The Cys allele of the DRD2 Ser311Cys polymorphism has a dominant effect on risk for schizophrenia: evidence from fixed- and random-effects meta-analyses.

Previously we derived independent estimates of the effect of the dopamine D2 receptor (DRD2) Ser311Cys polymorphism on risk for schizophrenia using fixed- and random-effects meta-analyses. Both analyses identified a significant association between the Cys allele and schizophrenia, but neither included all available data. Furthermore, genotype data were not evaluated in either analysis, thus precluding any determination of the mode of inheritance. The present study was conducted to resolve discrepancies between the existing meta-analyses, and provide more comprehensive and accurate estimates of the nature and magnitude of the influence of the Ser311Cys polymorphism on risk for schizophrenia. All discrepancies between the two sets of previously meta-analyzed studies were identified and resolved to the mutual satisfaction of the authors, and the final dataset was analyzed independently by fixed- and random-effects meta-analyses. A total of 27 samples, comprising 3,707 schizophrenia patients and 5,363 control subjects, were included in the analyses of allelic association, while smaller numbers of studies and subjects were included in each of the genotypic association analyses. A significant effect of the Cys allele was observed under both fixed-effects (odds ratio [OR] = 1.4; P = 0.002) and random-effects (OR = 1.4; P = 0.007) models. Cys/Ser heterozygotes were at elevated risk for schizophrenia when compared to Ser/Ser homozygotes (fixed- and random-effects OR = 1.4, p(s) or= 0.948). There was no evidence of heterogeneity, excessive influence of any single study, or publication bias in any of the analyses, suggesting that the effect of this DRD2 polymorphism on schizophrenia risk is reliable and uniform across populations, and our estimates of its magnitude are robust and accurate.     

Prevention of Descending Pneumonia in Rats with Perflubron-delivered Tobramycin

OBJECTIVES: Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia. METHODS: Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons. RESULTS: All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05). CONCLUSIONS: Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP.     

Utility of the Brief Symptom Inventory in the Assessment of Psychological Distress

Introduction People with intellectual disabilities are now acknowledged to be susceptible to the full range of mental health disorders. This acknowledgement has resulted in the need to develop and evaluate instruments for the assessment and detection of mental health problems. This research evaluates the use of the Brief Symptom Inventory (BSI) with 200 people with mild intellectual disabilities representing community, clinical and forensic populations. Results and conclusions Results illustrate the reliability of the BSI for each of the groups and demonstrates how the Positive Symptom Total (PST) index effectively discriminates between study groups. Case rates for each group are provided. The study illustrates that the BSI could be employed as a brief multitrait assessment instrument and as a treatment outcome measure with people with an intellectual disability.     

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis

Introduction Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1β, tumor necrosis factor α, and interleukin-6. Methods We studied 32 outpatients (18 females; mean age: 26.2 ± 7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1β and BMD at all sites. Results In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. Conclusions These findings may have therapeutic implications for enhancing bone density in these patients.     

Mycophenolate Mofetil Use Is Associated with Decreased Risk of Late Acute Rejection in Adult Liver Transplant Recipients

Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection > or = 6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan-Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6-12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.     

Vagal nerve stimulator implantation: an otolaryngologist's perspective.

OBJECTIVE: This study was conducted to compare an otolaryngologist's experience with a cohort of epilepsy patients implanted with a vagal nerve stimulator (VNS) to previously published data. METHODS: Demographics, preoperative seizure frequency, medications, and complications were retrospectively collected from patients implanted by the senior author. Postoperative medications and seizure frequency were obtained from referring neurologists. RESULTS: Seventeen patients were implanted over a 24-month period. Average age was 28.3 years. Patients presented with petit mal (n = 3), tonic-clonic (n = 6), complex partial (n = 5), and grand mal (n = 8) seizures. Mean follow-up postimplantation was 13.5 months. Most patients had at least a 50% reduction of seizure frequency, with 3 patients being seizure free. There were no postoperative infections. One patient had left vocal cord immobility. The most common side effect was voice disturbance during device activation. CONCLUSION: Otolaryngologists are well equipped to perform VNS implantation and to diagnose and treat possible laryngeal side effects. EBM rating: C-4.     

Chronic hepatitis B: current testing strategies.

The worldwide burden of hepatitis B mandates accurate and timely diagnosis of patients infected with the hepatitis B virus (HBV) and the use of treatment strategies derived from evidence-based guidelines. HBV is a DNA virus that produces a series of viral protein products circulating HBV DNA. Serologic and nucleic acid testing are critical to disease prevention and treatment objectives. Information from such testing helps determine patients' infectivity and immune status, appropriate monitoring strategies, and the efficacy of treatment, as well as providing data that contributes to a better understanding of the natural history and epidemiology of the disease. This article reviews the clinical use of state-of-the-art serologic and nucleic acid tests, including the relevance of hepatitis B e antigen and antibody and HBV DNA measurements as markers of disease activity. Viral load can be used to distinguish between active and inactive disease, define response to therapy, and detect the development of antiviral resistance. Some recent reports have suggested that high viral load is associated with poorer patient outcomes (eg, more rapid progression to cirrhosis and a higher incidence of hepatocellular carcinoma). Durable suppression of HBV DNA is evolving to become the primary goal of therapy, although all currently licensed medications have used histology as the primary end point of therapy. Suggested frequencies for HBV DNA monitoring are presented.