Infections in surgical patients continue to be a major source of morbidity and mortality, especially in patients admitted to intensive care units. Studies have been designed to improve resistance to infection by means of nutritional therapy and improvement of gut barrier functions. Routine and immunofluorescent light microscopy, transmission and immuno-electron microscopy, and isotope techniques will be used to determine how and where microbes and endotoxin traverse the epithelial barrier of the intestine, and follow their disposition within various cells and tissues. Quantitation of translocation will employ probes of 14C endotoxin, 3H- labeled and unlabeled E. coli and 3H labeled and unlabeled C. albicans in mice and guinea pigs. Rates and amounts of translocation will be correlated with mortality in burn and burn infected animals, extent of activation in various macrophages, stimulation of catabolic hormone release, stimulation of resting energy expenditure, the ability to clear S. aureus from inoculated sites, and stimulation of resting energy expenditure, the ability to clear S. aureus from inoculated sites, and selected immunologic responses. The following variables will be evaluated for their ability to reduce translocation of endotoxin after burn injury: intestinal hormones, growth hormones, endotoxin binders, prostaglandin analogues, allopurinol and various types of dietary lipids, various soluble fibers, tocopherol, vitamin A, glutamine, and proteins in different physical states. Potential synergism between modulatory agents and dietary components will be studies as well as the effects of reducing translocation by these means on outcome. Selected fatty acids of the omega 3, 6, 9 families will be studied in vitro and in vivo for their influence on macrophage functions. The investigators have previously shown that survival in animals with protracted peritonitis is improved with diets which are hypocaloric, low in protein, high in both omega 3 and 6 fatty acids, and high in vitamins C and E. Further studies will define the optimal amounts of vitamin A, selenium, and soluble fibers for this partially formulated diet. The investigators have also shown that hypocaloric diets, enriched in protein and omega 6 fatty acids and vitamin E will improve survival of normal animals given an infectious challenge. Further investigations will determine the roles of vitamins A, C, and E, and selenium in resistance to infection in normal and malnourished animals given a septic challenge. The biological effects of these diets on bacterial virulence, toxin production, and immune function will be studied in additional experiments.
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