Synchronous intestinal transplantation inhibits post resection adaptation.
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Anastomosis, Surgical↗
Biomedical subjects
J A Vanderhoof
Publications and source records attributed to J A Vanderhoof.
Lack of inhibitory effect of octreotide on intestinal adaptation in short bowel syndrome in the rat.
BACKGROUND: Octreotide is a long-acting analogue of somatostatin, which is effective in the treatment of secretory diarrhea in a number of disorders including short bowel syndrome. Its use in this syndrome has been limited because of concerns about potential adverse effect on intestinal adaptation, because it inhibits a number of trophic hormones. This study was conducted to determine whether octreotide inhibits intestinal adaptation in a rat model of short bowel syndrome. METHODS: Thirty male Sprague-Dawley rats were divided into four treatment groups, eight receiving 80% small-bowel resection and treated with 2.25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection and treated with 25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection with saline control, and six receiving sham operation with saline control. Mucosal weight, protein, and sucrase levels were subsequently analyzed after 2 weeks of therapy. RESULTS: Massive adaptation occurred in all three groups relative to sham-operated controls. However, neither the pharmacologic nor the much higher dose of octreotide demonstrated any adverse effects on intestinal adaptation. CONCLUSION: In our animal model, octreotide does not inhibit intestinal adaptation after massive small-bowel resection.
Adaptation, Physiological↗
Treatment strategies for small bowel bacterial overgrowth in short bowel syndrome.
BACKGROUND: Small bowel bacterial overgrowth is a common complication of short bowel syndrome, and although it is often controlled with antimicrobial therapy, alternative strategies may occasionally be needed. METHODS: Six patients with bacterial overgrowth are described, who did not respond to antimicrobial therapy and required additional medical or surgical measures to control the overgrowth. RESULTS: Recalcitrant bacterial overgrowth was successfully treated with periodic small bowel irrigation with a balanced hypertonic electrolyte solution, colonic flushes, encouraging frequent stooling, intestinal lengthening procedure, or probiotic therapy with Lactobacillus plantarum 299V and Lactobacillus GG. CONCLUSIONS: Small bowel bacterial overgrowth should be aggressively evaluated in patients with short bowel syndrome who are not progressing in a normal manner. Inadequate or incomplete response to antibiotic therapy is common, and several additional treatment possibilities are available.
Anti-Bacterial Agents↗
Use of probiotics in childhood gastrointestinal disorders.
Probiotics appear to be useful in the prevention or treatment of several gastrointestinal disorders, including infectious diarrhea, antibiotic diarrhea, and traveler's diarrhea. Results of preliminary human and animal studies suggest that patients with inflammatory diseases, and even irritable bowel syndrome, may benefit from probiotic therapy. Probiotics represent an exciting therapeutic advance, although much investigation must be undertaken before their role in gastroenterology is clearly delineated. Questions related to probiotic origin, survivability, and adherence are all important considerations for further study. More important, each probiotic proposed must be studied individually and extensively to determine its efficacy and safety in each disorder for which its use may be considered.
Anti-Bacterial Agents↗
Pretransplant management and small bowel-liver transplantation in an infant with microvillus inclusion disease.
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Atrophy↗
Food hypersensitivity in children.
Adverse reactions to foods involving abnormal immune reactions to food antigens occur in 2-7% of the North American population; the numbers are perhaps higher in children. Both IgE-mediated and non-IgE-mediated allergic responses occur. IgE-mediated allergic responses to foods are the most dramatic and perhaps the most easily diagnosed type of food allergy. Non-IgE-mediated food hypersensitivity is more chronic, less acute, less obvious in its clinical presentation, and often more difficult to diagnose. It usually presents in infants between one week and three months of age with vomiting and diarrhea, although irritability, poor feeding, and failure to thrive are not uncommon. A thorough history and physical examination are often key in establishing a diagnosis of food protein hypersensitivity. In non-IgE-mediated disease, skin tests and immunological studies are not helpful. Eliminating the food allergen is the only means of dealing with a food allergy in most patients. About 85% of infants who have formula protein intolerance will outgrow their symptoms somewhere between 1 month and 3 years of age, older children and adults are somewhat less likely to lose their sensitivity, although approximately one-third will after 1-2 years of dietary restriction.
Allergens↗
Chronic diarrhea.
The differential diagnosis of chronic diarrhea varies markedly with age. In infants, it is usually a problem with formula intolerance. Because there is up to a 50% crossover intolerance between milk and soy, the infant should be given an extensively hydrolyzed formula. If such intervention is delayed, he or she may develop intractable diarrhea of infancy. Most affected toddlers have either irritable colon of infancy or protracted viral enteritis with low-grade mucosal injury and are consuming hypertonic feedings. In either case, institution of a high-fat, low-carbohydrate diet that includes whole milk often results in significant improvement. Dietary lactose rarely is a problem. A likely cause of diarrhea among children and adolescents is inflammatory bowel disease. With the exception of toddlers, chronic diarrhea suggests the presence of significant organic disease.
Adolescent↗
Correlation of mucosal disaccharidase activities with histology in evaluation of rejection following intestinal transplantation.
Following intestinal transplantation, we have found that recovery from severe rejection may be difficult to identify. In this study we sought to ascertain whether concurrent determination of mucosal disaccharidase activities and histologic assessment improves the accuracy of diagnosis of rejection. Histologic changes were graded blindly using a standard set of diagnostic criteria, and these changes were compared over time to maltase, sucrase, lactase, and palatinase activities in four pediatric patients under treatment for severe rejection. The histologic criteria, which included magnitude of enterocyte loss, degree of granulation tissue, severity of villus atrophy, and frequency of apoptosis and cryptitis, were found to correlate with one another over time irrespective of outcome (r = 0.72 to r = 0.85). Enzyme activities were also correlated with each other over time (r = 0.64 to r = 0.80). However, the correlation between histologic diagnosis and enzyme activity was weaker (r = -0.48 to r = -0.57). Furthermore, neither histologic nor enzyme evaluation early in the course of rejection predicted ultimate clinical outcome. The results of this investigation show that determination of mucosal disaccharidase activity provides no additional useful information concerning efficacy of anti-rejection therapy as compared to histologic analysis alone.
Child↗
Transplanted small bowel and expression of the insulin-like growth factor binding proteins.
The insulin-like growth factor binding proteins (IGFBPs) act to modulate the growth and differentiation of the gastrointestinal mucosa by regulating cellular responses to the important mitogens, the insulin-like growth factors (IGFs). The transplanted small bowel must maintain the normal growth factor interrelationships and signaling pathways despite the potential of host rejection. Ostomy effluent of patients after small bowel or combined liver/small bowel transplantation was assayed for IGFBPs to investigate the effect of rejection on the IGF-IGFBP axis. Seventeen patients were studied over an 18-month period. The transplanted small bowel produced no measurable IGFBPs in the ostomy effluent under normal circumstances. However, when rejection was taking place the ostomy effluent was found to have measurable IGFBP levels in 6 of 12 episodes, the 6 episodes occurring in 6 different patients. Mostly, the IGFBPs present did not exhibit a serum-like pattern indicating the secretion of IGFBPs into the effluent was not the result of loss of mucosal barrier integrity. There were no statistically significant differences in protein content of the ostomy fluids in the presence or absence of rejection. Our results suggest that the gastrointestinal IGF axis is altered during some instances of transplanted small bowel rejection, with increased secretion of IGFBPs.
Adolescent↗
Intolerance to protein hydrolysate infant formulas: an underrecognized cause of gastrointestinal symptoms in infants.
The purpose of this study was to determine the effectiveness of an amino acid-based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were receiving casein hydrolysate formula (CHF). Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms. Sigmoidoscopy with rectal biopsy was performed in all infants. The infants then received an amino acid-based infant formula, Neocate, for 2 weeks. After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. The histologic features in these infants varied from eosinophilic infiltration to normal. We conclude that not all infants with apparent formula protein-induced colitis respond to CHF and that these infants may have resolution of their symptoms when fed an amino acid-based infant formula.
Dietary Proteins↗
Influence of bacterial overgrowth and intestinal inflammation on duration of parenteral nutrition in children with short bowel syndrome.
OBJECTIVES: Massive intestinal resection results in short bowel syndrome and necessitates prolonged parenteral feeding. The purpose of this work was to assess the impact of late complications of short bowel syndrome, including intestinal bacterial overgrowth and enterocolitis, on the duration of parenteral nutrition (PN) in comparison with factors evident in the neonatal period. METHODS: Retrospective chart review. RESULTS: Of 49 children, 42 were weaned from parenteral nutrition after a treatment course of 17 +/- 14 months. In these 42, postresection small intestinal length equaled 81 +/- 65 cm; 45% had an ileocecal valve. Small intestinal length in the seven children who were PN dependent was 31 +/- 30 cm (p < 0.05); none had an ileocecal valve (p < 0.05). Bacterial overgrowth occurred in all seven PN-dependent children and in 23 of 42 children eventually weaned from PN (p < 0.05). When bacterial overgrowth was identified before weaning (n = 12), the duration pf PN was 28 +/- 17 months, but when bacterial overgrowth was first identified only after weaning (n = 11), the duration of PN was 16 +/- 13 months (p < 0.05). Small intestinal inflammation correlated with bacterial overgrowth (r = 0.69). Those children with severe enteritis identified before weaning remained on the PN regimen for 36 +/- 15 months, in comparison with 21 +/- 14 months in those with mild enteritis and 13 +/- 11 months in those without inflammation (p < 0.02). CONCLUSIONS: Although the length of small intestine remaining after resection is the best immediate predictor of final success in terminating PN in children with short bowel syndrome, PN is prolonged by bacterial overgrowth and associated enteritis in those who will ultimately be weaned.
Bacteria↗
Short-bowel syndrome in children and adults.
Short-bowel syndrome is the malabsorptive state that follows extensive resection of the small intestine. Potential long-term survival without parenteral nutrition heavily depends on stimulation of the process of intestinal adaptation, through which the remaining small intestine gradually increases its absorptive capacity. This process is heavily nutrient dependent, and aggressive use of enteral nutrition is required to stimulate its completion. A combination of osmotic sensitivities, nutrient malabsorption, bowel dilatation and dysmotility, and changes in bacterial flora influence the symptoms and the management of this disorder. Chronic complications include parenteral nutrition-induced liver disease, nutrient deficiency states, and, frequently, small bowel bacterial overgrowth. Intestinal transplantation has been successfully developed in some centers in the United States, and preliminary experience suggest a long-term survival of 50%-75%, better in patients receiving an isolated intestinal transplant than a combined liver/bowel transplant. The ultimate role of intestinal transplantation is still undergoing evaluation.
Adaptation, Physiological↗
Diagnosis and treatment of chronic intestinal pseudo-obstruction in children: report of consensus workshop.
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Chronic Disease↗
Soy-polysaccharide-supplemented soy formula enhances mucosal disaccharidase levels following massive small intestinal resection in rats.
BACKGROUND: Addition of soy polysaccharide to infant formulas has previously been shown to reduce the duration of diarrhea in infants with acute gastroenteritis. Fiber is metabolized to short-chain fatty acids that have been shown to be beneficial in inducing adaptation in the small bowel. We therefore hypothesize that a soy-polysaccharide-supplemented infant formula may be potentially advantageous in the treatment of patients with short bowel syndrome and could have a trophic effect on the remaining small intestine. METHODS: Male Spraque-Dawley rats weighing 250 g were divided into two groups. One group received Isomil, a standard infant soy formula. The second group received Isomil supplemented with fiber, Isomil DF. Half the animals in each dietary group were subjected to 80% jejunoileal resection and the reminder were sham operated. Animals were pair-fed one of two diets for 14 days. At the conclusion of the 14-day period, mucosal weight and sucrase and lactase levels in the remaining duodenum and ileum were determined. RESULTS: Resected animals fed fiber-supplemented formulas had significantly higher sucrase and lactase levels in the proximal bowel. Comparable results were not observed in the sham-operated animals. CONCLUSIONS: The addition of soy polysaccharide to infant formulas fed to children with short bowel syndrome might potentially improve small intestinal functional adaptation as well as positively affecting stool consistency.
Animals↗
Growth hormone and glutamine do not stimulate intestinal adaptation following massive small bowel resection in the rat.
BACKGROUND: Certain nutrients and other trophic factors are highly sensitive stimulants of intestinal adaptation following short bowel syndrome. Growth hormone and glutamine in a modified diet have been shown to enhance nutrient absorption in patients with severe short bowel syndrome. However, neither growth hormone nor glutamine is capable of enhancing adaptation in an animal model. This study was conducted to determine if the combination of glutamine and growth hormone could enhance gut adaptation following massive small bowel resection in the rat. METHODS: Thirty-four male rats received 70% jejunoileal resection. The first group received glycine and rat growth hormone, the second glutamine and rat growth hormone, and the third glycine but no growth hormone. RESULTS: There was no evidence that the combination of glutamine and growth hormone could enhance mucosal mass, mucosal protein, or mucosal DNA levels relative to the other two control groups of animals. Likewise, sucrase activities were not enhanced by glutamine and growth hormone. CONCLUSIONS: It is unlikely that the combination of glutamine and growth hormone will be of benefit in the treatment of patients with short bowel syndrome. The results in previous human studies can be alternatively explained by the long-term nonspecific effect of enteral nutrition on gut adaptation.
Adaptation, Physiological↗
Use of soy fiber in acute diarrhea in infants and toddlers.
Soy fiber has been shown to reduce the duration of watery stools during acute diarrhea caused by bacterial and viral pathogens in underdeveloped countries. A randomized blinded clinical trial was conducted with middle-class American children to assess the efficacy of soy fiber-supplemented infant formula. Stool characteristics, intake, and weight were recorded. Infants > 6 months of age (n = 44) fed soy fiber-supplemented formula (Isomil DF) had a significantly shorter estimated median duration of diarrhea (9.7 hours vs. 23.1 hours) than those fed soy formula (Isomil). The use of fiber-supplemented soy formula may reduce the duration of diarrheal symptoms in U.S. infants more than 6 months of age with acute diarrhea.
Acute Disease↗
Gastroenteric inflammation in children with ulcerative colitis.
This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.
Adolescent↗
Expression of insulin-like growth factor-II and insulin-like growth factor binding proteins during Caco-2 cell proliferation and differentiation.
The components of the insulin-like growth factor (IGF) axis and their roles in regulating proliferation and differentiation of the human colon adenocarcinoma cell line, Caco-2, have been investigated. Caco-2 cells proliferated in serum-free medium at 75% the rate observed in medium containing 10% fetal bovine serum. IGF-I (10 nM) increased Caco-2 cell growth in serum-free medium, but not to the rate seen with serum. Multiple IGF-II mRNA species were produced by Caco-2 cells, but IGF-I mRNA was undetectable. Secretion of radioimmunoassayable IGF-II corresponded with steady-state levels of IGF-II mRNA, neither of which was observed to change markedly over the course of 16 days of Caco-2 cell differentiation. Levels of sucrase-isomaltase mRNA, a marker for enterocytic differentiation, increased 12-fold between days 5 and 16 of culture. Northern blotting of total RNA and ligand blot and immunoblot analyses of serum-free conditioned medium revealed that Caco-2 cells produce several IGF binding proteins (IGFBPs), including IGFBP-2, -3, and -4, as well as a 31,000 M(r) species that was not identified. The pattern of IGFBP secretion changed dramatically during Caco-2 cell differentiation: IGFBP-3 and IGFBP-2 increased 8.5-fold and 5-fold, respectively, whereas IGFBP-4 and the 31,000 M(r) species decreased 43% and 90%. Caco-2 cell clones stably transfected with a human IGFBP-4 cDNA construct exhibited a 60% increase in steady-state level of IGFBP-4 mRNA, and secreted twice as much IGFBP-4 protein as controls. Moreover, IGFBP-4-overexpressing cells proliferated at only 25% the rate of control cells in serum-free medium, in conjunction with a 70% increase in expression of sucrase-isomaltase. In summary, these studies indicate that a complex IGF axis is involved in autocrine regulation of Caco-2 cell proliferation and differentiation.
Caco-2 Cells↗