一个原发性痛风家系致病易感基因染色体定位

目的 对一原发性痛风家系进行致病基因的染色体定位。方法 收集痛风家系成员的临床资料及血液样本。选择其中一典型家系为研究对象（包括6例患者，9例正常人），抽提外周血基因组DNA，进行全基因组扫描和连锁分析，初步明确致病基因所在的染色体区段。结果 在微卫星引物D4S1572处获得最大LOD值（θ=0．00时LOD=1．50），表明该痛风家系的致病基因与该位点连锁。结论 由于D4S1572位于4q25，因此该家系致病基因位于4q25附近。     

The implications of the ezetimibe and simvastatin in hypercholesterolemia enhances atherosclerosis regression trial: a return to first principles

To outward appearances, the publication of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial has led to a monolithic backlash against the use of ezetimibe by cardiologists for the treatment of hyperlipidemia. Rather than be swayed by popular opinion, we should each put the results of ENHANCE into context and ask the questions: should I put my trust in an imaging surrogate or in low‐density lipoprotein (LDL) cholesterol (LDL‐C), and how do the safety and efficacy of ezetimibe compare with other nonstatin lipid‐lowering agents? Copyright © 2008 Wiley Periodicals, Inc.     

UK prospective diabetes study (UKPDS)

Summary The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective, randomised, intervention trial of 5100 newly-diagnosed patients with Type 2 (non-insulin-dependent) diabetes mellitus which aims to determine whether improved blood glucose control will prevent complications and reduce the associated morbidity and mortality. Newly presenting Type 2 diabetic patients aged 25–65 years inclusive, median age 53 years, median body mass index 28 kg/m² and median fasting plasma glucose 11.3 mmol/l, were recruited and treated initially by diet. Ninety five percent remained hyperglycaemic (fasting plasma glucose > 6 mmol/l) and were randomly allocated to different therapies. In the main randomisation, those who were asymptomatic and had fasting plasma glucose under 15 mmol/l were allocated either to diet policy, or to active policy with either insulin or sulphonylurea aiming to reduce the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with 7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes Study has been included in a factorial design to assess whether improved blood pressure control will be advantageous. Patients with blood pressure 160/90 mm Hg were randomly allocated to tight control aiming for < 150/85 mm Hg with either an angiotensin-converting enzyme inhibitor or a Beta-blocker or to less tight control aiming for < 200/105 mm Hg. The endpoints of the studies are major clinical events which affect the life and well-being of patients, such as heart attacks, angina, strokes, amputations, blindness and renal failure. To date, 728 patients have had at least one clinical endpoint. Surrogate endpoints include indices of macrovascular and microvascular disease detected by ECG with Minnesota Coding, retinal colour photography and microalbuminuria. The studies also aim to evaluate potential risk factors for the development of diabetic complications such as smoking, obesity, central adiposity, plasma LDL-and HDL-cholesterol, triglyceride, insulin, urate and other biochemical variables. The studies are planned to terminate in 1994, with a median follow-up of 9 years (range 3–16 years) for the glucose study and 5 years (range 2–6 years) for the hypertension study.     

Fluticasone in mild to moderate atopic dermatitis relapse: A randomized controlled trial

Background

The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD.

Steroids in chronic B-hepatitis. A randomized,double-blind,multinational trial on the effect of low-dose,long-term treatment on survival

ABSTRACT- The effect of long-term, low-dose prednisolone treatment on the survival of patients with chronic B-hepatitis was studied in a randomized, double-blind multicentre trial. Twenty-two centres from 11 European countries included 99 patients in the trial. Survival analysis showed 2.9 (95% confidence limit 0.9-9) times greater mortality in the prednisolone than in the placebo group (P = 0.07). In a Cox regression analysis, correcting for the influence of other prognostic factors, the detrimental effect of prednisolone treatment was unchanged. Mortality increased significantly with age, and patients without piece-meal necrosis had 7 times higher mortality than those with this change on entry to the trial. It is concluded that long-term, low-dose prednisolone treatment is very unlikely to be beneficial, and should be considered harmful in chronic B-hepatitis, particularly in the most severe and advanced cases.     

Dietary fiber and colorectal neoplasia

PURPOSE: Dietary fiber has been implicated in colorectal neoplasia, despite conflicting evidence. This is a review of the currently available data on the role of dietary fiber in colorectal carcinogenesis. METHODS: A literature search was conducted using the MEDLINE database. All case-control, longitudinal, and randomized, controlled studies published in English between 1988 and 2000 were identified, as were animal model studies in the period 1986 to 2000. Data from the various studies were tabulated and systematically analyzed, with particular emphasis on the effect of dietary fiber on tumor incidence and luminal parameters such as short chain fatty acids. RESULTS: Epidemiologic correlation studies show a high intake of dietary fiber to be associated with a lower risk of colorectal neoplasia. Thirteen of the 24 case-control studies reviewed demonstrated a protective effect of dietary fiber against colorectal neoplasia, and 16 showed a protective effect of vegetables or vegetable fiber. On the other hand, of 13 longitudinal studies in various cohorts, only 3 demonstrated a protective effect of fiber and 4 a protective effect of vegetables or vegetable fiber. The five published randomized, controlled trials all investigated the effect of increased fiber intake on short-term adenoma recurrence; however, none showed any significant protective effect. Among 19 experimental studies in animal models, 15 showed a protective effect of fiber against tumor induction compared with controls. Animal studies also showed that poorly fermentable fibers (e.g., wheat bran and cellulose) were more protective than soluble fibers (e.g., guar gum and oat bran), which sometimes enhanced carcinogenesis. No clear correlation was found between luminal pH or short chain fatty acids and tumor induction. CONCLUSIONS: On the basis of current data, there is little evidence to support the use of dietary fiber supplements to reduce the risk of colorectal neoplasia. Lifelong and early exposure may be important but are difficult to study. Other risk factors interact with the effects of dietary fiber.     

The Diabetes Atherosclerosis Intervention Study (DAIS): a study conducted in cooperation with the World Health Organization

Summary The incidence of coronary artery disease is greatly increased in those with diabetes mellitus. The largest number of those who have coronary artery disease have non-insulin-dependent diabetes (NIDDM). Lipoprotein abnormalities have been identified among the several risk factors that could account for this increase in atherosclerosis. There have been many studies demonstrating that correction of dyslipoproteinaemias will reduce the risk of coronary disease in non-diabetic populations. Current advice to those with diabetes is based on extrapolations from such studies. However, the justification for this, and the treatment targets are unclear as there has been no direct test of the lipid hypothesis in diabetes. This paper describes the protocol of the first intervention trial designed to examine directly whether correcting dyslipoproteinaemia in men and women with NIDDM will reduce their coronary artery disease. The Diabetes Atherosclerosis Intervention Study (DAIS), is a multinational angiographic study using the 200 mg micronized form of fenofibrate in a double-blind, placebo-controlled protocol. [Diabetologia (1996) 39: 1655–1661]     

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities

ObjectivesDespite substantial morbidity and mortality associated with acute pancreatitis (AP), only one small randomized controlled drug trial (RCT) is available in the past few decades from the United States. Hence, we conducted a single-center, double-blind, placebo-controlled RCT of pentoxifylline in AP.MethodsA total of 9 doses of oral pentoxifylline 400 mg or placebo tablet, three times daily, was administered within 72 h of diagnosis, using randomization blocks by pharmacy. Primary outcome was a composite outcome including any of the following: death, peripancreatic and/or pancreatic necrosis, infected pancreatic necrosis, persistent organ failure, persistent systemic inflammatory response syndrome, hospital stay longer than 4 days, need for intensive care, and need for intervention for necrosis.ResultsBetween July 7, 2015, and April 4, 2017, we identified 685 patients with AP, 233 met eligibility criteria and 176 were approached for the study. Of these, 91 (51.7%) declined and finally 45 in pentoxifylline group and 38 in placebo group (83 total) were compared. There were no significant differences in primary outcome (27 [60.0%] vs 15 [39.5%]; P = .06). Pentoxifylline group was not associated with any benefit, but withlonger stay (42% vs. 21%; P = .04) and higher readmission rates (16 %vs 3%; P = .047).ConclusionsWe could not demonstrate superiority of pentoxifylline over placebo. Smaller sample size and inclusion of all types of severity might be the reasons for lack of efficacy. The challenges observed in the present study indicate that, in order to conduct a successful drug trial in AP, a multi center collaboration is essential.     

Prenatal management of congenital diaphragmatic hernia

Recently, two randomized controlled, prospective trials, the Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trials, reported the outcomes on fetal endoluminal tracheal occlusion (FETO) for isolated left congenital diaphragmatic hernia (CDH). FETO significantly improved outcomes for severe hypoplasia. The effect in moderate cases, where the balloon was inserted later in pregnancy, did not reach significance. In a pooled analysis investigating the effect of the heterogeneity of the treatment effect by the time point of occlusion and severity, the difference may be explained by a difference in the duration of occlusion. Nevertheless, FETO carries a significant risk of preterm birth. The primary objective of this review is to provide an overview of the rationale for fetal intervention in CDH and the results of the randomized trials. The secondary objective is to discuss the technical aspects of FETO. Finally, recent developments of potential alternative fetal approaches will be highlighted.