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J Pediatr Gastroenterol Nutr

Transpyloric enteral feeding in critically ill children.

Panadero E. Lopez-Herce J. Caro L. Sanchez A. Cueto E. Bustinza A. Moral R. Carrillo A. Sancho L.
Pediatric Intensive Care Section, Gregorio Maranon General University Hospital, Madrid, Spain.
BACKGROUND: Nutrition is important in childhood because the child has a lower energy reserve than the adult and a higher demand for calories because of ongoing growth. In this study, the utility of transpyloric enteral feeding (TEF) in critically ill children was evaluated. METHODS: A prospective, descriptive study was made in a pediatric intensive care unit of a tertiary pediatric center of 41 critically ill children, 30 after surgical procedures and 11 with nonsurgical illness, aged 8 days to 12 years, who received transpyloric enteral feeding with 8- or 10-Fr weighted feeding tubes. Analysis was made of tolerance and complications (vomiting, abdominal distension, excessive gastric residual, diarrhea, and pulmonary aspiration) of TEF. RESULTS: The mean duration of TEF was 19.5 +/- 26.8 days (range, 1-120 days). The administration of sedative agents or inotropic drugs did not alter toleration of TEF. Eight of 12 patients treated with continuous infusion of vecuronium tolerated TEF without complications. Eleven gastrointestinal complications occurred in 10 patients, abdominal distension and excessive gastric residual in 7 (17%), and diarrhea in 4 (9.7%). In 7 patients gastrointestinal complications improved, with decreasing use or transitory interruption of TEF, but in 4 patients (9.7%), TEF had to be withdrawn. Gastrointestinal complications were more frequent in postsurgical than in nonsurgical patients (p < 0.001). No patients suffered from pulmonary aspiration, and the incidence of pulmonary infection and hepatic dysfunction diminished during TEF. CONCLUSIONS: Transpyloric enteral feeding is a good method of nutritional support in critically ill children and can be used in patients treated with neuromuscular blocking agents. The frequency and severity of complications and the risks of pulmonary infection and hepatic dysfunction related to TEF are low.

Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease.

Narkewicz MR. Smith D. Gregory C. Lear JL. Osberg I. Sokol RJ.
Department of Pediatrics, University of Colorado School of Medicine, Denver, USA.
BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve pruritus, alanine aminotransferase (ALT), and cholesterol levels in children with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncertain. METHODS: A 2.5-year, open label, crossover study, was designed to determine the effect of UDCA (15-20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months) on clinical symptoms, biochemical test results, galactose and caffeine elimination half-lives (t1/2), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis. RESULTS: Pruritus improved with UDCA in the 6 patients with pruritus on entry into the study. At 12 months, there was a significant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. After therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) or worsening pruritus (n = 3). Galactose t1/2 increased after 12 months, with no further increases after 24 months of UDCA therapy, whereas caffeine t1/2 did not change. There were no significant changes in hepatic scintigraphy throughout the study. CONCLUSIONS: These data suggest that although UDCA therapy improves pruritus and results in a reduction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with intrahepatic cholestasis.

Small bowel and fecal microbiology in children suffering from persistent diarrhea in Bangladesh.

Bardhan PK. Albert MJ. Alam NH. Faruque SM. Neogi PK. Mahalanabis D.
International Cenre for Diarrhoeal Disease Research, Bangladesh Dhaka.
BACKGROUND: The etiology of persistent diarrhea in children is multifactorial. The objective of the current study was to ascertain the role of microorganisms in the etiology and pathogenesis of persistent diarrhea in a group of children in Bangladesh. METHODS: Enteric pathogens and total aerobic microflora were studied in the duodenal aspirates of 100 children with persistent diarrhea and compared with those in aspirates of 30 children with acute diarrhea, and those in aspirates of 15 healthy control children. The enteric pathogens in the stools of these children and in stools of an additional 38 patients with persistent diarrhea and 12 with acute diarrhea were also studied. RESULTS: Approximately two thirds of the patients with acute diarrhea and persistent diarrhea, and half of the control subjects had more than 10(5) organisms per milliliter of duodenal fluid. Significantly, more patients with persistent diarrhea had a greater variety of flora than did patients with acute diarrhea and control subjects. The predominant organisms in patients with acute diarrhea and in those with persistent diarrhea were Gram-negative rods, whereas those in control subjects were Gram-positive cocci. Significantly more acute diarrhea patients and persistent diarrhea patients had enteric pathogens isolated from stool than did control subjects. Diarrheagenic Escherichia coli, as a whole, were present in significantly more persistent diarrhea patients than in acute diarrhea patients and control subjects. Among diarrheagenic E. coli, enteroaggregative E. coli were significantly associated only with persistent diarrhea. Other organisms significantly associated with persistent diarrhea were Aeromonas spp. and Klebsiella spp. Some patients in the acute diarrhea and the persistent diarrhea groups had the same pathogens isolated from both the duodenal fluid and stool. CONCLUSIONS: In accordance with results of other studies, an association between enteroaggregative E. coli and persistent diarrhea was found in the present study. This suggests that therapy directed against enteroaggregative E. coli can be evaluated for management of some cases of persistent diarrhea.

Dientamoeba fragilis masquerading as allergic colitis.

Cuffari C. Oligny L. Seidman EG.
Department of Pediatrics, Hopital Sainte-Justine, Universite de Montreal, Canada.
BACKGROUND: Dientamoeba fragilis is a rare cause of chronic infectious diarrhea and colitis in children. METHODS: Review of the clinical manifestations, diagnostic methods, and clinical course of D. fragilis infection in our hospital. RESULTS: Eleven pediatric patients are discussed, seven of whom had a history of recent travel. Clinical manifestations of infectious diarrhea included anorexia, intermittent vomiting, abdominal pain, and diarrhea, ranging from 1 to 100 weeks in duration. Peripheral eosinophilia was present in seven patients. One patient with well-documented bovine protein allergy had intermittent episodes of diarrhea and abdominal pain, despite an appropriate elimination diet. Eosinophilic colitis documented by colonoscopy, was due to D. fragilis. Metronidazole was effective in treating five patients, and iodoquinol was effective in treating four others. CONCLUSIONS: D. fragilis should be included in the differential diagnosis of chronic diarrhea and eosinophilic colitis. The identification of this pathogen requires clinical awareness of epidemiologic risk factors and presenting complaints, as well as the laboratory staining procedures essential to its proper identification.

Nitric oxide and inflammatory bowel disease: evidence for local intestinal production in children with active colonic disease.

Levine JJ. Pettei MJ. Valderrama E. Gold DM. Kessler BH. Trachtman H.
Division of Gastroenterology and Nutrition, Schneider Children's Hospital, New Hyde Park, NY 11040, USA.
BACKGROUND: Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients. METHODS: Nitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization. RESULTS: Urinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells. CONCLUSION: Increased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.

Vomiting and gastroesophageal motor activity in children with disorders of the central nervous system.

Ravelli AM. Milla PJ.
Department of Gastroenterology, Institute of Child Health, London, United Kingdom.
BACKGROUND: Vomiting is common in children with disorders of the central nervous system (CNS) and is usually ascribed to gastroesophageal reflux (GER). However, recent acquisitions on the pathophysiology of vomiting suggest that the dysmotility of the foregut may be more widespread. METHODS: Fifty-five children with CNS disorders, 50 of whom suffered from retching and/or vomiting (18 following fundoplication) were studied. We assessed GER by 24 hour pH monitoring and endoscopy, gastric electrical activity by electrogastrography, and gastric half-emptying time (T1/2) of a milk meal be electrical impedance tomography. RESULTS: Of the 50 vomiting patients, 29 had GER (reflux index of 5.7%-87.4%; controls: < 5%), and 31 had gastric dysrhythmias (12 tachyarrhythmia at 5.5-11.2 cpm, 4 bradyarrhythmia at 1.7-1.9 cpm, 15 unstable electrical activity; controls; 2.2-4.0 cpm). Sixteen patients had GER and gastric dysrhythmias. Eleven of 18 patients with fundoplication had gastric dysrhythmias. Gastric T1/2 was delayed in 12 of 13 patients with gastric dysrhythmia (6 with GER), versus 2 of 5 with GER alone. No abnormalities were detected in the 5 patients who did not suffer from vomiting. CONCLUSIONS: Children with CNS disorders who vomit have abnormal gastric motility as often as GER. Following fundoplication, many patients continue to have symptoms possibly related to gastric dysrhythmias, the effects of which may be unmasked by fundoplication. Foregut dysmotility may be related to abnormal modulation of the enteric nervous system by the CNS or to involvement of the enteric nervous system by the same process affecting the brain.

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

Stevens JC. Maguiness KM. Hollingsworth J. Heilman DK. Chong SK.
Section of Pediatric Pulmonology, Indiana University School of Medicine, Indianapolis, USA.
BACKGROUND: In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS: We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS: In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS: Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

A position paper of the North American Society for Pediatric Gastroenterology and Nutrition. Pediatric gastroenterology Workforce Survey and future supply and demand.

Colletti RB. Winter HS. Sokol RJ. Suchy FJ. Klish WJ. Durie PR.
Department of Pediatrics, University of Vermont College of Medicine, Burlington, USA.
BACKGROUND: The North American Society for Pediatric Gastroenterology and Nutrition (NASPGN) performed a Workforce Survey to determine the current number and distribution of pediatric gastroenterologists in the United States and Canada and to estimate the supply and demand in the future in the United States. METHODS: The response rate was more than 90%. There were 624 pediatric gastroenterologists in the United States, and 48 in Canada. RESULTS: There were 2.4 pediatric gastroenterologists per million population in the United States, ranging from 3.1 per million in the Northeast to 1.9 per million in the West, and 1.6 per million in Canada. In the United States, fewer than 5 pediatric gastroenterologists retire each year, but more than 40 fellows per year complete training. In the United States, 30% of pediatric gastroenterologists believe there is already an excess supply; only 12% believe there is a shortage (p < 0.001). CONCLUSIONS: If the number of fellows who complete training each year remains unchanged, in 10 years there will be more than 950 pediatric gastroenterologists in the United States (3.3 per million population). At the same time, if the demand for pediatric gastroenterologists remains 2.4 per million population, there will be a demand for only 675. If these assumptions are correct, it is necessary to reduce the number of fellows to be trained. Although it is difficult to predict future workforce needs reliably, we recommend that the number of fellowship positions in training programs in the United States be reduced by 50% to 75%. Changes in health care in the coming years will be challenging, and effective planning is necessary for pediatric gastroenterologists to achieve their clinical, research, and educational missions.

Reducing parenteral requirement in children with short bowel syndrome: impact of an amino acid-based complete infant formula.

Bines J. Francis D. Hill D.
Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Victoria, Australia.
BACKGROUND: The aim of this study was to assess the impact of an amino acid-based complete infant formula on enteral feeding tolerance and parenteral nutrition requirement in children with severe short bowel syndrome. METHODS: Four children (23 months-4.75 years) with short bowel syndrome who required long-term parenteral nutrition due to persistent feeding intolerance while receiving an extensively hydrolyzed formula were assessed before and after the commencement of an amino acid-based complete infant formula for a mean follow-up period of 48 months (range 39-51 months). Assessment included clinical monitoring of feeding tolerance and nutritional status, biochemistry, stool analysis, skin-prick testing to common food antigens, esophagogastroduodenoscopy and colonoscopy or jejunoscopy with biopsies, and measurement of disaccharidase levels and intestinal permeability. RESULTS: All patients ceased parenteral nutrition within 15 months as a result of decreased stool output and resolution of vomiting. Patients had a reduction in hospitalization (mean: 198 versus 98 days/patient/year), episodes of proven (mean: 4.3 versus 3.3/patient/year) and suspected (mean: 6.5 versus 4.0/ patient/year) bacterial sepsis and central line insertions (mean: 2.5 versus 1.5/patient/year). Intestinal permeability to lactulose fell markedly (mean: 69% versus 2.7%). Disaccharidase levels increased in all three patients undergoing repeat studies. CONCLUSIONS: An amino acid-based complete infant formula improved feeding tolerance and eliminated the need for parenteral nutrition in four children with short bowel syndrome who had previously required long-term parenteral nutrition. The clinical improvement was mirrored by improvement in measurements of intestinal function.

Vitamins A and E serum levels in children and young adults with inflammatory bowel disease: effect of disease activity.

Bousvaros A. Zurakowski D. Duggan C. Law T. Rifai N. Goldberg NE. Leichtner AM.
Combined Program in Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
BACKGROUND: Hypovitaminosis and fat-soluble vitamin deficiency have been reported in adults with inflammatory bowel disease (IBD). A prospective study was undertaken to determine the prevalence of low serum levels of vitamins A and E in children and young adults with IBD. METHODS: Clinical information and serum for vitamin levels was gathered prospectively from 61 patients with Crohn's disease, 36 patients with ulcerative colitis, and 23 control subjects. Disease activity and disease location were determined for IBD patients. Serum retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography. RESULTS: The prevalence of hypovitaminosis A (defined as serum vitamin A < 20 micrograms/dl) or hypovitaminosis E (defined as serum vitamin E < 5 mg/l) was 16% in the pediatric IBD population studied. Low vitamin A levels were more common than low vitamin E levels. Serum retinol levels correlated significantly with alpha-tocopherol levels. Hypovitaminosis was significantly more prevalent in the Crohn's disease patients who had active disease, an erythrocyte sedimentation rate of more than 25 mm/hour, or a serum albumin level less than 3 mg/dl. CONCLUSIONS: Children and young adults with active IBD frequently have low serum levels of vitamin A or vitamin E. The severity of disease activity is a better predictor of risk for hypovitaminosis than is nutritional status. Further work is necessary to determine whether the hypovitaminosis seen in children with IBD reflects true deficiency.

Effect of pancreatic enzymes on zinc absorption in cystic fibrosis.

Easley D. Krebs N. Jefferson M. Miller L. Erskine J. Accurso F. Hambidge KM.
Department of Pediatrics, University of Colorado Center for Human Nutrition, University of Colorado School of Medicine, Denver, USA.
BACKGROUND: The trace metal zinc has a wide range of important physiologic roles. Indirect evidence suggests that fat malabsorption is associated with malabsorption of zinc. The objective of this study was to evaluate the effect of pancreatic enzyme replacement on zinc absorption in children and adolescents with cystic fibrosis. METHODS: Subjects were four boys and four girls ranging in age from 7 to 17 years of age. All were pancreatic insufficient. Stable isotope labels, 70Zn and 67Zn, were administered orally in divided doses on consecutive days with meals. Meals were identical on the first 2 study days. Subjects were randomized to have pancreatic enzyme replacement withheld on the first or second day. All fecal samples were collected quantitatively for 10 days after label administration and were analyzed individually for total zinc and isotopic enrichment using atomic absorption spectrophotometry and fast atom bombardment mass spectrometry, respectively. Fractional absorption of zinc was calculated from cumulative fecal excretion of unabsorbed label. RESULTS: Fractional absorption while receiving enzymes was 0.50 +/- 0.29 versus 0.38 +/- 0.24 while not taking enzymes (p = 0.05). CONCLUSIONS: These results indicate that fractional absorption of zinc is impaired by pancreatic insufficiency in patients with cystic fibrosis, and is improved by exocrine pancreatic enzyme replacement.

Superior mesenteric artery blood flow in children with celiac disease.

Ertem D. Tuney D. Baloglu H. Pehlivanoglu E.
Division of Pediatric Gastroenterology, Marmara University Faculty of Medicine, Istanbul, Turkey.
BACKGROUND: Knowledge of splanchinic hemodynamics in celiac disease is scarce. The hemodynamic parameters of the superior mesenteric artery were evaluated by duplex Doppler ultrasonography in children with celiac disease to show whether histomorphologic changes in small bowel mucosa led to any alteration in splanchinic blood flow. METHODS: The hemodynamic parameters of the superior mesenteric artery were evaluated by Doppler ultrasonography in 23 children with celiac disease. Ten patients were studied at the time of diagnosis. The remaining 13 children were studied after complete clinical and histologic recovery induced by gluten-free diet. Additionally, 9 patients out of 13 who were on a gluten-free diet for about 2 years were given gluten challenge, and superior mesenteric artery blood flow was measured after the challenge. The results were compared with those of healthy children. RESULTS: Peak systolic velocity of the superior mesenteric artery was higher in untreated celiac patients than in healthy controls and treated celiac patients. Peak systolic velocity of the superior mesenteric artery in the treated group of children was close to that of control subjects, implying that successful treatment with gluten-free diet improves hemodynamic changes. The comparison of Doppler ultrasonographic measurements of the challenge group before and after the gluten challenge revealed that the peak systolic velocity, resistive index, and blood flow of the superior mesenteric artery were changed significantly. CONCLUSIONS: The pathophysiologic events in small bowel mucosa during the active phase of celiac disease induce some hemodynamic changes that can be detected noninvasively by duplex Doppler ultrasonography.

Impact of gastroesophageal reflux on growth and hospital stay in premature infants.

Frakaloss G. Burke G. Sanders MR.
Department of Pediatrics, University of Connecticut School of Medicine, Farmington, USA.
BACKGROUND: Gastroesophageal reflux (GER) is associated with failure to thrive in term infants with severe GER; however, this association has not been shown in premature infants. A retrospective case-control study of growth velocities, caloric intake, and length of hospital stay in premature infants with GER was conducted to determine the impact of GER on their growth. METHODS: Twenty-three patients with clinically significant GER were identified from a database containing records for all infants admitted to the University of Connecticut Health Center Neonatal Intensive Care Unit. Patients and control subjects (n = 23) were matched for gestational age, birth weight, gender, and severity of bronchopulmonary dysplasia. Each infant's average weekly weight gain and average weekly caloric intake were calculated, using daily bedside nursing flow sheets. Comparisons were also made of the number of days it took each infant to achieve full oral feedings, number of days from full oral feedings to discharge, and length of hospital stay. RESULTS: There were no significant differences between patients and control subjects for each week in average weekly weight gain, caloric intake, grams gained per calorie given, or weekly increments gained in length and head circumference. There were, however, significant differences in time required to achieve full oral feedings (32 +/- 13 days versus 19 +/- 12 days; p < 0.0008) and length of hospital stay (99 +/- 27 days versus 70 +/- 31 days; p < 0.002) as well as postmenstrual age (PMA) at discharge (43 +/- 3 weeks versus 39 +/- 3 weeks, p < 0.001). CONCLUSIONS: GER did not have a significant impact on caloric intake, effective use of calories, or growth velocities in the study population. It is more likely that the constant monitoring of weight gain and caloric intake while in the intensive care environment protects against the failure to thrive often seen in older infants with GER. Premature infants with GER had a significantly increased length of hospital stay. More aggressive medical management and consideration of alternative feeding strategies may help facilitate discharge for premature infants diagnosed with GER.

Syndrome of intractable diarrhoea with persistent villous atrophy in early childhood: a clinicopathological survey of 47 cases.

Goulet OJ. Brousse N. Canioni D. Walker-Smith JA. Schmitz J. Phillips AD.
Department of Pediatrics, Hopital des Enfants Malades, Paris, France.
BACKGROUND: The syndrome of intractable diarrhoea of infancy is heterogeneous and includes several diseases with diverse aetiologies. This study determines whether diagnostic categories can be defined on the basis of clinicopathological analysis. METHODS: European Society of Paediatric Gastroenterology, Hepatology and Nutrition members were surveyed to identify cases of intractable diarrhoea with persisting small intestinal enteropathy. A retrospective clinicopathological analysis was performed on cases showing life-threatening diarrhoea within the first 24 mo of life and requiring total parenteral nutrition, which were characterized by persistent villous atrophy, and resistance to therapy. RESULTS: Forty-seven infants were identified with intractable diarrhoea. Villous atrophy was of varying degrees with (group I, n = 24) or without (group II, n = 18) lamina propria mononuclear cell infiltration. Group I presented later, had gut autoantibodies, and a higher prevalence of protein-losing enteropathy; a subset (group Ia, n = 12) also had extraintestinal symptoms of autoimmunity associated with a later onset of larger volume diarrhoea. Group II presented early; 8 cases (group IIa) had phenotypic abnormalities and a low birth weight; the remaining 10 (group IIb) showed mild-to-moderate villous atrophy, epithelial tufting, and abnormal crypts. Group III included five patients in whom no specific features were recognised. Twenty-one (45%) died at a median age of 24 months, 20 (43%) remained dependent on parenteral (n = 16) or enteral tube (n = 4) feeding, 4 (9%) received elimination diets plus other therapies, and 2 (4%) were lost to follow-up. CONCLUSIONS: Clinicopathological analysis allowed distinct disease groups to be identified, allowing a provisional classification to be made. This straightforward approach forms a basis for future research in this exceptionally difficult paediatric condition.

Activated protein C resistance in pediatric inflammatory bowel disease.

Levine A. Lahav J. Zahavi I. Raz A. Dinari G.
Division of Gastroenterology and Nutrition, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.

Pediatric duodenal biopsies: mucosal morphology and glycohydrolase expression do not change along the duodenum.

Van Beers EH. Einerhand AW. Taminiau JA. Heymans HS. Dekker J. Buller HA.
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Emma's Childrens Hospital AMC, The Netherlands.
BACKGROUND: Duodenal mucosal biopsies are routinely taken for diagnosis in children with complaints of the upper gastrointestinal tract. Surprisingly, little is known about the usefulness of proximal duodenal versus distal duodenal biopsies for routine diagnostic purposes. This study evaluated the comparability of proximal and distal duodenal biopsies with respect to mucosal morphology as well as glycohydrolase expression as an indicator of intestinal epithelial function. METHODS: Specimens obtained in duodenal endoscopic biopsies from 64 children, ranging in age from 3 months to 18 years with normal or affected mucosa, were studied. Biopsies were performed in anatomically defined regions in the bulbus duodeni (the very proximal part of the duodenum) and distally of the papilla of Vater (distal of the pancreatic duct). Biopsy specimens were paraformaldehyde-fixed for histologic examination and immunohistochemical evaluation or were homogenized to isolate RNA. Crypt/villus morphology was assessed as is routinely determined by pathologists. In addition, several aspects of lactase and sucrase-isomaltase expression as paradigms of intestinal brush border enzymes were assessed: localization at the cellular level, semiquantitative immunohistochemistry, and quantitative measurement of the messenger RNA levels of the respective brush border glycohydrolases. RESULTS: As anticipated, there was a wide interpatient variation in mucosal morphology and expression of lactase and sucrase-isomaltase. Nonetheless, the consistent finding was that in each patient, measurements of morphology and lactase and sucrase-isomaltase gene expression were very similar between samples obtained in the proximal and distal biopsies. CONCLUSIONS: Biopsies performed in either location in the duodenum are equally suitable for diagnostic workup of patients suspected of mucosal abnormalities affecting morphology or small intestinal brush border glycohydrolase activities.

Increased levels of prostaglandins and nitric oxide in esophageal mucosa of children with reflux esophagitis.

Zicari A. Corrado G. Cavaliere M. Frandina G. Rea P. Pontieri G. Cardi E. Cucchiara S.
Dipartimento di Medicina Sperimentale e Patologia, Universita La Sapienza, Rome, Italy.
BACKGROUND: Prostaglandin E2 (PGE2) is said to be both protective and detrimental for esophageal mucosal integrity. Nitric oxide (NO) controls several esophageal neuromuscular functions, including relaxation of the lower esophageal sphincter. The purpose of this study was to verify PGE2 and NO levels in esophageal mucosa of children with reflux esophagitis. METHODS: The patients were 10 children, age range 7 to 12 years, affected by reflux esophagitis. The control subjects were 10 children, age range 6 to 11 years, with recurrent abdominal pain. Tissue fragments obtained by esophageal biopsies were placed in a culture medium and processed to obtain a cell suspension. Cells were incubated for 24 hours at 37 degrees C. Thereafter, supernatants were collected and divided into aliquots to determine the amounts of PGE2 and NO metabolites. RESULTS: Esophageal cells obtained from reflux esophagitis patients synthesize and release a significantly higher (p < 0.01) amount of PGE2 and NO (PGE2 1.9 +/- 0.56 ng/10(6) cells per 24 hours; NO 124.94 +/- 18.36 microM/10(6) cells per 24 hours) than did the control group (PGE2 0.66 +/- 0.14 ng/10(6) cells per 24 hours; NO 68.03 +/- 12.3 microM/10(6) cells per 24 hours). CONCLUSIONS: These results suggest that in esophageal mucosa, PGE2 and NO, in low concentrations, are protective, whereas, at high doses, they can be harmful. Higher amounts of PGE2 and NO in the esophageal mucosa of reflux esophagitis patients suggest that similar noxious stimuli trigger the inducible forms of the respective enzyme.

Discrepancies between males and females with cystic fibrosis in dietary intake and pancreatic enzyme use.

Year 1998
Collins CE. O'Loughlin EV. Henry R.
Department of Nutrition and Dietetics, John Hunter Children's Hospital, New South Wales, Australia.
BACKGROUND: Length of survival of females with cystic fibrosis is worse than it is in males. Results of current research have shown an important correlation among dietary intake, nutritional status, lung function, and survival. The purpose of this study was to explore gender differences in dietary intake and pancreatic enzyme replacement therapy in males and females with cystic fibrosis. METHODS: The study was a cross-sectional measurement of clinical characteristics, energy, and fat intakes in males and females attending the cystic fibrosis outpatients clinics of the John Hunter Hospital, Newcastle, Australia. Twenty-nine subjects, (17 females and 12 males), completed 4-day weighed food records to measure total energy intake and the contribution of macronutrients and to document use of pancreatic enzyme replacement therapy. Energy intake was assessed as the percentage of the recommended energy intake for age and sex. RESULTS: Females with cystic fibrosis had significantly lower energy and fat intakes than males, whereas the females used significantly more pancreatic enzyme replacement therapy. There were no significant differences in clinical characteristics between groups. CONCLUSION: The results support the possibility that gender differences in the energy and fat intakes of older patients may contribute to differential median survival time of males and females with cystic fibrosis.

Gastroesophageal reflux and Nissen fundoplication following percutaneous endoscopic gastrostomy in children.

Year 1998
Sulaeman E. Udall JN Jr. Brown RF. Mannick EE. Loe WA. Hill CB. Schmidt-Sommerfeld E.
Louisiana State University Medical Center, Department of Pediatrics, New Orleans 70112-2822, USA.
BACKGROUND: Abnormal gastroesophageal reflux after percutaneous endoscopic gastrostomy is a serious problem in neurologically impaired children. Protective fundoplication has been advocated. Whether esophageal pH monitoring before percutaneous endoscopic gastrostomy will predict later problems with gastroesophageal reflux is unclear. METHODS: Eighty-five mostly neurologically impaired pediatric patients who underwent percutaneous endoscopic gastrostomy were studied retrospectively regarding complications, success of nutritional rehabilitation, and the incidence of pathologic gastroesophageal reflux. Follow-up period was 1 to 4 years. Twenty-four-hour esophageal pH monitoring was performed in 46 patients before percutaneous endoscopic gastrostomy. RESULTS: There were no deaths. Two major complications occurred that required surgical intervention, and 14 minor complications occurred related to the procedure. Z-scores for weight increased significantly after percutaneous endoscopic gastrostomy. pH probe results were normal in 22 patients (group 1). Five required medical treatment for gastroesophageal reflux after percutaneous endoscopic gastrostomy, but only 1 (5%) later required Nissen fundoplication. pH probe results were abnormal in 24 patients (group 2). Nineteen required medical therapy for gastroesophageal reflux, and 7 (29%) later needed fundoplication (p < 0.05, incidence of fundoplication group 1 vs. group 2). Improvement in Z-scores was similar in patients requiring and not requiring fundoplication. CONCLUSIONS: Percutaneous endoscopic gastrostomy is a safe and effective technique for long-term nutritional support in children. Abnormal gastroesophageal reflux is common. Normal findings in an esophageal pH study before percutaneous endoscopic gastrostomy may be predictive of a favorable outcome with respect to gastroesophageal reflux. This is in contrast to patients with abnormal results in pH studies before percutaneous endoscopic gastrostomy of whom a relatively large percentage may later require fundoplication. Improved nutritional status after percutaneous endoscopic gastrostomy does not appear to have an impact on the severity of gastroesophageal reflux.

Intestinal absorption of ursodeoxycholic acid in children and adolescents with inflammatory bowel disease.

Year 1998
Fujisawa T. Kimura A. Ushijima K. Nakashima E. Inoue T. Yamashita Y. Kato H.
Department of Pediatrics and Child Health, Kurume University, School of Medicine, Asahimachi, Japan.
BACKGROUND: Ursodeoxycholic acid absorption in the proximal intestine may be impaired in patients with inflammatory bowel disease. METHODS: We examined the intestinal absorption of ursodeoxycholic acid by the oral ursodeoxycholic acid tolerance test in 19 children and adolescents with inflammatory bowel disease at various stages, including 8 patients with unoperated Crohn's disease, 3 patients with ileal-resected Crohn's disease, 8 with ulcerative colitis, and 8 healthy control subjects. RESULTS: Ursodeoxycholic acid malabsorption was present in all patients with unoperated Crohn's disease in the first diagnosed active stage, in 3 of 5 patients in a relapsing active stage, and in 2 of 8 patients in remission. Ursodeoxycholic acid absorption was significantly lower in patients in the first diagnosed active stage than in the healthy controls (p < 0.01) or in patients in remission (p < 0.01). There was no significant difference between healthy controls and the patients in a relapsing active stage or in remission. Ursodeoxycholic acid absorption was abnormal during the first postoperative month in patients with ileal-resected Crohn's disease, but normalized over time. Malabsorption of ursodeoxycholic acid was not observed in any patients with ulcerative colitis. CONCLUSIONS: These findings suggest that absorption of ursodeoxycholic acid in the proximal intestine is impaired in patients with Crohn's disease and that the oral ursodeoxycholic acid tolerance test is a convenient and useful means of evaluating the absorption of bile acid in the proximal intestine in pediatric patients with ileal or ileocolic Crohn's disease.

Lack of correlation between genotype and phenotype in celiac disease.

Year 1998
Greco L. Percopo S. Clot F. Bouguerra F. Babron MC. Eliaou JF. Franzese C. Troncone R. Clerget-Darpoux F.
Department of Pediatrics, University of Naples, Italy.
BACKGROUND: Celiac disease has a wide range of clinical features. The goal of this study was to evaluate whether specific HLA genotypes are associated with particular clinical appearances. METHODS: One hundred forty-five patients with confirmed celiac disease were oligotyped for DR and DQ HLA genes. Clinical notes, physical examination, and a questionnaire provided their personal data. Patients were grouped into nine genotypic categories, according to the presence of the specific DQ heterodimer DQA1*0501-DQB1*0201 (hence termed alpha0beta0), in single or double dose, and the presence of the DRB4 antigen. RESULTS: Age at first symptoms and age at beginning of gluten-free diet were not significantly different in the nine groups. The initial symptoms of the disease had a similar distribution in all groups. In twenty-seven patients, disease was diagnosed by family screening: they shared a similar HLA genotype with those who had relevant symptoms. The actual growth status-evaluated by standardized height, percentage of median weight for age, and percentage of median weight for height--was not different in the nine groups. Presence of unusual health complaints was not associated with a specific genotype. CONCLUSIONS: There is no evidence that clinical features of celiac disease are associated with different HLA genotypes. Genes outside the HLA may play a relevant role.

Peptide excretion in celiac disease.

Year 1998
Reichelt WH. Ek J. Stensrud M. Reichelt KL.
Department of Pediatric Research, University of Oslo, Rikshospitalet, Norway.
BACKGROUND: In celiac disease, the mucosa in the small intestine is damaged. This study was conducted to determine whether the normal peptide and protein uptake from the gut is increased in patients with celiac disease. METHODS: The low-molecular-weight peptides were measured in urine from children and adults with untreated celiac disease. A reversed-phase technique was used. RESULTS: The excretion of peptides increased compared with that in an age- and sex-matched reference group. CONCLUSIONS: Celiac patients have hyperpeptiduria. It is possible that some of these peptides are bioactive and may mediate varying systemic effects also found in untreated celiac disease.

Growth of prepubertal children with inflammatory bowel disease.

Year 1998
Saha MT. Ruuska T. Laippala P. Lenko HL.
Department of Pediatrics, Tampere University Medical School, Finland.
BACKGROUND: Growth retardation has been reported in children with chronic inflammatory bowel disease, especially in those with Crohn's disease. Most of these studies concern adolescent patients. METHODS: The growth of 47 prepubertal children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory bowel disease was studied at Tampere University Hospital, Department of Paediatrics. The mean height and height velocity standard deviation scores were calculated at diagnosis and, after that, yearly. The cumulative doses of oral and rectal prednisone per year were calculated. The severity of the disease was scored. The statistical analysis was carried out using the analysis of variance for repeated measurements. RESULTS: During the year preceding the diagnosis, children with inflammatory bowel disease had grown more slowly than their healthy peers. At diagnosis, they were slightly shorter as a group than are healthy children. During treatment and follow-up the mean height velocity of children with inflammatory bowel disease increased (change in the mean height velocity standard deviation scores from -0.84 to +1.08), normalizing the mean heights of these children compared with those of their healthy peers (change in the mean height standard deviation scores from -0.32 to +0.05). In the analysis of covariance, the poorest growth was seen in children with Crohn's disease, scored as severe, and the best growth in children with mild ulcerative colitis. No difference was seen in groups with or without prednisone treatment. CONCLUSIONS: Growth retardation is an important sign of chronic inflammatory bowel disease in prepubertal as well as adolescent children. During treatment, increasing growth velocity brings these children as a group to normal heights for age and sex.

Acute pancreatitis after orthotopic liver transplantation in children: incidence, contributing factors, and outcome.

Year 1998
Tissieres P. Simon L. Debray D. Branchereau S. Soubrane O. Gauthier F. Devictor D.
Unite de Soins Intensifs, Departement de Pediatrie, Hopital de Bicetre, Le Kremlin-Bicetre, France.
BACKGROUND: Acute pancreatitis after orthotopic liver transplantation is a well-known complication in adults that has never been described in children. In adults, end-stage liver disease related to hepatitis B, intraoperative pancreatic injury caused by extensive peripancreatic dissection, the type of biliary anastomosis performed, and numerous drugs, have all been described as predisposing factors in acute pancreatitis after liver transplantation. The current retrospective review was undertaken to identify the incidence, the contributing factors, and the outcome of acute pancreatitis after liver transplantation in children. METHODS: During a 10-year period, 375 children underwent 434 liver transplantations in the authors' institution. In seven patients (1.9%), clinical acute pancreatitis developed after orthotopic liver transplantation. Indication for initial liver transplantation was biliary atresia (n = 3), acute liver failure (n = 3), and type 1 Crigler-Najjar syndrome. In all seven patients, liver graft function was initially adequate. The diagnosis of acute pancreatitis was based on clinical, biochemical, ultrasonographic, and surgical signs. RESULTS: In six patients, acute pancreatitis appeared within the first week after transplantation. The diagnosis was confirmed by abdominal laparotomy in five children. In the current series, emergency liver transplantation (p < 0.001), retransplantations (p < 0.001), and infectious peritonitis (p < 0.001) were contributing factors. Despite supportive measures, three patients died (43%) because of multiple organ dysfunction syndrome. CONCLUSIONS: Acute pancreatitis is an uncommon but life-threatening complication after liver transplantation in children. Early diagnosis and aggressive treatment of infectious complications are major elements in the management of acute pancreatitis after liver transplantation.

Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids.

Year 1998
Liacouras CA. Wenner WJ. Brown K. Ruchelli E.
Division of Gastroenterology and Nutrition, The University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia 19104, USA.
BACKGROUND: The histologic appearance of esophageal eosinophils has been correlated with esophagitis and gastroesophageal reflux disease in children. Esophageal eosinophilia that persists despite traditional antireflux therapy may not represent treatment failure, but instead may portray early eosinophilic gastroenteritis or allergic esophagitis. In this study, a series of pediatric patients with severe esophageal eosinophilia who were unresponsive to aggressive antireflux therapy were examined and their clinical and histologic response to oral corticosteroid therapy assessed. METHODS: Of 1809 patients evaluated prospectively over 2.5 years for symptoms of gastroesophageal reflux, 20 had persistent symptoms and esophageal eosinophilia, despite aggressive therapy with omeprazole and cisapride. These patients were treated with 1.5 mg/kg oral methylprednisolone per day, divided into twice-daily doses for 4 weeks. All patients underwent clinical, laboratory, and histologic evaluation before and after treatment. RESULTS: Histologic findings in examination of specimens obtained in pretreatment esophageal biopsies in children with primary eosinophilic esophagitis indicated significantly greater eosinophilia (34.2+/-9.6 eosinophils/high-power field [HPF]) compared with that in children with gastroesophageal reflux disease who responded to medical therapy (2.26+/-1.16 eosinophils/HPF; p < 0.001). After corticosteroid therapy, all but one patient with primary eosinophilic esophagitis had dramatic clinical improvement, supported by histologic examination (1.5 +/-0.9 eosinophils/HPF, p < 0.0001). CONCLUSIONS: Pediatric patients in a series with marked esophageal eosinophilia and chronic symptoms of gastroesophageal reflux disease unresponsive to aggressive medical antire-flux therapy had both clinical and histologic improvement after oral corticosteroid therapy.

Antineutrophil cytoplasmic antibody subtypes in children and adolescents after ileal pouch-anal anastomosis for ulcerative colitis.

Year 1998
Kaditis AG. Perrault J. Sandborn WJ. Landers CJ. Zinsmeister AR. Targan SR.
Division of Pediatric Gastroenterology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age,

Persistent hepatitis G virus infection after neonatal transfusion.

Year 1998
Woelfle J. Berg T. Keller KM. Schreier E. Lentze MJ.
Children's Hospital, University of Bonn, Germany.
BACKGROUND: Recently two Flaviviridae-like viruses have been discovered and named GB virus C and hepatitis G virus. Molecular characterization showed them to be different subtypes of the same virus. An association with posttransfusion hepatitis and with sporadic and fulminant hepatitis was reported, but most infected people remain asymptomatic. Data concerning hepatitis G virus infection in infants and children have not been reported to date. The prevalence of hepatitis G virus infection in children after transfusion of blood products in the neonatal period was studied. METHODS: Serum samples from 251 children, who had received blood products in the first 4 weeks of life and who had been reexamined as part of another study at a mean interval of 37 months (range, 10-70) after last transfusion, were analyzed for hepatitis G virus infection. Follow-up examinations were performed in 14 of 19 hepatitis G virus-positive children 12 to 17 years after the last transfusion. Presence of hepatitis G virus RNA in serum was determined by a reverse transcription polymerase chain reaction assay with nested primers from the helicase region of the hepatitis G virus. To prove specificity of the hepatitis G virus, reverse transcription polymerase chain reaction assay and compare follow-ups with initial sequences, direct sequencing of the NS3 and NS5 regions of the hepatitis G virus was performed. RESULTS: Hepatitis G virus RNA was detected in 19 of 251 patients (7.6%); sequence analysis showed the isolates to be of hepatitis G virus type. None of the patients with hepatitis G virus infection had evidence of liver disease, although 3 patients were coinfected with hepatitis C virus. Four of 14 patients who were reinvestigated after a mean of 15 years showed persistent hepatitis G virus infection. Each of the 4 children was healthy. In none were clinical signs of liver disease observed; liver function test results were within the normal range. CONCLUSIONS: Children receiving blood transfusions in the neonatal period are at increased risk of hepatitis G virus infection with a high rate of chronic infection. However, as in the findings in several studies of adult transfusion recipients, in the current results, no association between hepatitis G virus infection and clinical or biochemical signs of hepatitis or extrahepatic disease could be seen.

Lipid digestion in cystic fibrosis: comparison of conventional and high-lipase enzyme therapy using the mixed-triglyceride breath test.

Year 1998
De Boeck K. Delbeke I. Eggermont E. Veereman-Wauters G. Ghoos Y.
Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium.
BACKGROUND: Fat maldigestion occurs in most patients with cystic fibrosis. Conventional pancreatic enzyme replacement therapy partially corrects this defect. In this study, the mixed-triglyceride breath test was used to evaluate whether high-lipase enzymes are equivalent to conventional enzymes in improving fat maldigestion in children with cystic fibrosis. METHODS: Fat digestion was studied in 11 patients with a mean age of 10.5 years. The mean intake of conventional enzyme capsules a day was 19. Four 13C mixed-triglyceride tests were performed on separate days and in random order. One test was taken without enzyme substitution, one with three capsules of 8,000 FIP units Creon (pancreatinum, Kali-chemie Pharma, Hannover, Germany) and one with one capsule of 25,000 FIP units. The fourth test was made with 13C octanoic acid to study gastric emptying time. RESULTS: Without enzyme intake, the mean cumulative percentage of 13C dose exhaled after 6 hours was 7.2+/-3.7%. This increased to 14.4+/-4% with intake of conventional pancreatinum and to 14.3+/-5.1% with intake of high-lipase pancreatinum (p = 0.0008 for both; paired t-test). There was no difference between both treatments. Also, the time course of 13C exhalation measured by percentage of 13CO2 exhaled per hour did not differ between enzyme treatments. CONCLUSIONS: The 13C mixed-triglyceride test is noninvasive and documents improved lipid digestion with pancreatic enzyme replacement therapy. If the lipase dose is kept constant, results obtained with high-lipase preparations are equivalent to those obtained with conventional preparations.

T-cells and HLA-class II expression in the large intestine of infants in the early postnatal period.

Year 1998
Ormala T. Rintala R. Savilahti E.
Department of Pediatrics, Kuopio University Hospital, Finland.
BACKGROUND: There is only limited knowledge of the development of the immune responses of the gut in very young infants after exposure to bacterial and food antigens at birth. METHODS: In this study, 49 large intestinal biopsy specimens, which were judged to have normal morphology, were taken from 49 young infants. Eleven patients had Hirschsprung's disease (group 1) and 38 had miscellaneous conditions (group 2). The densities of T cells, their subsets expressing surface antigens CD8 and CD4, and T-cell receptors alpha/beta or gamma/beta were measured, as well as densities of mononuclear and epithelial cells expressing HLA-class II antigens. RESULTS: T-cell densities in groups 1 and 2 were similar. Patients with Hirschsprung's disease had significantly more HLA-DR (p = 0.006) and HLA-DP-expressing cells (p = 0.003) in the lamina propria than did the patients in group 2. In group 1, HLA-DR- (r = 0.58; p = 0.46) and HLA-DP-expressing cells (r = 0.66; p = 0.03) showed a significant positive regression with age in the lamina propria, whereas in group 2, HLA-DR+ cells in the lamina propria showed marked (r = -0.9; p = 0.006) negative regression during the first 1.5 months of life. In contrast to results in previous reports, in the current results, HLA-D region antigens were present in the epithelium in a considerable proportion (up to one fourth) of specimens from the large intestine in both groups. CD3+ (r = -0.59; p = 0.006) and CD4+ (r = -0.64; p = 0.002) cells showed a strong negative regression with age in the lamina propria during the first 2.5 months; and thereafter, there was a weak, insignificant rise in the numbers of these cells. The distribution of CD4+, CD8+, and TCR alpha/beta or gamma/beta T cells of the epithelium of the young infants did not differ significantly from that in the epithelium of adults. CONCLUSIONS: These results show that several significant changes occur in the mucosal immune system during the first few weeks of life.

Functional results of laparoscopic fundoplication in children.

Year 1998
Tovar JA. Olivares P. Diaz M. Pace RA. Prieto G. Molina M.
Department of Pediatric Surgery, Hospital Infantil Universitario La Paz, Madrid, Spain.
BACKGROUND: There is no evidence that the results of laparoscopic fundoplication in children match those of the open procedure. In the current report, pre- and postoperative function of the antireflux barrier is examined in children having laparoscopic fundoplication for gastroesophageal reflux. METHODS: Twenty-seven patients with gastroesophageal reflux, aged 7.2+/-4.5 years, were operated on for unremitting gastrointestinal symptoms (n = 24), with respiratory tract disease (n = 11), cystic fibrosis (n = 2), or brain damage (n = 11). Gastrostomy was added in 5 cases. Barium contrast study, pH-metering, endoscopic examination, and biopsy were performed before and after a median of 19 months (range, 8 to 46) after operation. RESULTS: At diagnosis, 15 of 21 patients had esophagitis that was moderate or severe in 11 (1 with Barrett's esophagus). Symptoms disappeared after fundoplication in all but 2 patients, in whom they became milder. The reflux index decreased from 20.2+/-20% to 4.9+/-9% and became normal in all except 4 children (2 with brain damage and 1 with cystic fibrosis). Open repair of the failed wrap was considered necessary in only 1 of them. CONCLUSIONS: Laparoscopic fundoplication is as effective as the open procedure (14% overall failure rate). However, the failure rate in neurologic patients (18%) suggests that before reaching conclusions on the benefits of this approach, careful long-term assessment of the functional results is necessary.

Celiac disease and Turner syndrome.

Year 1998
Bonamico M. Bottaro G. Pasquino AM. Caruso-Nicoletti M. Mariani P. Gemme G. Paradiso E. Ragusa MC. Spina M.
Department of Pediatrics, University La Sapienza, Rome, Italy.
BACKGROUND: Short stature is one of the features of Turner syndrome and a form of presentation of monosymptomatic celiac disease. METHODS: The recognition of celiac disease in two antiendomysium antibody-positive Turner syndrome girls who did not respond to growth hormone treatment led us to perform as a screening for celiac disease IgA and IgG antigliadin antibodies and antiendomysium antibodies determination in other 35 Turner syndrome patients. Intestinal biopsy was proposed to the antiendomysium antibodies-positive girls; in the former, subtotal villous atrophy was found; in the latter, one parent's consent for intestinal biopsy was not obtained. RESULTS: The prevalence of celiac disease in Turner syndrome patients observed in the present study (8.1 if we consider 3 villous atrophy, 10.8 if we consider 4 antiendomysium antibody-positive) is quite high and seems to indicate that the association of these two disorders could not be coincidental. As to the clinical picture, celiac disease appeared atypical in one case, typical in another one and as a silent form in the third case. Of the 3 cases with villous atrophy on gluten-free diet growth hormone therapy was not effective in two girls, who were older than 16 years, while in the younger patient, detected by the screening, a significant increment of height velocity and height Standard Deviation Score for Chronological Age according to Turner references was observed. CONCLUSIONS: This study suggests that celiac disease can be associated with Turner syndrome and even responsible for a failure of growth hormone therapy. Therefore we propose to perform in Turner syndrome patients antiendomysium antibody determination as a screening followed by intestinal biopsy in positive cases. This would be advisable at least before starting growth hormone treatment.

Serum leptin in children and young adults with inflammatory bowel disease.

Year 1998
Hoppin AG. Kaplan LM. Zurakowski D. Leichtner AM. Bousvaros A.
Combined Program in Pediatric Gastroenterology and Nutrition, Harvard Medical School, Massachusetts General Hospital, Boston 02114-2696, USA.
BACKGROUND: Pediatric inflammatory bowel disease is often associated with growth failure and inadequate energy intake. Although several circulating cytokines are known to be elevated in inflammatory bowel disease, the mechanism for the related anorexia has not been described. Leptin is a newly recognized circulating protein that is an important regulator of appetite and energy metabolism; leptin levels are elevated in several animal models of inflammation. This study was conducted to determine whether serum leptin levels are elevated in young patients with inflammatory bowel disease. METHODS: One hundred twelve children and young adults with Crohn's disease or ulcerative colitis were studied prospectively. Forty-two patients with other gastrointestinal illnesses were used as control subjects. Height, weight, erythrocyte sedimentation rate, serum albumin concentration, and clinical information were collected prospectively, and leptin was measured by radioimmunoassay of stored serum. RESULTS: No significant differences in leptin levels were found among disease groups or control subjects. Body mass index and gender were the only independent predictors of serum leptin in all groups examined. Disease activity varied inversely with serum leptin in patients with Crohn's disease, but these differences were explained entirely by variations in body mass index. CONCLUSIONS: The determinants of serum leptin were the same in young patients with inflammatory bowel disease as in normal populations, indicating that alterations in leptin levels are unlikely to mediate the anorexia and growth failure associated with this disease.

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