Energy intake and stress as determinants of nitrogen excretion in rats.
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Biomedical subjects
Publications and source records attributed to S J Dudrick.
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A prospective randomized trial was conducted comparing the addition of iv hyperalimentation (IVH) to Corynebacterium parvum, isophosphamide, and adriamycin (CIA) chemoimmunotherapy in 26 patients with extensive squamous cell lung cancer. Thirteen patients were entered in each treatment arm of the study and IVH was administered before and after the first course of CIA for a total of 31 days. The major dose-limiting toxic effect of CIA was leukopenia. Less myelosuppression was observed for the patients receiving IVH. The difference in the lowest recorded leukocyte and neutrophil counts between the two groups was significant (P = 0.03 and 0.01, respectively). Also, a significant decrease (P = 0.06) in nausea and vomiting associated with chemotherapy administration was found for the IVH gorup. The differences in toxic effects between each group were not maintained over subsequent courses of therapy when both groups received CIA alone. The prevention of the toxic effects of chemotherapy by IVH suggests a means of giving higher chemotherapy doses with the intent of increasing tumor response and patient survival.
Ten consecutive malnourished patients with undifferentiated squamous cell carcinoma of the esophagus underwent operation for colon interposition. They received intravenous hyperalimentation preoperatively and/or postoperatively for an average time of 21.5 days and had an average weight gain of 6.5 lb. There was no significant gastrointestinal morbidity, but one patient succumbed to aspiration pneumonia. All ten patients had postoperative gastrografin swallow radiography which showed no leaks in either anastomosis. With proper use of intravenous hyperalimentation, morbidity and mortality following colon interposition in the malnourished patient for either palliative or curative bypass can be decreased to acceptable levels.
Radiation therapy may induce anorexia with resultant weight loss and inanition that can limit the dose of radiation therapy administered. The purpose of this study was to evaluate 39 nutritionally-depleted patients who had a variety of malignant diseases treated with radiation therapy and concomitant nutritional support with intravenous hyperalimentation (IVH). The average dose of radiation delivered was 3827 rads in an average of 3.5 weeks. Ninety-five percent of the patients completed their planned course of radiation therapy and improved symptomatically. Fifty-four percent of the patients responded with a greater than 50% reduction in tumor size. Responding patients gained an average weight of 13.0 +/- 6.5 lbs. during IVH (av. 36.2 days) and radiation therapy (av. 3832 rads), whereas non-responding patients gained only 4.9 +/- 8.8 lbs. (p less than 0.001) during IVH (av. 42.8 days) and radiation therapy (av. 3819 rads). Serum albumin concentrations rose from 3.12 +/- 0.49 gm/100 ml to 3.51 +/- 0.68 gm/100 ml (p less than 0.05) during treatment in responding patients but did not rise significantly from 3.09 +/- 0.48 gm/100 ml in non-responding patients. In conclusion, IVH allowed a planned course of radiation therapy to be delivered to a group of poor-risk, malnourished cancer patients, and a positive correlation between tumor response and nutritional status was identified. Moreover, IVH was a valuable adjunct in the treatment of six patients who had enteric fistulas that originated from radiated bowel.
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Small intestinal morphologic and biochemical changes were studied following jejuno-ileal bypass for obesity after body weight stabilization had occurred. Four patients underwent biopsy of in-continuity and bypassed jejunal and ileal segments of the small intestine 11 to 22 months after the bypass operation. Microscopically, marked mucosal villus hypertrophy of the in-continuity bowel was observed, especially in the ileum. Bypassed jejunal mucosa underwent atrophy compared with pre-bypass jejunum, whereas bypassed ileum appeared similar microscopically to pre-bypass ileum. The specific activities of mucosal disaccharidase enzymes (maltase, sucrase, lactase and trehalase) in units per mg protein remained similar to pre-bypass levels in segments of the in-continuity jejunum and the bypassed jejunum and ileum. On the other hand, elevated mucosal disaccharidase levels were measured in biopsy specimens of the in-continuity ileum. Total enzyme activity per unit length of intestine, however, was estimated to be elevated in both in-continuity jejunum and ileum secondary to mucosal villus hypertrophy. These data indicate that following small bowel bypass: (1) the in-continuity ileum undergoes greater biochemical and morphologic adaptation than the jejunum; and (2) intraluminal nutrients and chyme appear to be essential to maximal intestinal adaptation.
The current technique of total parenteral nutrition (intravenous hyperalimentation) is relatively safe and efficacious, but will undoubtedly undergo change and modification as improved techniques and materials become available. With judicious application of the technique as a clinical therapeutic and investigative tool, new indications for general and specific total parenteral nutrition will likely expand and extend into every medical discipline. As relatively few of the potential applications for total parenteral nutrition have been thoroughly explored or exploited, the clinical and laboratory research possibilities appear to be virtually limitless. Thus, as increasing knowledge and experience are gained, application of total parenteral nutrition will inevitably be expanded and will become more specific, and the hazards will no doubt decrease.
Three dogs were surgically prepared with gastric fistulas and Heidenhain (vagally denervated) pouches. Acid and pepsin responses to pentagastrin and food were determined before, at the end of a 1-mo period of total parenteral feeding, and 1 mo after the resumption of a normal oral diet. Acid and pepsin output from the denervated pouch in response to pentagastrin and food decreased significantly (P less than 0.001) after parenteral feeding and returned to control levels after the dogs resumed a normal diet. Secretory outputs from the gastric fistula in response to pentagastrin remained unchanged throughout the experiment. Basal serum gastrin levels decreased 50% during the period of intravenous feeding and returned to levels approximately twice the control levels following resumption of normal oral food intake. Serum gastrin responses to a meal also decreased during intravenous alimentation and returned to higher than normal levels following a 1-mo period of oral intake. These studies indicate that the absence of oral food intake in the dog does not result in decreased acid secretion from the innervated stomach. Vagal innervation in some way is responsible for the preservation of normal secretion during the absence of food from the gastrointestinal tract of the dog.
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If a patient is expected to respond optimally to one or more forms of oncologic therapy, he should simultaneously be in the best possible nutritional and metabolic condition. When the alimentary tract cannot be used effectively for feeding cancer patients, parenteral nutrition can be lifesaving. Moreover, patients who are poor candidates or noncandidates for any antineoplastic therapy because of their debility or cachexia can be converted to reasonable candidates following a course of i.v. hyperalimentation. This i.v. hyperalimentation can significantly reduce the morbidity and mortality of cancer patients without stimulating tumor growth when applied conscientiously according to the established principles and techniques and when integrated with specific tumor therapy. With the use of ambulatory or home hyperalimentation techniques, normal nutritional status can be restored or maintained during prolonged periods of antineoplastic therapy on a practical and relatively economical outpatient basis. It is anticipated that specific nutrient substrate formulas and parenteral therapy techniques will be developed to maintain optimal host nutrition while adversely affecting the neoplasm.
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A patient with liver dysfunction following small-bowel bypass for obesity was treated successfully with intravenous hyperalimentation. The hepatic steatosis and dysfunction were most likely caused by the preferential absorption of carbohydrate in the remaining small bowel, with resulting relative protein starvation. Routine use of high-protein, low-carbohydrate diets postoperatively until weight stabilization has occurred may prevent this complication.