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Biomedical subjects

R G Settle

Publications and source records attributed to R G Settle.

47 records · Page 3Linked to original sources

A primate model for enteral nutrition by tube.

To establish an animal model for the controlled study of enteral nutrition by tube, five adult chair-adapted primates (Macaca fasicularis) had gastrostomy and jejunostomy tubes placed for the delivery of a modified protein isolate diet. Following 7 days of postoperative depletion with a hypocaloric infusion of dextrose (20 kcal, 0 g N/kg/day), the animals were repleted for 10 days with tube feedings (124 kcal, 0.73 g N/kg/day). There was no operative mortality or morbidity and each animal demonstrated conversion to anabolism by significant weight gain, positive nitrogen balance, and net protein synthesis as determined by [15N]glycine protein turnover rates. Significant correlation was found between caloric intake and nitrogen balance at the level of nitrogen provided in this diet (r = 0.88, p less than 0.05). This model was found to be well suited for the surgical and nutritional techniques required for the long-term study of enteral nutrition by tube.

Animals↗

Nitrogen utilization from elemental diets.

Repletion experiments were performed in malnourished, chair-adapted primates to explore recently reported differences in nitrogen utilization from elemental diets. Two elemental diets were fed consecutively for 8 days through a gastrostomy. Diet C (maltodextrins, peptides, crystalline amino acids) resulted in: larger weight gain (F1,6 = 17.93, p less than 0.01); smaller decrease of serum albumin (F1,5 = 11.2, p less than 0.015), larger increase in total iron binding capacity (F1,6 = 30.6, p less than 0.002), and a more positive nitrogen balance (F1,6 = 30.4, p less than 0.002) than diet V (glucose oligosaccharides, crystalline amino acids). Diet C was considered to be more effective in the nutritional repletion of the study animals. Additional experiments were performed in normal human volunteers to investigate the metabolic fate of ingested glutamine and whether the rapid catabolism and excretion of the amido nitrogen of this amino acid, which constitutes 11.56% of total nitrogen in diet V, could explain the differences observed in primates in our study and in human subjects by other authors. Six normal volunteers were fed 15N amino glutamine, 15N alanine, or 15N H4Cl. Similar amounts of 15N from Gln and Ala were excreted in 10 hr. The amido group of glutamine does not seem to be metabolized differently from the alpha-amino group of alanine under the conditions of the study. The marked differences in nitrogen utilization from the study diets could not be explained by the presence of relatively large amounts of glutamine in one of them.

Adult↗

Detection of total parenteral nutrition-induced fatty liver infiltration in the rat by in vitro proton nuclear magnetic resonance.

In an effort to determine if NMR techniques might be used to detect TPN-induced hepatic steatosis, the NMR spin-lattice (T1) and spin-spin (T2) relaxation times were measured on liver tissue from rats who received one of five dietary regimens: (1) 100% of nonprotein calories as lipid (Fat); (2) a mixture of 50% lipid and 50% glucose nonprotein calories (50/50); (3) 100% of nonprotein calories as glucose (CHO); (4) intravenous saline and standard laboratory rat chow (Saline); and (5) rat chow alone (Oral). The parenteral diets were isonitrogenous and isocaloric. Serum liver function tests were also measured. Animals in the Fat and 50/50 groups had the greatest amounts of liver fat and significantly longer T1 and T2 times (p less than 0.01) than any other group. Furthermore, the correlation of T2 time with liver fat content (r = 0.82) was far superior (p less than 0.001) to that of serum SGPT (r = 0.48) which was the only liver function test which correlated significantly with liver fat content. In a multiple linear regression analysis, T1 and T2 predicted liver fat content with an r value of 0.84 (p less than 0.001). These data suggest that in vivo NMR imaging techniques might be used to detect TPN-induced fatty infiltration of the liver noninvasively.

Animals↗

Harry M. Vars award. The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection.

The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection in the rat was investigated in this study. Sixty adult Sprague-Dawley rats underwent placement of a feeding gastrostomy and swivel apparatus. Control animals (N = 16) were then returned to their cages while the remaining animals underwent an 80% small bowel resection and anastomosis (resected, N = 44). Postoperatively, animals were randomly assigned to receive either a fat- and fiber-free elemental diet (no pectin) or the same diet supplemented with 2% pectin (pectin). After 8 days of full strength diet, samples of jejunum, ileum, and colon were obtained for analysis. The weights per unit length of the ileum and colon were significantly greater in the resected pectin group than either the resected no pectin or pectin control groups. Mucosal parameters (unit weight, DNA, RNA, and protein content) were significantly increased in the jejunum and ileum of both the resected pectin and resected no pectin groups relative to their respective control groups. However, jejunal and ileal mucosal parameters were significantly greater (1.3- to 2-fold) for the resected pectin group than for the resected no pectin group. All the mucosal parameters of the colons were significantly greater for the pectin resected group than for the pectin control group, while only colonic mucosal RNA was significantly greater for the no pectin resected group than for the no pectin control group. These data indicate that the addition of pectin to an elemental diet significantly enhanced intestinal adaptation to massive small bowel resection in the rat.

Adaptation, Physiological↗

Application of electromagnetic and sound waves in nutritional assessment.

Four relatively new techniques that apply electromagnetic or sound waves promise to play a major role in the study of human body composition and in clinical nutritional assessment. Computerized axial tomography, nuclear magnetic resonance, infrared interactance, and ultrasonography provide capabilities for measuring the following: total body and regional fat volume; regional skeletal muscle volume; brain, liver, kidney, heart, spleen, and tumor volume; lean tissue content of triglyceride, iron, and high-energy intermediates; bone density; and cardiac function. Each method is reviewed with regard to basic principles, research and clinical applications, strengths, and limitations.

Carbon Isotopes↗

Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis.

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.

Animals↗

Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acids.

Dietary fiber, which stimulates intestinal mucosal growth, is fermented by anaerobic bacteria in the rat hindgut to the short-chain fatty acids (SCFA) acetate, propionate, and butyrate. Butyrate is the preferred oxidative fuel of the colonocyte in vitro, and the provision of preferred intestinal fuels has been shown to stimulate mucosal proliferation in vivo. This study determined whether chronic colonic infusion of butyrate or a combination of SCFA would stimulate intestinal mucosal growth in an animal deprived of its normal source of SCFA, fiber fermentation in the cecum. Adult male Sprague-Dawley rats were fed a fat- and fiber-free elemental liquid diet and underwent cecectomy, ileocolic anastomosis, and insertion of a proximal colonic infusion catheter. Rats were then assigned to receive either a continuous infusion of butyrate (20 mM, 40 mM, or 150 mM), SCFA (70 mM acetate + 35 mM propionate + 20 mM butyrate), or saline, or to receive no infusion. A seventh group underwent proximal colonic transection and reanastomosis. After 7 days, jejunal, ileal, and proximal colonic segments were analyzed for mucosal weight, protein, RNA, and DNA. In the colon, the 40-mM butyrate infusion resulted in significant elevations in all mucosal parameters relative to all three control groups, saline infusion, no infusion, and transection. Both the 20-mM butyrate and the SCFA groups showed increased colonic mucosal DNA compared to controls. In the jejunum and ileum, mucosal DNA content was significantly greater in the SCFA group than in the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Isotonic tube feeding formula induces liquid stool in normal subjects: reversal by pectin.

Diarrhea is one of the most common complications in patients who receive tube-feeding formulas. Since the colon is the final site of water and electrolyte absorption and ultimately determines fecal composition, diarrhea during tube feeding may result from altered colonic function. The lack of dietary fiber, such as pectin, in tube-feeding formulas may be one of the means by which colonic function is affected. The purpose of this study was to determine the effect of a standard, liquid, commercially available, isotonic tube-feeding formula (ITFF) and the effects of supplementing the ITFF with pectin on colonic function as measured by stool consistency and colonic fluid composition in 13 normal adults. Data were obtained when subjects consumed their regular diet, ITFF, and ITFF supplemented with pectin using the technique of in vivo dialysis of colonic fluid. Ingestion of the ITFF resulted in a significant increase in the percentage of liquid stools compared to a regular diet [median (interquartile range) = 0% (0), 60% (64); p less than 0.01]. Ingestion of the ITFF also resulted in significant decreases in the concentrations of sodium, potassium, and short-chain fatty acids, and increases in pH and osmotic gap in colonic fluid compared to the subjects' regular diet. Supplementing the ITFF with pectin significantly reduced the incidence of liquid stools [0% (0)] and promoted a normalization of colonic fluid composition. The results suggest that the addition of pectin may enhance tolerance to ITFFs.

Adult↗

Tube feeding-related diarrhea in acutely Ill patients.

Acutely ill patients received tube feeding for an average of 15.8 days and, on average, 35% of those days were spent in the intensive care unit (ICU). Patients were prospectively assigned either a fiber-free formula (FFF-OSMOLITE HN, Ross; n = 50) or a fiber-supplemented (soy polysaccharide 14.4 g/L) formula (FSF = JEVITY, Ross; n = 50). Diarrhea was defined as three or more loose or watery stools per day and occurred in 30% of all patients. Diarrhea developed in 29 (41%) of the 71 patients who received antibiotics during, or within 2 weeks prior to, the feeding period, whereas only 1 (3%) of the 29 patients not receiving antibiotics developed diarrhea (p less than 0.005); and this patient developed diarrhea on the day of death. Among the 30 patients with diarrhea, stool Clostridium difficile (CD) toxin was positive in 15 (50%), negative in 11 (37%), and was not measured in four. The mean serum albumin was significantly lower in patients with diarrhea (2.43) than in those without diarrhea (2.75) (p = 0.043). There were no significant differences in age, sex, diagnoses, number of feeding days, and percent ICU days between patients with and without diarrhea. While not statistically significant, patients who received FSF were observed to have a lower incidence of diarrhea, a lower percentage of diarrhea days per total feeding days, and a lower frequency of positive CD toxin assays than patients who received FFF. In this patient population, antibiotic usage was the factor most strongly associated with diarrhea during tube feedings.

Acute Disease↗

Insulin-like growth factor 1 and endotoxin-mediated kidney dysfunction in critically ill, parenterally fed rats.

Endotoxemia is an important contributor to the pathogenesis of acute kidney failure in sepsis. Data suggest insulin-like growth factor 1 (IGF-1) can increase creatinine clearance in healthy humans. The influence of recombinant human IGF-1 on kidney function in endotoxemia was investigated in 34 male Sprague-Dawley rats. After venous cannulation and postoperative parenteral nutrition (PN), the animals were randomly assigned to receive PN only, PN plus Escherichia coli lipopolysaccharide (LPS), or PN plus LPS plus IGF-1. Urine output was significantly higher for the IGF-1 and control groups compared with the LPS group (18.9 +/- 5.7, 13.0 +/- 3.8, and 17.7 +/- 3.1 ml/day for control, LPS, and IGF-1 groups, respectively, analysis of variance, p < 0.05). Creatinine clearance was significantly higher in the IGF-1 group than the LPS group and exceeded the control group (0.49 +/- 0.27, 0.36 +/- 0.14, and 0.65 +/- 0.27 ml.min-1.100(-1) g body wt) for control, LPS, and IGF-1, respectively (analysis of variance, p < 0.05). IGF-1 ameliorates the effects of endotoxin on kidney function as measured by creatinine clearance and urine output in endotoxemic parenterally fed rats.

Acute Kidney Injury↗