bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackgroundThere 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.MethodsCord 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.ResultsThere 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.ConclusionThis 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

ABSTRACTBackgroundChemical 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.MethodsAll 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.ResultsTwenty‐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.ConclusionsAs 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

ABSTRACTBackgroundThere 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.MethodsNinety‐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.ResultscagA 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.ConclusionsThe 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

ABSTRACTBackgroundHealthy 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.MethodsPurified 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.ResultsThe 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.ConclusionsIt 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

ABSTRACTBackgroundIn 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.MethodsIn 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.ResultsDietary 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.ConclusionsThe 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

ABSTRACTBackgroundThere 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.MethodsFive 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.ResultsThe 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).ConclusionUnder 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

ABSTRACTObjectivesTissue 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.MethodsImmunoglobulin 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.ResultsThe 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.ConclusionIgA‐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

ABSTRACTObjectivesCurrent 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.MethodsMedian 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.ResultsMedian 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.ConclusionsIn 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

ABSTRACTBackgroundThe 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.MethodsSeventeen 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.ResultsBody 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.ConclusionsCirculating 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

ABSTRACTIntroductionMigration 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.MethodsThe 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.ResultsAt 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).ConclusionsThe 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

ABSTRACTObjectivesThe 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.MethodsIn 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.ResultsThe 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.ConclusionsProthrombin 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

ABSTRACTBackgroundColonization 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.MethodsTo 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.ResultsColonization 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.ConclusionThe 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.