bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton Pump Inhibitors in Pediatrics: Relevant Pharmacokinetics and Pharmacodynamics
Authors: Kearns Gregory L. , Winter Harland S. 
Published: January 2024

ABSTRACTA marked discordance between the disposition of proton pump inhibitors (PPIs) in plasma and the kinetics of effect suggests the need for new approaches to characterize the clinical pharmacology of PPIs in infants and children. An assessment of pharmacokinetics and pharmacodynamics must take into account the genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the PPIs and, thus, their plasma clearance. In addition, the potential effects of extemporaneous formulations of the drugs on their rate and extent of absorption must be considered. Because of the apparent safety of PPIs and a well‐demonstrated dose–response–effect relationship in adults, pediatric pharmacokinetic data and an exposure correlate, such as the dose–area‐under‐the‐plasma‐concentration‐versus‐time‐curve relationship, can be used as a bridge to determine pediatric dosing.
Autonomic Neuropathy and Gastrointestinal Motility Disorders in Children and Adolescents With Type 1 Diabetes Mellitus
Authors: Vazeou A. , Papadopoulou A. , Papadimitriou A. , Kitsou E. , Stathatos M. , Bartsocas C. S. 
Published: January 2024

ABSTRACTIntroductionThere is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM).MethodsThe authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non‐T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age‐ and gender‐matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth‐to‐anus transit time (MATT) were measured in patients with CD and CC, respectively.ResultsCAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non‐T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03).ConclusionAutonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.
Supplementary Feeding of Underweight, Stunted Malawian Children With a Ready‐To‐Use Food
Authors: Maleta Kenneth , Kuittinen Juha , Duggan Maureen B. , Briend André , Manary Mark , Wales Jerry , Kulmala Teija , Ashorn Per 
Published: January 2024

ABSTRACTObjectiveMaize and soy flour mixes are often used in the treatment of moderate malnutrition in Malawi. Their efficacy has not been formally evaluated. A recently developed ready‐to‐use food (RTUF) effectively promotes growth among severely malnourished children. The authors compared the effect of maize and soy flour with that of RTUF in the home treatment of moderately malnourished children.MethodsSixty‐one underweight, stunted children 42 to 60 months of age were recruited in rural Malawi, in southeastern Africa. They received either RTUF or maize and soy flour for 12 weeks. Both supplements provided 2 MJ (500Kcal) of energy daily but had different energy and nutrient densities. Outcome variables were weight and height gain and dietary intake.ResultsBefore intervention, the mean dietary intake and weight and height gain were similar in the two groups. During the supplementation phase, the consumption of staple food fell among children receiving maize and soy flour but not among those receiving RTUF. There was thus higher intake of energy, fat, iron, and zinc in the RTUF group. Both supplements resulted in modest weight gain, but the effect lasted longer after RTUF supplementation. Height gain was not affected in either group. Periodic 24‐hour dietary recalls suggested that the children received only 30% and 43%, respectively, of the supplementary RTUF and maize and soy flour provided.ConclusionsRTUF is an acceptable alternative to maize and soy flour for dietary supplementation of moderately malnourished children. Approaches aimed at increasing the consumption of supplementary food by the selected recipients are needed.
Recurrent Abdominal Pain: Symptom Subtypes Based on the Rome II Criteria for Pediatric Functional Gastrointestinal Disorders
Authors: Walker Lynn S. , Lipani Tricia A. , Greene John W. , Caines Karen , Stutts John , Polk D. Brent , Caplan Arlene , Rasquin‐Weber Andree 
Published: January 2024

ABSTRACTObjectivesRecurrent abdominal pain (RAP) is a common childhood complaint rarely associated with organic disease. Recently, the Pediatric Rome Criteria were developed to standardize the classification of pediatric functional gastrointestinal disorders (FGIDs) using a symptom‐based approach. The authors tested the hypothesis that most patients with childhood RAP could be classified into one or more of the symptom subtypes defined by the Pediatric Rome Criteria.MethodsUsing a prospective longitudinal design, new patients with RAP (n = 114) were studied at a tertiary care children's medical center. Before the medical evaluation, parents completed a questionnaire about their child, assessing symptoms defined by the Pediatric Rome Criteria.ResultsOf the 107 children for whom medical evaluation revealed no organic etiology for pain, 73% had symptom profiles consistent with the Pediatric Rome Criteria for one of the FGIDs associated with abdominal pain (irritable bowel syndrome, 44.9%; functional dyspepsia,15.9%; functional abdominal pain, 7.5%; abdominal migraine, 4.7%)ConclusionsThis study provides the first systematic empirical evidence that RAP, originally defined by Apley, includes children whose symptoms are consistent with the symptom criteria for several FGIDs defined by the Rome criteria. The pediatric Rome criteria may be useful in clinical research to (1) describe the symptom characteristics of research participants who meet Apley's broad criteria for RAP, and (2) select patients with particular symptom profiles for investigation of potential biologic and psychosocial mechanisms associated with pediatric FGIDs.
Prolonged Monitoring of Esophageal Motor Function in Healthy Children
Authors: Chitkara Denesh K. , Fortunato Christine , Nurko Samuel 
Published: January 2024

ABSTRACTObjectiveTo describe diurnal variations of esophageal motor function in children using combined ambulatory 24‐hour esophageal manometry and continuous intraluminal pH measurement (MP24).MethodsMedical records of all patients referred for the performance of MP24 from 1995 to 2002 at a tertiary care center were reviewed. Patients were selected retrospectively for this study using the following inclusion criteria: (1) no dysphagia, (2) normal upper gastrointestinal barium radiograph, (3) normal esophagogastroduodenoscopy and biopsies, (4) normal stationary esophageal manometry, (5) normal esophageal pH probe, and (6) no gastrointestinal pathology appearing after long‐term follow‐up. Data from the MP24 of these children were retrospectively analyzed for differences between meal, upright, and supine periods using nonparametric univariate analysis.ResultsOne hundred twenty‐three children had MP24 during the study period. Eleven met the criteria for normality and were included. Their mean age was 12.4 ± 1.5 years. The number of contractions/minute in the upper, middle, and lower esophageal body differed significantly during meals and in the upright and supine periods (P < 0.01). A significant increase in motor activity occurred during meals (P < 0.01). There was less motor activity observed in the supine position than in the upright position (P < 0.01). There were significant differences in effective (P < 0.05) and total propagated peristalsis among the meal, upright, and supine periods (P < 0.01), with the largest percentage of propagated contractions observed during meals.ConclusionThis study provides the first information on prolonged esophageal motor activity in pediatric patients without esophageal disease. MP24 in children demonstrates significant diurnal variations in esophageal motor function that is similar to the findings in studies of healthy adults.
Anti‐Inflammatory and Growth‐Stimulating Effects Precede Nutritional Restitution During Enteral Feeding in Crohn Disease
Authors: Bannerjee Kaushik , Camacho‐Hübner Cecilia , Babinska Katarzyna , Dryhurst Kay M. , Edwards Ray , Savage Martin O. , Sanderson Ian R. , Croft Nicholas M. 
Published: January 2024

ABSTRACTObjectivesExclusive enteral feeding reduces inflammation and improves well being, nutrition and growth in children with active Crohn disease. Whether improved growth and increases in growth‐related proteins are a consequence of improved nutrition or a reduced inflammation is not known. This study was undertaken to test the hypothesis that changes in growth‐related proteins are related to decreased inflammation, rather than improvement in nutritional status.MethodsTwelve children with active Crohn disease treated for 6‐weeks with exclusive enteral feeding were studied at days 0, 3, 7, 14, 21, 28, and 56. The Paediatric Crohn's Disease Activity Index (PCDAI), weight, triceps skinfold thickness, and midupper arm circumference were recorded. C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin‐6 (IL‐6), insulin‐like growth factor (IGF‐I), IGF‐binding protein (IGFBP‐3), and leptin were measured at each visit. Wilcoxon matched‐pairs signed‐rank test was used to compare day 0 with follow‐up data.ResultsSignificant improvements (P < 0.05) occurred by day 3 in inflammatory parameters (ESR, IL‐6) and by day 7 in PCDAI, CRP, and IGF‐I. These changes preceded any significant changes in nutritional parameters (weight‐for‐age Z score and midupper arm circumference day 14, triceps skinfold thickness day 21).ConclusionsEarly increases in IGF‐I during treatment of Crohn disease are attributable to the anti‐inflammatory effect of the enteral feed rather than nutritional restitution.
Acidified Milk Formula Supplemented With Bifidobacterium lactis: Impact on Infant Diarrhea in Residential Care Settings
Authors: Chouraqui Jean‐Pierre , Van Egroo Louis‐Dominique , Fichot Marie‐Claire 
Published: January 2024

ABSTRACTObjectivesProbiotics may be useful in preventing acute infectious diarrhea. Bifidobacteria are particularly attractive as probiotics agent because they constitute the predominant colonic flora of breastfed infants and are thought to play a role in the decreased incidence of diarrhea in breastfed infants.MethodsThis was a multicenter, double‐blind, controlled study to evaluate the efficacy of a milk formula supplemented with viable Bifidobacterium lactis strain Bb 12 (BbF) in the prevention of acute diarrhea in infants younger than 8 months living in residential nurseries or foster care centers.ResultsNinety healthy children received either the BbF or a conventional formula (CF) daily. The mean duration of the stay in the residential center was similar (137 v 148 days). At enrollment, there were no differences between the two groups with respect to age (3.7 ± 2.1 months), gender, anthropometric data, history of allergy or gastrointestinal disease, frequency of breast‐feeding in the neonatal period or timing of introduction of solid food. Altogether, 28.3% of the BbF infants had diarrhea during the study compared with 38.7% of controls (NS). There was a statistically insignificant trend for shorter episodes of diarrhea in the BbF group (5.1 ± 3.3 days v 7 ± 5.5 days, NS). The number of days with diarrhea was 1.15 ± 2.5 in the BbF group with a daily probability of diarrhea of 0.84 versus 2.3 ± 4.5 days and 1.55, respectively, in the CF group (P = 0.0002 and 0.0014). Feeding infants with the BbF reduced their risk of getting diarrhea by a factor of 1.9 (range, 1.33–2.6). Analysis of the cumulative incidence of diarrheal episodes showed a trend that the first onset of diarrhea occurred later in the BbF group.ConclusionThese results provide some evidence that viable Bifidobacterium lactis strain Bb 12, added to an acidified infant formula, has some protective effect against acute diarrhea in healthy children.
Prenatal Stress Alters Bacterial Colonization of the Gut in Infant Monkeys
Authors: Bailey Michael T. , Lubach Gabriele R. , Coe Christopher L. 
Published: January 2024

ABSTRACTObjective:The hypothesis that prenatal stress lowers the levels of protective microflora and increases the risk for postpartum Gram‐negative pathogens was tested in infant monkeys.Methods:Female monkeys were left undisturbed or were stressed during pregnancy using an acoustical startle paradigm for 6 weeks either early or late in their 24‐week gestation. Several types of intestinal microflora were repeatedly enumerated by fecal culture while infants were reared normally by their mothers.Results:Significant changes in microflora concentrations occurred during the first 6 months of life. The profile of total aerobes and facultative anaerobes was biphasic, with peak concentrations occurring between 2 and 16 weeks of age. The numbers of bifidobacteria and lactobacilli were low at 2 days after birth but rapidly increased to a peak between 8 and 16 weeks of age. Although similar temporal patterns were evident in all infants, prenatal stress reduced the overall numbers of bifidobacteria and lactobacilli.Conclusions:Moderate disturbance during pregnancy was sufficient to alter the intestinal microflora in the newborn infant. These alterations could result in enhanced susceptibility to infection and suggest a mechanism for some effects of maternal pregnancy conditions on infant health.
Helicobacter pylori Eradication Rate and Glycemic Control in Young Patients With Type 1 Diabetes
Authors: Candelli Marcello , Rigante Donato , Marietti Giovanni , Nista Enrico C. , Crea Francesca , Schiavino Alessandra , Cammarota Giovanni , Pignataro Giulia , Petrucci Stefano , Gasbarrini Giovanni , Gasbarrini Antonio 
Published: January 2024

ABSTRACTObjectives:Eradication of Helicobacter pylori is more difficult in adult patients with diabetes than in patients with dyspepsia. It has also been suggested that eradication of H. pylori in children with type 1 diabetes mellitus improves their metabolic control. The aim of the current study was to assess the eradication rate of a standard triple therapy and its effects on glycemic control in young patients with type 1 diabetes.Methods:The authors enrolled 29 type 1 diabetic patients with H. pylori, 29 type 1 diabetic patients without H. pylori, and 29 dyspeptic children with H. pylori. Groups were matched for gender and age and had similar geographical origin and socioeconomic status. H.pylori status was investigated before and 6 weeks after therapy by 13C‐urea breath test. All enrolled patients with H. pylori were prescribed a standard triple therapy for eradicating H. pylori. Glycosylated hemoglobin A and daily insulin requirement were evaluated at enrollment and 6 months later in all patients with diabetes. The prevalence of the most common gastrointestinal symptoms also was investigated by means of a questionnaire in all subjects at enrollment and 6 months later.Results:Eradication of H. pylori was similar in patients with diabetes (24/29) and those with dyspepsia (23/29) (83%v 79%; P = NS). No difference in metabolic control was observed before or after antibiotic treatment in the patients who experienced H. pylori eradication. No difference in glycemic control was observed after 6 months of follow‐up.Conclusions:The eradication rate of H. pylori infection was similar for young patients with type 1 diabetes and those with dyspepsia and did not improve metabolic control in a short‐term follow‐up.
Association of Schatzki Ring With Eosinophilic Esophagitis in Children
Authors: Nurko Samuel , Teitelbaum Jonathan E. , Husain Khaled , Buonomo Carlo , Fox Victor L. , Antonioli Donald , Fortunato Christine , Badizadegan Kamran , Furuta Glenn T. 
Published: January 2024

ABSTRACTObjective:To describe the clinicopathologic characteristics of children with Schatzki ring and to determine if Schatzki ring is associated with eosinophilic esophagitis.Methods:The authors report 18 adolescents with radiographically diagnosed Schatzki ring (SR). Their clinical and histologic characteristics were reviewed in a blinded fashion.Results:The mean age of the patients was 15.8 ± 0.8 years and mean duration of symptoms was 2.6 ± 0.4 years. By histologic criteria, two groups of patients were defined. Eight had clinical and histologic criteria of eosinophilic esophagitis (EE) and 10 of peptic esophagitis. There were no differences in the symptoms or radiographic findings in the two groups. The SR was not identified by endoscopy in any EE patient and was identified in 70% of peptic esophagitis patients. Grossly apparent mucosal features associated with EE were significantly more common in those with EE. Those with peptic esophagitis had a significantly higher acid exposure than did those with EE (12.6 ± 2.9 v 2.0 ± 1.1%; P < 0.01) by esophageal pH probe. Patients with peptic esophagitis responded to proton pump inhibitors and/or dilatation, whereas those with EE did not have good response and required specific therapy for EE.Conclusions:EE may play a role in the pathogenesis of some patients with SR.
Developmental Pharmacokinetics and Pharmacodynamics of Nizatidine
Authors: Abdel‐Rahman Susan M. , Johnson Franklin K. , Connor James D. , Staiano Annamaria , Dupont Christophe , Tolia Vasundhara , Winter Harland , Gauthier‐Dubois Ginette , Kearns Gregory L. 
Published: January 2024

ABSTRACTObjectives:To characterize the impact of development on the pharmacokinetics and pharmacodynamics of nizatidine.Methods:Children (age range, 5 days–18 years) and adults (age range, 18–50 years) were enrolled in four open‐label trials. Nizatidine formulation and dose were determined by age: infants received 2 or 4 mg/kg IV, children 2.5 or 5 mg/kg in one of three oral liquid formulations, and adolescents and adults received a fixed 150‐mg capsule. Nizatidine and N‐desmethylnizatidine concentrations were measured in serial post‐dose plasma samples by a high‐performance liquid chromatographic assay with mass spectrometric detection. Intragastric pH was recorded during a 24‐hour post‐dose interval.Results:Data on 93 subjects were combined with previous values from 36 individuals to cover an age group not adequately captured and to control for formulation effects. Dose‐normalized exposure estimates revealed no apparent age dependence; however, maximum plasma concentration (298.5 ± 100.7 v 552.8 ± 152.4 ng/mL per mg/kg dose) and AUC0‐∞ (954.4 ± 379.8 v 1,573.0 ± 347.4 ng*hour/mL per mg/kg dose) were reduced in extemporaneous formulations in apple juice. The apparent modest age dependence observed for total body clearance (Cl/F) (r2 = 0.365) and Vss/F (r2 = 0.221) reflected a formulation‐dependent decrease in bioavailability rather than a true age effect. The age‐associated changes in λz observed for nizatidine and its metabolite were predictable and consistent with developmental acquisition of renal function. Mean and median pH, as well as fraction of time that the dosing interval remained above target pH values, were significantly greater with administration of the drug than without.Conclusions:The biodisposition of nizatidine in children and adults is similar; however, response after a comparable weight‐based dose is equal and potentially greater in children.
Innate Immunity of the Gut: Mucosal Defense in Health and Disease
Authors: Yuan Qian , Walker W. Allan 
Published: January 2024

ABSTRACTThe intestine is an important immune organ consisting of a complex cellular network, secreted peptides and proteins and other host defenses. Innate immunity plays a central role in intestinal immune defense against invading pathogens. It also serves as a bridge to the activation of the adaptive immune system. Pattern recognition molecules of microorganisms are an essential component for identifying invading pathogens. Toll‐like receptors (TLRs), CARD15/NOD2 and scavenger receptors all serve as the pattern recognition receptors in the innate immune defense system. Secreted bactericidal peptides or defensins produced by the intestinal epithelia represent another crucial element of innate mucosal immune defense. Mutations in pattern recognition receptors and dysfunction of secretory bactericidal peptides may impair host immune defenses leading to an invasion of pathogens resulting in chronic inflammation of the gut. This review updates our current understanding of innate immunity of the gastrointestinal tract.
Malnutrition: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Fuchs George , Ahmed Tahmeed , Araya Magdalena , Baker Susan , Croft Nick , Weaver Lawrence 
Published: January 2024

Research
Protocolized management of malnutrition.
Prevention and management of low birth weight.
Micronutrients.
Intervention
Promote universal application of WHO guidelines for inpatient treatment of severe malnutrition.
Establish a system for the nutritional assessment and management of hospitalized children.
Implement national programs to encourage proper infant feeding and to prevent malnutrition.
Education
Rehabilitation diets for the treatment of severely malnourished children using locally available foods.
Infant feeding practices.
Effects of Protein Deprivation on Growth and Small Intestine Morphology Are Not Improved By Glutamine or Glutamate in Gastrostomy‐Fed Rat Pups
Authors: Li Nan , Lassman Beth J. , Liu Zhiwei , Liboni Kellym , Neu Josef 
Published: January 2024

ABSTRACTObjectives:Critically ill neonates often have their enteral intake severely limited shortly after birth. Whether glutamine (Gln) or glutamate (Glu) can preserve intestinal structure and function in the neonate undergoing limited enteral feeding is not clear. We hypothesize that Gln and Glu can similarly preserve intestinal structure in the developing small intestine of infant rats fed a low protein diet.Methods:Using a gastrostomy‐fed “pup‐in‐a‐cup” rat model, the effects of Gln and Glu on the developing rat small intestine were examined. Four groups of 6‐ to 7‐day‐old pups were fed rat milk substitute (RMS) via gastrostomy tube. One group was provided 100% and three were provided 25% of the protein normally received from their mothers. Two of the groups fed 25% protein received additional Gln or Glu for 6 days.Results:Pups receiving the 100% protein RMS were larger than pups receiving the 25% protein RMS with or without Gln/Glu supplementation (P < 0.001). Average villus height (P < 0.01) and area (P < 0.01) were greater in pups receiving 100% protein RMS than in pups given 25% protein RMS formula. There was no significant difference among the groups in mucosal maltase or alkaline phosphatase activities. Tight junction protein claudin‐1 was significantly higher in the group fed 100% protein RMS diet, while occludin did not differ among the 4 groups. Neither Gln nor Glu increased claudin‐1 or occludin in rats fed 25% protein.Conclusions:These results suggest that neither Gln nor Glu supplementation can substitute effectively for whole protein in the developing rat small intestine for the outcomes that were evaluated.