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Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.

Background & Aims: Home nutrition support, especially when delivered parenterally, is very costly. The aim of this study is to examine current usage of home parenteral and enteral nutrition (HPEN) in the United States and the quality of therapy outcome., Methods: Medicare HPEN use from 1989 to 1992 was analyzed to assess use, growth, and costs. National Registry information collected on 9288 patients treated with HPEN from 1985 to 1992 was used to assess disease distribution and therapy outcome., Results: In the United States, there were approximately 40,000 parenteral and 152,000 enteral home patients in 1992. The usage of HPEN doubled between 1989 and 1992, and a large proportion was in patients with short survival. The prevalence of HPEN in the United States was 4-10 times higher than in other Western countries. Outcome data showed both therapies were relatively safe. The primary disease strongly influenced survival and rehabilitation, and age, per se, was not a reason to deny HPEN., Conclusions: Predicted quality survival at home for several months, rather than a specific diagnosis, seems to be the soundest justification for HPEN. Its role in terminal conditions and patients without primary gastrointestinal diseases needs further evaluations.

We describe a 21-year-old man who developed copper deficiency manifested as a demyelinating neuropathy, chronic intestinal pseudo-obstruction, osteoporosis, testicular failure, retinal degeneration, and cardiomyopathy with a tortuous aorta. His serum copper was low and did not increase despite administration of large doses of intravenous copper sulfate. The ceruloplasmin level as measured by an antibody technique was normal, yet ceruloplasmin (Cp) oxidase activity was very low. The Cp amino acid sequence was normal. This suggests that the copper deficiency was caused by a defect in hepatic processing of copper for incorporation into Cp.

Corticosteroids remain the primary therapeutic agent to induce remission in moderate to severe ulcerative colitis (UC) and Crohn's disease because of their rapidity of action in comparison to other agents. Mild UC and/or Crohn's disease of the colon and terminal small bowel may be treated with azulfidine first. However, if patients are intolerant of these medications, dipentum or asacol may be used. Occasionally, patients with Crohn's colitis but not UC may respond to metronidazole. Immunosuppressive agents such as 6-mercaptopurine are very useful for steroid-dependent inflammatory bowel disease, as a substitute for long-term corticosteroids. Cyclosporine, although it has been proposed as an alternative to other antimetabolite or immunosuppressive therapy, is of benefit in fewer than 25% of cases of UC or Crohn's disease. Rowasa enemas are useful for left-sided disease in UC or Crohn's disease of the colon; however, use in children may be difficult in view of psychosocial issues that must be considered.

Plasma-free choline levels have previously been found below normal in patients receiving long term parenteral nutrition (TPN). In a group of 15 patients receiving home TPN who had low plasma free choline levels (6.3 +/- 0.8 mmol/L), we found 50% had hepatic steatosis. These patients were given oral lecithin or placebo in a double-blind randomized trial for 6 weeks. Lecithin supplementation led to an increase in plasma free choline of 53.4% +/- 15.4% at 2 weeks (P = 0.04), which continued at 6 weeks. The placebo group had no change in plasma-free choline at 2 weeks, but a significant decrease of 25.4% +/- 7.1% (P = 0.01) at 6 weeks. A significant and progressive decrease in hepatic fat was indicated by increased liver-spleen CT Hounsfield units at 2 and 6 weeks (7.5 +/- 1.7 units, P = 0.02; 13.8 +/- 3.5 units, P = 0.03) in the lecithin supplemental group. Nonsignificant changes were seen in the placebo group. It was concluded that hepatic steatosis in many patients receiving long term TPN is caused by plasma-free choline deficiency and may be reversed with lecithin supplementation. Choline is a conditionally essential nutrient in this population.

One hundred and forty-two pediatric patients between age 1 month and 20 years had 163 endoscopic procedures. Of 66 with chronic abdominal pain, 21 had a source identified endoscopically that was seen in only 15 by esophagogram and upper gastrointestinal series. Of 31 with nausea, vomiting, dysphagia, and/or odynophagia and retrosternal pain, endoscopy demonstrated the source in 19 patients and radiographic studies in 14. Of 34 with hematemesis and/or melena, 26 had a bleeding site identified endoscopically but only 4 of 28 had an identified source by radiographic studies. Duodenal and gastric ulcers and hemorrhagic gastritis were the commonest cases of upper gastrointestinal bleeding and organically of chronic adbominal pain. Functional abdominal pain was the commonest cause of chronic abdominal pain in those endoscoped. Foreign bodies were removed from the esophagus and stomach of 6 patients and dislodged in 2 others. Caustic ingestion was recognized in the esophagus and stomach of 2 patients who did not have mouth burns. The GIF-P2-prototype with four-way tip control and ability to retroflex 180 degree up, 60 degree down, and 100 degree right and left was superior to GIF-P1 and CF-P-prototype for visualization of the entire esophagus, stomach, duodenal bulb, and postbulbar area in patients less than 10 years old. Visualization of the duodenal bulb was possible in 28 of 29 pediatric patients, and of the postbulbar area in 25 of 26 in whom it was attempted. Infants who weighed as little as 3 to 5 kg were successfully examined. Retroflexion was possible in 29 of 30 to see the fundus and cardioesophageal junction. Patients older than 10 years were better examined with the GIF-D because of its increased ability to transmit light. Sedation for the school-age child with 0.5 to 1.0 mg per kg of diazepam and 1 to 2 mg per kg of meperidine given intravenously provides excellent sedation in most instances. General anesthesia is preferable for the preschooler and infant. Minor complications occurred in 2 patients who received less than adequate sedation and in 1 patient with general anesthesia.

Thirty-two infants and their mothers were studied to determine the source of elevated serum gastrin concentrations in umbilical blood and to learn whether neonates hypersecreted acid in response to hypergastrinemia. Gastrin concentrations in the umbilical artery and vein were similar. Both were significantly higher than maternal gastrin concentrations. No significant amount of gastrin could be measured in placental extracts. These results suggest that the increased neonatal gastrin concentrations were fetal in origin. Continuous basal acid secretory studies done for 4 hr in 32 infants and for 8 hr in 9 infants demonstrated hyposecretion of gastric acid for the first 5 hr of life. Acid secretion from hour 6 to 8 was similar to that in older children. Increased gastrin levels were still present at hour 8 and were associated with normal gastric acid secretion.

Individual l-amino acids were instilled intragastrically to determine possible differences in stimulation of gastric acid secretion and gastrin and pancreatic polypeptide release. Phenylalanine and tryptophan were significantly more potent stimulants of gastric acid secretion and of pancreatic polypeptide and gastrin release than any of the other amino acids tested. Smaller, but significant, responses were obtained with threonine for pancreatic polypeptide and with serine for acid secretion. We conclude that a major part of the acid-stimulating action of mixed amino acid solution can be explained by the aromatic amino acids, phenylalanine and tryptophan, which are also the most potent stimulants of gastrin and pancreatic polypeptide release. These studies suggest that the specific composition of amino acid mixtures determines the net effects of such mixtures on gastric secretion, and on release of both the antral hormone gastrin and the pancreatic hormone, pancreatic polypeptide.

Recent anecdotal reports suggest that total parenteral nutrition may be associated with an increased incidence of both acalculous cholecystitis and cholelithiasis. The validity of this association, however, has not been tested in a large population of patients on long-term total parenteral nutrition. Therefore, we assessed the incidence of gallbladder disease among our patients 15 yr and older who had received a minimum of 3 mo of total parenteral nutrition. Of the patients meeting these criteria, 128 were on total parenteral nutrition a mean of 13.5 mo. Nineteen had gallbladder disease before receiving total parenteral nutrition, leaving 109 patients at risk. Of these patients, 25 (23%) developed gallbladder disease after the initiation of total parenteral nutrition. Because of their known propensity for cholelithiasis, 94 of our patients with ileal disorders (Crohn's disease or ileal resection, or both) were considered separately. The 40% incidence of gallbladder disease in these 94 patients was significantly higher than expected from a series of similarly defined patients with ileal disorders not receiving total parenteral nutrition (p less than 0.05). We propose that the enhanced risk of gallbladder disease among patients on long-term total parenteral nutrition results from multiple factors working in concert to promote gallbladder stasis.

Fiberoptic upper intestinal endoscopy has been shown in the last decade to be the most sensitive technique to diagnose upper gastrointestinal disease. Diagnostic endoscopy has been shown to be safe, with a low complication rate of less than 2 per cent, and most of those reported have been minor. Furthermore, therapeutic endoscopy has been used to treat bleeding varices by sclerotherapy, avoiding the need for shunting procedures, which often fall in young children. Dilation of strictures with wire-guided dilators, endoscopic incision of antral mucosal diaphragms, and percutaneous placement of gastrostomy tubes are other ways endoscopy is being used as a means of treatment. Electrocoagulation and photocoagulation of bleeding upper gastrointestinal lesions have not been used.

A 3-yr 8-mo-old female was diagnosed as having a congenital stricture of the common hepatic duct. She demonstrated hepatomegaly with marked elevations of serum transaminases, alkaline phosphatase, and bile acids without clinical jaundice or hyperbilirubinemia. Liver biopsy suggested extrahepatic obstruction. Ultrasonography was nondiagnostic, but percutaneous cholangiography demonstrated blockage at the bifurcation of the hepatic ducts. A Roux-en-Y anastomosis of the jejunum to the common hepatic ducts relieved the obstruction and ameliorated clinical evidence of liver disease.

Celiac sprue and Crohn's disease have very rarely been documented in the same patient. We report a case involving an adolescent male with known Crohn's disease who had extreme wasting, growth retardation, intractable diarrhea, and delay in development of secondary sexual characteristics. Peroral jejunal biopsy showed a nonspecific flat mucosal lesion compatible with celiac sprue. An 8.0-kg weight increase occurred within 4 weeks of institution of a gluten-free diet. Jejunal rebiopsy documented significant improvement with a mild to moderate villous abnormality. After 2 years on a gluten-free diet, a rebiopsy of the jejunum documented only a mild villous abnormality.

During the past 3 yr, 17 patients with chronic ulcerative colitis and 6 with Crohn's disease who had severe rectal and colonic involvement underwent excision of the rectal mucosa without removal of the rectal muscle in combination with total colectomy and cutaneous ileostomy as a 1- or 2-stage procedure. This operative technique has cured each of the patients of their primary colonic and rectal disease and has obviated many of the unpleasant complications that often occur after total proctectomy, such as impotence, prolonged perineal drainage, and bladder dysfunction. The operation has the further advantages of lower operative blood loss, shorter operative time, and earlier safe ambulation. On the basis of the favorable experience with mucosal proctectomy, sphincterotomy, and perineal drainage in 23 patients, none of whom experienced major complications, we believe that this operation warrants further clinical trial in patients with inflammatory bowel disease involving the rectum, which is refractory to medical therapy. Total proctectomy might eventually find scant application in patients with inflammatory bowel disease.

Rates of gastric hydrochloric acid secretion were compared in 10 children with active duodenal ulcer (DU) and 14 non-duodenal ulcer children. Duodenal ulcer was diagnosed by gastroduodenoscopy or by evidence of an ulcer crater on upper gastrointestinal radiographs. Duodenal ulcer disease was excluded in the comparison group by similar criteria. Basal acid output in DU children tended to be higher, but the difference was not statistically significant (P greater than 0.05). Maximal acid output was significantly higher in DU children than in the comparison group whether expressed as milliequivalents per hour (P less than 0.025) or as milliequivalents per kilogram per hour (P less than 0.005). Peak acid output also showed a statistically significant difference (milliequivalents per hour, milliequivalents per kilogram per hour, (P less than 0.05). These findings demonstrate that, on the average, hypersecretion of gastric acid does occur in children with duodenal ulcer disease.

Twin brothers whose monozygosity was demonstrated by analysis of dermatoglyphic patterns, chromosome banding, HLA typing, and gene markers developed Crohn's disease within 8 mo of each other. Both had involvement of the terminal ileum, colon, and rectum, as well as arthritis. However, one had severe esophagitis and recurrent pancreatitis, and the other had severe arthritis and oral mucosal involvement. Both twins had manifestations controlled by parenteral nutrition. This report describes the similarities and differences in the complicated course of Crohn's disease in identical twins and demonstrates that while the development of Crohn's disease may be genetically influenced the site of gastrointestinal involvement is affected by other factors. This experience does not support previously held concepts of the role of genetics in the clinical manifestations of Crohn's disease.

The effects of enteral feeding on the maintenance of gastrointestinal function in human infants are unknown. The effects of enteral feeding on gastric acid secretory function were studied by investigating three groups of infants: infants fed normally, infants with gastrointestinal disease fed by a combination of enteral and parenteral means, and infants fed by total parenteral nutrition. In 14 infants with gastrointestinal disease fed with total parenteral nutrition for a mean of 7 mo (range 1.5-24 mo), basal gastric acid secretion and pentagastrin-stimulated maximal gastric acid secretion were significantly less than in 26 normal infants (p less than 0.01) and in 11 infants with gastrointestinal disease nourished with a combination of enteral and parenteral feeding (p less than 0.01). In each of seven infants fed with total parenteral nutrition for a mean of 5 mo (range 1.5-10 mo), basal and maximal gastric acid secretion increased after a 6-8-wk trial of enteral feeding, a highly significant difference. In one infant, the ability to secrete normal amounts of acid in response to pentagastrin (achieved after an initial trial of enteral feeding) was lost after a 4-mo enteral fast, but returned after a second trial of enteral feeding. These results demonstrate that, in human infants, enteral feedings are necessary for normal oxyntic mucosal secretory function.

Nine children (age range, 5 weeks to 13 years) with gastroesophageal reflux unresponsive to medical management were evaluated with esophageal manometry studies before and after Nissen fundoplications were performed. All patients had a postoperative increase in lower esophageal sphincter (LES) pressure. The mean preoperative LES pressure was 11.3 mm Hg and the mean postoperative pressure was 22.3 mm Hg. The mean LES pressure increase after surgery was 10.9 mm Hg (range: 5.3 to 22.5 mm Hg). All patients ceased vomiting immediately after surgery and have gained weight at a rate greater than that expected for their age.

Intravenous metoclopramide (M) was compared to placebo (P) by a double blind crossover design to determine whether M was superior to P in difficult cases of intubation of the small intestine, using a multipurpose biopsy tube and capsule. Metoclopramide decreased intubation time in 20 volunteers successfully intubated with M and P (P less than 0.05). Of 9 subjects, 8 were intubated to ligament of Treitz with M but not with P (P less than 0.01). Of 29 volunteers, 22 were successfully intubated by 15 min when M was given, but only 9 of the 29 could be intubated in 15 min with P (P less then 0.001). Of 29 volunteers receiving M, 9 experienced side effects but none were serious. This study demonstrated that M is superior to P in decreasing intubation time of a small intestinal biopsy capsule and is particularly useful in patients who may not otherwise be sucessfully intubated.

This study describes the clinical, radiologic, esophageal function test, endoscopic, and histologic findings of Barrett's esophagus in 11 children aged 6-14 yr. All had long-standing symptoms of gastroesophageal reflux, which had begun in the first year of life in 10 of the 11. Eight of the 11 patients had mid or upper esophageal strictures and 10 of the 11 required fundoplication. Most patients had low lower esophageal sphincter pressures and abnormal pH probe studies. Only 6 of the 11 children had the characteristic pink-red appearance of the mucosa at endoscopy. Fifty endoscopic biopsy specimens taken at multiple levels in the esophagus contained columnar-lined epithelium above the gastroesophageal junction. Five of the patients had specialized (intestinal-type) epithelium as part of the histologic spectrum. The clinical expression of Barrett's esophagus in children is similar to that in adults except that strictures appear to be more common in children, and the endoscopic appearance of the mucosa is not always typical in color. As in adults, gastroesophageal reflux appears to be the etiology. In children beyond infancy, Barrett's esophagus is the most common indication for antireflux surgery at our institution. Biopsy specimens should be taken from multiple levels in the esophagus to avoid overdiagnosis and to establish the diagnosis with certainty.

Seventeen pediatric patients, ages 9.25--20.5 yr, were placed on a program of home parenteral nutrition (HPN) for severe, symptomatic Crohn's disease. Prior therapy with sulfasalazine in 14, adrenocorticosteroids in 12, inpatient total parenteral nutrition in 7, and/or surgical resections in 6 failed to suppress disease activity. Remission was attained in 12 of the 17 after one course of HPN alone. Four patients had surgical procedures and 1 required steroids in addition to HPN. Remissions have been maintained in 4 of those 12 for a mean duration of 315 days after discontinuation of HPN. Of the 8 who relapsed after a mean duration of 68 days, second courses of HPN were undertaken in 7 and third courses in 2. All 17 had a marked improvement in disease symptoms while receiving HPN in addition to gaining weight sufficient to place them at a higher percentile on standard growth charts. Ten patients demonstrated "catch-up" growth and 4 others increased their height appropriately. A chromium 51-labeled albumin stool collection of greater than 1% in 5 of 7 patients at the completion of a HPN course correlated with relapse within 4 mo. Serial radiographic contrast studies and erythrocyte sedimentation rates were not predictive of prolonged remissions. Home parenteral nutrition complications were minimal, with only one episode of sepsis per 5.8 catheter experience years. It is concluded that HPN is a safe and effective means of inducing remissions and providing optimal nutritional support in pediatric patients with severe Crohn's disease. Patients with less than adequate response to standard medical management should be considered candidates for this therapeutic modality.