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Biomedical subjects

K J Rothman

Publications and source records attributed to K J Rothman.

At least 145 records · Page 8Linked to original sources

Epidemiology of head and neck cancer.

The epidemiology of head and neck cancer can be accounted for largely in terms of known carcinogens introduced into the body through the mouth. Though there are many environmental exposures--such as asbestos, radon, nickel and arsenic--which have strong carcinogenic effects, most of these have only a small impact on the general population because exposure is limited, usually to small occupational groups. Two prevalent exposures, however, tobacco and alcohol, are strong risk factors for nearly all sites in the head and neck, and together account for about 80%-90% of all cancers of the head and neck. There is evidence for biologic interaction between some occupational exposures and cigarette smoking for cancer of the lung, and tobacco and alcohol for cancer of the mouth. Based on this evidence for biologic interaction and the prevalence of smoking, it seems likely that tobacco is related to about 80% of all cancers of the head and neck in the United States.

Esophageal Neoplasms↗

Oral contraceptives and nonfatal stroke in healthy young women.

The Boston Collaborative Drug Surveillance Program obtained medical histories on 29 premenopausal women with a discharge diagnosis of stroke. Of these women, 14 were otherwise healthy with no known predisposing illnesses. Eleven of the 14 patients were taking oral contraceptives just before admission compared with seven of 56 otherwise healthy control women (13%). The relative risk estimate for stroke among oral contraceptive users compared with nonusers is 26 (lower 90% one-sided confidence bound = 7.0). Cigarette smoking was only weakly associated with stroke in this group of women.

Adult↗

Fetal loss, twinning and birth weight after oral-contraceptive use.

To evaluate the effect of oral-contraceptive use on subsequent offspring, I reviewed information on the pregnancies of 19,887 women who indicated, in response to a mail questionnaire, that they had used oral contraceptives. The rates of spontaneous abortion and stillbirth were smaller for former users than for nonusers--a finding consistent with previous studies. Twinning was more frequent among births of infants conceived soon after cessation of oral contraceptives, the rate being approximately twice the expected value for women who had used oral contraceptives for more than six months (P = 0.1). The sex distribution of the twins indicated that the increase was mainly in dizygous twins (P = 0.02), in accordance with predictions about increased twinning after cessation of oral contraceptive use. No relation was evident between oral contraceptive use and birth weight.

Abortion, Spontaneous↗

Epidemiologic methods in clinical trials.

Epidemiologic methods developed to control confounding in non-experimental studies are equally applicable for experiments. In experiments, most confounding is usually controlled by random allocation of subjects to treatment groups, but randomization does not preclude confounding except for extremely large studies, the degree of confounding expected being inversely related to the size of the treatment groups. In experiments, as in non-experimental studies, the extent of confounding for each risk indicator should be assessed, and if sufficiently large, controlled. Confounding is properly assessed by comparing the unconfounded effect estimate to the crude effect estimate; a common error is to assess confounding by statistical tests of significance. Assessment of confounding involves its control as a prerequisite. Control is most readily and cogently achieved by stratification of the data, though with many factors to control simultaneously, multivariate analysis or a combination of multivariate analysis and stratification might be necessary.

Clinical Trials as Topic↗

Epidemiology of endometrial cancer.

For a population-based, case-control study of cancer of the endometrium in Greater Boston from 1965 through mid-1969, 440 cases were drawn from nearly all hospitals in the area; controls were drawn at random from the general population. The age-adjusted incidence rate was 18.1/100,000 woman-years, with a peak at ages 55-59 and a gradual decline thereafter. Information was provided from 212 cases and 1,198 controls by mall questionnaire. A trend of reduced risk of endometrial cancer with increased parity was noted, the relative incidence (RI) for multiparous women being 0.3 compared to a RI of unity for married nulliparous women. The association of risk with age at first birth was irregular. Early menarche (RI=1.6) and late menopause (RI=1.7) were associated with increased risk of disease. Endometrial cancer risk was also found to be directly related to socioeconomic status, relative weight, diabetes, hypertension, and arthritis. The findings supported the idea that hormone activity during, and perhaps after, reproductive life is an important cause of this disease.

Adenocarcinoma↗

Gender of offspring after oral-contraceptive use.

We examined the sex of offspring born after oral-contraceptive use according to duration of contraceptive use and the interval between cessation of use and conception for 6109 live births. The overall proportion of male births (with 90 per cent confidence) falls between 0.491 and 0.512. These data exclude with high probability a shift in the sex distribution of the magnitude previously hypothesized, and are not consistent with even a moderate shift in sex distribution. Sex of offspring was not related to total duration of oral-contraceptive use, duration of use since any previous pregnancy or interval between termination of use and conception. It appears that oral contraceptives have no bearing on the sex of subsequent offspring.

Birth Weight↗

Association of congenital heart defects with season and population density.

Infants born in New England with congenital heart defects were examined for association with time of year or population density. Moderate seasonal peaks in births were noted for complex ventricular septal defect, malposition defects, and transposition of the great arteries. Positive associations with population density were found for pulmonary atresia with ventricular septal defect, ventricular septal defect with secondary anomalies, and tricuspid atresia.

Adult↗

Place and time aspects of the occurrence of Down's syndrome.

Prevalence rates at birth for Down's syndrome were compared for Massachusetts communities of different population densities. Overall, there was a small positive association between the rate of Down's syndrome and population density, entirely attributable to a strong association for the children of older mothers. An analysis for space and time clustering of births of 2469 children born in Massachusetts with Down's syndrome revealed no aggregation of cases, except for a slight seasonal peak in the summer.

Demography↗

Sex, birth order, and maternal age characteristics of infants with congenital heart defects.

The records of the New England Regional Infant Cardiac Program, a service program covering all of New England, provide a useful source of information about the characteristics of children born with congenital heart defects. Data were analyzed on more than 2000 children born in New England who were diagnosed with a congenital heart defect before the first birthday. Children with arterio-venous fistula, aortic stenosis, transposition of the great arteries or hypoplastic left ventricle were predominantly male; children with persistent ductus arteriosus and endocardial cushion defect were predominantly female. Positive trends in risk with increasing birth order were present for pulmonic stenosis and transposition of the great arteries, and a negative trend was seen for persistent ductus arteriosus. What evidence there was for associations with maternal age was greatly reduced after controlling for confounding by birth order.

Adult↗

Causes.

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Disease↗

Effect of Corynebacterium parvum on the response to irradiation of a C3H fibrosarcoma.

A methylcholanthrene-induced fibrosarcoma of C3H mice has been used as 5th- to 6th-generation syngeneic transplant in an investigation of the role of Corynebacterium parvum as an adjuvant to the therapeutic effect of local irradiation of established tumors. The most effective route for administration of C. parvum in this tumor system was i.v., and the greatest effect of the C. parvum-mediated tumor graft rejection was observed for tumor growing intracutaneously or s.c. An intermediate level of effectiveness was obtained for tumor growing i.m. The combined C. parvum and local irradiation studies were performed using tumors growing in the leg muscle and measuring 8 mm in diameter at the time of local irradiation. Several routes of administration of C. parvum, dose levels of C. parvum, and time relationships between administration of C. parvum and irradiation were investigated. The outstanding finding was that very low doses of radiation were quite effective when administered to tumors growing in animals pretreated with C. parvum. This was true for radiation administered as a single or fractionated dose (10 equal doses spread over 18 days). For single-dose irradiation the effect was relatively dose independent over the range of 200 to 3000 rads. Some indication was obtained that local irradiation may impair the tumor graft rejection reaction. No evidence was obtained of an enhanced growth of tumor. Regression of tumor following irradiation was not modified by pretreatment with C. parvum. The mice that were unsuccessfully treated by radiation and C. parvum had a lower incidence of metastatic disease in the lung than did the mice treated unsuccessfully with radiation alone.

Adjuvants, Immunologic↗

Birth weight of children with Down's syndrome.

The difference in birth weight between children with Down's syndrome and their siblings was estimated to be in the interval from .18 to .37 kg with 90 percent confidence, the Down's syndrome infants having the smaller mean birth weights. When we adjusted their birth weight, using a multiple linear regression analysis, to take into account several factors known to affect it, the difference in birth weight was only slightly less than the unadjusted difference. The data support the hypothesis that an extra chromosome No. 21 results in a smaller than expected birth weight.

Birth Order↗

Birthweight of children with phenylketonuria.

The assumption that children with phenylketonuria (PKU) develop normally until birth was brought into question by the recent report that PKU children weigh several hundred grams less at birth than their unaffected siblings. We have examined intrafamily differences in birthweight in 40 sibships with at least one affected and one unaffected child. The difference in mean birthweights computed by taking a weighted average of the intrafamily differences was 69 gm, and the adjusted estimate of the birthweight difference between children with PKU and their siblings, obtained from a fitted multiple regression function, is -51 gm. The findings are not consistent with the large difference in birthweight reported previously and are compatible with the assumption that the intrauterine physical growth of children with classical PKU is not adversely affected.

Birth Weight↗