Airway smooth muscle: immunomodulatory cells that modulate airway remodeling?

Although the pathogenesis of asthma remains unclear, substantial progress has been made over the past decades in the characterization of airway inflammation as a pathogenetic mechanism in asthma. New evidence suggests that airway smooth muscle (ASM), the most important cell modulating bronchomotor tone, plays an important immunomodulatory role in the orchestration and perpetuation of airway inflammation. Evidence now suggests that the signaling pathways that modulate leukocyte function may be disparate from those found in resident effector cells such as ASM, fibroblasts and epithelial cells. Further investigation and understanding of the critical signaling pathways that modulate ASM cell release, secretion of chemokines/cytokines and expression of cell adhesion molecules (CAMs) may offer new therapeutic approaches in the treatment of asthma.     

Genetic variants in a haplotype block spanning IDE are significantly associated with plasma Abeta42 levels and risk for Alzheimer disease

Risk for late onset Alzheimer disease (LOAD) and plasma amyloid beta levels (Abeta42; encoded by APP), an intermediate phenotype for LOAD, show linkage to chromosome 10q. Several strong candidate genes (VR22, PLAU, IDE) lie within the 1-lod support interval for linkage. Others have independently identified haplotypes in the chromosome 10q region harboring IDE that show highly significant association with intermediate AD phenotypes and with risk for AD. To pursue these associations, we analyzed the same haplotypes for association with plasma Abeta42 in 24 extended LOAD families and for association with LOAD in two independent case-control series. One series (MCR, 188 age-matched case-control pairs) did not show association (p=0.64) with the six haplotypes in the 276-kb region spanning three genes (IDE, KNSL1, and HHEX) previously shown to associate with LOAD. The other series (MCJ, 109 age-matched case-control pairs) showed significant (p=0.003) association with these haplotypes. In the MCJ series, the H4 (odds ratio [OR]=5.1, p=0.003) and H2(H7) haplotypes (OR=0.60, p=0.04) had the same effects previously reported. In this series, the H8 haplotype (OR=2.7, p=0.098) also had an effect similar as in one previous case control series but not in others. In the extended families, the H8 haplotype was associated with significantly elevated plasma Abeta42 (p=0.02). In addition, the H5(H10) haplotype, which is associated with reduced risk for AD in the other study is associated with reduced plasma Abeta42 (p=0.007) in our family series. These results provide strong evidence for pathogenic variant(s) in the 276-kb region harboring IDE that influence intermediate AD phenotypes and risk for AD.     

8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer''s disease

Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2′-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10⁵ 2′-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.     

Molecular analysis of HLA-D region genes in seropositive rheumatoid arthritis

Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10(-3), relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2 x 10(-5), RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10(-2), RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, -7, -9 and -w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQw1. Using probes specific for the 5' or 3' regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5' end and the 4.8 and 7.0 kb RFLPs to the 3' end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5' location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes.     

Dielectric behavior of pulmonary edema induced in the rat lung

The dielectric properties (conductivity, kappa and relative permittivity, epsilon) of excised rat lung are modified by lung air and water content. The measurements of these quantities were made over the frequency range of 10 kHz to 100 MHz with an open-ended coaxial probe. The following relationships were analyzed in an oleic acid-induced pulmonary edema model using 18 animals: the spectra of kappa, epsilon and the loss tangent as a function of lung air and water content. Secondly, an isolated-perfused lung system was produced to induce a gradual increase in lung water. The time course of kappa, epsilon and the loss tangent for one excised lung was analyzed. The principal findings were: (i) a decrease in kappa and epsilon with increasing air content, (ii) an increase in kappa and epsilon with increasing water content, and (iii) a good correlation between lung water content and maximum loss tangent that was insensitive to changes in air content. We conclude that this technique could provide a quantitative assessment of lung water during pulmonary edema formation.     

Cartilage degradation products as markers for evaluation of patients with rheumatic disease

Markers of cartilage degradation hold a great, but so far underutilized potential in the research and clinical management of joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). With the rapid pace of development of such markers, they are likely to emerge as promising clinical tools for several uses. These roles may include: improving preclinical and clinical development in arthritis research; differentiation of patients with high and low turnover states at disease diagnosis; selection of optimal therapy and therapy dose for the individual patient; monitoring disease progression; and predicting disease outcome.This review focuses on the cartilage matrix components and the metabolites from this very special tissue that have been proposed as biochemical markers. Special attention is focused on the challenges facing the development of such markers to the standards required for widespread practical use. Examples are provided on the current use of cartilage derived biochemical markers and perspectives for the future use of markers and required clinical documentation are presented.     

Periodic breathing and genetics

The episodic waxing and waning of ventilation is a fundamental event in sleep apnea syndromes. Post-hypoxic frequency decline (PHFD) and periodic breathing (PB) are evoked by brief hypoxic exposures in unanaesthetized and unrestrained inbred C57BL/6J mice, but not in A/J mice; and expression of PHFD differs not only among these mice strains but in among rat strains as well. These observations along with the current literature on genetic factors that operate on ventilatory behavior at rest and with chemosensory drive lead to the hypothesis that genetic factors infer some proportion of risk for the ventilatory instability observed in human sleep apnea syndromes.     

以单病种过程质量管理促进临床诊疗同质化

单病种质量管理丰富了过程质量管理的内涵,是提升医疗质量管理水平的重要手段。利用单病种过程质量管理实现医疗质量管理同质化,需要从临床诊疗工作同质化、数据同质化、医疗质量评价同质化三方面发力,引导医疗机构运用单病种质量监测信息项开展国家、省级和院内、院际间的质量比较,从而推进临床诊疗过程质量管理同质化。     

单病种质量管理信息化平台建设与应用

信息化建设是医院实现单病种质量管理要求的必要手段。浙江大学医学院附属第二医院结合单病种质量管理实践,运用信息化手段,构建了单病种质量管理信息化平台。依托平台,可自动采集单病种质量管理数据并实现网络直报,便于开展单病种质量控制与过程管理,使单病种质量管理流程高效、便捷的同时,进一步提升了医疗质量管理水平。     

川崎病门诊临床路径管理系统构建与应用

川崎病遗留冠状动脉损害长期存在,需要对患儿进行长期监测。借助医院信息系统,设计了川崎病门诊临床路径管理系统。系统具备路径设置、医生工作站路径、科研统计分析、患者预约提醒等功能,可满足川崎病临床治疗和科研需求。但系统使用率、系统操作的精细化水平等有待进一步提升,可从系统支持、临床管理两方面持续改进。