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Title: The pathogenesis and treatment of severe acute pancreatitis
Author: Powell, James John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The aim of this thesis is to investigate the basis for disease severity in acute pancreatitis, and to assess a novel therapeutic intervention in patients with severe acute pancreatitis. 1) To provide evidence for the presence of endothelial cell activation the kinetics of serum soluble E-selectin and P-selectin in 18 patients with acute pancreatitis were determined. In all patients soluble P-selectin concentrations decreased significantly over the study period. Non-survivors had significantly higher levels of soluble P-selectin than survivors. In contrast, soluble E-selectin increased significantly over the study period in patients with organ dysfunction, whilst remaining constant in patients without evidence of organ dysfunction. 2) Cytokines such as TNFa and IL1b and their endogenous antagonists such as ILlRA are important mediators of disease severity in acute pancreatitis. Because secretion of these cytokines is partly determined by genetic factors the distribution of TNF-308, TNFB, ILlb Taq1 and IL lRN gene polymorphisms were determined for 190 individuals with acute pancreatitis. The frequency of the polymorphisms studied were similar in patients with mild or severe acute pancreatitis. Moreover there was no significant difference in genotype frequency in patients with acute pancreatitis when compared to 102 healthy controls. 3) To further assess the influence of genetic factors, cytokine phenotype for TNFa, ILlb and IL1RA was determined in 51 individuals following recovery. With respect to phenotype, secretion of TNFa was similar in patients with previous mild or severe acute pancreatitis, however the ILlb:IL1RA ratio was significantly lower in patients with previous severe acute pancreatitis than those with mild disease. 4) To assess the potential benefits from the introduction of enteral nutrition in patients with severe acute pancreatitis a randomised clinical trial was undertaken. Patients were randomised to receive either enteral nutrition or conventional therapy consisting of a nil-by-mouth regime. Of 27 patients, 13 patients received enteral nutrition. A median of 21% of calorific requirements were delivered over the first 4 days by enteral nutrition. There were no significant complications of enteral nutrition. The introduction of enteral nutrition did not significantly affect the concentrations of serum IL6, serum sTNFR-1 or serum CRP over the first 4 days of the study period. Although there were no significant differences in intestinal permeability between the two patient groups at admission, by day 4 abnormal intestinal permeability occurred more frequently in patients receiving enteral nutrition.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available