Acute Adaptation to Volume Unloading of the Functional Single Ventricle in Children Undergoing Bidirectional Glenn Anastomosis

Objective. Volume unloading of the functional single ventricle after a bidirectional Glenn anastomosis (BDG) prior to 1 year of age leads to improved global ventricular function as measured by the myocardial performance index (MPI), a Doppler‐derived measurement of combined systolic and diastolic ventricular function. Systolic function remains unchanged after BDG according to previous studies; however, acute changes in global and diastolic function have not been previously investigated in this cohort. Our objective was to assess the short‐term effects of the BDG on global ventricular function in patients with a functional single ventricle. Design. Echocardiograms to obtain MPI, isovolumic contraction time, and isovolumic relaxation time were performed at four time periods: in the operating room, in the operating room prior to BDG, shortly after separation from cardiopulmonary bypass, less than 24 hours postoperatively, and either prior to hospital discharge or at the first clinic follow‐up visit. Results. Twenty‐six patients were enrolled. There was significant ventricular dysfunction noted shortly after separation from cardiopulmonary bypass, median MPI 0.63 (0.39–0.81), that persisted in the short term postoperatively median MPI 0.50 (0.40–0.63). Isovolumic contraction time did not change, however, isovolumic relaxation time was significantly prolonged following BDG. Conclusion. In the postoperative patient after BDG, systolic function is preserved; however, there is evidence of diastolic and global ventricular dysfunction, at least in the short term.     

Drinking patterns, dependency and life-time drinking history in alcohol-related liver disease

Aims   To examine the hypothesis that increases in UK liver deaths are a result of episodic or binge drinking as opposed to regular harmful drinking.
Design   A prospective survey of consecutive in-patients and out-patients.
Setting   The liver unit of a teaching hospital in the South of England.
Participants   A total of 234 consecutive in-patients and out-patients between October 2007 and March 2008.
Measurements   Face-to-face interviews, Alcohol Use Disorders Identification Test, 7-day drinking diary, Severity of Alcohol Dependence Questionnaire, Lifetime Drinking History and liver assessment.
Findings   Of the 234 subjects, 106 had alcohol as a major contributing factor (alcoholic liver disease: ALD), 80 of whom had evidence of cirrhosis or progressive fibrosis. Of these subjects, 57 (71%) drank on a daily basis; only 10 subjects (13%) drank on fewer than 4 days of the week—of these, five had stopped drinking recently and four had cut down. In ALD patients two life-time drinking patterns accounted for 82% of subjects, increasing from youth (51%), and a variable drinking pattern (31%). ALD patients had significantly more drinking days and units/drinking day than non-ALD patients from the age of 20 years onwards.
Conclusions   Increases in UK liver deaths are a result of daily or near-daily heavy drinking, not episodic or binge drinking, and this regular drinking pattern is often discernable at an early age.     

Assessment of clinical risk predictive rules for invasive candidiasis in a prospective multicentre cohort of ICU patients

Purpose  

To assess the generalisability of published clinical risk predictive models for invasive candidiasis in ICU patients.     

Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin results in reduced sarcolemmal integrity and increased susceptibility to muscle damage. The α₇β₁-integrin is a laminin-binding protein up-regulated in the skeletal muscle of DMD patients and in the mdx mouse model. Transgenic overexpression of the α₇-integrin alleviates muscle disease in dystrophic mice, making this gene a target for pharmacological intervention. Studies suggest laminin may regulate α₇-integrin expression. To test this hypothesis, mouse and human myoblasts were treated with laminin and assayed for α₇-integrin expression. We show that laminin-111 (α₁, β₁, γ₁), which is expressed during embryonic development but absent in normal or dystrophic skeletal muscle, increased α₇-integrin expression in mouse and DMD patient myoblasts. Injection of laminin-111 protein into the mdx mouse model of DMD increased expression of α₇-integrin, stabilized the sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscle from exercised-induced damage. These findings demonstrate that laminin-111 is a highly potent therapeutic agent for the mdx mouse model of DMD and represents a paradigm for the systemic delivery of extracellular matrix proteins as therapies for genetic diseases.