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Fetal effects on prolactin secretion in late pregnancy and at term were studied in gilts with small litters of intact, hypophysectomized, partially hypophysectomized or dead fetuses. Litter size was reduced at surgery at Days 30-40 of gestation and fetal hypophysectomy or sham procedure attempted on Days 90-95 of gestation using an electrocoagulating probe. Plasma prolactin concentrations rose markedly before parturition in three gilts with normal litters (P = 0.05) and to lower peak concentrations in two gilts with a single fetus. Plasma prolactin did not change from basal concentrations in 4 gilts with small litters (1-2 fetuses) of hypophysectomized fetuses or, in 2 gilts with dead fetuses. Basal plasma prolactin concentrations were significantly lower in gilts carrying hypophysectomized or dead fetuses, compared to normal gilts (P = 0.01). A surge of prolactin secretion preceded delivery in 2 gilts with fetuses with incomplete hypophysectomy and in 1 gilt with 1 of 3 hypophysectomized fetuses. Abnormal patterns of prolactin secretion were seen in 1 gilt with 3 of 5 hypophysectomized fetuses and in 1 gilt with 1 partially hypophysectomized fetus. The results suggest that the fetus may be associated with a mechanism regulating plasma prolactin concentration at term. It is possible that this association may be by way of the fetal pituitary endocrine axes, and/or a function of conceptual mass.

Pregnancy outcome and maternal morbidity were analysed in 302 pregnant women with positive Machado-Guerreiro Complement Fixation Test (MGCFT) for antibodies to Trypanosoma cruzi and 302 women with a negative MGCFT resident of Córdoba, Argentina. A comparison of positive and negative cases was employed to investigate the association between MGCFT reaction and pregnancy outcome assessed from abortion and perinatal infant mortality rates; similarly, the data were analysed for demographic and socio-economic factors, numbers of previous pregnancies (birth order) and maternal complications. A twofold increase in the risk of pregnancy loss associated with a positive MGCFT was found. The incidence of polyhydramnios and varicosities of the leg was significantly higher in the serologically reactive group.

Three previous investigations have reported a relationship between clonal chromosome abnormalities in marrow of patients with acute nonlymphocytic leukemia and employment in occupations involving mutagenic chemicals, but the effects of other exposures were not described. Environmental exposure profiles, gathered by questionnaire, were therefore compared using a case-control study design in 235 newly diagnosed patients with acute nonlymphocytic leukemia: 126 with abnormal and 109 with normal karyotypes. The univariate odds ratio for occupation at diagnosis was 4.6, which, when adjusted for demographic and other exposures by logistic regression, was reduced to 2.5 (95% confidence interval, 0.5 to 12.8). Adjusted point estimates for other exposures were 4.3 (1.4 to 13.3) for prior cytotoxic therapy, 1.7 (0.9 to 3.1) for cigarette smoking, and 1.9 (1.0 to 3.4) for alcohol use. Dose-response relationships were present for both tobacco and alcohol consumption. Associations between specific abnormalities (+8, -7I-7q, [corrected] inv16, t[8;21]) and certain exposures were also present. These results suggest that life-style exposures may be associated with cytogenetic lesions in persons with acute nonlymphocytic leukemia.

The findings from a double-blind multicenter clinical trial of aspirin for treatment of cerebral ischemia are reviewed. Of 303 patients who had carotid transient ischemic attacks (TIAs), 125 were selected for carotid reconstructive surgery and were then randomly assigned treatment with aspirin or placebo. The remaining 178 patients were also randomly assigned to an aspirin or placebo regimen. Analysis of the first 6 months of follow-up showed a differential in favor of aspirin when death, nonfatal cerebral or retinal infarction and the occurrence of TIAs were grouped and considered together as end points. Restriction of end points to death or nonfatal cerebral or retinal infarction yielded no statistically significant differential between the aspirin and placebo groups. After these results were published, a study group from Canada reported that aspirin was effective in preventing threatened stroke, but that this effect was limited to males. Review of our nonsurgical group with respect to sex shows findings consistent with those of the Canadian study for the end points of stroke or death. Inclusion of the occurrence of TIAs in the group of end points, however, revealed that aspirin is effective in females as well as males.

Adouble-blind trial of aspirin for the treatment of cerebral ischemia was begun in 1972 and continued for 37 months. This was accomplished despite difficulties in controlling a long-term study of a drug which has widespread availability and consumption. The study design, criteria for selection of patients, follow-up surveillance, and methods of data analysis are presented. We report only subjects without carotid surgery before randomization. Patients (178) who had carotid transient ischemic attacks (TIAs) were randomly allocated to aspirin or placebo and followed to determine the incidence of subsequent TIAs,death, cerebral infarction or retinal infarction. Analysis of the first six months of follow-up revealed a statistically significant differential in favar of aspirin when death or cerebral or retinal infarction and the occurrence of TIAs were grouped and considered together as end points. Significance in favor of aspirin treatment was mainly revealed in patients with a history of multiple TIAs and was most evident in those individuals having carotid lesions appropriate to the TIA symptoms. It cannot be inferred from this study that aspirin prevents stroke because when end points were restriced to death or cerebral or retinal infarction, there was no statistically significant differential between the aspirin and placebo treatments.

Patients (125) who had carotid transient ischemic attacks (TIAs) and one or more accessible carotid lesions visualized angiographically had reconstructive operations of the carotid artery and were then randomly assigned to aspirin or placebo treatment. The were followed to determine the incidence of subsecquent TIAs, death, cerebral infarction, or retinal infarction. Life table analysis (for 24 months follow up) that eliminated deaths which were not stroke-related revealed a significant difference in favor of aspirin. Because of the small number of patients and the short period of follow up, these results should be interpreted only as consistent with those reported in the initial publication but not conclusive of an aspirin effect in preventing cerebral infarction.

This paper examines the effect of random unequal censoring on the size and power of two-sample logrank and Wilcoxon types of tests for comparing two survival distributions by simulation with small samples from censored exponential distributions. We compared equal-sized samples of n = 8, 16, and 32 with 1000 (size) and 500 (power) simulation trials for 16 combinations of the censoring proportions of 0, 20, 40, and 60 per cent in each of the two samples. For n = 8, the asymptotic normality (AN), Peto-Peto, and the two Wilcoxon-type tests performed at nominal 5 per cent size expectations, but the Mantel test exceeded the 5 per cent size acceptance region in 6 of 16 censoring combinations. For n = 16 and 32, all tests showed proper size, with the Peto-Peto test being most conservative in the presence of unequal censoring. We compared powers of all tests for exponential hazard ratios of 1.4 and 2.0. The Mantal test showed 90 to 95 per cent power efficiency relative to the parametric AN test. Both Wilcoxon tests performed identically and had the lowest relative power of all tests examined but appeared most robust to the differential censoring patterns studied. A modified version of the Peto-Peto test showed power comparable to the Mantel test.

Paternal occupational exposures to hydrocarbons have been associated with childhood nervous system cancer, but study results have not been consistent. This population-based case-control study was designed to examine this association using a large sample size to increase the precision of risk estimates. The birth certificates of 499 children who died in Texas from intracranial and spinal cord tumors were compared with 998 control certificates randomly selected from all Texas live births. Information on parental job title and industry at the time of birth was obtained from the birth certificates. No significant associations were identified for the dichotomized variable of all hydrocarbon-related occupations combined, as variously defined in previous studies, or for most of the specific jobs affiliated with exposures to hydrocarbons. Significant, relatively stable odds ratios (OR) were found for printers and graphics arts workers (OR = 4.5; 95% confidence interval (CI) = 1.4-14.7) and chemical and petroleum workers with high exposure levels (OR = 3.0; CI = 1.1-8.5). A discussion of the biases involved in this type of study design is presented.