Topographic anatomy and CT correlations in the untreated glioblastoma multiforme

To provide baseline information for the "local" therapy of the glioblastoma multiforme (GBM), whole-brain histological sections of 15 untreated GBM's were studied to determine the distribution of neoplastic cells. These findings were then compared with the computerized tomography (CT) scans in 11 cases in order to determine the extent to which the peripheral portion of the neoplasm can be estimated by the presence of a low-density area without contrast enhancement. The results of the histological study confirmed the marked heterogeneity of GBM's and disclosed a great variability in the geometry, extent, and character of the peripheral "infiltrating" margin. In spite of the widely held concept that glioblastomas are localized within 2 cm of the contrast-enhanced rim, there were three cases in this two-dimensional study in which this distance was exceeded, and it seems likely that three-dimensional reconstructions would have detected additional cases in which neoplastic cells extended beyond this arbitrary limit. Only three of the 15 GBM's were restricted to the distribution of one internal carotid or one vertebral artery. To the extent that the neoplasms in the present series are representative, this suggests that glioblastomas will be difficult to treat successfully by intra-arterial therapy using existing therapeutic agents. Correlations of histological sections with the CT scans revealed that the vast majority of the neoplastic tissue was contained within the contrast-enhancing and "peritumoral" areas of low density, but that in five cases fingers of neoplasm extended for short distances beyond the outer margin of the latter region. This indicates that the distribution of cells of a GBM cannot be inferred from CT images since the "peritumoral" area of low density can over- or underestimate the extent of the lesion.     

PJA-BP expression and TCR delta deletion during human T cell differentiation

Recombination of deltaRec to psiJalpha will delete the TCR delta gene, which is thought to play an important role in the bifurcation of the TCR alphabeta versus TCR gammadelta differentiation lineages. We recently detected a DNA-binding protein in human thymocytes, the so- called PJA-BP, which recognizes the psiJalpha gene segment and might be one of the factors involved in the regulation of preferential deltaRec- psiJalpha rearrangements. We now investigate PJA-BP expression and its correlation with TCR delta gene deletion in thymocytes. Our electrophoretic mobility shift assay experiments showed that the PJA-BP is evolutionary conserved in human, murine and simian thymocytes. Using a large series of human hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is thymocyte specific and seems to be restricted to thymocytes committed to the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte subpopulations showed that preferential deltaRec-psiJalpha rearrangements as well as PJA-BP expression can be detected from the immature CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage onwards. These experiments indicate that expression of PJA-BP in human thymocytes starts simultaneously with preferential deltaRec-psiJalpha rearrangements, which supports our hypothesis that PJA-BP is one of the factors involved in the preferential recombination of deltaRec to psiJalpha.      

Association between hormonal changes at menopause and the risk of a coronary event: a longitudinal study

OBJECTIVE: To investigate the association of hormone levels at menopause, lifestyle variables, and body composition with the predicted 10-year risk of a coronary event, calculated using the PROCAM scoring system, in a population-based sample of Australian-born, middle-aged women. DESIGN: A 9-year prospective study of 438 Australian-born women, who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months. Interviews, fasting blood, and physical measurements were taken annually. The risk of an acute coronary event was calculated using the PROCAM scoring system (includes: age, low-density lipoprotein cholesterol, smoking, high-density lipoprotein cholesterol, systolic blood pressure, family history of premature myocardial infarction, diabetes mellitus, and triglycerides). RESULTS: Retention rate after 8 years of follow-up was 88% (n = 387). In women not using hormone therapy (HT): higher than average body mass index (BMI) (P < 0.001), BMI that increased (P < 0.005), lower than average estradiol levels (P < 0.005), estradiol levels that decreased (P < 0.001), and high free testosterone levels (P < 0.05) were associated with increased risk of a coronary event. There was a trend for high exercise frequency to be associated with a decreased risk (P < 0.07). After BMI and lifestyle variables were taken into account, use of HT did not have a significant effect on risk of a coronary event. CONCLUSION: In this longitudinal observational study of middle-aged Australian-born women, high BMI, an increase in BMI, high free testosterone, low estradiol, and a decrease in estradiol levels were the main determinants of increased risk of an acute coronary event, based on the PROCAM scoring system calculation. More frequent exercise tended to lower the risk.     

What is an Oligodendroglioma?

With this issue, we begin a new series of articles entitled “Controversies in neuropathology.” These will represent brief position papers on controversial topics in our specialty. They are not intended to be review articles, rather will represent “position papers” on topical issues, with a relatively circumscribed and selective bibliography. Authors of these papers are encouraged to present and defend their own views on the subject in question. Most of these papers will be by invitation, but authors who would like to submit an article for this series are encouraged to contact the Brain Pathology editorial office. HVV     

The Development of the Pathologic Changes of Alzheimer''s Disease and Senile Dementia in Patients with Down''s Syndrome

Senile plaques, neurofibrillary change and granulovacuolar degeneration characterize Alzheimer's disease (presenile dementia) and senile dementia and are also seen in the aged human brain. The development of these lesions was studied in 13 patients with Down's syndrome, ages 12 to 65, with the purpose of defining similarities and dissimilarities, if any, between their morphologies in these four conditions. Evaluation by light and, when applied, electron microscopy established apparent identities. The findings suggest that Down's syndrome, with its partially characterized genotypic and phenotypic abnormalities, is an appropriate model for the study of the pathogenesis of these lesions.     

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.     

Food granules elicit heavy drinking in polydipsic rats independently of meal duration.

Excessive drinking, in rats made polydipsic on intermittent delivery of food pellets, is inversely related to the time the rat spends with its head in the feeder, early in the interfood interval. In a sensitization model, this explains why food textures that induce more oral activity, e.g., powder, do not elicit drinking. This hypothesis was examined by coding the behavior of polydipsic rats and varying the duration of the meal delivered in each interval, while holding texture constant. Polydipsic rats were presented with pellets, food granules, or food powder. The food granules were dispensed over periods lasting 1, 14, 21, and 28 s. All food deliveries were of the same mass. The food was delivered periodically at 60-s intervals in each condition. The 14 rats in the experiment served as their own controls by experiencing every condition. The food granule conditions induced the expected increases in feeding early in the interval. However, instead of progressively reducing drinking, the excessive drinking simply occurred later in the interval. By contrast, the powder condition resulted in the immediate elimination of polydipsia. The results suggest that food texture elicits excessive drinking independently of temporal factors and that elicitation of the sensitized drinking response must depend on other factors.