Genetic linkage analysis of pulmonary fibrotic response to silica in mice.

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.     

Cause-specific and total mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population: a 15-year follow-up study.

AIMS: To establish all-cause and cause-specific death rates, and risk factors for mortality in insulin-treated diabetic individuals living in the province of Canterbury, New Zealand. METHODS: Insulin-treated diabetic subjects (n = 995) on the Canterbury Diabetes Registry were followed up over 15 years and vital status determined. Death rates were standardized and hazard regression was used to model the effects of demographic covariates on relative survival time. RESULTS: There were 419 deaths in 11 226.3 person-years of follow-up with a standardized mortality ratio (SMR) of 2.0 (95% confidence interval (CI) 1.8-2.2). Relative mortality was greatest for the group aged 0-29 years (SMR 3.0 (95% CI 2.4-3.7)). After controlling for diabetes duration and gender, a 10-year increment in age of onset was associated with a 33% decrease in relative hazard (95% CI 29-36%), indicating that excess mortality due to diabetes declines with rising age of onset. After controlling for age of onset and gender, each 10-year increment in duration of diabetes is associated with a 26% decrease in relative hazard (95% CI 24-29%), indicating that with longer survival the mortality hazard approaches the general population hazard. Relative mortalities were increased for cardiovascular, renal and respiratory disease, but not malignancy. Relative mortality from acute metabolic complications was increased in the subgroup with age of onset of diabetes < 30 years and requiring insulin within 1 year of diagnosis. CONCLUSIONS: Mortality rates are high for insulin-treated diabetic individuals relative to the general population.     

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.     

胶囊内镜与常规上消化道内镜检查诊断食管静脉曲张准确性的比较：一项前瞻性、3中心先导性研究

背景与研究目的：静脉曲张破裂出血是肝硬化的一个主要并发症，与6周内20％的死亡率有关。目前国际指南推荐肝硬化患应常规行上消化道内镜检查（食管胃十二指肠内镜检查，EGD）来筛查是否有食管静脉曲张。新近出现的食管胶囊内镜在对胃食管反流和Barrett食管的研究中已经显示出准确的诊断效应。该研究比较胶囊内镜和EGD对肝硬化患食管胃底静脉曲张和门脉高压性胃病的检出率。患与方法：在3个中心进行了先导试验。有进行EGD临床指征的肝硬化患，在EGD检查后48h内用胶囊内镜来筛查或监视食管静脉曲张。研究采用盲法，即由1名事先不知道患病史和EGD检查结果的研究评估胶囊视频成像。结果：在32例纳入的患中，EGD和胶囊内镜检查发现有食管静脉曲张23例患。有1例患经胶囊内镜发现有轻度静脉曲张，但EGD未检出。胶囊内镜和EGD诊断食管静脉曲张和门脉高压性胃病的总体一致性分别为96．9％和90．6％。没有与胶囊内镜相关的不良事件。     

Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis

Background  

Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery.     

Sociodemographic characteristics of the neighborhood and depressive symptoms in older adults: using multilevel modeling in geriatric psychiatry.

OBJECTIVE: Neighborhood sociodemographic characteristics may be important to the mental health of older adults who have decreased mobility and fewer resources. Our objective was to examine the association between neighborhood context and level of depressive symptomatology in older adults in a diverse geographic region of central North Carolina. METHODS: The sample included 2,998 adults 65 or older residing in 91 census tracts. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression scale (CES-D). Neighborhoods were characterized by five census-based characteristics: socioeconomic disadvantage, socioeconomic advantage, racial/ethnic heterogeneity, residential stability, and age structure. RESULTS: In ecologic level analyses, level of census tract socioeconomic disadvantage was associated with increased depressive symptoms. To determine whether neighborhood context was associated with depressive symptoms independently of individual characteristics, the authors used multilevel modeling. The authors examined the ability of each of five neighborhood (level 2) characteristics to predict a level 1 outcome (CES-D symptoms) controlling for the effects of individual (level 1) characteristics. Younger age, being widowed, lower income, and having some functional limitations were associated with increased depression symptoms conditional on census tract random effects. However, none of the neighborhood characteristics was significantly associated with depression symptoms, conditional on census tract random effects, either unadjusted or adjusted for individual characteristics. CONCLUSION: Any observed association between neighborhood sociodemographic characteristics and individual depressive symptoms in our sample may reflect the characteristics of the individuals who reside in the neighborhood rather than the neighborhood characteristics themselves. The use of multilevel modeling is important to separate these effects.     

Gender ratio of migraine without aura: observations over time

Abstract Migraine without aura is typically considered a female condition. The purpose of this study was to determine if there have been any changes in the female-to-male ratio of the disease over time. We included in the study all patients with migraine without aura (n=3457) referred to the Parma University Headache Centre between 1976 and 1995. They were divided into subgroups with respect to gender and year-range of onset of migraine (before 1960, in the 1960s, in the 1970s, in the 1980s, and between 1990 and 1995). Gender ratio ranged from 3.6:1 (in patients with onset before 1960) to 2.8:1 (in patients with onset in the 1980s), with no statistically significant changes during the observation period.