University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Recommendations for comprehensive stroke centers: a consensus statement from the Brain Attack Coalition.

Abstract: Background and Purpose—To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. Summary of Review—A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. Conclusions—There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center. (Stroke. 2005;36:1597-1618.)

Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure

Abstract: Objective: The HepatAssist liver support system is an extracorpo-real porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective. random-ized, controlled, multicenter trial in patients with severe acute liver failure. Summary Background Data: In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results. Methods: A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site. Results: For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P = 0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL Versus 59% for control (it = 147; P= 0.12). When Survival was analyzed accounting for confounding factors. in the entire patient Population, there was no difference between the 2 groups (risk ratio = 0.67; P = 0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio 0.56: P = 0.048). Conclusions: This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.

Neutrophil elastase–mediated degradation of IRS-1 accelerates lung tumor growth

Abstract: Lung cancer is the leading cause of cancer death worldwide. Recent data suggest that tumor-associated inflammatory cells may modify lung tumor growth and invasiveness. To determine the role of neutrophil elastase (encoded by Elane) on tumor progression, we used the loxP-Stop-loxP K-ras(G12D) (LSL-K-ras) model of mouse lung adenocarcinoma to generate LSL-K-ras-Elane(-/-) mice. Tumor burden was markedly reduced in LSL-K-ras-Elane(-/-) mice at all time points after induction of mutant K-ras expression. Kaplan-Meier survival analysis showed that whereas all LSL-K-ras-Elane(+/+) mice died, none of the mice lacking neutrophil elastase died. Neutrophil elastase directly induced tumor cell proliferation in both human and mouse lung adenocarcinomas by gaining access to an endosomal compartment within tumor cells, where it degraded insulin receptor substrate-1 (IRS-1). Immunoprecipitation studies showed that, as neutrophil elastase degraded IRS-1, there was increased interaction between phosphatidylinositol 3-kinase (PI3K) and the potent mitogen platelet-derived growth factor receptor (PDGFR), thereby skewing the PI3K axis toward tumor cell proliferation. The inverse relationship identified between neutrophil elastase and IRS-1 in LSL-K-ras mice was also identified in human lung adenocarcinomas, thus translating these findings to human disease. This study identifies IRS-1 as a key regulator of PI3K within malignant cells. Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling.

A genome-wide linkage and association scan reveals novel loci for autism

Abstract: Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.

Effects of Digoxin on Morbidity and Mortality in Diastolic Heart Failure The Ancillary Digitalis Investigation Group Trial

Abstract: Background— About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. Methods and Results— Ambulatory chronic heart failure patients (n=988) with normal sinus rhythm and ejection fraction >45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n=492) or placebo (n=496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P=0.136) experienced the primary combined outcome of heart fai...