Annotations

and radiotherapy for the primary treatment of smallcelled or oat-celled carcinoma of the bronchus, Lancet 2:979, 1966. Medical Research Council: Five year follow-up of the operative treatment with radiotherapy of small-celled or oat-celled carcinoma of the bronchus, Lancet 2:501, 1969. Medical Research Council: Ten year follow-up of the operative treatment with radiotherapy of small-celled or oat-celled carcinoma of the bronchus, Lancet 63. July 14, 1973. Lennox, S. C., Flavell, G., Pollock, D. J., Thompson, V. C., and Wilkins, J. L: Resection for oat cell cancer of the lung, Lancet 2:925, 1968. Medical Research Council: Two year study of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus, Br. Med. J. 2:421, 1971.

dose not exceeding 2,000 rads so that the surgeon may elect to perform a lobectomy if thought desirable, without the fear of radiation pneumonitis occurring in the remaining lobe, a short course of cytotoxic drugs to cover the operation to destroy any neoplastic cells disseminated at the time of surgery, and the resection of the lung tumor which the radiotherapy in itself will not have been sufficient to cure. Michael Rates, F.R.C.S. Lkpartment of Thoracic Surgery North Middlesex Hospital London, England REFERENCES

1. Bromley, L. L., and Szur, L.: Combined radiotherapy and resection for carcinoma of the bronchus: experiences with 66 aatients. Lancet 2937.1965. 2. Medical -Research Council: Comparative trial of surgery

A retrospective case-control study of diiases associated with oral contraceptive use

In 1972, the Boston Collaborative Drug Surveillance Program undertook a large-scale epidemiologic survey to evaluate associations between drug use by ambulatory patients and disease states requiring hospitalization.’ Trained nurse monitors were stationed on general medical and surgical wards in 24 community and university hospitals in the Boston area. A detailed history of all drugs, including oral contraceptives, used prior to hospitalization was obtained from approximately 25,000 consecutively admitted patients aged 20 to 75 years. Drug histories, demographic data, and discharge diagnoses were stored on magnetic tape. Retrospective case-control analysis was used in the present study. A total of 6,472 females aged 20 to 44 years was monitored. From this group were selected 042 controls, consisting of premenopausal women free of any known chronic disease who were hospitalized only for acute illness (trauma, respiratory infections, gastroenteritis, appendicitis) or elective surgery. None of the controls had any disorder which might contraindicate or be caused by oral contraceptive use. Cases also were selected stringently. Only patients having “idiopathic” venous thromboembolism with no apparent predisposing cause were included (n = 43). All cases of gallblad-

Table I. Risk ratios and estimated

Disease Venous thromboembolism Gallbladder disease Benign breast tumor

American

Heart Journal

der disease were confirmed surgically (n = 212). Cases of benign breast tumor were confirmed histologically (n = 98). Since oral contraceptive use becomes less common with increasing age, risk ratios were age-standardized2 (Table I). The association between venous thromboembolism and oral contraceptive use is highly signitlcant. Duration of use did not influence the risk. The results of other case-control studies are simiIar.3-5 Because idiopathic venous thromboembolism is a relatively rare event, the risk may not become apparent in prospective studies.6 Enhancement of coagulability induced by oral contraceptives’ probably explains the aesociation with venous thromboemboliem as well as other thromboembolic disorders. The association of oral contraceptive use with gallbladder disease also is significant (Table I) and has not been reported previously. The disease tended to develap within the first year of oral contraceptive use. Although the relative risk (2.0) is smaller than for venous thromboembolism Gl.O), the attack rates attributable to oral contraceptives are similar because gallbladder disease is more common in the population. Women are known to develop gallbladder disorders more frequently than men, particularly during the

attack rates

Age-standardized risk ratio 11 2.0 0.47

X2

Summary value (d.f. = 1) 57 15.0 5.4

Significance level p < .OOOl p < .OOl p = .02

Yearly attack rate attributable to OC’s per 100,000 GC users 60 79 -

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Annotations REFERENCES

childbearing age.sIt is possible that hormonal differences account for the increased prevalence of the disease in women, and that oral contraceptives potentiate the risk. Benign breast tumors are negatively associated with oral contraceptive use (Table Il. Similar findings are reported by Vessey and associates.gThere was no association, either positive or negative, of oral contraceptive use with newly diagnosed breast cancer, although the number of cases in our study (231 was too small to allow statistical comparison. The data suggest that oral contraceptives are “protective” against the development of benign breast tumors. Since patients with benign tumors appear to be at risk to develop subsequent malignant breast disease,” the protective effect of oral contraceptives might also extend to breast cancer. The associations reported in this study are not likely to be due to chance. The findings are not explained by differences in age, race, hospital, marital status, parity, or cigarette smoking. We doubt that the results are significantly influenced by bias on the part of nurse monitors or admitting physicians. The study documents associations-positive and negative- between oral contraceptive use and three important disease states, Furthermore, it demonstrates the value of the case-control method in epidemiologic research. David J. Greenblatt, M.D. Boston Collaborative Drug Surveillance Program 400 Totten Pond Road Waltham, Mass. 02154

1. Boston Collaborative Drug Surveillance Program: Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease, and breast tumors, Lancet 1:1399, 1973. 2. Mantel, N., and Haenszel, W.: Statistical aspects of the analysis of data from retrospective studies of disease, J. Natl. Cancer Inst. 22:719, 1959. 3. Vessey, M. P., and Doll, R.: Investigation of relation between use of oral contraceptives and thromboembolic disease, Br. Med. J. 2:199, 1968. 4. Vessey, M. P., and Doll, R.: Investigation of relation between use of oral contraceptives and thromboembolic disease: a further report, Br. Med. J. 2:651, 1969. 5. Sartwell, P. E., Masi, A. T., Arthes, F. G., et al.: Thromboembolism and oral contraceptives: an epidemiologic case-control study, Am. J. Epidemiol. 90~366, 1969. 6. Fuertes-de la Haba, A., Curet, J. O., Pelegrina, I., et al.: Thrombophlebitis among oral and nonoral contraceptive users, Obstet. Gynecol. 38:269, 1971. 7. Dugdale, M., and Masi, A. T.: Hormonal contraception and thromboembolic disease: effects of the oral contraceptives on hemostatic mechanisms, J. Chronic Dis. 23:775,1971. 8. Kaye, M. D., and Kern, F.: Clinical relationships of gallstones, Lancet 1:1228, 1971. 9. Vessey, M. P., Doll, R., and Sutton, P. M.: Oral contraceptives and breast neoplasia: a retrospective study, Br. Med. J. 3:719, 1972. 10. Potter, J. F., Slimbaugh, W. P., and Woodward, S. C.: Can breast carcinoma be anticipated? A follow-up of benign breast biopsies, Ann. Surg. 167:829, 1968.

Keep legs up

It is well known that arteriosclerotic obliterative arteritis with gangrene occurs frequently in the feet and legs, but is rare in the arms and hands, The feet and legs of many people with this disease must be amputated, but extremely rarely, if ever, is amputation necessary for this disease in the arms and hands. It is also known that arteriosclerosis is a disease of high pressure vessels and not of low pressure vessels even though the same blood with all its chemical ingredients flows through all vessels.’ Intralurninal pressure is, therefore, an important factor that predisposes to arteriosclerosis. The higher the arterial blood pressure the more severe the associated arteriosclerosis tends to be. Furthermore, it is known that the pressure in the vessels of the feet and legs becomes considerably higher upon standing due to the force of gravity’ and is lower with the feet and legs at heart level. Placing the feet at heart level can be done as a preventive measure by lying down frequently during the day, using footrests, reclining chairs, rockers and couches, lying on the floor, and even putting feet on the desk in the office. This practice is certainly beneficial for normal people who wish to prevent or delay arteriosclerosis of the legs and for patients with impairment of arterial blood flow. Keeping the feet up, at heart level, also assists venous return2 and further reduces arterial blood pressure. Standing still frequently and for long

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periods of time impairs venous return and in turn increases the pressure head which the arterial flow must overcome. Walking and contracting the leg muscles pumps blood back to the heart2 and assists arterial flow by reducing vis a tergo. Arteries of the legs are prone to obliterative arteriosclerotic endarteritis, and anything that reduces arterial blood pressure cannot be injurious but certainly could be beneficial. The peculiarities of the vessels and circulation to the legs and feet have been described previously in detail.2 With quiet standing and with the full effects of gravity, capillary pressure in the toes and feet must exceed the pressure in the ascending aorta. Keeping the legs and feet up could reduce the degree of arteriosclerosis in the lower extremities. Keep the legs and feet at heart level. lldane

G. E. Burch, M.D. University School of Medicine and Charity Hospital New Orleans, La.

REFERENCES

1. Burch, G. E., and Phillips, J. H.: Hypertension and arteriosclerosis, AM. HEART J. 60:163,1960. 2. Burch, G. E.: A primer of venous pressure, 2nd printing, Springfield, Ill. 1972, Charles C Thomas, Publisher.

May, 1975, Vol. 89, No. 5

A retrospective case-control study of diseases associated with oral contraceptive use.

Annotations and radiotherapy for the primary treatment of smallcelled or oat-celled carcinoma of the bronchus, Lancet 2:979, 1966. Medical Research C...
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