DIET, DISEASE, AND PANCREATIC ENZYME SYNTHESIS IN HUMANS

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DESCRIPTION: Acute pancreatitis is a disease of high mortality, induced by premature activation of digestive enzymes in the pancreas, and accompanied by a severe systemic immunoinflammatory response and protein catabolism. Meeting nutritional needs is difficult because food-induced pancreatic stimulation may exacerbate the disease process, and intravenous nutrition (TPN), while "resting the pancreas," increases the risk of septicemia and mucosal atrophy. Recent controlled clinical trials suggest that tube-feeding with elemental diets has advantages over TPN with regard to cost, safety (less infective complications), and efficacy (more anticatabolic). However, it is unknown in humans whether elemental diets stimulate the pancreas, and the beneficial effects may simply reflect better metabolic control and fewer serious complications. Consequently, Dr. O'Keefe and colleagues plan to measure the effects of duodenal infusions of elemental diets on pancreatic enzyme synthesis and secretion in normal volunteers and patients with acute pancreatitis using a unique method that they have developed, based on the 6-hr intravenous and enteral infusion of two isotope-labeled amino acids and measurement of their uptake into trypsin and amylase proteins extracted from duodenal secretions. The method also allows them to obtain simultaneous measurements of the rates of protein catabolism and utilization of dietary amino acids for the synthesis of mucosal proteins (obtained by endoscopic biopsy). Studies will be conducted in groups of 8 normal volunteers to compare the relative effects of complex and elemental diets given as duodenal infusions, versus TPN, on the normal response to a complex oral diet. The results will then be used to evaluate the responses in 20 patients with acute pancreatitis randomized to receive enteral elemental or TPN. The results of these investigations are expected to provide valuable new information on both the stimulatory effects of food on the human digestive system and the nutritional value of modern nutritional support techniques, and help determine why elemental diets are more effective than TPN in the management of patients with acute pancreatitis. The results are also expected to form a scientific basis for the design of disease-specific diets for patients with acute pancreatic disease.