largest age-group in the table. For all the other age-groups (not shown) there were significantly higher total cholesterol levels in the C.H.D. group than in controls and, save for those aged 40-49, in the P.V.D. group also (r<002). H.D.L.-cholesterol as % of total was consistently below normal in both patient groups (p<0-01). No significant difference could be found between patients with e.H.D. and P.V.D. Our results suggest that patients with P.v.D. show signifi- cantly lower H.D.L. cholesterol values than normals, in terms of absolute concentration and in relation to total cholesterol. Statitical significance seemed to be more pronounced if H.D.L.-cholesterol was expressed as a percentage of total cho- lesterol, so this relative figure may be the more reliable indi- cator of the risk of atheromatous disease. LOW H.D.L. concen- trations seem to be a general risk factor for atheromatosis in- dependent of the site of the disease. Cardiological University Clinic and II Medical University Clinic Vienna, Austria H. ZILCHER J. KALIMAN M. M&Uuml;LLER PREGNANCY, BREAST-CANCER RISK, AND MATERNAL-FETAL GENETICS SIR,-Dr Janerich (Feb. 10, p. 327) has constructed an in- genious hypothesis to account for the observation that the pro- portion of women who are single is less among those with REGISTRY DATA FOR BIRMINGHAM REGION: INCIDENCE PER 100 000 WOMEN PER YEAR (1968-72) breast cancer than among those with other types of cancer between 20 and 24 years of age, but that the deficiency diminishes with increasing age until it is converted into an excess at 40 years of age and over. There is, however, a much simpler and, I fear, less interesting explanation. At young ages the marriage-rate is appreciable, so that the proportion of single women at 24 years of age is less than at 20 years of age. The incidence of breast cancer under 40 years of age increases more rapidly with age than does the incidence of other cancers taken as a group, as is shown by figures published by the Birm- ingham Cancer Registry.’ It follows that the proportion of breast-cancer patients who are single will be less than that of patients with other types of cancer when women of marriage- able age are grouped together in five-year age-groups. As the marriage-rate declines, this effect gradually disappears, until finally the greater incidence among single women becomes evi- dent. If Janerich examines the proportion of single women sep- arately for each single year of age, he will probably find that it is higher for breast cancer than for all other cancers com- bined at all ages. Department of Regius Professor of Medicine, Radcliffe Infirmary, Oxford RICHARD DOLL HIGHLY PURIFIED INSULINS SIR,-Your editorial (Feb. 17) is informed on facts but con- fused on fancy. We are warned that impure insulin provokes immunity to endogenous hormones and that it would be com- placent to assume this immunity to be innocuous. We are also told that the decision to use highly purified insulin in new insu- lin-requiring diabetics is based more on emotion than fact. Faced with a new diabetic needing insulin, what do you recom- mend ? Emotion or complacency? Diabetic Department, Whittington Hospital, London N19 ARNOLD BLOOM PSEUDOMEMBRANOUS COLITIS SIR,-We would like to comment on Dr Price and Dr Lar- son’s letter (Feb. 24, p. 443). We agree that between March and July, 1978, there were a very large number of patients with antibiotic associated pseudomembranous colitis. We have undertaken an epidemiological study of all patients admitted to the surgical gastroenterological unit of this hospital before and after a period of extensive ward cleaning. Fxcal excretion of Clostridium difficile was never observed in the staff or amongst new patierits admitted to the ward. Repeated searches in the ward environment detected C. difficile only on one occa- sion from the shelf on which bed-pans are stored. Five patients who previously had had pseudomembranous colitis and who required readmission were found to be carriers of C. difficile. It is possible that they could have infected other patients on the ward but a vector was never demonstrated.2 Furthermore, eradication of a carrier state by vancomycin therapy, and ward cleaning has not abolished antibiotic-associated colitis in this hospital. We continue to believe, therefore, that pseudomembranous colitis is primarily due to overgrowth of a toxin-producing clos- tridium resident in the colon, but that, as with any disease due to a microorganism, cross-infection can be expected to occur. As Price and Larson suggest this would seem to have happened during the period in which we carried out the vancomycin trial. As part of our epidemiological studies we are typing the strains of C. difficile isolated from our patients during the past year. When this is completed it may be possible to replace spec- ulation with fact and resolve this contentious issue. The problems of nomenclature require clarification. Antibio- tic-associated colitis is inappropriate since some of these pa- tients have never received antibiotics.’ We believe the term pseudomembranous colitis should be restricted to patients with 1. Waterhouse, J., Muir, C., Correa, P., Powell, J. (editors). Cancer Incidence in Five Continents; vol. iii. International Agency for Research on Cancer, Lyon, 1976. 2. Mogg, G. A. G. and others. Gut (in the press). 3. Goulston, S. J. M., McGovern, V. J. ibid. 1965, 6, 207.

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559

CHOLESTEROL AND TRIGLYCERIDE STUDIES IN VASCULAR

DISEASE: ALL PATIENTS AGED 50-59

Statistical significance as compared with controls (Student’s t test).

between normal and low H.D.L.-cholesterol in the range20-25%. The findings of Bradby et al. differ from our experi-ence. We measured enzymatically triglyceride and total andH.D.L.-cholesterol (heparin/manganous chloride method) in 96patients with P.V.D., 80 patients with C.H.D., and 72 controls.P.V.D. was confirmed by angiography and C.H.D. by coronaryangiography and/or exercise tests. Controls were free of signsof coronary, cerebral or peripheral vascular disease. The dataare shown for the largest age-group in the table. For all theother age-groups (not shown) there were significantly highertotal cholesterol levels in the C.H.D. group than in controls and,save for those aged 40-49, in the P.V.D. group also (r<002).H.D.L.-cholesterol as % of total was consistently below normalin both patient groups (p<0-01). No significant differencecould be found between patients with e.H.D. and P.V.D.Our results suggest that patients with P.v.D. show signifi-

cantly lower H.D.L. cholesterol values than normals, in termsof absolute concentration and in relation to total cholesterol.Statitical significance seemed to be more pronounced ifH.D.L.-cholesterol was expressed as a percentage of total cho-lesterol, so this relative figure may be the more reliable indi-cator of the risk of atheromatous disease. LOW H.D.L. concen-trations seem to be a general risk factor for atheromatosis in-dependent of the site of the disease.

Cardiological University Clinicand II Medical University Clinic

Vienna, Austria

H. ZILCHER

J. KALIMANM. M&Uuml;LLER

PREGNANCY, BREAST-CANCER RISK, ANDMATERNAL-FETAL GENETICS

SIR,-Dr Janerich (Feb. 10, p. 327) has constructed an in-genious hypothesis to account for the observation that the pro-portion of women who are single is less among those with

REGISTRY DATA FOR BIRMINGHAM REGION: INCIDENCE PER

100 000 WOMEN PER YEAR (1968-72)

breast cancer than among those with other types of cancerbetween 20 and 24 years of age, but that the deficiencydiminishes with increasing age until it is converted into anexcess at 40 years of age and over. There is, however, a muchsimpler and, I fear, less interesting explanation. At young agesthe marriage-rate is appreciable, so that the proportion of

single women at 24 years of age is less than at 20 years of age.The incidence of breast cancer under 40 years of age increasesmore rapidly with age than does the incidence of other cancerstaken as a group, as is shown by figures published by the Birm-ingham Cancer Registry.’ It follows that the proportion ofbreast-cancer patients who are single will be less than that ofpatients with other types of cancer when women of marriage-able age are grouped together in five-year age-groups. As themarriage-rate declines, this effect gradually disappears, untilfinally the greater incidence among single women becomes evi-dent. If Janerich examines the proportion of single women sep-arately for each single year of age, he will probably find thatit is higher for breast cancer than for all other cancers com-bined at all ages.

Department of Regius Professor of Medicine,Radcliffe Infirmary,Oxford RICHARD DOLL

HIGHLY PURIFIED INSULINS

SIR,-Your editorial (Feb. 17) is informed on facts but con-fused on fancy. We are warned that impure insulin provokesimmunity to endogenous hormones and that it would be com-placent to assume this immunity to be innocuous. We are alsotold that the decision to use highly purified insulin in new insu-lin-requiring diabetics is based more on emotion than fact.Faced with a new diabetic needing insulin, what do you recom-mend ? Emotion or complacency?Diabetic Department,Whittington Hospital,London N19 ARNOLD BLOOM

PSEUDOMEMBRANOUS COLITIS

SIR,-We would like to comment on Dr Price and Dr Lar-son’s letter (Feb. 24, p. 443). We agree that between Marchand July, 1978, there were a very large number of patientswith antibiotic associated pseudomembranous colitis. We haveundertaken an epidemiological study of all patients admittedto the surgical gastroenterological unit of this hospital beforeand after a period of extensive ward cleaning. Fxcal excretionof Clostridium difficile was never observed in the staff or

amongst new patierits admitted to the ward. Repeated searchesin the ward environment detected C. difficile only on one occa-sion from the shelf on which bed-pans are stored. Five patientswho previously had had pseudomembranous colitis and whorequired readmission were found to be carriers of C. difficile.It is possible that they could have infected other patients onthe ward but a vector was never demonstrated.2 Furthermore,eradication of a carrier state by vancomycin therapy, and wardcleaning has not abolished antibiotic-associated colitis in thishospital.We continue to believe, therefore, that pseudomembranous

colitis is primarily due to overgrowth of a toxin-producing clos-tridium resident in the colon, but that, as with any disease dueto a microorganism, cross-infection can be expected to occur.As Price and Larson suggest this would seem to have happenedduring the period in which we carried out the vancomycintrial. As part of our epidemiological studies we are typing thestrains of C. difficile isolated from our patients during the pastyear. When this is completed it may be possible to replace spec-ulation with fact and resolve this contentious issue.The problems of nomenclature require clarification. Antibio-

tic-associated colitis is inappropriate since some of these pa-tients have never received antibiotics.’ We believe the term

pseudomembranous colitis should be restricted to patients with

1. Waterhouse, J., Muir, C., Correa, P., Powell, J. (editors). Cancer Incidencein Five Continents; vol. iii. International Agency for Research on Cancer,Lyon, 1976.

2. Mogg, G. A. G. and others. Gut (in the press).3. Goulston, S. J. M., McGovern, V. J. ibid. 1965, 6, 207.