bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated Duodenal Mucosal Eosinophils in Children With Dyspepsia: A Pilot Transmission Electron Microscopic Study
Authors: Friesen Craig A. , Andre Linda , Garola Robert , Hodge Charles , Roberts Charles
Published: January 2024

Background

Activated eosinophils can be identified by electron microscopy (EM) Previous studies have shown EM evidence of eosinophil activation in a variety of gastrointestinal conditions associated with inflammation. The purpose of this study was to evaluate the activation state by EM of duodenal mucosal eosinophils in children who presented with dyspepsia and to determine if eosinophils are activated in patients with normal eosinophil counts on routine histology.

Methods

Twenty patients (ages 7–15 years) with dyspepsia were evaluated. All had normal gross endoscopies and Helicobacter pylori was excluded. Each patient had two endoscopic forceps biopsies taken from both the duodenal bulb (DB) and the second portion of the duodenum (DS) for routine histology to determine eosinophil counts. Two additional biopsies were taken from the adjacent mucosa of each site for EM evaluation. The eosinophil activation state was determined for each specimen and a degranulation index was calculated for DB specimens.

Results

On routine histology, peak eosinophil counts were greater than or equal to 20 per hpf in three patients, 11 to 19 per hpf in 12 patients, and less than or equal to 10 per hpf in 5 patients. All patients showed evidence of EM activation on DB specimens and 95% showed activation on DS specimens. The mean degranulation index was 50.5 + 12.0% with 65% of specimens revealing moderate (20 – 60%) degranulation and 30% of specimens revealing extensive (greater than 60%) degranulation.

Conclusions

Eosinophils present in the duodenal mucosa of children with dyspepsia are activated in a significant proportion of patients, even in those with normal eosinophil counts. The degree of degranulation is similar to that seen in other conditions where eosinophils have a pathogenic role.
Protective Effect of Bilirubin in Ischemia‐Reperfusion Injury in the Rat Intestine
Authors: Hammerman C. , Goldschmidt D. , Caplan M. S. , Kaplan M. , Bromiker R. , Eidelman A. I. , Gartner L. M. , Hochman A.
Published: January 2024

Background

Although bilirubin, which crosses the blood–brain barrier, can cause irreversible brain damage, it also possesses antioxidant properties that may be protective against oxidative stress. Intestinal ischemia–reperfusion (IR) injury results in cell destruction, mediated via the generation of reactive oxygen species. Although increased serum bilirubin is correlated with increased antioxidant potential in the face of hyperoxia, evidence of bilirubin‐associated protective effect against IR injury remains nonspecific. We therefore sought to investigate whether hyperbilirubinemia would be protective against IR injury to the intestine.

Methods

Young adult rats were randomly assigned to one of three groups: 1) IR/control (n = 12); 2) IR/hyperbilirubinemia (n = 10), in which IR was generated while the rats were treated with a continuous infusion of bilirubin; and 3) hyperbilirubinemia controls (n = 10). Blood and intestinal tissue samples were obtained to determine serial thiobarbituric acid reducing substances (index of lipid peroxidation) and for xanthine oxidase/xanthine dehydrogenase and glutathione/glutathione disulfide ratios. Intestinal histopathology was graded from 1 (normal) to 4 (severe necrotic lesions).

Results

Histopathologic scoring and circulating and tissue thiobarbituric acid reducing substances were highest in the IR/control animals compared with either the IR/hyperbilirubinemics or the controls. All of these are consistent with the most severe injury in this group. Xanthine oxidase/xanthine dehydrogenase ratios were not significantly different among the groups.

Conclusion

Hyperbilirubinemia ameliorates the extent of intestinal IR injury in our model and appears to act as an antioxidant. This study supports the concept that bilirubin possesses some beneficial properties in vivo, although no direct clinical conclusions can be drawn from these data.
Lactobacillus plantarum Reduces the In Vitro Secretory Response of Intestinal Epithelial Cells to Enteropathogenic Escherichia coli Infection
Authors: Michail Sonia , Abernathy Frank
Published: January 2024

Objective

Enteropathogenic Escherichia coli (EPEC) is a Gram‐negative bacillus that causes diarrhea. Secretory responses of intestinal epithelial cells can be seen after EPEC infection. Probiotics, which are live bacteria that have proven benefit to the host, play a role in the treatment and prevention of the different enteric pathogens. The goals of the study were to determine whether the probiotic agent Lactobacillus plantarum (LBP) strain 299v alters the secretory changes seen in EPEC infection and, if so, what underlying mechanism is possible.

Methods

Caco‐2 cell monolayers were rapidly infected with EPEC strain E2348/69 and immediately mounted in Ussing chambers. The monolayers were exposed to LBP before, after, and simultaneously with EPEC infection. Short circuit current (Isc) was measured in the Ussing chamber.

Results

EPEC infection caused an increase in short circuit current that was reduced by preincubation with LBP (P < 0.01). No direct bactericidal effect was observed, but LBP reduced the attachment of EPEC to Caco‐2 cells.

Conclusion

LBP can play an important role in reducing the secretory change in response to EPEC infection, possibly through inhibition of its binding. However, the presence of the probiotic agent before the infection is necessary. In this setting, its role is more preventive rather than therapeutic.
Histologic Activity of Childhood Chronic Hepatitis B Related to Viremia Levels, Genotypes, Mutations, and Epidemiologic Factors
Authors: Söderström Ann , Norkrans Gunnar , Conradi Nils , Krantz Marie , Horal Peter , Lindh Magnus
Published: January 2024

Background

Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long‐term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults.

Methods

We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non‐Swedish origin.

Results

None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 104.6 copies/mL (mean 103.2); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg‐positive children had a mean HBV DNA level of 108.0 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg‐positive children, and in four and nine HBeAg‐negative children, respectively, without association to liver damage. C‐1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver.

Conclusions

Severe HBeAg‐negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C‐1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.
Intestinal Transport of Insulin‐Like Growth Factor‐I (IGF‐I) in the Suckling Rat
Authors: Philipps Anthony F. , Kling Pamela J. , Grille James G. , Dvořák Bohuslav
Published: January 2024

Objectives

Insulin‐Like Growth Factor‐1 is a potent growth‐promoting peptide that is present in mammalian milk. Previous studies have suggested that milk‐borne IGF‐1 may be absorbed intact from the gastrointestinal tract of the suckling but the mechanism responsible for such transport is not well documented. The present study was designed to investigate in an in vivo suckling rat model whether or not intestinal absorption of IGF‐1 is a saturable phenomenon.

Methods

Suckling rats (10–12 days postnatal age) were studied under anesthesia. A jejunal loop from each rat pup was isolated and injected intraluminally with 1–2 × 105 cpm of rh125I‐IGF‐I. Injections were performed in paired littermates either with or without a preceding injection of unlabeled IGF‐I of 20, 500, or 1000 ng/ml concentration. After flushing, the loops and livers were homogenized and counted in a gamma counter. In addition, homogenates of jejunum and liver were precipitated with trichloroacetic acid (TCA) and the precipitates also counted. In selected instances (jejunum), acid gel chromatography of homogenates was also performed.

Results

Retention of radioactivity was observed in all jejunal specimens, but the pre‐incubation of jejunal loops with unlabeled IGF‐1 was associated with a biphasic response, i.e. at low dose (20 ng/ml) pre‐incubation limited retention of radioactivity, but at a high dose (1000 ng/ml), retention was enhanced (P < 0.05). Linear regression analysis confirmed this inverse relationship. Liver radioactivity followed a similar pattern. Between 40 and 49% of the radioactivity in jejunal and liver homogenates was TCA precipitable. Chromatography of jejunal homogenates showed that approximately 40% of cpm migrated in a position identical with that of intact IGF‐1.

Conclusions

The intestinal uptake of IGF‐1 in the suckling is nonsaturable, confirming previous in vitro studies and suggesting that a nonreceptor‐dependent method of transepithelial transport is important in this process.
Evaluation of Dietary Fiber Intake in Belgian Children With Cystic Fibrosis: Is There a Link With Gastrointestinal Complaints?
Authors: Proesmans M. , De Boeck K.
Published: January 2024

Background

Pancreatic enzyme replacement is the cornerstone of treating pancreatic insufficiency in patients with cystic fibrosis. Additionally, a high‐calorie/high‐fat diet is required to compensate for the increased energy requirement and the incomplete fat digestion. Even with adequate enzyme treatment, gastrointestinal problems, varying from simple constipation to inspissated stools, and distal intestinal obstruction syndrome (DIOS) may occur. Apart from residual fat malabsorption, a low fiber intake is suspected to be an underlying factor in gastrointestinal complaints.

Methods

We evaluated fiber intake in 40 patients with cystic fibrosis based on the dietary history method. Patients were classified according to gastrointestinal problems: group 1, no gastrointestinal complaints; group 2, nonspecific and mild gastrointestinal complaints; and group 3, documented DIOS.

Results

Overall fiber intake was adequate when compared with current recommendations. We could not show a relation between fiber intake and gastrointestinal complaints or DIOS. On the contrary, in patients with DIOS, fiber intake was higher, possibly as a therapeutic response to their gastrointestinal complaints.

Conclusion

Overall fiber intake is adequate in our cystic fibrosis population. We could show no relation between low fiber intake and gastrointestinal problems in our patients with cystic fibrosis.
Enterovirus Infection During Pregnancy is Not a Risk Factor for Celiac Disease in the Offspring
Authors: Carlsson Annelie K. , Lindberg Bengt A. , Bredberg Anders C. A. , Hyöty Heikki , Ivarsson Sten‐A.
Published: January 2024

Background

There is a strong genetic influence on the susceptibility to celiac disease but it is also evident that environmental factors play a role in the development of the disease. Diverging studies about adenovirus infection as a possible triggering factor in the pathogenesis have been reported. Our study was undertaken to determine whether enterovirus infection during pregnancy is a risk factor for the development of celiac disease later in childhood.

Methods

Cord blood from 76 mothers whose children developed celiac disease before 15 years of age were analyzed for IgA, IgG, and IgM antibodies for enteroviruses and Ig‐A endomysium antibodies. The control group comprised cord blood from 327 mothers with children without known celiac disease.

Results

There were no significant differences in antibody titers for enterovirus between the two groups. IgA‐endomysium antibodies were elevated in 3 of the 76 mothers, whereas none had known celiac disease.

Conclusion

This study does not show that enterovirus infection during pregnancy is associated with the development of celiac disease in childhood. Of the mothers whose children developed celiac disease, 4% had Ig‐A endomysium antibodies, which may reflect a silent celiac disease.
Chemical Gastropathy: A Distinct Histopathologic Entity in Children
Authors: Pashankar Dinesh S. , Bishop Warren P. , Mitros Frank A.
Published: January 2024

Background

Chemical gastropathy, also known as chemical or reactive gastritis, is a well‐described histopathologic entity in adults. It is characterized by presence of foveolar hyperplasia, vascular congestion, lamina propria edema, and prominent smooth muscle fibers in the absence of inflammatory cells in the gastric antral mucosa. There are no data in children on this condition.

Methods

All children showing features of chemical gastropathy in antral biopsy specimens were identified from pathology database from 1997 to 2000. Antral biopsy specimens were reviewed to assess the diagnosis of chemical gastropathy using standard diagnostic criteria. Charts of the children diagnosed with chemical gastropathy were reviewed for clinical course, endoscopic findings, and risk factors.

Results

Twenty‐one children (12 male, 9 female) with chemical gastropathy were identified. Common presenting symptoms were epigastric pain and vomiting. Eleven children were taking multiple medications, including nonsteroidal anti‐inflammatory drugs. Endoscopy revealed esophagitis in 12, antral erythema in 7, and thick bile in the stomach in 7 children. Antral histology revealed foveolar hyperplasia in 19, congestion in 20, lamina propria edema and smooth muscle fibers in 16, and absence of inflammation in 19 patients. Acid suppression was the treatment in all patients. Mean follow‐up duration was 11 months in 17 children. Symptoms resolved completely in 11 and partially in 6 patients.

Conclusions

As in adults, chemical gastropathy occurs in children. The factors associated with chemical gastropathy in this survey were gastroesophageal reflux disease and intake of multiple medications, including nonsteroidal anti‐inflammatory drugs.
Helicobacter pylori Genotypes in Israeli Children: The Significance of Geography
Authors: Benenson Shmuel , Halle David , Rudensky Bernard , Faber Joseph , Schlesinger Yechiel , Branski David , Rabinowitz Nina , Wilschanski Michael
Published: January 2024

Background

There is substantial genetic variation among different isolates of Helicobacter pylori, which may affect the clinical outcome. The aims of this study were to find the common H. pylori genotypes in Israeli children and to look for a possible genotype–phenotype correlation.

Methods

Ninety‐eight H. pylori cultures were isolated from antral biopsy specimens of symptomatic Israeli children and were analyzed for vacA and iceA genotype and cagA and cagE status by polymerase chain reaction.

Results

cagA and cagE genes were present in only 25.5% and 24.5%, respectively. The common vacA genotype was s2m2, which was found in 65%. Eleven specimens (11%) contained multiple vacA genotypes. iceA1 was found in 37% and iceA2 in 52% of cases. Both iceA alleles were found in 11%. Increased prevalence of iceA1 and cagE were observed in children with duodenal disease, although it did not reach significance.

Conclusions

The low prevalence of cagA and the high prevalence of vacA genotype s2m2 in Israeli pediatric patients are different from the genotype prevalence reported globally. However, similar findings have been reported in Egypt, indicating a possible geographic influence. There is a possible correlation between duodenal ulcer and cag E and ice A1 genotype, but the power of the study was too low to prove it.
Ribonucleic Acid Hydrolysis by Intestinal Explants of Neonatal Piglets
Authors: Rueda Ricardo , Gómez‐León Carmen , Gil Angel
Published: January 2024

Background

Healthy human adults are able to hydrolyze dietary nucleic acids and nucleotides in the gastrointestinal tract, thus facilitating absorption of the resulting nucleosides. However, little is directly known of the ability of infants to hydrolyze nucleic acids early in life.

Methods

Purified RNA (50, 100, 250, and 500 mg/L) in a suitable medium was exposed to jejunal explants of weaning piglets to determine if enzymes expressed by the explants were sufficient to hydrolyze the nucleic acid. Aliquots from the media were taken at time intervals, from 0 to 6 hours, and assayed for ribonucleoside content by high‐performance liquid chromatography.

Results

The investigators found a significant increase of free ribonucleosides during the study period and for all RNA concentrations tested, thus suggesting that intestinal explants are able to hydrolyze RNA. The kinetics of nucleoside concentrations varied for each nucleoside. For example, inosine increased over the entire 6‐hour period and adenosine increased for the first 2 hours, decreasing afterward.

Conclusions

It is concluded that cells from the intestinal epithelium are capable of hydrolyzing RNA. These results suggest that RNA present in human milk is hydrolyzed in the intestinal tract of the breast‐fed infant, thus providing an additional source of nucleosides. The results indicate that current supplementation of infant formulas with nucleotides should be reconsidered to take into account the contribution of RNA present in human milk to the pool of bioavailable nucleotides.
Dietary Threonine Reduces Plasma Phenylalanine Levels in Patients With Hyperphenylalaninemia
Authors: Sanjurjo P. , Aldamiz L. , Georgi G. , Jelinek J. , Ruiz J. I. , Boehm G.
Published: January 2024

Background

In order to achieve normal intellectual development, the plasma phe‐nylalanine (PHE) levels of patients with hyperphenylalaninemia should not exceed toxic levels. This goal is usually accomplished by employing special diets in which the patient's protein intake is in the form of PHE‐free mixtures of amino acids. There is evidence from our own observations in animals and a preliminary observation in patients with hyperphenylalaninemia that supplemental dietary threonine (THR) might decrease plasma PHE concentrations.

Methods

In this placebo‐controlled crossover study, the effect of supplemental oral THR on the plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was investigated. Before starting the first treatment period of this cross‐over study, the patients were randomly assigned to one of two groups supplemented either with approximately 50 mg THR/kg per day or with a similar amount of maltodextrin as placebo. After a feeding period of 8 weeks and a wash‐out period of 8 weeks, the supplements were crossed over and the study continued for an additional 8 weeks. Blood was obtained at the start and the end of each supplementation period.

Results

Dietary THR supplementation of approximately 50 mg/kg per day resulted in a significant decrease of plasma PHE levels (P = 0.0234). There was a close positive correlation between plasma and urinary PHE concentrations (P < 0.001) indicating that the lower plasma PHE levels in the THR supplemented patients were not caused by higher urinary excretion of PHE.

Conclusions

The data of the present study show that oral THR supplementation has a clear plasma‐PHE‐reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. Although it seems attractive on the basis of the present data to use THR supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.
Lack of Cholesterol‐Lowering Effect of Graded Doses of Cholestyramine in Children With Alagille Syndrome: A Pilot Study
Authors: Larrosa‐Haro Alfredo , Sáenz‐Rivera Cecilia , González‐Ortiz Manuel , Coello‐Ramírez Pedro , Vázquez‐Camacho Gonzalo
Published: January 2024

Background

There is controversy about the potential risk of sustained high concentrations of cholesterol and triglyceride in patients with cholestatic chronic liver disease. However, it is currently accepted that cholesterol‐lowering therapy may reduce morbidity and mortality rates in hypercholesterolemic patients without preexisting coronary heart disease, as well as in those with coronary heart disease. The objective of this study was to evaluate the effect of cholestyramine on the serum lipid profile of a group of children with Alagille syndrome and hypercholesterolemia.

Methods

Five children with Alagille syndrome and basal serum cholesterol concentrations greater than 230 mg/dL were included. Total serum cholesterol, triglyceride, low‐density, and high‐density lipoprotein cholesterol concentrations were measured on days 0, 10, 20, and 30 after the administration of oral cholestyramine 100, 250, and 500 mg(kg·d), respectively. Lipid fractions were reported as mean ± 1 SD. Statistical analysis was performed with Friedman analysis of variance.

Results

The basal values and those of the three 10‐day subsequent 100‐, 250‐, and 500‐mg(kg·d) cholestyramine periods were as follows: total cholesterol: 327.6 ± 77.1, 305.4 ± 52.1, 290.6 ± 24.1, and 320.6 ± 32.3, respectively (P = 0.668); triglyceride: 136.4 ± 14.6, 144.8 ± 41.3, 161 ± 30.9, and 165.4 ± 40.7, respectively (P = 0.356); low‐density lipoprotein cholesterol: 245.4 ± 57.8, 239.8 ± 48.6, 242.2 ± 68.6, and 246.4 ± 49.5, respectively (P = 0.782); and high‐density lipoprotein cholesterol: 44.4 ± 11.2, 41.8 ± 12.8, 44.6.2 ± 13.2, and 47 ± 8.5, respectively (P = 0.431).

Conclusion

Under the conditions of the current study, no significant effect of variable doses of cholestyramine could be demonstrated on the serum lipid profile of a series of children with Alagille syndrome. While the controversy on the potential atherogenic risk of low‐density lipoprotein hypercholesterolemia in patients with chronic liver disease persists, new, prospective pharmacologic or nutritional trials are required.
Tissue Transglutaminase Immunoglobulin Isotypes in Children With Untreated and Treated Celiac Disease
Authors: Agardh Daniel , Borulf Stefan , Lernmark Åke , Ivarsson Sten A.
Published: January 2024

Objectives

Tissue transglutaminase (tTG) autoantibodies are serologic markers for celiac disease (CD). The aim was to determine the diagnostic sensitivity and specificity of different immunoglobulin isotypes against tTG.

Methods

Immunoglobulin A (IgA)‐tTG, IgG‐tTG, and IgG1‐tTG were measured in radioligand binding assays in 67 children with untreated and 89 children with treated CD and compared with 48 biopsy controls. IgM‐tTG was measured in children with untreated CD and in biopsy controls. IgA endomysial autoantibodies (EMA) were analyzed in all children using an immunofluorescence method.

Results

The sensitivity of IgA‐tTG and IgG‐tTG was 85.1% (57 of 67) and 83.6% (56 of 67), respectively, which both increased to 93.8% (45 of 48) in children diagnosed at age 2 years or older. Both had a specificity of 93.8% (45 of 48). IgA‐EMA had a sensitivity of 80.6% (54 of 67) and a specificity of 91.7% (44 of 48). In treated CD, IgA‐tTG and IgG‐tTG were detected in 21.3% (19 of 89) and in 14.6% (13 of 89), respectively, despite negative EMA titers. IgG1‐tTG was correlated to age (r = −0.47, P = 0.0005) and detected in 50.7% (34 of 67) with untreated CD compared with 11.2% (10 of 89) with treated CD and with 4.2% (2 of 48) of biopsy controls (P < 0.0001, respectively). IgM‐tTG was detected in 1.5% (1 of 67) with untreated CD and in none of biopsy controls.

Conclusion

IgA‐tTG and IgG‐tTG analyzed in radioligand binding assays are equivalent to IgA‐EMA as screening tests for CD during childhood, but an intestinal biopsy is still the method of choice to establish the diagnosis. Although IgG1‐tTG was more common at young age of diagnosis, both IgG1‐tTG and IgM‐tTG had low specificity and sensitivity and may not be useful as screening tests for CD.
Mesenterico‐Left Portal Vein Bypass in Children With Congenital Extrahepatic Portal Vein Thrombosis: A Unique Curative Approach
Authors: Fuchs Jörg , Warmann Steven , Kardorff Rüdiger , Rosenthal Herbert , Rodeck Burkhard , Ure Benno , Melter Michael
Published: January 2024

Objectives

Current management of extrahepatic portal vein thrombosis (EPVT) comprises endoscopic eradication therapy of esophageal varices and conventional shunt surgery. The authors have used the novel technique of mesenterico‐left portal bypass (Rex shunt) in seven children with symptomatic EPVT, and report their results here.

Methods

Median age of the children was 12 years (range, 2–16 years). All children had portal hypertension with hypersplenism and recurrent bleeding from esophageal varices. Furthermore, one patient suffered from a severe hepatopulmonary syndrome. Preoperative evaluation included liver function tests, liver biopsy, hepatic duplex ultrasonography, and radiologic evaluation of the intrahepatic and extrahepatic vascular anatomy. The internal jugular vein was used as vein graft in all patients.

Results

Median follow‐up period was 15 months (range, 3–28 months). Ultrasound scans revealed sufficient perfusion in all shunts (median, 35 cm/s; range, 28–60 cm/s). The intrahepatic portal perfusion in segment 4 improved from a median of 6 cm/s before surgery to 18 cm/s postoperatively. The platelet count increased within 3 months from a mean of 50,625/μL to 137,750/μL. The clinical signs of hypoxemia in the child with hepatopulmonary syndrome disappeared within 6 months.

Conclusions

In accordance with the limited experience published by others, the authors' data confirmed the mesenterico‐portal Rex shunt as the therapy of choice for children with EPVT. Furthermore, this report is the first to show that a hepatopulmonary syndrome can be abolished by mesenterico‐portal Rex shunt.
The Insulin‐Like Growth Factor Axis in Children With Inflammatory Bowel Disease
Authors: Corkins Mark R. , Gohil Ajay D. , Fitzgerald Joseph F.
Published: January 2024

Background

The insulin‐like growth factor (IGF) axis consists of two IGFs and six IGF‐binding proteins (IGFBPs) that regulate proliferation and differentiation of many cell types. Malnutrition and inflammation alter the IGF axis. The authors evaluated circulating IGFs and IGFBPs in patients with inflammatory bowel disease (IBD) at the time of presentation and compared them with values obtained during remission.

Methods

Seventeen newly diagnosed pediatric IBD patients were studied on presentation and during remission. Nutritional status was assessed by body mass index (BMI) and serum protein assay. The Lloyd‐Still and Green IBD clinical scoring system was used. IGF‐I and IGF‐II levels were measured by radioimmunoassay, and IGFBP‐3 levels were measured by immunoradiometric assay. IGFBPs were quantified on ligand blots with a PhosphorImager.

Results

Body mass index and IBD clinical scores improved after treatment: 18.7 ± 3.0 versus 21.3 ± 3.0 kg/m2 (P = 0.023) and 74.6 ± 16.7 versus 93.1 ± 7.4 (P < 0.001), respectively. Protein changes were insignificant. IGFBP‐3 levels increased from time of first evaluation to remission: 3,470 ± 850 versus 4,700 ± 473 ng/mL (P < 0.001). The ratio of IGFBP‐3 to IGFBP‐2 increased from first evaluation to remission: 1.7 ± 1.9 versus 3.9 ± 1.9 (P = 0.003). IGF‐I and IGF‐II levels also increased: 139 ± 167 versus 223 ± 118 ng/mL (P = 0.011) and 307 ± 111 versus 386 ± 73 ng/mL (P = 0.007), respectively.

Conclusions

Circulating IGFBP‐3 levels were low during active IBD and increased at remission in parallel with the IGF‐I levels. The IGFBP‐3 to IGFBP‐2 ratio was altered in the presence of active disease in a manner that would reduce IGF‐I action. This abnormality improved after treatment.
Enteropathogenic Escherichia coli: Stimulating Neutrophil Migration Across a Cultured Intestinal Epithelium Without Altering Transepithelial Conductance
Authors: Michail Sonia K. , Halm Dan R. , Abernathy Frank
Published: January 2024

Introduction

Migration of neutrophils across the intestinal epithelium is the hallmark of inflammatory conditions of the bowel. In cultured intestinal epithelial monolayer models, neutrophils can be induced to migrate along a chemotactic gradient such as n‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP). Physical passage of the neutrophils across the epithelium could disrupt the tight‐junctions, possibly leading to a large increase in the transepithelial conductance (Gt). The goal of this study is to determine whether transepithelial migration of neutrophils induced by enteropathogenic Escherichia coli (EPEC) causes changes in Gt comparable with those seen with fMLP.

Methods

The apical side of T84 monolayers were rapidly infected with EPEC E2348/69 or exposed to 1μM fMLP. A third group of monolayers exposed to neither EPEC nor fMLP served as control. Indium‐labeled neutrophils were added to the serosal side of monolayers grown on a cell culture insert membrane (12 μm pores). Gt was measured at fixed intervals up to 4 hours. After a 150‐minute incubation, radioactivity of the neutrophils that migrated to the apical side was assayed and the number of migrating neutrophils was calculated.

Results

At 150 minutes, EPEC induced similar neutrophil chemotactic capability compared to fMLP (231 ± 34 · 103 and 193 ± 48 · 103, respectively, n = 13, P > 0.05). However, EPEC‐induced neutrophil migration was not associated with significant increase in Gt, 1.13 ± 0.16 fold of baseline Gt, in distinction with fMLP groups, 13.3 ± 0.48 fold, n = 7 (P < 0.05). Gt changes with EPEC were seen after 4 hours of infection, but were not different in the presence or absence of neutrophil migration (1.37 ± 0.12 fold and 1.42 ± 0.17 fold of baseline Gt, respectively).

Conclusions

The results indicate that EPEC‐induced neutrophil migration can occur without significant disruption of barrier function. In addition, the chemo‐attractant recruiting neutrophils during EPEC infection is unlikely to be fMLP; and, the Gt increase seen with fMLP‐driven recruitment may indicate a discretionary compromise of barrier function during neutrophil migration.
Hepatic Dysfunction Following the Fontan Procedure
Authors: Narkewicz Michael R. , Sondheimer Henry M. , Ziegler James W. , Otanni Yvonne , Lorts Angela , Shaffer Elizabeth M. , Horgan J. Gerard , Sokol Ronald J.
Published: January 2024

Objectives

The Fontan procedure offers a palliation for the hemodynamic derangements associated with congenital heart lesions characterized by a single functional ventricle, but it causes a chronically elevated systemic venous pressure that may result in hepatic congestion. The objective of this study was to characterize hepatic function and its relationship to cardiac function in children who had undergone the Fontan procedure.

Methods

In a cross‐sectional study of 11 children aged 38 months to 216 months (mean, 149 months), the authors evaluated indices of cardiac and hepatic function, including galactose clearance, Doppler hepatic ultrasonography, synthetic function, and markers of liver injury, at 9 months to 176 months (mean, 100 months) after children had undergone the Fontan procedure.

Results

The most common biochemical abnormality of hepatic function was a prolongation of the prothrombin time and a low factor V level. There was a trend toward progressive abnormality in prothrombin time with increasing interval since the Fontan procedure. Galactose elimination half‐life and galactose elimination capacity were inversely correlated with the time after Fontan (R2 = 0.65, P = 0.004). There was no relationship between cardiac functional measurements and liver function.

Conclusions

Prothrombin time and galactose elimination half‐life are abnormal in children who have undergone the Fontan procedure and may be useful markers of hepatic function in the longitudinal assessment of these patients.
Effects of Oral Lactobacillus GG on Enteric Microflora in Low‐Birth‐Weight Neonates
Authors: Agarwal Ramesh , Sharma Nidhi , Chaudhry Rama , Deorari Ashok , Paul Vinod K. , Gewolb Ira H. , Panigrahi Pinaki
Published: January 2024

Background

Colonization patterns, especially by anaerobic flora, may play an important role in neonatal gut function. Probiotics could affect disease risk either directly through colonization or indirectly by promoting changes in gut microbial ecology.

Methods

To study the ability of Lactobacillus GG (LGG) to colonize the neonatal gut and modify its microbial ecology, a prospective, randomized study was performed in 71 preterm infants of less than 2000 g birth weight. Infants less than 1500 g (24 treated, 15 control) received 109 LGG orally twice daily for 21 days. Those infants weighing 1500 to 1999 g (23 treated, 9 control) were treated for 8 days. Stools were collected before treatment and on day 7 to 8 (and day 14 and 21, in the infants weighing less than 1500 g) for quantitative aerobic and anaerobic cultures.

Results

Colonization with LGG occurred in 5 of 24 (21%) infants who weighed less than 1500 g versus 11 of 23 (47%) in larger infants. Colonization was limited to infants who were not on antibiotics within 7 days of treatment with LGG. There was a paucity of bacterial species at baseline, although larger infants had more bacterial species (1.59 ± 0.13 (SEM) vs 1.11 ± 0.12;P < 0.03) and higher mean log colony forming units (CFU) (8.79 ± 0.43 vs 7.22 ± 0.63;P < 0.05) compared with infants weighing less than 1500 g LGG. Treatment in infants weighing less than 1500 g resulted in a significant increase in species number by day 7, with further increases by day 21. This increase was mainly the result of increased Gram (+) and anaerobic species. No difference in species number was noted in controls. Mean log CFU of Gram (−) bacteria did not change in treated infants weighing less than 1500 g. However, Gram (+) mean log CFU showed a significant increase on day 21 (6.1 ± 0.9) compared with day 0 (3.5 ± 0.9) (P < 0.05). No significant changes in species number or quantitative counts were noted after LGG treatment in the infants weighing 1500 to 1999 g LGG was well tolerated in all infants.

Conclusion

The neonatal response to a probiotic preparation is dependent on gestational and post‐natal age and prior antibiotic exposure. Although LGG is a relatively poor colonizer in infants, especially those infants weighing less than 1500 g at birth, it does appear to affect neonatal intestinal colonization patterns.
Feeding Behavior Problems in Children With Cystic Fibrosis in the UK: Prevalence and Comparison With Healthy Controls
Authors: Duff Alistair James Aitken , Wolfe Susan Pamela , Dickson Corrine , Conway Steven Phillip , Brownlee Keith Graham
Published: January 2024

Background

Feeding behavior problems contribute to inadequate dietary intake for many patients with cystic fibrosis (CF). However, to establish effective intervention programs, more needs to be known about the occurrence and distribution of these difficulties. The aims of this study were to establish the prevalence and range of disruptive child behaviors (DCB) in patients with CF and the inappropriate parental responses (IPR) during mealtimes and to compare the results with those of healthy children.

Methods

In study A, parents of 108 patients (aged 1–7 years) completed a Behavioural Paediatric Feeding Assessment Scale comprising two domains: DCBs and IPRs during mealtimes. Parents rated the frequency of the behaviors and responses and identified those they considered problematic. In study B, data from the CF group (n = 69, aged 1–12 years) were compared with 69 age‐ and sex‐matched control subjects.

Results

Parents of children with CF aged 5 to 8 years recorded significantly more DCBs than those in all other age ranges. These parents also reported significantly more IPRs than did parents of children aged 9 to 12 years and 13 to 17 years. Parents of children with CF reported significantly more DCBs and IPRs than did those of the control subjects. There were significantly more problematic DCBs and IPRs in the CF group than in the control group for children aged 5 to 8 years and 9 to 12 years but not for those aged 1 to 4 years.

Conclusions

Parents of children with CF report more feeding behavior problems than do those of healthy control subjects. The high prevalence of feeding behavior problems in older children suggests that preventative and reactive interventions must continue throughout childhood and vary according to the child's developmental abilities.
Culturing Helicobacter pylori from Clinical Specimens: Review of Microbiologic Methods
Authors: Ndip Roland N. , MacKay William G. , Farthing Michael J. G. , Weaver Lawrence T.
Published: January 2024

Helicobacter pylori is probably the most common chronic bacterial infection of humankind, and is usually acquired first in childhood. Microbiologic culture of H. pylori is the “gold standard” for diagnosis in a patient with suspected infection. Although not currently recommended for routine use, culture allows testing for susceptibility to antimicrobials, especially in populations with a high prevalence of drug resistance. Gastric biopsies are the specimens most commonly used to culture H. pylori, but stool, vomitus, saliva, and dental plaque offer opportunities. This review examines the current methods used to culture H. pylori from biologic specimens and suggests useful hints to enhance its recovery rate.
Low Plasma Cholecystokinin Levels in Colicky Infants
Authors: Huhtala Virpi , Lehtonen Liisa , Uvnäs‐Moberg Kerstin , Korvenranta Heikki
Published: January 2024

Objectives:

Cholecystokinin (CCK) plays an important role in postprandial gallbladder contraction and may also have pacifying behavioral effects, such as inducing satiety and calming in infants. The authors hypothesized that colicky infants have impaired CCK secretion, which contributes to their gallbladder hypocontractility (reported earlier) and excessive crying.

Methods:

Cholecystokinin levels of 40 colicky and 37 control infants were evaluated at a mean of age 5 weeks. Plasma CCK levels were drawn before, immediately after, and 1 hour after a regular milk feeding and analyzed using radioimmunoassay (RIA). The contraction of the gallbladder was calculated using ultrasound measurements before and 1 hour after the feeding. The two‐tail t test for independent samples was used to test continuous data.

Results:

The preprandial and 1‐hour postprandial plasma levels of CCK were lower in the colicky infants than in the control subjects (P < 0.05). The immediate postprandial CCK levels were also lower in the colicky infants, although this difference did not reach a statistical significance. The proportion of gallbladder contractions did not differ between the study groups.

Conclusions:

The authors conclude that low CCK levels in colicky infants may predispose them to excessive crying in the absence of the calming effect of CCK.
Correlation Between Helicobacter pylori Infection and Vitamin C Levels in Whole Blood, Plasma, and Gastric Juice, and the pH of Gastric Juice in Korean Children
Authors: Park Jae H. , Kim Su Y. , Kim Dong W. , Lee Woo G. , Rhee Kwang H. , Youn Hee S.
Published: January 2024

Background:

It is well known that chronic gastritis induced by Helicobacter pylori may be associated with hypochlorhydria and may also be accompanied by low levels of vitamin C in plasma and gastric juice in adults. This study investigates the relationship between H. pylori infection and vitamin C levels in the blood, plasma and gastric juice and the gastric juice pH of Korean children.

Methods:

During a 5‐year period, multiple gastric antral biopsies were taken from 452 children who underwent gastroduo‐denoscopy. The biopsy specimen was inoculated into phenol red buffered urea broth and incubated for 48 hours to detect color changes. The histopathologic findings were evaluated using the Sydney System. Concentrations of vitamin C in whole blood, plasma, and gastric juice aspirate were measured using the 2,4‐dinitrophenylhydrazine method.

Results:

Four hundred fifty‐two patients (228 boys, 224 girls) aged 1 to 15 years were enrolled in this study. H. pylori was detected in 112 patients (24.8%) using histology, whereas it was found in 204 patients (45.1%) using the urease test. One hundred seven patients (23.7%) had active gastritis, and 421 patients (93.1%) had chronic gastritis. Vitamin C levels in whole blood, plasma, and gastric juice exhibited significant negative correlation with the age of patients, the histologic density of H. pylori, the degree of active and chronic gastritis, and the severity of H. pylori infection (based on urease positivity and histologic density of H. pylori). Gastric juice pH was correlated with the degree of chronic gastritis and was significantly higher in urease‐positive patients.

Conclusions:

The data demonstrate that vitamin C levels in whole blood, plasma, and gastric juice and the gastric juice pH in Korean children are closely related to the severity of H. pylori infection and the histologic changes in the stomach. These data suggest that vitamin C may play a role in determining infection and progression, and vitamin C supplementation may be an important axis for the management of H. pylori infection in children. JPGN 37:53‐62, 2003.
Intestinal Protein Loss and Hypoalbuminemia in Children with Pneumonia
Authors: Klar Aharon , Shoseyov David , Berkun Yaakov , Brand Abraham , Braun Jacques , Shazberg Gila , Jonathan Moise , Gross‐Kieselstein Eva , Revel‐Vilk Shoshana , Hurvitz Haggit
Published: January 2024

Background

Intestinal protein loss has been reported mainly in diseases affecting the gastrointestinal tract. Intestinal protein loss during pneumonia with effusion has not been reported to date. The authors attempted to assess the associations between pneumonia with effusion and intestinal protein loss and hypoalbuminemia in children.

Methods

This was a prospective consecutive case series study of in children hospitalized with pneumonia and effusion during a period of 4½ years. Serum albumin, C‐reactive protein (CRP), and fecal α‐1 antitrypsin (α‐1‐AT) were measured in the first 72 hours of hospitalization. Two control groups were studied: one consisted of 50 febrile children hospitalized because of viral or mild bacterial infections, and the other consisted of 20 afebrile children hospitalized because of convulsive disorders.

Results

Sixty‐seven children ages 4 months to 14 years hospitalized with pneumonia and effusion were enrolled in the study. Fifty‐nine percent (40 children) were found to have elevated fecal α‐1‐AT excretion (range, 2–10 mg/g) compared with none in the two control groups (P < 0.000).

Fifty‐two percent (35 children) of the children with pneumonia and effusion had mild to moderate hypoalbuminemia (range, 22–34 g/L). Only one child (2%) in the febrile control group had a low albumin of 34 g/L; none were found in the afebrile control group. The level of fecal α‐1‐AT was inversely correlated with serum albumin level.

Conclusions

Pneumonia with effusion in children is often associated with an intestinal protein loss that can be monitored by measuring gastrointestinal loss of protein, namely fecal α‐1‐AT. In most cases the development of hypoalbuminemia correlates with the development of intestinal protein loss.
No Association of CTLA4 Gene With Celiac Disease in the Basque Population
Authors: Martín‐Pagola Ainhoa , de Nanclares Guiomar Pérez , Vitoria Juan C. , Bilbao J. Ramón , Ortiz Lourdes , Zubillaga Paul , Castaño Luis
Published: January 2024

Background

Celiac disease (CD) is an autoimmune disorder caused by intolerance to ingested gluten that develops in genetically susceptible individuals. The contribution of human leukocyte antigen (HLA) genes to the genetic risk to CD has been known for a long time; however, non‐HLA genetic factors are likely to be required for the development of the disease. Several studies have associated the CD28/CTLA4 region on chromosome 2q33 with the disease in different populations. The CTLA4 gene encodes a receptor involved in the control of T‐cell proliferation and mediates T‐cell apoptosis.

Aim

To determine the contribution of two polymorphisms of the CTLA4 to the disease: the A/G dimorphism at position +49 in exon 1 and the (AT)n microsatellite in the 3´ untranslated region.

Patients

Forty‐one celiac families of Basque origin (43 patients with CD and 80 first‐degree relatives).

Methods

Restriction enzyme digestion of polymerase chain reaction amplified genomic DNA for the A/G dimorphism and polymerase chain reaction followed by high‐resolution electrophoresis for the (AT)n microsatellite. For disease association studies, the Affected Family Based Controls approach was used.

Results

The frequency of the A allele of 49 A/G polymorphism was 67.47% in the celiac allele group compared with 70.13% in the Affected Family Based Controls group. These differences were not significant. Analysis of the (AT)n polymorphism identified 17 different alleles, ranging from 262 to 312 bp in length, but no allele was significantly associated with the disease.

Conclusions

Our results did not show any evidence of association of any of the CTLA4 gene polymorphisms with the disease. This may result from population‐specific differences in genetics and environmental susceptibility to CD.
A Human Flora‐Associated Rat Model of the Breast‐Fed Infant Gut
Authors: Edwards Christine A. , Rumney C. , Davies M. , Parrett A. M. , Dore J. , Martin F. , Schmitt J. , Stahl B. , Norin E. , Midtvedt T. , Rowland I. R. , Heavey P. , Köhler H. , Stocks B. , Schroten H.
Published: January 2024

Objectives

Bacterial colonization of the infant gut may have important influences on the development of gastrointestinal, respiratory, and allergic disease. Early diet is a major determinant of the gut microflora. It is very difficult to carry out studies in human infants that can investigate the interaction of diet, flora, and mucosa. In this study we have developed an infant human flora‐associated (IHFA) rat model to allow such investigation.

Methods

Germ‐free infant rats were infected with fecal bacteria from exclusively breast‐fed infants and were maintained on a modified infant formula for 8 weeks. The fecal and cecal contents were collected and compared with feces of breast‐fed infants for bacterial populations, bacterial metabolites, and enzymes and for the ability to inhibit adhesion of pathogenic bacteria to human mucosal cells.

Results

The IHFA cecum and feces were dominated by lactic acid bacteria, Bifidobacterium, and lactobacilli, which were representative of the infant feces. The fecal short‐chain fatty acid profile was dominated by acetic and lactic acid in a similar manner to human infant feces. Other bacterial metabolites were similar to those of the human infant. Rat intestinal samples were able to inhibit the adhesion of pathogens to mucosal cells, but to a lesser extent than the human samples.

Conclusions

This IHFA infant model of the intestinal flora of the breast‐fed infant is considered valid for studying the effect of diet on bacterial colonization and metabolism.