Novel 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study

In this study, we report the ring transformation of 3-arylsydnone into 1-aryl-1H-pyrazole-3-carbonitriles via [3 + 2] cycloaddition with acrylonitrile. 1-Aryl-1H-pyrazole-3-carbonitrile underwent [2 + 3] cycloaddition with sodium azide to afford 5-(1-aryl-1H-pyrazol-3-yl)-1H-tetrazoles which were further subjected to N-alkylation with aryl/heteroaryl alkyl halides to afford 1,5- and 2,5-disubstituted tetrazoles. Furthermore, the title compounds were screened for in vivo antihyperglycemic activity using albino Wistar rats of either sex. Compounds 4a , 6b , 7a , 7b , 8b , and 9b showed maximum fall in the blood glucose levels in streptozotocin-induced diabetic rats after 5–7 days of administration. In support of antidiabetic activity, we also performed the experimental in vivo studies, namely, effect of compounds on enzymes (serum glutamic oxaloacetic transaminase, serum glutamic-pyruvic transaminase, creatinine, urea, and total protein), antihyperlipidemic, and histopathology. Moreover, the molecular docking study has been performed for potent molecules among the series with glycogen phosphorylase as target enzyme, and this study corroborated the experimental in vivo results.     

Role of self-expanding metal stents in patients with malignant colorectal obstruction: A systematic review and meta-analysis

AIM: To assess the safety and efficacy of self-expandable metal stents(SEMSs) for malignant colorectal obstruction. METHODS: Data regarding technical success, clinical success, and procedure related complications were collected from included studies. Der Simonian-Laird random effects model was used to generate the overall outcome. Thirty international studies with a total of 2058 patients with malignant colorectal obstruction were included. RESULTS: The technical and clinical success rates for SEMS placement were 94%(95%CI: 92-96) and 91%(95%CI: 88-93), respectively. Overall complication rate for SEMS was 23%(95%CI: 18-29). Stent migration8%(95%CI: 6-10) and stent obstruction 8%(95%CI: 6-11) were the most common complications, followed by perforation 5%(95%CI: 4%-7%). Surgical or endoscopic re-interventions were needed in 14%(95%CI: 10-18) of patients. Endoscopic repeat stent placement was required in 8%(95%CI: 6-10), while surgical intervention was needed in 6%(95%CI: 4-8).CONCLUSION: SEMS are effective when used as palliation or bridge to surgery for malignant colorectal obstruction with high technical and clinical success. About 14% of patients require repeat endoscopic or surgical intervention for stent failure or to manage stent related complications.     

Use and misuse of cost-effectiveness terminology in the gastroenterology literature: a systematic review

OBJECTIVES: The increased popularity of economic analyses for evaluating medical interventions has given rise to concern about the rigor with which economic constructs and terminology are used. True cost-effectiveness analysis considers both the costs and outcomes of alternative interventions. A systematic review of the gastroenterology literature was undertaken to evaluate how appropriately cost-effectiveness is assessed. METHODS: A structured MEDLINE search identified all studies published in major gastroenterology journals between 1980 and 1998 that claimed in their abstracts to have assessed the cost-effectiveness of an intervention. Blinded copies of eligible studies were assessed by two independent reviewers who used standard criteria to evaluate the use of economic terminology and key economic constructs. Discrepancies were resolved by consensus. Studies met a "broad criterion" for appropriateness by evaluating both costs and effects and a "strict criterion" by demonstrating dominance of one strategy or considering both incremental costs and incremental effects. RESULTS: Of 110 eligible studies, 77 (70.0%) met the broad criterion and 62 (56.4%) met the strict criterion for appropriateness. This did not seem to vary with either journal impact factor or publication year. Only eight of 18 studies reporting an incremental cost-effectiveness ratio compared its value to an external standard. Few studies explicitly stated their analytic perspective, and a minority of those with time horizons longer than 1 yr had discounted future costs or effects. CONCLUSIONS: Although most studies seem to use cost-effectiveness terminology well, there remains room to improve the rigor with which economic terminology and constructs are applied.     

Computer-assisted personalized sedation

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of new or emerging endoscopic technologies that have the potential to have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent preclinical and clinical studies on the topic, and a MAUDE (Manufacturer and User Facility Device Experience; U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported complications of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized but, in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. For this review, the MEDLINE database was searched through January 2010 using the keywords "computer," "computerized," "computer-assisted," "sedation," "propofol." Reports on Emerging Technology are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. These reports are scientific reviews provided solely for educational and informational purposes. Reports on Emerging Technology are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.     

Training minimal invasive approaches in hepatopancreatobilliary fellowship: the current status

BackgroundThere has been an increasing role of advanced minimally invasive procedures in hepatopancreatobilliary (HPB) surgery. However, there are no set minimum laparoscopic case requirements.MethodsA 14-question electronic survey was sent to 82 worldwide HPB fellowship programme directors.ResultsForty-nine per cent (n = 40) of the programme directors responded. The programmes were predominantly university based (83%). Programmes had either one (55%) or two fellows (40%) each year. Programmes (35–48%) had average annual volumes of 51–100 hepatic, 51–100 pancreatic and 25–50 biliary cases. For many programmes, <10% of hepatic (48%), pancreatic (40%) and biliary (70%) cases were done laparoscopically. The average annual fellow case volumes for hepatic, pancreatic and biliary surgeries were 25–50 (62%), 25–50 (47%) and <25 (50%), respectively. The average annual number of hepatic, pancreatic and biliary cases done laparoscopically by a fellow was 9, 9 and 4, which constitutes 36%, 36% and 16%, respectively, of the International Hepato-Pancreato-Billiary Association (IHPBA) requirement.ConclusionWe surmise that the low average number of surgeries performed by minimally-invasive techniques by HPB fellows is not sufficient in today's practice. Should there be an increase in the minimal number of hepatic, pancreatic and complex biliary cases to 50, 50, and 25, with at least 50% of these performed laparoscopically?