Biomedical subjects
Publications and source records attributed to S J Dudrick.
Experiences gained in 150 newborns and infants receiving a complete parenteral nutrition are summarized. An infusion pattern for the complete parenteral nutrition of newborns is presented. Technical questions of parenteral nutrition are discussed. Finally the treatment of 2 newborns with inborn errors of the gastrointestinal tract is reported.
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Experiments were desinged to test the hypothesis that structural and chemical changes in the small intestine associated with total parenteral nutrition (TPN) alter relationships between hosts and enteric parasites. Parenteral feeding of rats immunized to Trichinella spiralis (nematoda) led to a decrease in gut mass. This was reflected by a significant drop in gut wet weight and reductions in mucosal dry weight, DNA, protein, carbohydrate and lipid. These changes were accompanied also by lowered brush border enzyme activity. When challenged orally with 8 X 10(3) T. spiralis larvae and switched immediately to oral feeding, more worms became established in the small intestines of these rats than in rats given similar doses of larvae, but maintained by oral feeding throughout the experiment. Despite the significant difference in initial worm burden, both enterally fed and parenterally fed rats completely expelled their parasites by 7 and 8 days postinfection, respectively. Results indicated that factors involved in preventing establishment of T. spiralis in immunized rats were suppressed by the prolonged absence of food from the GI tract, whereas factors responsible for expelling worms that were able to gain residence in the mucosa appeared to be unaltered or at least functionally reversible.
Forty-seven cancer patients were selected for study based on their candidacy for hyperalimentation. Each patient received selected skin test antigens intradermally in the forearm prior to the initiation of hyperalimentation, and at 7-day intervals throughout treatment with either chemotherapy, radiation therapy or surgery. Of 23 patients who received chemotherapy, 17 initially had negative skin tests. Thirteen of these patients had positive skin tests after an average of 11.4 +/- 5.5 days of hyperalimentation. Response to chemotherapy occurred only in hyperalimentation. Response to chemotherapy occurred only in those patients whose skin tests were positive, and conversion of skin test reactivity to positive occurred before clinical regression of metastatic disease. No patient who received radiation therapy developed or retained positive skin test reactivity, although nutritional repletion was considered satisfactory in each patient. Surgical patients whose skin tests converted to positive or remained positive preoperatively had an uncomplicated postoperative recovery, whereas 2 of 4 patients whose skin tests remained negative expired postoperatively. Absence of established delayed hypersensitivity in the cancer patient who is treated with chemotherapy or surgery is probably secondary to generalized malnutrition, and established cell-mediated immunity can be restored by proper nutritional repletion.
The Hunt pouch and its various modifications have been used as an esophagojujunostomy technic after total gastrectomy or esophagogastrectomy for benign and malignant conditions. This pouch procedure may be particularly useful for palliative gastric resections in which the patient's ability to ingest adequate foodstuffs might be enhanced by a larger reservoir, thereby improving nutritional status and possibly facilitating chemotherapy or radiation therapy or both. Intravenous hyperlimentation has been used to advantage preoperatively and postoperatively to help nutritionally depleted patients better tolerate such an operation and has been useful during treatment of complications related to the procedure. Three recent cases are discussed to illustrate the above propositions.
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Serum and antral gastrin were measured in rats infected with either Trichinella spiralis or Hymenolepis diminuta as a step in testing the hypothesis that parasites change certain aspects of host physiology by altering gastrointestinal (GI) hormone levels or responses to GI hormones. Parasitism with T. spiralis was associated with inflammatory changes in the small bowel mucosa and with a significant increase in serum gastrin. Neither changes in hormone level nor inflammation were induced in tapeworm-infected rats. These results reveal the capacity of tissue penetrating parasites to alter the level of circulating gastrin. This finding coupled with considerable indirect evidence suggests that some of the pathologic changes induced in hosts by enteric parasites may be due to changes in functions that are regulated by GI hormones.
UNLABELLED: Two groups of rats were kept on an oral diet after infection with 10(4) Trichinella spiralis or 10 Hymenolepis diminuta larvae. Sixteen days and 2 days after infection with H. diminuta and T. spiralis, respectively, 8 rats from each group were switched to intravenous (iv) alimentation, while the remaining animals were retained on oral nutrition as controls. Rats were killed during the following 21 days. The number of T. spiralis recovered from iv-fed rats was significantly higher than in controls, whereas the sex ratio and worm size were similar. Disaccharidase deficiencies normally associated with either infection or parenteral feeding were additive in the infected, parenterally nourished rats. The rise in peroxidase activity normally associated with intestinal trichinosis was not as great (P less than 0.05) in iv-fed rats. Intravenous feeding did not affect tapeworm number, but caused destrobilization. This was followed by secondary proglottization that led to development of worms of normal length and with gravid segments, but with an increased length: weight ratio. CONCLUSIONS: oral food deprivation in the host does not adversely affect development of established T. spiralis. The larger worm burden in iv-fed rats may be due to reduced inflammation normally involved in worm expulsion. Exogenous food in the gut is not necessary for maintaining established H. diminuta; factors necessary for sustenance and growth can be acquired by the worm entirely from the exocrino-enteric circulation.
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Experiments were designed to test the hypothesis that alterations of intestinal motility accompany enteric helminth infections. Motility was measured in rats during the intestinal phase of infection with the nematode Trichinella spiralis by following the transit of radioactive chromium through the gut. Intraduodenal catheters were surgically implanted in rats. One week after the operation one group of animals was infected with 8 x 10(3) T. spiralis larvae and a second group was infected with 16 x10(3) larvae. A third group of uninfected rats served as controls. Three, four, or five days postinfection, Na2 51CrO4 was injected through the catheter into the duodenum or fasted animals and its propulsion through the small bowel was allowed to progress for 15 min. The distribution of radioactivity throughout the small intestine and cecum was then plotted as a function of gut length. Intestinal transit was increased significantly by infection. The leading edge of radioactivity transversed 100% of the gut length in infected rats and 70% in controls. The amount of injected radioactivity transversing the midpoint of the small intestine was estimated by regression equations to be 38% of the injected dose for control rats and 59 and 57% for infected groups. Increased propulsive activity in parasitized rats was associated with inflammatory changes and a significant reduction in disaccharidase levels in the gut mucosa. The latter conditions were most marked in the proximal small bowel where the majority of worms resided.
Intravenous hyperalimentation was utilized to support nutritionally 23 malnourished patients with major head and neck tumors during surgical treatment, radiotherapy, or the convalescent period. Fifteen patients were treated during the perioperative period and 12 survived. Six patients received convalescent nutritional support successfully 4 to 24 months following operation or radiation treatment. Two patients received treatment with hyperalimentation throughout a protracted course of radiation therapy. Weight gain, wound healing, and recovery were achieved in all but 3 patients. Subclavian vein thrombosis occurred in 1 patient, and catheter-related sepsis occurred in 2 patients. Otherwise, hyperalimentation was safe and efficacious in the debilitated patients. These patients may now become acceptable risks for surgical treatment or radiation therapy by nutritional repletion with intravenous hyperalimentation.
A 36 per cent response rate was obtained in fifty-eight nutritionally depleted patients with cancer who would otherwise have been denied adequate antitumor therapy because of the fear of complications from malnutrition and inanition. A positive correlation between the nutritional status of the patient and the chemotherapeutic tumor response was identified. Intravenous hyperalimentation can be a valuable adjunct to cancer chemotherapy by improving the nutritional status, increasing the total deliverable dose of anticancer agent per unit of time, and reducing the incidence and severity of the toxic gastrointestinal side effects without adversely stimulating malignant cell growth or producing septic complications.
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The importance of the presence of food in the gastointestinal (GI) tract in maintaining normal enzyme activity in the small intestine was investigated in rats that were kept from eating for as long as 2 weeks. During this time animals were sustained on a nutrient solution administered intravenously. Enzyme activity and small bowel mass in these animals and similiar parameters in rats that were administered the same solution orally were compared with control groups fed an essentially isoenergetic diet of stock rat food and water. Disaccharidase and peroxidase levels in mucosal scrapings expressed as activity/milligram protein, activity/intestine, and activity/100 g body weight, were significantly reduced in intravenously nourished rats but not in rats receiving the solution orally. In addition to changes in enzyme activities, parenteral feeding was accompanied by a significant reduction in the small bowel weight:body weight ratio as compared with that of rats fed the stock diet or nutrient solution orally. Results support the conclusion that normal activity of intestinal enzymes spatially distributed with regard to depth within the mucosa depends on the presence of food in theGI tract and cannot be maintained at normal levels by total intravenous nutrition.