The pathogenesis of diabetic retinopathy

Diabetic retinopathy remains a major cause of loss of vision. The Diabetes Control and Complications Trial (DCCT) has implicated hyperglycaemia as a probable major direct causative factor in the pathogenesis of diabetic retinopathy. There are several plausible mechanisms by which high glucose concentrations could lead to the functional and later structural changes characterising diabetic retinopathy. These include increased activity of the aldose reductase pathway, increase de novo synthesis of diacylglycerol from glucose, causing protein kinase C activation, increased non-enzymatic glycation and increased oxidative damage. The demonstration of the potential roles of these pathways and the subsequent effects of growth factors in enhancing angiogenesis provide potential new approaches to the prevention and treatment of diabetic retinopathy.     

Air pollution exposure estimation using dispersion modelling and continuous monitoring data in a prospective birth cohort study in the Netherlands

Background

High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors.

Methods

We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs) comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression.

Results

Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age.

Conclusions

Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

中国健康志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学

目的:研究中国健康成年男性志愿者单剂静滴甲磺酸加替沙星注射液的药代动力学。方法:按药物临床试验管理规范(GCP)指导原则设计试验方案。选择9名受试者分别依次单刘静滴100,200和400mg的甲磺酸加替沙星注射液后,应用HPLC测定血药浓度,采用3P97软件进行数据处理,求出药代动力学参数。结果:受试者分别给药后,药-时曲线符合二房室模型,主要药代动力学参数C_(max)分别为1.10±0.19,2.17±0.33和3.16±0.47mg·L~(-1);t_(1/2)β分别为7.42±1.99,8.41±2.72和8.46±2.83h;AUC_(0-∞)分别为4.45 ±0.71,11.10±1.81和23.03±3.83mg h·L~(-1)。原形药主要经肾排泄,48h尿药累积排泄率分别为(43.08±15.79)％,(51.33±23.69)%和(45.67±18.22)％。结论:9名静滴甲磺酸加替沙星注射液后,药-时曲线符合二房室模型。提示甲磺酸加替沙星在100～400mg剂量内药物体内过程基本呈线性动力学特征而无饱和性,主要排泄途径为肾脏。     

外旋外展推顶法治疗肩关节前脱位

目的：探讨外旋外展推顶法治疗肩关节前脱住可行性及疗效。方法：自1995年1月～2009年12月,采用外旋外展推顶法治疗肩关节前脱住500例,治疗后根据恢复症状及并发症,分析治疗方法的可行性及疗效。结果：所有患者均获得随访,时间为6个～1年;500例治愈432例。好转68例,无效O例。结论：外旋外展推项法治疗肩关节前脱住是一种可行的方法,较其他方法有更大的优点。     

Mammography using an ultrahigh-strip-density, stationary, focused grid

A 1-mm-thick, stationary, ultrahigh-strip-density, focused grid was evaluated with respect to patient radiation dose and mammographic image quality as it affected the resolution of microcalcifications and masses. Radiographic technique was varied to determine the most useful alteration to improve image quality with the grid. Results from 89 patients demonstrated that no improvement in diagnostic ability was found in women with fatty breasts. As breast density increased, the advantage of the grid technique became more apparent. Grid mammography also often solved the problem of questionable microcalcifications with improved visualization of their number and geometry.     

Comparative pharmacology of chemically distinct NADPH oxidase inhibitors

BACKGROUND AND PURPOSE

Oxidative stress [i.e. increased levels of reactive oxygen species (ROS)] has been suggested as a pathomechanism of different diseases, although the disease-relevant sources of ROS remain to be identified. One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re-interpreted.

EXPERIMENTAL APPROACH

We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947. We used several assays for detecting cellular and tissue ROS, as none of them is specific and artefact free.

KEY RESULTS

DPI abolished NADPH oxidase-mediated ROS formation, but also inhibited other flavo-enzymes such as NO synthase (NOS) and xanthine oxidase (XOD). Apocynin interfered with ROS detection and varied considerably in efficacy and potency, as did AEBSF. Conversely, the novel NADPH oxidase inhibitor, VAS3947, consistently inhibited NADPH oxidase activity in low micromolar concentrations, and interfered neither with ROS detection nor with XOD or eNOS activities. VAS3947 attenuated ROS formation in aortas of spontaneously hypertensive rats (SHRs), where NOS or XOD inhibitors were without effect.

CONCLUSIONS AND IMPLICATIONS

Our data suggest that triazolo pyrimidines such as VAS3947 are specific NADPH oxidase inhibitors, while DPI and apocynin can no longer be recommended. Based on the effects of VAS3947, NADPH oxidases appear to be a major source of ROS in aortas of SHRs.     

原发性乳腺恶性淋巴瘤六例临床分析

目的 分析原发性乳腺恶性淋巴瘤的临床特点,探讨其诊断、分期和治疗方法。方法回顾分析我院自1995～2002年收治的6例原发性乳腺恶性淋巴瘤和1980～2002年国内主要文献报道的279例原发性乳腺恶性淋巴瘤的临床特征、诊断情况和治疗方法,进行对比分析。结果 285例病例均为非霍奇金淋巴瘤(NHL),免疫学检查证实有282例为B细胞源性(98.9％);女性268例,占94.0％;病灶位于右侧163例,占57.2％;Ⅰ期和Ⅱ期的原发性乳腺恶性淋巴瘤占89.8％。经手术、化疗、放疗等综合治疗后,生存期2～206个月,中位生存期最短23个月,最长56个月。结论 原发性乳腺恶性淋巴瘤绝大部分为B细胞源性非霍奇金淋巴瘤(NHL),Ⅰ期、Ⅱ期多见。对于原发性乳腺恶性淋巴瘤,诊断是关键,确诊后经手术、化疗、放疗等综合治疗,可以获得较长的生存期,疗效十分满意。