Biomedical subjects

Michael T Schell

Publications and source records attributed to Michael T Schell.

3 recordsLinked to original sources

PubMed2006

Applying Ockham's razor to pancreatitis prognostication: a four-variable predictive model.

OBJECTIVE: We sought to develop a simple yet accurate prognostic scoring system to determine the severity of acute pancreatitis at admission. SUMMARY BACKGROUND DATA: Because acute pancreatitis has a variable and frequently unpredictable course, identifying individuals at greatest risk for significant, life-threatening complications and stratifying their care appropriately remain a concern. Previous prognostic scoring systems predict severity reasonably well but are limited by time constraints, are unwieldy to use, or both. METHODS: Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model. We then compared the model's ability to predict the severity of acute pancreatitis with the Ranson, Glasgow, and APACHE II systems. RESULTS: The model (BALI), which included BUN >or=25 mg/dL, Age >or=65 years, LDH >or=300 IU/L, and IL-6 >or=300 pg/mL, measured at admission, was similar to the Ranson, Glasgow, and APACHE II systems in its ability to identify increased mortality from acute pancreatitis. The receiver operating characteristic curve area for the BALI model was >or=0.82 +/- 0.03 (mean +/- SD) versus 0.75 +/- 0.04 (Ranson), 0.80 +/- 0.03 (Glasgow), and 0.79 +/- 0.03 (APACHE II). Furthermore, at a prevalence of 15%, the positive and negative predictive values for increased mortality were similar for all systems. CONCLUSION: The prognostic ability of the BALI 4-variable model was similar to the Ranson, Glasgow, and APACHE II systems but is unique in its simplicity and ability to accurately predict disease severity when used at admission or anytime during the first 48 hours of hospitalization.

APACHE↗

PubMed2005

Heat shock inhibits NF-kB activation in a dose- and time-dependent manner.

BACKGROUND: The heat shock response (HSR) attenuates NF-kappaB mediated activation of the acute inflammatory response by inhibiting IkB degradation. The HSR also confers a protective phenotype upon cells through production of heat shock proteins (HSP). However, the exact conditions that induce the HSR and stimulate the production of protective HSP are poorly defined. Consequently, we hypothesized that the inhibition of NF-kappaB activation through the HSR is dependent both on the degree of cellular injury and the length of the recovery period from the heat shock. METHODS: RAW 264.7 murine macrophages were heated to 43 degrees C for 15 (mild heat shock), 45 (moderate heat shock), or 90 min (severe heat shock), allowed to recover at 37 degrees C for 0 to 24 h, and then exposed to 100 ng/ml of Escherichia coli (055:B5) lipopolysaccharide (LPS). Cellular viability, HSP expression, and the activation of NF-kappaB after LPS exposure were determined by alamarBlue assay, immunoblot, and electrophoretic mobility shift assay, respectively. RESULTS: Transient attenuation of NF-kappaB activation and IkappaB preservation was observed only with moderate heat shock and 1 h of recovery. Mild heat shock had no effect on LPS-induced NF-kappaB activation or IkappaB degradation. Severe heat shock completely inhibited NF-kappaB activation and preserved IkappaB protein levels. Heat shock proteins were detectable 30 min after moderate heat shock, with maximal and sustained levels 2 to 24 h after heat shock. CONCLUSION: The attenuation of NF-kappaB activation after heat shock is both dose- and time-dependent.

Animals↗

PubMedDate not supplied

Early nonenhanced abdominal computed tomography can predict mortality in severe acute pancreatitis.

We wondered whether nonenhanced computed tomography (CT) within 48 hours of admission could identify individuals at risk for higher mortality from acute pancreatitis. Data from the international phase III study of the platelet-activating factor-inhibitor Lexipafant was used to analyze noncontrast CT versus acute pancreatitis mortality. Nonenhanced CT examinations of the abdomen from the trial were classified by disease severity (Balthazar grades A-E) and then correlated with patient survival. Among the 477 individuals who underwent CT within 48 hours of admission and 220 individuals who did so over the subsequent 6 days, higher CT grades were associated with increased mortality. Each unit increase in Balthazar grade during the initial 48 hours was associated with an estimated increase in the risk of mortality of 33%, and this trend increased to 50% if pancreatic enlargement and peripancreatic stranding (grades B and C) were combined (P<0.05). CT grade correlated minimally with Ranson, Glasgow, or APACHE II score during the initial 48 hours; however, this correlation improved over 3-8 days. Early nonenhanced abdominal CT in patients with acute pancreatitis is a valuable prognostic indicator of mortality in acute pancreatitis, even among patients without clinical features of severe acute pancreatitis.

APACHE↗