Meningiomas occur more commonly in females. The coincidence between meningioma and breast cancer and case reports of tumor growth during pregnancy support a hormonal hypothesis. A case control study was conducted to investigate this. Female subjects treated between 1987 and 1992 were identified from 3 hospitals in the Chicago area. Female spouses of male back pain patients were recruited as controls. A self-administered mail questionnaire focused on exogenous, endogenous and other hormonal factors, personal and family medical history as well as radiation exposures. Odds ratios and 95% confidence intervals were estimated using crude, stratified and multivariable logistic models including 219 cases and 260 controls. Participation rates were 86% among cases and 75% among controls. An increased odds ratio (OR) was observed comparing African Americans to Caucasians [OR 5 2.4, 95% confidence interval (CI) 5 1.0-6.1]. A protective effect was observed for pregnancy, which increased with number and age at first pregnancy. The odds ratio for 3 or more pregnancies compared to none was 0.3 (95% CI 5 0.2-0.6). Age at menarche or total period of hormonal activity was not protective. Ever smokers showed a decreased odds ratio for meningioma (OR 5 0.6, 95% CI 5 0.4-0.9). The increased odds ratios with African Americans was retained in post-menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. These data add to the evidence that factors known to influence endogenous hormones (pregnancy and indirectly smoking) may have protective effects for meningiomas primarily in premenopausal women. ' 2006 Wiley-Liss, Inc.Key words: case-control; meningioma; hormonal; reproductive The hypothesis of a hormonal influence on the occurrence of meningiomas was initially put forth because of the female preponderance in rates, the coincidence between meningioma and breast cancer 1 and case reports of tumor growth during pregnancy. 2 These indirect observations, stimulated studies of sex steroid receptors and a number of receptors and growth factors have been identified in tumor tissue. 3 Progesterone receptors predominate, although estrogen receptors may be present. 4 Although the role of these biologic markers in tumor development has not been established, it appears that the evidence for a role in tumor progression is stronger for progesterone receptors than for estrogen receptors. 5-7 A progesterone antagonist, mifepristone (RU-486), has been used therapeutically in an attempt to slow the growth of unresectable meningiomas, 8 but it has slowed the proliferation of meningioma tumor cells in vitro. 9 The role of hormone replacement therapy (HRT) in symptomatic postmenopausal women with previously treated disease or dormant tumors remains controversial. 6 A few small epidemiological studies suggested a potential role for both endogenous and exo...

Aqueductal CSF flow is strongly correlated with ventricular morphology, especially with the total ventricular volume and the third ventricle width, but not with the tested hydrodynamic parameters. In addition, ASV is linearly correlated with aqueductal lumen area, suggesting that the aqueductal CSF flow characteristics can be explained by oscillating pressure differences on the order of less than 0.01 mmHg. These findings may explain why a standalone ASV is a poor diagnostic marker and an insensitive indicator of shunt outcome in idiopathic normal pressure hydrocephalus.

The completion of the Human Genome Project combined with the development of microarray technology and recent advances in mathematical biology have set the stage for the genome-wide discovery of differential gene expression between any biological samples from any living system. The term discovery implies the extrapolation of data without the confound of pre-existing biases. This laboratory has developed a mathematical solution for discovering highly specific states of genetic expression between genetic samples (up-or down-regulated). The false discovery rate of the algorithm for microarrays that contain 19,200 CDNAs is Ͻ 0.001%. 1 To explore the idea that genomic expression discovery predicts pathways and functions behind the biological phenotypes of living systems, we compare a tumor to its normal host organ. The expression data accurately predict activation of signaling pathways and propose that unbalanced opposing genetic functions create "aberrant" phenotypes. In addition, known molecular interactions reveal a rich network of stimulatory and inhibitory genetic interconnections.We use microarrays containing 19,200 cDNAs to profile gene expression in 10 meningiomas versus normal brain. Meningiomas are compared with normal brain, its host organ, because both tissue types contain non-tumor cells such as blood vessels and cells of lymphocytic lineage. Meningiomas comprise 15-20% of all primary intracranial tumors. They are abundantly vascular, tend to bleed during surgery, and often show ectopic calcification on computed tomagraphic (CT) scanning. Multiple meningiomas occur in association with a mutated neurofibromatosis type II tumor suppressor gene, known as merlin or schwannomin. Merlin protein appears to stabilize F-actin (2-4). Normal brain RNA was pooled from the occipital lobes of four individuals with no known neurological disease whose brains were frozen less than 3 h postmortem. EXPERIMENTAL PROCEDURESReagents-Information on the antibodies used may be obtained from the corresponding web sites: anti-␤-catenin, www.upstatebiotech.com; anti-glyceraldehydes-3-phosphate dehydrogenase (G3PDH), www. trevigen.com.; anti-Akt, 2 anti-phospho-Akt (Ser-473), anti-p44/42 MAP kinase (ERK), and anti-phospho-p44/p42 Map kinase (Thr-202/Tyr-204, ERK-P), www.cellsignal.com.Tumors-Patients signed informed consents, and the study is approved by the Institutional Review Boards of Rush University and Cook County Hospital. Tumor samples are frozen in liquid nitrogen in the operating room. The quality of RNA is assayed by gel electrophoresis; only high quality reference and sample RNAs are processed.Microarray Experiments-All total RNA samples are analyzed in reference to a single standard obtained by pooling RNA from human occipital lobes. The latter are harvested and pooled from four individuals with no known neurological disease whose brains were frozen less than 3 h postmortem. Total RNA (5-10 g) is reverse-transcribed and the cDNA products labeled by the amino-allyl method with switching of probes between sample and refere...