Beth C. Gladen

This paper deals with some basis properties of screening tests. Such tests purport to separate people with disease from people without. Minimal criteria for such a process to be a test are discussed. Various ways of judging the goodness of a test are examined. A common use of tests is to estimate prevalence of disease; frequency of positive tests is shown to be a bad estimate, and the necessary adjustmants are given.

The reproductive system of male mice homozygous for a mutation in the estrogen receptor (ER) gene (ER knock-out; ERKO) appears normal at the anatomical level. However, these males are infertile, indicating an essential role for ER-mediated processes in the regulation of male reproduction. Adult ERKO male mice have significantly fewer epididymal sperm than heterozygous or wild-type males. Although spermatogenesis is occurring in some seminiferous tubules of 3- to 5-month-old ERKO males, other tubules either have a dilated lumen and a disorganized seminiferous epithelium with few spermatogenic cells or lack a lumen and contain mainly Sertoli cells. There are no obvious differences in seminiferous tubules at 10 days of age between wild-type and ERKO mice, but the lumen in ERKO males is dilated in all seminiferous tubules by 20 days. However, spermatogenesis progresses and similar numbers of sperm are present in the cauda epididymis of ERKO and wild-type males until 10 weeks of age. Disruption of spermatogenesis and degeneration of the seminiferous tubules become apparent after 10 weeks in the caudal pole of the testis and progresses in a wave to the cranial pole by 6 months. However, the seminal vesicles, coagulating glands, prostate, and epididymis do not appear to be altered morphologically in ERKO mice. Serum testosterone levels are somewhat elevated, but LH and FSH levels are not significantly different from those in wild-type males. Sperm from 8- to 16-week-old mice have reduced motility and are ineffective at fertilizing eggs in vitro. In addition, ERKO males housed overnight with hormone-primed wild-type females produce significantly fewer copulatory plugs than do heterozygous or wild-type males. These results suggest that estrogen action is required for fertility in male mice and that the mutation of the ER in ERKO males leads to reduced mating frequency, low sperm numbers, and defective sperm function.

In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by thermally degraded polychlorinated biphenyls. Because these chemicals persist in human tissue, children born to female patients after the outbreak were exposed in utero. In 1985, 117 children born to affected women and 108 unexposed controls were examined and evaluated. The exposed children were shorter and lighter than controls; they had abnormalities of gingiva, skin, nails, teeth, and lungs more frequently than did controls. The exposed children showed delay of developmental milestones, deficits on formal developmental testing, and abnormalities on behavioral assessment. These findings are most consistent with a generalized disorder of ectodermal tissue. This syndrome is one of very few documented to result from transplacental exposure to pollutant chemicals.