No abstract

No abstract

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnoverFindexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)Fin a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity  genotype interaction (P ¼ 0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender  genotype interaction (P ¼ 0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P ¼ 0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

No abstract

Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

Red blood cells (RBCs) undergo numerous changes during storage; however, the clinical relevance of these storage "lesions" is unclear. We hypothesized that the duration of storage of transfused RBCs is associated with mortality after repeat sternotomy for cardiac surgery, because these patients are at high risk for both RBC transfusion and adverse outcome. We retrospectively analyzed 434 patients who underwent repeat median sternotomy for coronary artery bypass graft or valve surgery and who received allogeneic RBCs. Three-hundred-twenty-one (74%) patients met the criteria for eligibility. After adjusting for the effects of confounders and the total number of RBC transfusions, the duration of storage of the oldest RBC unit transfused was found to be associated with both in-hospital mortality (Cox proportional hazard ratio (HR) = 1.151; P < 0.0001) and out-of-hospital mortality (HR = 1.116; P < 0.0001). The mean duration of storage of transfused RBCs was also an independent predictor of in-hospital mortality (HR = 1.036; P < 0.0001). Independent associations between the duration of storage of transfused RBCs and acute renal dysfunction and intensive care unit and hospital length of stay were also observed. The duration of storage of RBCs is associated with adverse outcome after repeat sternotomy for cardiac surgery. The clinical significance of this finding should be investigated in a large, randomized, blinded clinical trial.

No abstract

Background-The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. Methods and Results-We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level Ն10ϫ upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted PϽ0.05; false discovery rate Ͻ10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 Ϫ572GϾC; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98GϾT; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). Conclusions-Functional