Supplemental Digital Content is available in the text

No abstract

BackgroundTo examine the clinical characteristics of bacterial meningitis in elderly patients.Methods261 patients with adult bacterial meningitis (ABM), collected during a study period of 11 years (2000-2010), were included for study. Among them, 87 patients aged ≥ 65 years and were classified as the elderly group. The clinical and laboratory characteristics and prognostic factors were analyzed, and a clinical comparison with those of non-elderly ABM patients was also made.ResultsThe 87 elderly ABM patients were composed of 53 males and 34 females, aged 65-87 years old (median = 71 years). Diabetes mellitus (DM) was the most common underlying condition (34%), followed by end stage renal disease (7%), alcoholism (4%) and malignancies (4%). Fever was the most common clinical manifestation (86%), followed by altered consciousness (62%), leukocytosis (53%), hydrocephalus (38%), seizure (30%), bacteremia (21%) and shock (11%). Thirty-nine of these 87 elderly ABM patients had spontaneous infection, while the other 48 had post-neurosurgical infection. Forty-four patients contracted ABM in a community-acquired state, while the other 43, a nosocomial state. The therapeutic results of the 87 elderly ABM patients were that 34 patients expired and 53 patients survived. The comparative results of the clinical and laboratory characteristics between the elderly and non-elderly ABM patients showed that only peripheral blood leukocytosis was significant. Presence of shock and seizure were significant prognostic factors of elderly ABM patients.ConclusionsElderly ABM patients accounted for 34.8% of the overall ABM cases, and this relatively high incidence rate may signify the future burden of ABM in the elderly population in Taiwan. The relative frequency of implicated pathogens of elderly ABM is similar to that of non-elderly ABM. Compared with non-elderly patients, the elderly ABM patients have a significantly lower incidence of peripheral blood leukocytosis. The mortality rate of elderly ABM remains high, and the presence of shock and seizures are important prognostic factors.

Estrogens are essential for female reproduction and overall well-being, and estrogens in the circulation are largely synthesized in ovarian granulosa cells. Using primary cultures of ovarian granulosa cells from gonadotropin-primed immature rats, we have recently discovered that pituitary FSH and ovarian cytokine transforming growth factor beta 1 (TGFb1) induce calcineurin-mediated dephosphorylation-activation of cAMP-response element-binding protein (CREB)-regulated transcription coactivator (CRTC2) to modulate the expression of Star, Cyp11a1, and Hsd3b leading to increased production of progesterone. This study explored the role of calcineurin and CRTC2 in FSH and TGFb1 regulation of Cyp19a1 expression in granulosa cells. Ovarian granulosa cells treated with FSH displayed increased aromatase protein at 24 h post-treatment, which subsided by 48 h, while TGFb1 acting through its type 1 receptor augmented the action of FSH with a greater and longer effects. It is known that the ovary-specific Cyp19a1 PII-promoter contains crucial response elements for CREB and nuclear receptor NR5A subfamily liver receptor homolog 1 (LRH1/NR5A2) and steroidogenic factor 1 (SF1/NR5A1), and that the Nr5a2 promoter also has a potential CREB-binding site. Herein, we demonstrate that FSHCTGFb1 increased LRH1 and SF1 protein levels, and their binding to the Cyp19a1 PII-promoter evidenced, determined by chromatin immunoprecipitation analysis. Moreover, pretreatment with calcineurin auto-inhibitory peptide (CNI) abolished the FSHCTGFb1-upregulated but not FSH-upregulated aromatase activity at 48 h, and the corresponding mRNA changes in Cyp19a1, and Nr5a2 and Nr5a1 at 24 h. In addition, FSH and TGFb1 increased CRTC2 binding to the Cyp19a1 PII-promoter and Nr5a2 promoter at 24 h, with CREB bound constitutively. In summary, the results of this study indicate that calcineurin and CRTC2 have important roles in mediating FSH and TGFb1 collateral Key Words Journal of Molecular EndocrinologyResearch W-A LAI and others Calcineurin and CRTC2 in ovary Cyp19a1 Nr5a expression 53:2 259-270