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Biomedical subjects

D Slone

Publications and source records attributed to D Slone.

At least 19 recordsLinked to original sources

Comparison of the aflatoxin B1-8,9-epoxide conjugating activities of two bacterially expressed alpha class glutathione S-transferase isozymes from mouse and rat.

The complementary DNAs of rat glutathione S-transferase (GST, EC 2.5.1.18) Yc1 and of mouse Yc were expressed from a prokaryotic expression vector in E. coli. The purified proteins were analyzed for their activity toward aflatoxin B1-8,9-epoxide (AFBO), the reactive intermediate of the fungal mycotoxin aflatoxin B1 (AFB). The mouse Yc isozyme had about 50-fold higher conjugating activity toward AFBO than the rat Yc1 isozyme (144 nmol/mg/min versus 3.3 nmol/mg/min). The rat Yc1 isozyme had specific activities toward 1-chloro-2,4-dinitrobenzene, cumene hydroperoxide and ethacrynic acid of 10.7, 0.98 and 0.92 mumol/mg/min, respectively, whereas the mouse Yc isozyme had specific activities of 5.7, 2.1 and 0.1 mumol/mg/min for these substrates, respectively. These data provide further support for the hypothesis that the constitutive presence of the alpha class GST Yc isozyme in mouse liver protects mice from the hepatocarcinogenic effects of aflatoxin B1.

Aflatoxin B1

Oral-contraceptive use in relation to myocardial infarction.

The effect of oral-contraceptive use on the risk of myocardial infarction and, in particular, the possible accentuation of that effect by cigarette smoking, was investigated in 234 premenopausal women with a first infarction and 1742 hospital controls. The overall rate ratio estimate of acute myocardial infarction for women who had used oral contraceptives in the preceding month was 4.0 (95% confidence interval, 2.5--6.3). Women who smoked heavily and used oral contraceptives had a point estimate of 39 (lower two-sided 95% confidence limit, 22) compared with those who did neither. This value was appreciably larger than could be accounted for by the separate effects of cigarettes and oral contraceptives, and this suggests a considerable accentuation by cigarette smoking of the effect of oral contraceptive use on myocardial infarction.

Acute Disease

Patterns and determinants of conjugated estrogen use.

In view of the carcinogenic potential and widespread use of conjugated estrogens (CEs), this study evaluated patterns and determinants of oral ambulatory CE use. Among 1273 women 30 to 69 years of age interviewed in Greater-Boston hospitals, there were 161 (13%) ever-users of CEs; 88 (7%) had used the drug within the preceding year. The median duration of use was three years. Prominent determinants of use were age, menopause and history of menopausal symptoms. Physician prescription survey data from an independent source suggest that CE use has been common throughout the United States, and may have declined after the reports linking CEs to endometrial cancer were published in 1975. If CE use indeed increases the risk of endometrial cancer some fivefold, an important public health problem exists.

Adult

Drug utilization and reported adverse reactions in hospitalized children.

An intensive drug surveillance program has been developed to study the clinical effects of drugs in hospitalized children. This program collects information on drug exposures and the occurrence of adverse clinical events. The 1669 children monitored to date received an average of 7.6 drugs during an average hospital stay of 8.4 days. A group of specified adverse clinical events, whether or not drug attributed, occurred in 45.7% of the patients; drug-attributed events (adverse drug reactions) occurred in 16.8%. Both drug use and reported adverse reactions tended to increase with age, except that newborns received many drugs but had the lowest reported adverse reaction rates. Newborns, however, had the highest rate of adverse events not attributed to drugs, suggesting that perhaps some of these latter events include presently unrecognized adverse drug reactions.

Adolescent

Drug evaluation after marketing.

After marketing, drugs should be evaluated for safety and for efficacy. Present national systems are inadequate for both tasks. Safety can be evaluated by means of nonexperimental research, whereas evaluation of efficacy in a variety of settings representing normal medical practice generally requires experiments, randomized and blinded. Research into safety requires the maintenance of routine, yet flexible, multipurpose data systems, different for established and newly marketed drugs. Ad hoc studies on safety and on efficacy can be mounted more swiftly and economically through the maintenance of "standby" capabilities, in addition to maximal use of resources outside the actual national system.

Drug Evaluation

Drugs and pregnancy.

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Abnormalities, Drug-Induced

Relation of cigarette smoking to myocardial infarction in young women.

To examine the relation between myocardial infarction and cigarette smoking in young women, we investigated the smoking habits of women under the age of 50 who had survived a recent myocardial infarction. They had not been using oral contraceptives, and other identifiable risk factors were excluded. Among 55 such women and 220 control matched for age and area of residence, the proportions of cigarette smokers were 89 per cent and 55 per cent respectively (P less than 0.001). A dose-response relation was evident; among women smoking 35 or more cigarettes per day the rate of myocardial infarction was estimated to be some 20-fold higher than among those who had never smoked. This study demonstrates that cigarette smoking is a risk factor for myocardial infarction in young women who are otherwise apparently healthy.

Adult

Antenatal exposure to doxylamine succinate and dicyclomine hydrochloride (Benedectin) in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score.

In a prospective cohort study of 20, 282 gravidas and their offspring, congenital malformation rates were similar in the children of over 1,000 women exposed and those not exposed to two components of Bendectin (doxylamine succinate and dicyclomine hydrochloride) during the first four lunar months of pregnancy. In a cohort reduced to 41,337 mother-child pairs for technical reasons, mean birth weight and perinatal mortality rates were similar according to exposure or nonexposure to either drug, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter these findings.

Abnormalities, Drug-Induced

Antenatal exposure to the phenothiazines in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score.

In a prospective cohort study of 50,282 gravidas and their offspring, over-all rates of congenital malformations were similar in 1,309 children of women exposed to phenothiazine drugs during the first four lunar months of pregnancy and in 48,973 children of women who were not exposed. There was a suspicion of association between phenothiazine exposure and cardiovascular malformations. In a cohort reduced to 41,337 mother-child pairs for technical reasons, perinatal mortality rates and mean birth weight were similar according to phenothiazine exposure or nonexposure, as were intelligence quotient scores measured at four years of age in 28,358 of the children. Control of potential confounding factors with a variety of multivariate techniques did not materially alter the findings.

Abnormalities, Drug-Induced

Cardiovascular birth defects and antenatal exposure to female sex hormones.

In a cohort of 50,282 pregnancies 19 children with cardiovascular defects were born to 1042 women who received female hormones during early pregnancy (18.2 per 1000). Among 49,240 children not exposed in utero to these agents there were 385 with cardiovascular malformations (7.8 per 1000). Six children with cardiovascular defects were born to a sub-group of 278 women who used oral contraceptives during early pregnancy (21.5 per 1000). After the data were controlled for a wide variety of potentially confounding factors by multivariate methods, the association between in utero exposure to female hormones and cardiovascular birth defects was statistically significant.

Adult

Hypotension due to chlorpromazine. Relation to cigarette smoking, blood pressure, and dosage.

The frequency of hypotension attributed to orally administered chlorpromazine hydrochloride was compared among 187 nonsmokers, 223 "light" smokers, 87 "intermediate" smokers, and 18 "heavy" smokers. Hypotension attributed to the drug occurred in10%, 8%, 5% and 0%, respectively. Other factors found to be independently related to hypotension were high diastolic blood pressure on admission and high dosage of chlorpromazine. The results suggest that smoking status, dosage, and blood pressure must be evaluated in order to estimate the likelihood that a patient may become hypotensive after receiving chlorpromazine.

Administration, Oral