Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements

In a longitudinal prospective study of 1,529 women pregnant in 1974-1975, aspirin and acetaminophen were the two medications most frequently taken during the first half of pregnancy (46 and 41%, respectively). In a selected cohort of 421 offspring of these women, examined at 4 years of age, maternal aspirin use during the first half of pregnancy was significantly related to IQ and attention decrements in the exposed children. Multiple regression analyses were used to statistically adjust for a variety of potentially confounding factors including demographic characteristics, child characteristics, other exposures, and lifestyle/environmental variables. Continuous dose-response and step-function parameterizations of aspirin exposure were both statistically significant and not clearly distinguishable from each other. The estimated aspirin effect is significantly greater for girls than boys. Aspirin effects on offspring function were found in the absence of effects on physical size both at birth and at 4 years. Maternal acetaminophen use was not significantly related to child IQ or attention. As this exploratory research originated from observations of a data set gathered for other purposes, it would be desirable to have these findings replicated in other studies. Further follow-up of the children at a later age is planned.     

Genetic heterogeneity in tuberous sclerosis

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.     

The effect of inhibition of cholesterol esterification on the fate of cholesterol derived from HDL in rat hepatocyte monolayers

Rat HDL2 is known to stimulate bile acid synthesis in rat hepatocyte monolayers. The intracellular fate of the cholesterol derived from the HDL2 was studied using the inhibitor of cholesterol esterification, Sandoz compound 58-035. Rat HDL2 added to rat hepatocyte monolayers caused a stimulation of cholesterol esterification of 32%. This stimulation could be inhibited by 58-035. A small significant increase in bile acid synthesis was also observed in cells in the presence of HDL2, confirming our earlier observations. 58-035 prevented this increase. These observations imply that cholesterol entering the cell from HDL2 is first esterified and can only enter the substrate pool for bile acid synthesis after subsequent intracellular hydrolysis.