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Biomedical subjects

J A Vanderhoof

Publications and source records attributed to J A Vanderhoof.

At least 73 records · Page 4Linked to original sources
PubMed1993

Postnatal development of circulating cholecystokinin and secretin, pancreatic growth, and exocrine function in guinea pigs.

Concentrations of cholecystokinin (CCK) and secretin from neonatal guinea pig plasma were evaluated in relation to pancreatic growth, and secretion from dispersed pancreatic acini. Plasma CCK was low at birth (3.1 +/- 0.8 pmol/L) but rose markedly by day 15 (11.0 +/- 0.8 pmol/L, p < 0.001). Plasma secretin was also low at birth (3.8 +/- 0.8 pmol/L) but peaked on day 4 (17.0 +/- 1.4 pmol/L, p < 0.001) and remained elevated through d 15. Adult nonfasting plasma CCK and secretin levels were 12.3 +/- 0.8 and 8.9 +/- 1.5 pmol/L, respectively. Pancreatic weight more than doubled during the first week of life, with the greatest increase during the first 4 d (156 +/- 4 to 262 +/- 10 mg/100g body wt, p < 0.001). Body weight increased most dramatically during the second week (126 +/- 9 to 190 +/- 7 g p < 0.001). Amylase secretion from isolated acini stimulated by CCK-8, carbachol, phorbol ester, forskolin, and calcium ionophore (A23187) was present at birth. The percentage of total amylase content secreted in response to CCK, carbamylcholine, and secretin did not change during the first 2 wk of neonatal life, and was independent of surges in circulating CCK and secretin. These results indicate that functional maturity of the guinea pig pancreas for amylase secretion occurs early and is different from the rat, mouse, pig, and human. Since results can readily be compared between animals of different postnatal ages, the neonatal guinea pig is ideally suited for the study of hormonal effects on acinar cell function.

Amylases↗
PubMed1993

Olsalazine versus sulfasalazine in mild to moderate childhood ulcerative colitis: results of the Pediatric Gastroenterology Collaborative Research Group Clinical Trial.

The safety and efficacy of olsalazine sodium was compared to sulfasalazine over 3 months in a multicenter, randomized, double-blind study of 56 children with mild to moderate ulcerative colitis. Twenty-eight children received 30 mg/kg/day of olsalazine (maximum, 2 g/day) and 28 received 60 mg/kg/day of sulfasalazine (maximum, 4 g/day). Side effects were frequent in both groups. Eleven of 28 patients (39%) on olsalazine reported headache, nausea, vomiting, rash, pruritus, increased diarrhea, and/or fever. Thirteen of 28 on sulfasalazine (46%) reported similar side effects and/or neutropenia, and four patients had the drug stopped because of an adverse reaction. After 3 months, 11 of 28 (39%) on olsalazine were asymptomatic or clinically improved, compared to 22 of 28 (79%) on sulfasalazine (p = 0.006). In addition, 10 of 28 patients on olsalazine versus one on sulfasalazine required prednisone because of lack of response or worsening of colitis (p = 0.005). The dose of olsalazine used in this clinical trial was thought to be equivalent to a standard dose of sulfasalazine, but fewer patients on olsalazine improved and a greater number had progression of symptoms when compared to sulfasalazine. Although side effects were slightly less frequent for olsalazine, the number of patients was too small to detect a clinically significant difference.

Adolescent↗
PubMed1993

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome 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 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven 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 cyclic vomiting syndrome in childhood. As 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 cyclic vomiting syndrome.

Adolescent↗
PubMed1992

Truncated and native insulinlike growth factor I enhance mucosal adaptation after jejunoileal resection.

It has been shown previously that insulinlike growth factors (IGFs) stimulate the proliferation of intestinal crypt cells in vitro. To examine the in vivo effects of IGF-I on mucosal adaptation, three groups of Sprague-Dawley rats underwent 80% jejunoileal resection. Miniosmotic pumps were then inserted under the skin immediately after resection to deliver vehicle (resected control), 1.5 mg/kg per day of IGF-I, or 1.5 mg/kg per day of des-(1-3)-IGF-I (des-IGF-I). Des-IGF-I is a truncated form of IGF-I that binds as well to type I IGF receptors but less tightly to several forms of IGF-binding proteins (IGFBPs) than IGF-I. Ad libitum food intake did not differ among the three resected groups. Body weight gains were greater in animals receiving des-IGF-I than in those receiving IGF-I, which were greater than resected controls. All animals were killed 7 days postoperatively, and the remaining small intestine was removed and divided at the anastomotic site. Both IGF-I and des-IGF-I induced hyperplasia (increased DNA and protein content) in the duodenojejunum but not in the ileum. IGF-I and des-IGF-I were equally active. In contrast, sucrase, maltase, and leucine aminopeptidase activities were greater only in the ileum of animals receiving IGF-I and des-IGF-I than in resected controls. Although more potent in stimulating overall body weight gain, des-IGF-I was not more potent than IGF-I when duodenal and ileal responses were determined. IGF infusion (IGF-I greater than des-IGF-I) increased the levels of circulating IGFBP-3 and IGFBP-2, which may act to modulate the biological effectiveness of the infused peptides. These results suggest that both IGF-I and des-IGF-I may have potential as therapeutic agents for short bowel patients.

Adaptation, Physiological↗
PubMed1992

Short bowel syndrome.

With utilization of the techniques discussed in this review, patients with short bowel syndrome can be expected to live prolonged lives, even after fairly massive resection. Advances in parenteral and home parenteral nutrition and changes in the long-term management of chronic complications have altered the lifestyles of patients with short bowel syndrome. Intestinal transplantation may become an effective mode of therapy within a short period of time. Many surgeons faced with the possibility of leaving a child with only 10-15 cm of bowel in the past have closed the abdomen with the dead bowel and let the child die. These recent advances raise interesting ethical dilemmas. Research into the process of intestinal adaptation as well as greater experience with intestinal transplantation and other modes of therapy may further improve prognosis.

Animals↗
PubMed1992

Secretion of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 by intestinal epithelial (IEC-6) cells: implications for autocrine growth regulation.

To identify the factors regulating the proliferation of intestinal epithelium, we examined the effects of various growth factors on [3H] thymidine incorporation into the DNA of IEC-6 cells, an intestinal epithelial cell line derived from rat jejunal crypts. Insulin-like growth factor-I (IGF-I), IGF-II, and insulin stimulated the DNA and protein synthesis of IEC-6 cells in serum-free medium supplemented with transferrin, dexamethasone, and BSA (basal medium). Concentration-response experiments demonstrated that IGF-I is approximately 10 times more potent than IGF-II or insulin in producing 2- to 3-fold stimulations of DNA and protein synthesis by IEC-6 cells. In addition, IEC-6 cells proliferated slowly in the basal medium without any added growth factors. Analysis of medium conditioned by IEC-6 cells by gel filtration chromatography, RIA, HPLC, and N-terminal sequencing revealed that IEC-6 cells synthesize and secrete mature, 7,500 mo wt (M(r)) IGF-II as well as high M(r) forms of IGF-II. In addition, ligand blot, immunoblot, and N-terminal sequence analyses showed that IEC-6 cells produce the 34,000 M(r) IGF-binding protein-2 (IGFBP-2). To determine if IGFBP-2 modulates IGF responses in IEC-6 cells, the IGF-I analogs, Des-(1-3)-IGF-I and [Gln3,Ala4,Tyr15,Leu16]IGF-I, both of which have a reduced affinity for IGFBPs, were tested for their effects on IEC-6 cell proliferation. Both analogs exhibited 10-fold greater potency than IGF-I, presumably because endogenously secreted IGFBPs depress IGF-I binding to cell surface receptors. Finally, purified IGFBP-2 attenuated the DNA synthesis of IEC-6 cells in a dose-dependent manner. We conclude that IGFBP-2 secreted by intestinal epithelial cells is capable of limiting the mitogenic activity of both exogenous and endogenous IGFs by blocking the association of the growth factors with cell surface binding sites. These results further suggest that the growth of IEC-6 cells is modulated by autocrine mechanisms involving IGF-II and IGFBP-2.

Amino Acid Sequence↗
PubMed1992

Effects of oral supplementation of glutamine on small intestinal mucosal mass following resection.

Following massive small bowel resection, the remaining small bowel increases in mucosal weight, protein, deoxyribonucleic acid (DNA) content and absorptive function. Enteral nutrients are known to be important in stimulating this response. Recently, glutamine has been described as an essential fuel for the small intestinal mucosa and is thought to be trophic to the small bowel. We investigated if glutamine, when added to the diet in large quantities, might stimulate mucosal adaptation beyond that which normally occurs following physiologic feedings. Male Sprague-Dawley rats were placed on powdered rat chow supplemented with either 5% glutamine, 5% glycine or 5% glucose. After 4 days rats underwent 70% jejunoileal resection. Fourteen days after resection, protein, DNA and sucrase activity in the duodenum of the glutaminefed animals were all significantly lower than results from both the glycine and glucose groups. Duodenal mucosal weight was lower in the glutamine group than in the glycine group. In the ileum, DNA content was significantly lower for the glutamine group than the glycine group. These results suggest that high concentrations of glutamine in the diet can have negative effects on intestinal adaptation.

Adaptation, Physiological↗
PubMed1992

A jejunoileal bypass rat model for rapid study of the effects of vitamin malabsorption.

Jejunoileal bypass operation was originally done to promote weight loss for treatment of morbid obesity. We used such a model to determine if dietary vitamin absorption is compromised by such an operation. Six rats were subjected to a jejunoileal bypass, 6 control rats were pair-fed to bypassed rats; and 6 were fed ad libitum. Vitamin content of folic, B6, riboflavin, nicotinate, pantothenate, thiamin, biotin, B12, vitamins A, E, and carotene in blood and liver was determined after 8 postoperative weeks. Aside from riboflavin, blood vitamin levels were significantly depressed in bypassed rats. The deepest depression was seen for B12, carotene and vitamin E. Liver vitamin stores of folate, riboflavin, thiamin, B12, clearly were significantly depressed in the bypassed animals compared to the pair-fed and ad libitum-fed controls. This model can serve for rapidly studying micronutrient depletion due to malabsorption without dietary manipulation or antibiotics for gut sterilization.

Animals↗
PubMed1991

Neonatal hepatitis and extrahepatic biliary atresia associated with cytomegalovirus infection in twins.

Prenatally acquired cytomegalovirus infection in twins was temporally associated with a discordant development of neonatal hepatitis and extrahepatic biliary atresia. This case presents evidence suggesting an association between perinatal cytomegalovirus infection and selected extrahepatic biliary atresia and neonatal hepatitis. Congenital cytomegalovirus infections and cytomegalovirus hepatitis are also discussed.

Biliary Atresia↗
PubMed1991

Experience with intestinal lengthening for the short-bowel syndrome.

Patients with the short-bowel syndrome frequently develop dilated intestinal segments that may lead to impaired motility and malabsorption. Although intestinal tapering alone improves motility, the intestine can be lengthened as well. We reviewed our experience with six children undergoing intestinal lengthening to improve intestinal absorption secondary to the short-bowel syndrome. The procedure was performed by dissecting the vessels along the mesenteric border and dividing the intestine longitudinally with a stapler. Five patients were receiving total parenteral nutrition (TPN) and one was becoming malnourished with enteral feedings alone. Bacterial overgrowth was documented in four patients and abnormal liver function in three patients. The intestinal segments were dilated up to 10 cm in diameter and remnant length ranged from 15 to 79 cm. Segments 5 to 25 cm in length were divided, resulting in an average increase in length of 52%. Necrosis of one of the divided limbs necessitated resection in one patient. Follow-up ranged from 2 to 84 months. TPN has been discontinued in four patients and avoided in another. Symptomatic improvement occurred in all patients. We feel the tapering and lengthening procedure should be considered in patients with symptomatic, dilated intestinal segments in whom the need for TPN may potentially be obviated.

Anastomosis, Surgical↗
PubMed1991

Effect of dietary menhaden oil on normal growth and development and on ameliorating mucosal injury in rats.

We evaluated the effects of menhaden oil on growth and development of the small intestinal mucosa in growing rats and on the progression and resolution of methotrexate-induced mucosal injury in the rats. One study compared effects of diets containing 10% safflower oil(SO), 9% SO and 1% menhaden oil (MO), 10% MO, or 9% MO and 1% SO on mucosal growth and development for 125 d. In another study, animals fed the 10% MO or the 10% SO diet for 5 wk were subjected to subcutaneous methotrexate injections for 3 consecutive days. Feeding rats a diet containing large amounts of menhaden oil resulted in lower prostaglandin E2 and leukotriene B4 synthesis and lower sucrase activities. Indicators of mucosal mass after methotrexate-induced injury were significantly improved in both the jejunum and ileum at 3 and 10 d after methotrexate administration. Our data suggest that dietary menhaden oil stimulates mucosal regeneration after methotrexate-induced injury.

Animals↗
PubMed1991

The intestinal absorption of 3-O-methyl-D-glucose in methotrexate-treated rats: an in vivo study of small bowel function.

The in vivo absorption of 3-O-methyl-D-glucose (3MG) as a marker of intestinal function has not been studied in an animal model. We evaluated the use of 3MG as a marker of intestinal absorption when given enterally to rats recovering from small bowel mucosal injury induced by methotrexate (MTX). Radiolabeled 3MG was administered into the duodenum of control (CON) and MTX-treated rats and blood samples were obtained at specified intervals. Mucosal permeability was also assessed using radiolabeled mannitol and polyethylene glycol 900 (PEG). Concentration time points were plotted, and area under the curve was calculated as an approximation of absorbed dose. Mucosal weight, maltase activity, and protein content were determined on mucosal scrapings. During the acute phase (day 5), 3MG absorption and maltase-specific activity were significantly decreased in the MTX group when compared to the CON group (p less than 0.001). The MTX group showed a trend toward greater permeability to mannitol when compared to the CON group; however, this was not statistically significant. Mucosal permeability to PEG was similar in both groups. During a later stage in the recovery process (day 12), the area under the curve calculations for 3MG absorption were the same for both CON and MTX animals, with maltase activity in the MTX group recovering to control values. Changes in 3MG absorption paralleled total maltase activities following severe injury. These results suggest that the combined active and passive transport of 3MG in vivo could be of use as a marker of intestinal absorption in states where the small intestine has sustained major damage resulting in compromised absorption as well as brush border digestion.

3-O-Methylglucose↗
PubMed1991

Elevated plasma aluminum levels in normal infants receiving antacids containing aluminum.

Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.

Aluminum↗
PubMed1990

Effects of dietary lipids on recovery from mucosal injury.

The present studies were conducted to determine if diets containing a large amount of fat stimulate the regeneration of damaged intestinal mucosa in the presence or absence of essential fatty acid deficiency. To simulate injury, male Sprague-Dawley rats were given methotrexate, 2.5 mg/kg body wt, subcutaneously for 3 consecutive days. Twenty-four hours after the last methotrexate injection, rats were placed on diets containing either 0%, 1%, or 10% safflower oil. Mucosal weight, protein, deoxyribonucleic acid, maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and fatty acids were all determined 3 and 12 days after methotrexate. Crypt-cell production rates were also determined. Essential fatty acid deficiency was confirmed in the 0% safflower oil group, in which triene-tetraene ratios were greater than 0.4. Mucosal weight, deoxyribonucleic acid, protein content, and villus height were all greater in the 1% safflower oil group than in the 0% group at 12 days. In the ileum, 1-h thymidine incorporation was greater in the 0% safflower oil group than in the other two groups. No differences in any of the parameters studied were observed between the 1% and 10% groups. These results suggest that diets deficient in essential fatty acids may impair the recovery of intestinal mucosa from injury.

Animals↗