bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of Toll‐Like Receptor 4 Explains Endotoxin Hyporesponsiveness in Human Intestinal Epithelium
Authors: Naik Sandhia , Kelly Eric J. , Meijer Lisa , Pettersson Sven , Sanderson Ian R. 
Published: January 2024

ABSTRACTBackgroundThe Toll protein in Drosophila regulates dorsal ventral patterning during embryogenesis, and participates in antibacterial and antifungal host defense. Mammalian homologues are termed Toll‐like receptors and, to date, nine have been cloned (TLR1–9) in humans. They are characterized by extracellular leucine‐rich repeats and a cytoplasmic domain similar to the interleukin 1 receptor. Both TLR2 and TLR4 recognize various bacterial cell wall components including lipopolysaccharide (LPS). This results in the activation of the NFκB pathway. Peripheral blood mononuclear cells (PBMCs) express both TLR2 and TLR4. The authors hypothesized that the expression of TLR 2 and TLR4 in human intestinal epithelial cells differs from PBMCs because of the abundance of LPS in the intestinal lumen.MethodsEpithelial cells were isolated from Caco‐2 cells, fetal gut explants, and small bowel resection specimens using Hanks/ethylenediamine tetraacetic acid solution. PBMCs were used as positive controls. Ribonucleic acid (RNA) was isolated using the TRIzol method. Standard reverse transcription–polymerase chain reaction examined TLR2 and TLR4 messenger RNA (mRNA) expression. NFκB expression was determined using a luciferase reporter assay.ResultsTLR2 mRNA was highly expressed in PBMCs and was present in all human intestinal epithelial cells. TLR4 mRNA was detected only in PBMCs. TLR4 is not present in epithelium from children with inflammatory bowel disease. In Caco‐2 cells, significant NFκB activation in response to LPS occurred only in the presence of TLR4 introduced by complementary deoxyribonucleic acid transfection.ConclusionAbsence of TLR4 is associated with endotoxin hyporesponsiveness of intestinal epithelial cells. TLR4 is not directly involved in inflammation of the intestinal epithelium. Although TLR2 is normally present in the epithelial cell, it plays a limited role in inflammation. It may be activated during conditions in which bacterial cell wall concentrations within the intestine are pathologically high.
Does Cisapride Influence Cardiac Rhythm? Results of a United States Multicenter, Double‐Blind, Placebo‐Controlled Pediatric Study
Authors: Levy Joseph , Hayes Constance , Kern Jeffrey , Harris Jennifer , Flores Alex , Hyams Jeffrey , Murray Robert , Tolia Vasundhara 
Published: January 2024

ABSTRACTBackgroundMajor concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program.Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use.MethodsChildren between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment.ResultsMean QTc among patients taking the drug was 408 ± 18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2 ± 20 ms.ConclusionsIn our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.
Proabsorptive Action of Gum Arabic: Regulation of Nitric Oxide Metabolism in the Basolateral Potassium Channel of the Small Intestine
Authors: Rehman Khalil , Wingertzahn Mark A. , Harper Rita G. , Wapnir Raul A. 
Published: January 2024

ABSTRACTBackgroundGum arabic, a high–molecular‐weight natural polysaccharide, has been shown to have proabsorptive properties in animal models of gastrointestinal disease that involve nitric oxide (NO). Gum arabic may indirectly regulate NO metabolism by creating an outward NO gradient, thus altering other intracellular NO–dependent mechanisms such as gating of the potassium (K + ) channel. This hypothesis was further investigated using the K + channel blocker, glybenclamide.MethodsFollowing intraperitoneal injection of 4.5 mg/kg glybenclamide or saline, the jejunum of anesthetized rats was perfused with a standard oral rehydration solution in the presence or absence of 2.5 g/L gum arabic, as well as 1 mmol/L l ‐arginine to enhance NO production. Sodium, net water, and glucose absorption and unidirectional water movement were determined.ResultsGum arabic showed regulatory capacity for NO–dependent metabolism by reducing net water absorption in the absence of arginine, and sodium absorption after arginine stimulation, in the absence of glybenclamide. Addition of gum arabic to oral rehydration solution, in glybenclamide pretreated animals, and in the absence of arginine, normalized sodium absorption, but was less effective in restoring net water transport. Injection of glybenclamide sharply decreased all absorption markers in arginine supplemented oral rehydration solution, which were at least partially restored by addition of gum arabic to the oral rehydration solution. In the presence of glybenclamide, the effects of arginine became antiabsorptive, as had those observed in preceding studies with high arginine concentration. Gum arabic partially or fully reversed alterations produced by perfused 1 mmol/L arginine.ConclusionsSome of the effects of gum arabic on the small intestine are likely caused by its ability to remove NO as it diffuses into the lumen, thus reducing NO concentration in the enterocyte and indirectly affecting the absorptive/secretory response of the gut, which leads to normalization of absorptive function. These findings are consistent with the previously shown gum arabic–scavenging properties of NO and support a potential therapeutic role for this product.
Fecal Calprotectin: Validation as a Noninvasive Measure of Bowel Inflammation in Childhood Inflammatory Bowel Disease
Authors: Bunn Susan K. , Bisset W. Michael , Main Margaret J. C. , Gray Elizabeth S. , Olson Shona , Golden Barbara E. 
Published: January 2024

ABSTRACTBackgroundCalprotectin is an abundant neutrophil protein, which is extremely stable in feces. This study aimed to validate fecal calprotectin as a marker of bowel inflammation against invasive measures in children with inflammatory bowel disease (IBD), including colitis and small bowel Crohn disease.MethodsFecal calprotectin was measured using a simple enzyme‐linked immunosorbent assay in 36 spot stool samples from 22 children before colonoscopy and from 14 children before technetium‐99 ( 99 Tc) scanning. Using standard scoring systems, the severity of inflammation was assessed macroscopically and histologically at six standard sites in those who underwent colonoscopy and also at six standard sites in those who underwent 99 Tc scanning. The subscores from each site were summated to give combined severity and extent scores for macroscopic and for histologic inflammation in the group undergoing colonoscopy and total inflammation in the group undergoing 99 Tc scanning.ResultsIn the 22 children who underwent colonoscopy, median fecal calprotectin was 4.9 mg/L (0.1–272.5 mg/L) (range). Disease groups included six normal cases, nine ulcerative colitis cases, two isolated Crohn colitis cases, two indeterminate colitis cases, and three allergic colitis cases. Fecal calprotectin correlated closely with colonic macroscopic inflammation (r = 0.75, P < 0.001) and histologic inflammation (r = 0.85, P < 0.001). Of the 14 children undergoing 99 Tc scanning, 10 had Crohn disease, 3 had ulcerative colitis, and 1 had allergic colitis. Median fecal calprotectin was 9.1 mg/L (0.3–141.7 mg/L), and this correlated closely with the 99 Tc scanning score (r = 0.80, P = 0.001).ConclusionFecal calprotectin correlates closely with the best invasive measures of colonic and small bowel inflammation in childhood inflammatory bowel disease. As a sensitive objective measure of bowel inflammation that is risk‐free and noninvasive, fecal calprotectin lends itself particularly to the monitoring of and assessment of therapeutic interventions in children with inflammatory bowel disease.
Laparoscopic Full‐Thickness Intestinal Biopsies in Children
Authors: Mazziotti Mark V. , Langer Jacob C. 
Published: January 2024

ABSTRACTBackgroundLaparoscopy may reduce postoperative pain and hospital stay, compared with laparotomy. The use of laparoscopic surgery to obtain full‐thickness intestinal biopsies in children has not been previously reported.MethodsEleven children aged 1.6 to 19 years (median, 4.5 years) underwent laparoscopic full‐thickness biopsy of the stomach, small bowel, colon, or a combination thereof. Each procedure used one 12‐mm and two 5‐mm ports.ResultsEight children with obstructive symptoms after a pull‐through for Hirschsprung disease underwent multiple colon and small bowel biopsies (range, 3–6; median, 5); intestinal neuronal dysplasia was found in two. Two patients with cystic fibrosis had diffuse colonic narrowing; a diagnosis of enzyme‐induced fibrosing colonopathy was made in one and nonspecific inflammation was found in the other. One child had a thickened stomach, and a gastroscopic‐directed full‐thickness biopsy revealed plasmacytoma. Nine of the 11 patients had a previous laparotomy, and ports were placed through preexisting scars. Median hospital stay was 2 days. No patient required more than 24 hours of narcotics. There were no leaks, and no other morbidity or mortality occurred. None of the patients required conversion to an open procedure. Biopsy results significantly affected treatment for each patient.ConclusionsLaparoscopic full‐thickness intestinal biopsy is safe and effective for a variety of gastrointestinal problems in children. This technique is associated with a short hospital stay, minimal pain, and a very low risk of complications and can be performed even in patients who have had a previous laparotomy.
Cancer in Children With Celiac Disease: A Survey of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition
Authors: Schweizer Joachim J. , Oren Anath , Mearin M. Luisa ,   The Working Group for Celiac Disease Malignancy of the European Society for Paediatric Gastroenterology Hepatology Nutrition
Published: January 2024

ABSTRACTBackgroundIn adults, the relation between celiac disease (CD) and cancer has been long recognized. In children, only four cases of CD and cancer have been described in Europe. We made a new inventory of cases with CD and cancer in children that were known by the members of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition between 1989 and 1999.MethodsPostal inquiry was made of all European Society for Paediatric Gastroenterology, Hepatology and Nutrition members mentioned on the society's web page. The members were asked if they had seen a child with CD and cancer between 1989 and 1999 and if so, to supply additional clinical data. Also, information on working place, experience, and number of celiac patients under their care was requested.ResultsFifty‐six percent of the members responded. Sixteen members reported 22 cases of cancer and CD in children. One case had been reported in the literature previously. The tumors that were reported originated from the brain, thyroid, larynx, liver, small bowel, adrenal, lymphoreticular system, and the musculoskeletal system. There were no differences between members reporting a case and those who did not.ConclusionsTwenty‐one new cases of cancer and CD in children in Europe were found. Cancer and CD in children are underreported. A remarkable number of thyroid and small bowel cancers were found, suggesting a possible relation with CD. It is important to evaluate whether these findings are coincidental. All cases of cancer and CD in children should be reported to the literature.
Intake and Blood Levels of Fatty Acids in Treated Patients With Phenylketonuria
Authors: Acosta Phyllis B. , Yannicelli Steven , Singh Rani , Eisas Louis J. , Kennedy Mary Jane , Bernstein Laurie , Rohr Fran , Trahms Cristine , Koch Richard , Breck Jane 
Published: January 2024

ABSTRACTBackgroundInvestigators in Italy and Spain have suggested that therapy for patients with phenylketonuria (PKU) may result in essential fatty acid (EFA) deficiency. Objectives of this study were to determine if the diets of patients with PKU in the United States provided adequate EFA intakes and whether patients could form long‐chain polyunsaturated fatty acids.MethodsPatients (1–13 years of age) with classic PKU undergoing therapy and their non‐PKU sibling closest in age were compared. Nutrient intakes were calculated from 3‐day diet diaries. Fatty acids in plasma and erythrocytes were identified and quantified. Paired t tests compared results for the patients and their non‐PKU siblings.ResultsTwenty‐eight patients and 26 siblings were studied. Mean fat intake was greatest by siblings (34.8 ± 1.3% of energy) and lowest by Phenyl‐Free–fed patients (19.5 ± 1.2% of energy;P < 0.05). Fat intake (30.4 ± 1.8% of energy) by Phenex‐fed patients did not differ from that of siblings. Percentage of energy ingested as C18:2n‐6 and C18:3n‐3 did not differ significantly between patients and siblings. No clinically significant, consistent differences were found in fatty acid levels (wt%) in plasma or erythrocytes between patients with PKU and siblings.ConclusionsNo patient in this study exhibited a Holman index of EFA deficiency. Siblings ingested animal protein containing C20:5n‐3 and C22:6n‐3 fatty acids, and this may account for their greater wt% of these plasma and erythrocyte fatty acids. Because patients with PKU do not ingest fatty acids >C18 but C20:4n‐6, C20:5n‐3, and C22:6n‐3 were found in their plasma and erythrocytes, in vivo synthesis from C18:2n‐6 and C18:3n‐3 appears to occur. Lack of EFA deficiency in patients in this study may be the result of the use of canola and soy oils containing C18:2n‐6 and C18:3n‐3 rather than olive oil in the diets.
Height and Weight Fail to Detect Early Signs of Malnutrition in Children With Cystic Fibrosis
Authors: Stapleton Denise , Kerr Deborah , Gurrin Lyle , Sherriff Jill , Sly Peter 
Published: January 2024

ABSTRACTBackgroundMany children with cystic fibrosis grow poorly and are malnourished. This study was undertaken to determine whether extensive anthropometry could detect early signs of malnutrition in prepubertal children with cystic fibrosis to prevent deficits in height and weight.MethodsHeight, weight, six skin folds (triceps, subscapular, supraspinale, abdominal, front thigh, and medial calf) and five girths (arm relaxed, forearm, chest, thigh, and calf) were measured in a cross‐sectional study of children aged 6 to 11 years with cystic fibrosis.ResultsThe children with cystic fibrosis were shorter and lighter for their age and gender than those in the reference groups. The mean weight and height z scores for the girls with cystic fibrosis were lower than those for the boys, significantly so for z weight (P < 0.05). Although, the mean percent ideal body weight value of 98.6% suggested that the children with cystic fibrosis were adequately nourished, most of the measures of muscularity and adiposity of the children with cystic fibrosis were significantly lower than those of the reference group (P < 0.05). The z scores of the anthropometric measures revealed that the deficit in muscularity of the children with cystic fibrosis was relatively much greater than the deficit in adiposity.ConclusionsThe percent ideal body weight index does not seem to be an adequate measure of nutritional status in children with cystic fibrosis. Anthropometric assessments should include skin‐fold and circumference measurements of numerous sites on the upper and lower body, the trunk, and the limbs to detect deterioration in nutritional status early. Early detection of deficits in nutritional status may result in the adverse effects of malnutrition on height and weight, and possibly clinical status, being prevented.
Probiotics in the Treatment and Prevention of Acute Infectious Diarrhea in Infants and Children: A Systematic Review of Published Randomized, Double‐Blind, Placebo‐Controlled Trials
Authors: Szajewska Hania , Mrukowicz Jacek Z. 
Published: January 2024

ABSTRACTBackgroundThis review was designed to assess the evidence from randomized controlled trials on effects of probiotics in the treatment and prevention of acute infectious diarrhea in infants and children.MethodsA systematic review of published, randomized, double‐blind, placebo‐controlled trials on probiotics in the treatment or prevention of acute diarrhea defined as >3 loose or watery stools per 24 hours in infants and children.ResultsThe use of probiotics as compared with placebo was associated with a significantly reduced risk of diarrhea lasting >3 days. The pooled estimate risk was 0.43 (95% CI, 0.34–0.53) with a fixed‐effect model, and remained significant in a random‐effect model (0.40; 95% CI, 0.28–0.57). Only Lactobacillus GG showed a consistent effect. Probiotics significantly reduced the duration of diarrhea when compared with placebo, particularly in rotaviral gastroenteritis—the pooled, weighted, mean difference (WMD) assuming the random‐effect model was −20.1 hours (95% CI, −26.1 to −14.2) and −24.8 (95% CI, −31.8 to −17.9) respectively. A meta‐analysis of the prevention studies was not feasible because of significant clinical and statistical heterogeneity.ConclusionsThere is evidence of a clinically significant benefit of probiotics in the treatment of acute infectious diarrhea in infants and children, particularly in rotaviral gastroenteritis. Lactobacillus GG showed the most consistent effect, although other probiotic strains may also be effective. Further research is needed. Clinical and statistical heterogeneity of the prophylactic interventions preclude drawing firm conclusions about the efficacy of probiotics in preventing acute gastroenteritis.
Childhood Peptic Ulcer in the Ural Area of Russia: Clinical Status and Helicobacter pylori–Associated Immune Response
Authors: Nijevitch Alexander A. , Sataev Valery U. , Vakhitov Vener A. , Loguinovskaya Valentina V. , Kotsenko Tatiana M. 
Published: January 2024

ABSTRACTBackgroundThe relation of between Helicobacter pylori and the symptoms in children is still controversial. Determination of specific immunoglobulin (Ig) G antibodies to H. pylori may represent a useful test to screen the patients with acid peptic disease in childhood. The aim of this study was to investigate the spectrum of clinical symptoms, endoscopic and histologic lesions, and clinical value of serum IgG response to H. pylori in school‐aged children residing in the Ural area of Russia for the identification of Helicobacter‐related acid–peptic disease.MethodsDuring 1998, 129 pediatric outpatients (mean age, 12.1 ± 2.3 years; age range, 10–15 years; 41 boys, 88 girls) were undergoing gastroduodenal endoscopy for evaluation of chronic abdominal pain. H. pylori colonization was determined by histology, urease test, and polymerase chain reaction. H. pylori IgG antibodies were found by using an enzyme‐linked immunosorbent assay.ResultsThere was a high prevalence of H. pylori infection (80%) and peptic ulcers (24%) among the study group. Duodenal ulcers were detected in 31 of the children; all of them were H. pylori positive. Family history of peptic ulcers, nighttime pain associated with nocturnal awakening, fasting pain relieved by food, pain associated with meals, postprandial pain, bitter taste, and heartburn were the clinical signs that helped to distinguish the ulcer‐positive children from the ulcer‐negative H. pylori group. Duodenal ulcer patients had higher anti–H. pylori IgG titers compared with the levels of IgG antibodies in the infected children without ulcers (P < 0.001). Peptic ulcer disease was a more common finding in the Ural ethnic group of Asians (Bashkirs) compared with the pediatric population of Russian origin.ConclusionsThese results provide further evidence for a causal relation between H. pylori–associated peptic ulcer disease in childhood and relevant clinical symptoms. High titers of anti–H. pylori IgG might serve as a useful noninvasive indicator of ulcer disease.
Developmental Changes in Cyclooxygenase mRNA Expression in the Gastric Mucosa of Rats
Authors: Tomomasa Takeshi , Ogawa Tetsushi , Hikima Akio , Tabata Masahiko , Kaneko Hiroaki , Morikawa Akihiro 
Published: January 2024

ABSTRACTBackgroundIn newborn rats, gastric mucosa is more susceptible to various damaging agents and recovers from injury more quickly than in older animals. To determine whether metabolism of prostaglandins is responsible for this mucosal protective mechanism in developing rats, we studied cyclooxygenase (COX) mRNA expression in the mucosa using quantitative real‐time polymerase chain reaction (PRC).MethodsCyclooxygenase‐1 and COX‐2 mRNA was extracted from the gastric mucosa of rats of various ages and quantitatively analyzed using real‐time PCR with dual‐labeled fluorogenic probes. The copy numbers of cDNA for COX‐1 and COX‐2 were standardized to glyceraldehyde‐3‐phosphate dehydrogenase from the same sample.ResultsCyclooxygenase‐1 mRNA expression was lowest in 1‐week‐old rats and highest in 4‐week‐old rats. Mucosal damage produced by 150 mmol/L HCl and 60% ethyl alcohol did not increase COX‐1 mRNA expression in any age group. Cyclooxygenase‐2 mRNA expression increased significantly with age. Mucosal injury increased COX‐2 mRNA in each age group, especially in 1‐week‐old rats. Intraperitoneal lipopolysaccharide also increased COX‐2 mRNA in both 1‐ and 4‐week old rats.ConclusionThe high level of COX‐2 mRNA expression in the gastric mucosa of 1‐week‐old rats may be responsible for the physiologic characteristics of gastric mucosal defenses in this age group.