Utility of a C-jun microsatellite marker in determining gene dosage for fatty (fa)

The Zucker fatty (fa) mutation provides a genetic model for obesity and non-insulin dependent diabetes mellitus. The molecular pathogenesis of the metabolic phenotype of these animals is not known. Detailed molecular maps of the region surrounding the fa locus on rat chromosome 5 can be used for positional cloning experiments as well as to permit genotyping of animals from appropriate crosses before the confounding metabolic effects of obesity have occurred. We describe the development of a polymerase chain reaction (PCR) assay for a polymorphic simple sequence repeat (SSR) in the promoter region of the protooncogene c-Jun. This assay was used to position c-Jun 4.5cM proximal to the fa locus in 111 F2 progeny of a 13MBN fa/+ F1 intercross. Concurrent use of the c-Jun SSR with a previously described assay for a microsatellite in the glucose transporter, Glut1, permits rapid and accurate assessment of genotypes at the fa locus in animals of any age using minimal amounts of DNA. A strategy is described which minimizes the error rate in assigning genotype at the fatty locus for backcross and intercross progeny.     

应用4650Ⅰ型压缩机雾化器进行支气管激发试验的研究

为了解Models 4650Ⅰ型压缩机雾化器(简称M)进行支气管激发试验的可行性,将92例支气管哮喘患者按用M雾化吸入时间的不同,分为1、1.5、2分钟三组,并与标准雾化装置Dosimeter及雾化器(简称D)进行支气管激发试验同步对比研究.结果显示 ,三组受试者用两种雾化装置所获测值间无显著性差异(P＞0.2～0.5),且皆呈直线正相关.M与D皆雾化吸入1分钟时,M所需药物浓度大于D,相关系数(0.285)偏低,延长M的雾化吸入时间至1.5分钟,与D雾化吸入1分钟相比,两者差值最小(-0.075 g/L), r =0.665;若再延长M雾化吸入时间,与D的差值又会扩大.提示:M雾化效果稍差于D,适当延长时间可弥补上述差异,建议M雾化吸入时间以1.5分钟为宜.     

99mTc-DTPA气溶胶显像测定呼吸道粘液纤毛清除功能

为进一步研究呼吸道疾病时的粘液纤毛清除功能,采用99mTc-DTPA气溶胶吸入显像,通过电影显示定性和定量指标分析.对18 例健康受试者和患者进行了显像研究,得到气道清除率和粘液纤毛清除率的正常值,并观察了32例慢性阻塞性肺病(COPD)患者气管-支气管纤毛清除功能的改变.结果显示,健康受试者与COPD患者粘液纤毛清除率(mm/min)分别为3.89±0.92和1.32±0.59,两者比较有显著性差异(P＜0.01),COPD患者不同时间气道清除率和粘液纤毛清除率均明显低于健康受试者(P＜0.01).本研究方法简便客观,具有定性观察和定量分析的优点,对于呼吸系统其它疾病(如支气管扩张、原发性纤毛无运动)的研究及药物疗效的评价具有重要的临床实用价值.     

A Phase 2 open label study of ledipasvir/sofosbuvir for 12 weeks in subjects with hepatitis B virus infection

Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log₁₀ IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

Success in Surgical Intervention for Morbid Obesity: Is Weight Loss Enough?

Varieties of gastric surgery have increasingly been used in the management of morbid obesity. Generally, however, research and commentary in this area have related to surgical technique, with weight loss or morbidity being regarded as the most important dependent measures. In the context of the publication of several papers relating to the effects of surgery in the long-term, we believe that it is timely for surgeons to examine their criteria for success. In this paper, we argue that weight loss is inadequate as a primary criterion for success in this context, and that the value of the intervention should be measured against a multidimensional concept of success.     

The effect of a model melanoidin mixture on faecal bacterial populations in vitro

The Maillard reaction produces coloured, macromolecular materials (melanoidins) in a variety of foods, on heating. Significant quantities may enter the human gut on a daily basis, but there is little information on their metabolism in the human colon. As the large bowel contains a diverse population of bacteria involved in normal bowel function, it is possible that melanoidins are metabolized therein. Depending on the bacteria involved, there may be disease or health implications. The aim of the present study was to use in vitro models to determine the digestibility of melanoidins and the effect of melanoidins on colonic bacteria in the gastrointestinal tract. Melanoidins were prepared and the effects of simulated upper-gut secretions on their stability determined in a model system. The effects of faecal bacteria were also determined, in batch culture, with a combination of phenotypic and genotypic (probes) criteria being used to identify the microbial diversity involved. Simulation of peptic and pancreatic digestion showed that the melanoidins did not produce detectable amounts of low-molecular-mass degradation products. However, melanoidins affected the growth of gut bacteria during mixed culture growth. The effect was to cause a non-specific increase in the anaerobic bacteria enumerated. This in vitro study indicates that melanoidins can affect the growth of human large-bowel bacteria and serves to demonstrate possible effects that may occur in vivo. Given the large and varied number of food items that contain Maillard reaction products, this may have relevance for lower-gut health.     

The voluntary community health movement in India: A strengths,weaknesses, opportunities,and threats (SWOT) analysis

There has been a prolific growth of voluntary organizations in India since independence in 1947. One of the major areas of this growth has been in the field of community health. The purpose of this article is to historically trace the voluntary movement in community health in India, analyze the current status, and predict future trends of voluntary efforts. A review of the literature in the form of a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was the method of this study. Some of the key trends which emerged as the priority areas for progress and for strengthening voluntary organizations in the future were enhancing linkages between health and development; building upon collective force; greater utilization of participatory training; establishing egalitarian and effectual linkages for decision making at the international level; developing self-reliant community-based models; and the need for attaining holistic empowerment at individual, organizational, and community levels through duty consciousness as opposed to merely asking for rights.The authors would like to express gratitude to Voluntary Health Association of India for sharing the necessary documents and to Dr. Rick Petosa for valuable editorial comments.     

Body mass index and cardiovascular risk factors in pacific Island Polynesians and Europeans in New Zealand

Objectives. To examine relationships between body mass index (BMI) and cardiovascular risk factors in 279 Europeans and 231 Polynesian Pacific Islanders in New Zealand.

Methods. Participants were recruited from Seventh‐Day Adventist church meetings or camps, and were surveyed by self‐administered questionnaire. Blood pressure, weight and height were measured. Fasting blood samples were analysed for lipids, glucose and fructosamine.

Results. Age‐adjusted BMI was higher in Pacific Islanders than in Europeans: 32.8(0.3) versus 25.6(0.3); means(SE); p = 0.0001). In Europeans, BMI was positively associated with systolic and diastolic blood pressures, triglycerides, total cholesterol, LDL cholesterol and fasting blood glucose, and negatively associated with HDL cholesterol. In Pacific Islanders, BMI was associated only with systolic and diastolic blood pressures, and with HDL cholesterol. These associations were stronger in Europeans than in Pacific Islanders.

Conclusions. In this group of Pacific Islanders, the association between BMI and cardiovascular risk factors was weaker than in Europeans. This suggests that either BMI is a poor measure of adiposity in Pacific Islanders, or that adiposity may be less strongly linked to cardiovascular disease in Pacific Islanders.