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Biomedical subjects

J A Vanderhoof

Publications and source records attributed to J A Vanderhoof.

At least 55 records · Page 3Linked to original sources

Short bowel syndrome in children and small intestinal transplantation.

This article discusses the management of short bowel syndrome from the time of intestinal resection until the patient either recovers free of supplemental parenteral and enteral nutrition or progresses to the point of needing intestinal transplantation. The importance of aggressive use of enteral feedings is emphasized, especially in relation to the process of intestinal adaptation. An approach to the various complications of short bowel syndrome, especially small bowel bacterial overgrowth, is discussed. Surgical options short of transplantation also are described. Intestinal transplantation and its present and future roles in the management of patients with short bowel syndrome are discussed.

Adaptation, Physiological↗

Growth hormone did not enhance mucosal hyperplasia after small-bowel resection.

BACKGROUND: Insulin-like growth factor (IGF)-I enhances the mucosal hyperplasia that normally occurs after massive small-bowel resection. The present studies examined whether growth hormone (GH) infusion increases serum IGF-I levels and, thereby, enhances mucosal hyperplasia after small-bowel resection. METHODS: Male Sprague-Dawley rats weighing approximately 140 g were subjected to 80% jejunoileal resection or sham operation (ileal transection). A mini-osmotic pump was then inserted under the skin immediately after surgery to deliver either vehicle or 3mg/kg/day GH. All animals were killed 7 days postoperatively, and the remaining intestine was removed and divided at the anastomotic site. RESULTS: Food intake did not differ between control and GH-infused groups. Resected rats infused with GH grew faster than resected rats infused with vehicle. However, GH did not stimulate the weight gain of sham-operated rats. In both duodenojejunum and ileum, GH infusion did not stimulate hyperplasia beyond that which normally occurs after small-bowel resection, nor did it increase mucosal mass in sham-operated rats. GH infusion did not alter serum IGF-I or IGF-binding protein (IGFBP) levels in either resected or sham-operated rats. GH infusion resulted in increased sucrase and maltase activities in the ileal mucosa of resected rats. CONCLUSIONS: The present results suggest that a pharmacologic dose of GH directly stimulates growth of resected animals and ileal sucrase and maltase activities without increasing serum IGF-I levels or increasing absorptive surface area in the small intestine.

Animals↗

Preliminary experience with intestinal transplantation in infants and children.

OBJECTIVE: This report discusses the preliminary experience with intestinal transplantation in children at the University of Nebraska Medical Center. PATIENTS: During the past 4 years, 16 intestinal transplants have been performed in infants and children. Thirteen have been combined liver and bowel transplants, and the reminder were isolated intestinal transplants. Nearly half of the patients were younger than 1 year of age at the time of surgery, and the vast majority were younger than 5 years of age. All but one had short bowel syndrome. RESULTS: The 1-year actuarial patient and graft survival rates for recipients of liver and small bowel transplants were 76% and 61%, respectively. Eight of 13 patients who received liver and small bowel transplants remain alive at the time of this writing, with a mean length of follow-up of 263 (range, 7 to 1223) days. Six patients are currently free of total parenteral nutrition. All three patients receiving isolated intestinal transplants are alive and free of parenteral nutrition. The mean length of follow-up is 384 (range, 330 to 450) days. Major complications have included severe infections and rejection. Lymphoproliferative disease, graft-versus-host disease, and chylous ascites have not been major problems. CONCLUSIONS: Although intestinal transplantation is in its infancy, these preliminary results suggest combined liver and bowel transplants and isolated intestinal transplantation may be viable options for some patients with intestinal failure caused by short bowel syndrome or other gastrointestinal disease in whom long-term total parenteral nutrition is not an attractive option.

Actuarial Analysis↗

Short bowel syndrome.

This article discusses the management of short bowel syndrome during the neonatal period. It includes information regarding etiology and pathophysiology and parenteral and enteral nutrition therapy. Finally, a discussion of the role of intestinal transplantation in the treatment of short bowel syndrome is included.

Enteral Nutrition↗

Growth stimulation by transfection of intestinal epithelial cells with an antisense insulin-like growth factor binding protein-2 construct.

IEC-6 cells, an intestinal epithelial cell line, produce insulin-like growth factor (IGF)-II and IGF-binding protein-2 (IGFBP-2). Exogenous IGFs stimulate and IGFBP-2 attenuates DNA synthesis. To investigate whether endogenously secreted IGFBP-2 inhibits proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA antisense expression construct. The steady-state level of IGFBP-2 mRNA decreased by 54% in the antisense cDNA-transfected cells (denoted revBP2) compared with vector-transfected controls. Moreover, revBP2 cells secreted less IGFBP-2 than controls (maximally a 68% decrease). In serum-containing medium, revBP2 cells exhibited a 35% increase in log-phase proliferation rate and growth-arrested at a maximum density 14% higher than controls. We conclude that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs.

Animals↗

Clinical denouement and mutation analysis of patients with cystic fibrosis undergoing liver transplantation for biliary cirrhosis.

OBJECTIVE: To describe the clinical characteristics of patients with cystic fibrosis considered for liver transplantation and the clinical outcome after transplantation. METHODS: Patient charts were reviewed. Mutation analysis was performed on blood or liver tissue samples with a panel of 17 mutations. RESULTS: Eight patients (five girls) with cystic fibrosis have undergone orthotopic liver transplantation for biliary cirrhosis. Mean age at transplantation was 12.0 years +/- 7.7 years (range, 9 months to 23 years). Preoperatively, seven patients had mild to moderate pulmonary dysfunction and one moderate to severe pulmonary dysfunction. All patients required pancreatic enzyme replacement, and four patients required insulin for diabetes mellitus. The 1-year survival rate was 75%, with no deaths related to septic events. Mean time of follow-up the six operative survivors was 4.1 years +/- 1.9 years. Pulmonary function testing, in those serially tested, showed that forced expiratory volume in 1 second was maintained or improved and that forced vital capacity improved after transplantation. Mutation analysis showed the following genotypes: four patients, delta F508/delta F508; one patient, delta F508/N1303K; and three patients, delta F508/unknown. CONCLUSIONS: Despite the high risk of transplantation, these encouraging results indicate that liver transplantation should be considered for patients with cystic fibrosis and complications of end-stage liver disease. We could not demonstrate an unusual pattern of CF gene mutations in these patients with severe liver disease. It appeared that immunosuppressive agents did not have a deleterious effect on pulmonary function.

Adolescent↗

Surgical approach to short-bowel syndrome. Experience in a population of 160 patients.

OBJECTIVE: The authors reviewed their experience with short-bowel syndrome to define the surgical approach to this problem in 160 patients. METHODS: Forty-eight adults and 112 children were evaluated over a 15-year period. RESULTS: Seventy-one patients (44%) adapted to resection and took enteral nutrition alone. Forty-four patients (28%) were supported by parenteral nutrition (PN). Forty-five patients (28%) have had 49 surgical procedures. Fifteen patients with adequate intestinal length (> 120 cm in adults) but dilated dysfunctional bowel underwent stricturoplasty (n = 4) or tapering (n = 11). Thirteen patients (87%) demonstrated clinical improvement. Fourteen patients with shorter remnants (90-120 cm) and rapid transit time received an artificial valve (n = 2) or a reversed segment (n = 1). All patients' conditions improved initially, but the reversed segment was revised or taken down. Fourteen patients with short remnants and dilated bowel underwent intestinal lengthening. Twelve patients' conditions improved (86%), one underwent transplantation, and one died. Sixteen patients with very short remnants (< 60 cm) and complications of PN underwent solitary intestine (n = 4) or combined liver-intestinal transplantation (n = 13). One-year graft survival was 65%. There have been five deaths. CONCLUSIONS: The surgical approach to short-bowel syndrome depends on the patient's age, remnant length and caliber, intestinal function, and PN-related complications. Nontransplant procedures have a role in the treatment of selected patients. Intestinal transplantation is emerging as a potential therapy for patients with significant PN-related complications.

Adolescent↗

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome (CVS) is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 24 children (10 boys, 14 girls). Many patients had mild associated abdominal pain with their vomiting. Fourteen patients had previously been given metoclopramide but none responded. Two patients were mildly developmentally delayed. Twenty-four patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in two to four divided doses for 7 days. This dose was repeated as needed when symptoms reappeared. Eighteen of 24 patients reported total resolution of symptoms when re-evaluated at 2 and 6 months. All males responded, eight of 18 responders were female, and all six with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of CVS in childhood. Because the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in CVS.

Adolescent↗

Effect of glutamine-supplemented elemental diet on mucosal adaptation following bowel resection in rats.

Glutamine is the major fuel for enterocytes and prevents mucosal atrophy in certain animal models. Previous studies in our laboratory have failed to show a trophic effect of glutamine on the small-bowel mucosa following massive resection when added to a chow diet. However, the complexity of the chow diet might potentially interfere with the adequate evaluation of the trophic effect of a single agent such as glutamine. This study was therefore designed to determine whether the addition of glutamine to an elemental diet would augment mucosal adaptation following massive small intestinal resection in a rat model. Male Sprague-Dawley rats were divided into two dietary groups, one receiving an amino acid-based pediatric elemental diet supplemented with 2% glutamine, and the other receiving the diet supplemented with 2% glucose. One half of the animals in each dietary group received 80% jejunoileal resection, and the remainder were sham operated. Fifteen days postsurgery, mucosal weight, DNA, protein, and sucrase activities were determined in both the proximal and the distal small intestine. While both groups of resected animals developed marked increases in all parameters of adaptation, the glutamine-supplemented group did not differ from the control diet group in any parameter. The addition of glutamine to an elemental diet had no enhancing effect on intestinal adaptation after bowel resection. These results are similar to those previously observed in our laboratory when glutamine was added to chow diet. The addition of glutamine to an elemental diet cannot be justified on the basis of its trophic effect in animals.

Adaptation, Physiological↗

On the importance of cholecystokinin in neonatal pancreatic growth and secretory development in guinea pigs.

The role of cholecystokinin (CCK) in pancreatic growth and secretory development in fetal and neonatal guinea pigs was investigated by CCK receptor blockade. For the last 20 days of gestation, sows received the CCKA receptor antagonist, MK329 (25 nmol/kg/h) by continuous subcutaneous infusion. Alternatively, neonates from untreated females received an MK329 infusion for the first 4 or 15 days following birth. Pancreatic weight, DNA, RNA, protein, and amylase content per 100 g body weight and secretory responses to CCK, carbamylcholine, and phorbol ester were determined at birth and 4 days in animals receiving MK329 in utero and were measured at 4 and 15 days in neonatally infused animals. No significant changes in pancreatic growth parameters were seen in MK329-treated animals compared to controls, except for a small (14%; p < 0.02) decrease in weight after 15 days of neonatal exposure. Enhanced amylase secretion in response to CCK and carbamylcholine was seen in all groups receiving MK329 (all p values < 0.00001). Pancreatic growth and secretion were not inhibited by CCKA receptor blockade, which suggests that the effects of CCK mediated by the CCKA receptor are not essential for growth or development of the pancreatic amylase secretory response in the neonatal guinea pig.

Amylases↗

Short bowel syndrome in children.

Short bowel syndrome is defined as malabsorption following small intestinal resection. There are many causes in children, most of whom present during infancy. The clinical presentation and physiologic consequences depend heavily on the segment of bowel removed and the extent of resection. The remaining intestine has the capacity to adapt anatomically and functionally, and stimulating the adaptation process is a major component of therapy. Clinical management of long-term complications, such as bacterial overgrowth, nutrient deficiency states, and parenteral nutrition-induced liver disease, are often key outcome determinants. The recent availability of intestinal transplantation now provides an additional therapeutic option for patients in whom all other forms of therapy fail.

Adaptation, Physiological↗

Effects of dietary menhaden oil on mucosal adaptation after small bowel resection in rats.

BACKGROUND/AIMS: Adaptive hyperplasia of the small intestine is important in the outcome of short bowel syndrome. Previous studies have shown that long-chain fats stimulate this process. In the present study, the trophic effects of dietary menhaden oil, a highly unsaturated fat source, on mucosal adaptation following small bowel resection in rats was evaluated. METHODS: Thirty weanling Sprague-Dawley rats and their controls were fed diets containing fats provided primarily as menhaden oil, safflower oil, or beef tallow. After 4 weeks, animals underwent a 70% jejunoileal resection. Mucosal mass, DNA, protein, and sucrase levels were assessed 14 days after a 70% jejunoileal resection or control feeding. Serum fatty acid composition and several gastrointestinal hormone levels were measured. RESULTS: Resected animals fed menhaden oil showed a marked increase in mucosal weight, DNA, and protein levels compared with rats fed the other fat sources. Enteroglucagon level was increased in all resected groups, but least increased in the menhaden-fed animals. In contrast, peptide YY concentrations were most increased in animals fed menhaden oil. CONCLUSIONS: Menhaden oil appears more effective in inducing intestinal adaptation than less highly unsaturated fats. Analysis of gastrointestinal hormones revealed no clear-cut explanation for this finding, other than a modest but associated increase in peptide YY levels.

Adaptation, Physiological↗

Dexamethasone inhibits mucosal adaptation after small bowel resection.

The present study examined the effects of dexamethasone on mucosal adaptation after massive small bowel resection. Rats underwent 80% jejunoileal resection or a sham operation and received either vehicle or 128 micrograms.kg-1.day-1 sc dexamethasone for 7 days. Dexamethasone infusion resulted in decreased weight, DNA content, and protein content in the duodenojejunal and ileal mucosa in both sham and resected rats. Sucrase, lactase, and maltase activities (all in mumol.g protein-1.min-1) in the duodenojejunal mucosa were elevated by dexamethasone infusion. By contrast, enzyme activities were elevated only in the ileal mucosa of dexamethasone-infused sham-operated rats compared with sham-operated control rats, and dexamethasone did not elevate enzyme activities in resected rats. We further examined whether the inhibitory effects of dexamethasone on mucosal adaptation may be related to changes in either insulin-like growth factor (IGF) or IGF binding protein (BP) serum levels. Serum IGF-I and IGF-II levels were markedly decreased in dexamethasone-infused resected and sham-operated rats. IGF BP-1 serum levels were elevated by dexamethasone treatment with a concomitant depression in serum IGF BP-2 levels. IGF BP-3 levels were lowered by dexamethasone treatment in sham-operated rats and by gut resection, and serum IGF BP-4 levels did not change. These results suggest that the growth-inhibiting effects of dexamethasone in small intestinal mucosa may be partially mediated by decreased serum IGF levels or by alterations in IGF activity associated with changes in serum levels of IGF BPs.

Adaptation, Physiological↗