Damage to the human cerebellum from prenatal alcohol exposure: the anatomy of a simple biometrical explanation

Since 1973, it has become clear that exposure of otherwise normal human fetuses to high levels of alcohol damages a substantial number of the exposed brains in a wide variety of ways nowadays referred to collectively as the fetal alcohol spectrum disorders (FASDs). Averages of images and measurements of brains with these disorders are quantitatively different from normal, and the cerebellum is one of the structures at which differences are typically noted. The present article extends these techniques to a simple, practical, and enlightening detection rule for fetal alcohol damage in adolescents and adults known to have been heavily exposed. The data arise from 180 clinical MR brain images (half of adolescents, half of adults; half male, half female; one-third each fetal alcohol syndrome, fetal alcohol effects, and unexposed). The 180 cerebellums were represented by 328-semilandmark triangulations covering most of the cerebellar surface. Statistical analysis exploited the now-conventional methods of Procrustes analysis in three dimensions, along with a recent extension to incorporate size information explicitly. If we reduce the data complexity even further, to just 23 points along the silhouette of the cerebellum as viewed from above along the aqueductal axis, the analysis becomes more precise. Now a single multivariate summary score, very strongly correlated with size, supports a discrimination (diagnosed vs. unexposed) with about 75% accuracy. About one-quarter of our FASD sample overlaps with the central range of the unexposed in the distribution of this size-based score, with the other three-quarters distinctly showing cerebellar damage. The finding, which corresponds quite closely to the fundamental finding of cerebellar hypoplasia in animal experiments, bears implications for fetal alcohol epidemiology, for geometric morphometrics, and for the geometric complexity of useful data structures derived from clinical brain imaging.     

Preoperative localization of virilizing tumors by selective venous sampling

Two postmenopausal patients with virilization had preoperative localization of ovarian tumors by selective blood sampling from both ovarian and adrenal veins and assay of hormone levels. In the first patient, the peripheral concentrations of testosterone (T), androstenedione, and estrone were 936, 1,508, and 73 pg. per milliliter, respectively, levels which are above the ranges found in normal postmenopausal women. The catheterization study showed an increase in the left ovarian vein of all hormones except cortisol. It was predicted that a tumor was present in the left ovary. At operation a 7 by 4 mm. lipid cell tumor was found. In the peripheral blood of the second patient, the T level (4,518 pg. per milliliter) was markedly elevated and the estradiol concentration (73 pg. per milliliter) was increased. At retrograde catheterization the concentration of T in the right ovarian vein was markedly elevated at 120,400 pg. per milliliter. At operation a hilus cell tumor of the right ovary was found. These two cases represent the third and fourth consecutive androgen-secreting tumors from this institution that have been localized by selective ovarian and adrenal vein catheterization and sampling.     

In vivo tumor suppression by adenovirus-mediated interferon alpha2b gene delivery

A replication-deficient adenovirus encoding human interferon alpha2b, driven by the human cytomegalovirus (CMV) promoter, was constructed and characterized. This construct was used to infect human cells derived from different types of cancer. The production of protein and its secretion into the culture medium were tested by Western blotting and immunoassay. Inhibition of cell proliferation and antiviral activity, two of the most important biological activities of interferon, were observed with this construct. PC-3 cells, derived from human prostatic cancer, or Hep3B cells, derived from human hepatocellular carcinoma, were injected subcutaneously to generate and establish in vivo tumors in athymic nude mice. Intratumoral injection with the recombinant adenovirus expressing interferon alpha2b resulted in complete regression of tumor growth. Our results demonstrate that interferon gene delivery using recombinant adenoviral vectors may be a useful approach to treat a variety of cancers.     

Comparing frontal cranial profiles in archaic and modern homo by morphometric analysis

Archaic and modern human frontal bones are known to be quite distinct externally, by both conventional visual and metric evaluation. Internally this area of the skull has been considerably less well-studied. Here we present results from a comparison of interior, as well as exterior, frontal bone profiles from CT scans of five mid-Pleistocene and Neanderthal crania and 16 modern humans. Analysis was by a new morphometric method, Procrustes analysis of semi-landmarks, that permits the statistical comparison of curves between landmarks. As expected, we found substantial external differences between archaic and modern samples, differences that are mainly confined to the region around the brow ridge. However, in the inner median-sagittal profile, the shape remained remarkably stable over all 21 specimens. This implies that no significant alteration in this region has taken place over a period of a half-million years or more of evolution, even as considerable external change occurred within the hominid clade spanning several species. This confirms that the forms of the inner and outer aspects of the human frontal bone are determined by entirely independent factors, and further indicates unexpected stability in anterior brain morphology over the period during which modern human cognitive capacities emerged. Anat Rec (New Anat): 257:217-224, 1999.