Evidence for down-regulation of beta-2-adreno-ceptors in cirrhotic patients with severe ascites

The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers

The influence of propanolol on portosystemic shunting

We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced by infecting C3H mice with 60 cercariae of Schistosoma mansoni. Propranolol was administered in drinking water to 20 animals for a period of 6 wk at a dose of 10 mg · kg −1 d −1 , starting at 5 wk of schistosomal infection. 32 age-matched mice with chronic schistosomal infection served as controls. All animals were studied 11 wk after the infection. Compared with controls the portal pressure (10.8 ± 0.40 mm Hg) was significantly lower ( P < 0.001) in the propranolol-treated animals (7.9 ± 0.80 mm Hg). Portal-systemic shunting was decreased by 79%, from 12.2 ± 3.34% in controls to 2.5 ± 0.99% in the propranolol group ( P < 0.05). Portal venous inflow was reduced by 38% in the propranolol treated animals (2.50 ± 0.73 ml/min; n = 6) compared with controls (4.00 ± 0.34 ml/min; n = 8; P < 0.05). The worm burden, the granulomatous reaction, the collagen content of the liver, and the serum bile acid levels were not significantly different between the two groups of animals. These results demonstrate that in chronic liver disease induced by schistosomiasis, the development of portal-systemic shunting can be decreased or prevented by the reduction of flow and pressure in the portal system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38367/1/1840140531_ftp.pd

Linkage mapping for complex traits : a regression-based approach

Linkage analysis makes use of genetic markers to measure genetic similarity between relatives. By comparing this index of genetic similarity with phenotypic similarity, we can identify chromosomal regions harbouring genes involved in the architecture of a phenotype of interest. Although linkage has been very successful in discovering genes responsible for simple Mendelian diseases, results have often been disappointing in gene mapping for complex traits. This thesis presents some attempts to improve the current design and analysis of linkage studies for complex traits. The statistical methodology adopted is driven by the fact that genes involved in complex traits have small effects, it therefore seems legitimate to use score tests because of their local optimality properties. In addition, score tests often give rise to tractable expressions, in the context of linkage these can be meaningfully interpreted in terms of regressions and quickly computed which is a crucial feature in genetics.Fonds Medische Statistiek - The Genomeutwin project (European Union Contract No QLG2-CT-2002-01254)UBL - phd migration 201

Challenges and opportunities for conducting pre-hospital trauma trials : a behavioural investigation

Acknowledgements We would like to thank the participants for dedicating their time to be interviewed. We extend our thanks to Claire Cochran for facilitating recruitment. Funding LL was supported by a Wellcome Trust Institutional Strategic Support Fund award (reference RG13793-49). The Health Services Research Unit, Institute of Applied Health Sciences (University of Aberdeen), is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The funders had no involvement in the study design, collection, analysis, and interpretation of data, reporting, or the decision to publish.Peer reviewedPublisher PD

Adjusting for sex and anti-CCP levels in linkage analysis of rheumatoid arthritis

We incorporate population effects of sex and antibodies directed against cyclic citrullinated peptides (anti-CCP) into the linkage analysis of rheumatoid arthritis (RA) with microsatellites data provided by the North American Rheumatoid Arthritis Consortium in Genetic Analysis Workshop 15

Automatic Mapping and Characterisation of Linear Depositional Bedforms: Theory and Application Using Bathymetry from the North West Shelf of Australia

publishedVersio

Prophylactic Β-blocker therapy: Clinical implications of an aggregate analysis

Background. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. Methods. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. Results. After two years, the mean (± SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 ± 3 percent in the beta-adrenergic-antagonist treatment group and 65 ± 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 ± 2 percent in the treatment group and 82 ± 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 ± 3 percent in the treatment group and 68 ± 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 ± 3 percent in the treatment group and 53 ± 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P < 0.001) and death (P < 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P < 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. Conclusions. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38371/1/1840150229_ftp.pd

Integration of gene ontology pathways with North American Rheumatoid Arthritis Consortium genome-wide association data via linear modeling

We describe an empirical Bayesian linear model for integration of functional gene annotation data with genome-wide association data. Using case-control study data from the North American Rheumatoid Arthritis Consortium and gene annotation data from the Gene Ontology, we illustrate how the method can be used to prioritize candidate genes for further investigation