bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Background

Gum 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.

Methods

Following 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.

Results

Gum 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.

Conclusions

Some 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

Background

Calprotectin 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.

Methods

Fecal 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.

Results

In 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).

Conclusion

Fecal 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

Background

Laparoscopy 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.

Methods

Eleven 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.

Results

Eight 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.

Conclusions

Laparoscopic 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

Background

In 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.

Methods

Postal 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.

Results

Fifty‐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.

Conclusions

Twenty‐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

Background

Investigators 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.

Methods

Patients (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.

Results

Twenty‐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.

Conclusions

No 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

Background

Many 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.

Methods

Height, 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.

Results

The 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.

Conclusions

The 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

Background

This 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.

Methods

A 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.

Results

The 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.

Conclusions

There 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

Background

The 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.

Methods

During 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.

Results

There 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.

Conclusions

These 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

Background

In 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).

Methods

Cyclooxygenase‐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.

Results

Cyclooxygenase‐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.

Conclusion

The 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.
Increased Parenteral Amino Acid Administration to Extremely Low‐Birth‐Weight Infants During Early Postnatal Life
Authors: Porcelli Peter J. , Sisk Paula M.
Published: January 2024

Background

Early administration of parenteral amino acids to infants with extremely low birth weight (birth weight ≤1,000 g) has been encouraged to foster growth. However, excessive intravenous intake of amino acids may cause metabolic acidosis and uremia in extremely low birth weight infants. The hypothesis for this study was that extremely low birth weight infants would tolerate slightly increased early postnatal parenteral amino acid administration and benefit.

Methods

The peak daily parenteral amino acid dosage was increased from 3 g/kg (standard group) to 4 g/kg (modified group). The corrected parenteral amino acid dosage was computed to account for enteral protein intake and keep the combined daily intravenous amino acid and enteral protein intake at or below 3 g · kg−1 · d−1 in the standard group and 4 g · kg−1 · d−1 in the modified group. The primary outcome measure was plasma bicarbonate concentration as an indicator of acid–base status. Data were collected for patient demographics, nutritional intake, serum bicarbonate and serum urea nitrogen concentrations, and outcome.

Results

The corrected parenteral amino acid intake of the modified group was 16% greater at postnatal week 1 (3.30 ± 0.83 g · kg−1 · d−1; mean, ±1 SD) and 18% greater (3.86 ± 0.94 g · kg−1 · d−1) at postnatal week 2 than the parenteral amino acid intake of the standard group. In the modified group, the mean serum bicarbonate concentration was 19.1 ± 1.8 mEq/dL at week 1 and 23.9 ± 2.9 mEq/dL at week 2, with no difference between the groups. At week 1, serum urea nitrogen concentrations were the same in both groups. The mean serum urea nitrogen concentration of the modified group at postnatal week 2 (18.2 ± 8.8 mg/dL) was unchanged from postnatal week 1, but was greater than that of the standard group at postnatal week 2. Weight gain was the same in both groups. Corrected parenteral amino acid intake at postnatal week 1 correlated directly with weight gain from birth to postnatal week 2 (P < 0.03) in both groups.

Conclusions

Infants with extremely low birth weight tolerated parenteral amino acid intake of approximately 4 g · kg−1 · d−1. Mild increases of mean serum urea nitrogen concentration and mean weight gain were associated with increased parenteral amino acid administration without significant acidosis.
Diet‐Related Adaptation of the Small Intestine at Weaning in Pigs Is Functional Rather Than Structural
Authors: Boudry Gaëlle , Lallès Jean Paul , Malbert Charles Henri , Bobillier Eric , Sève Bernard
Published: January 2024

Background

Incidence of diarrhea at weaning in commercial pigs is an important problem, and diet is thought to be a predisposing factor. The aim of this study was to determine the impact of switching from milk‐based to cereal‐based diets on the morphology and function of the small intestine of piglets using a model of delayed weaning to isolate the influence of the diet from that of environmental and social factors.

Methods

Forty‐five piglets received a milk‐based diet for 5 weeks after weaning. Thirty piglets were then switched from milk‐based to wheat‐ or barley‐based diets, mimicking the dietary change that occurs at weaning. The last 15 piglets remained on the milk‐based diet. Piglets were killed 4 days after the dietary switch. Jejunal mucosa morphometry and enzyme activities were measured. Ussing chambers were used to measure intestinal permeability to macromolecules, basal electrical properties, glucose absorption, and induced chloride‐secretion.

Results

Alkaline phosphatase– and sucrase‐specific activities were higher in both groups of cereal‐fed piglets than in milk‐fed piglets. Dipeptidylpeptidase IV activity was higher in wheat‐fed piglets than in the other groups. Na+‐dependent glucose absorption was 1.7‐fold higher in cereals‐fed piglets than in milk‐fed piglets. Serotonin‐induced and vasoactive intestinal polypeptide–induced chloride secretion was doubled in cereals‐fed piglets. Dietary transition did not influence the other parameters.

Conclusions

These results indicate that switching from milk to cereals increased some mucosal enzyme activities, intestinal Na+–dependent glucose absorption, and response to secretagogues. This supports the hypothesis that dietary factors could initiate diarrhea in the presence of other aggravating factors, such as pathogens or environmental stress.
Dosage‐Related Bifidogenic Effects of Galacto‐ and Fructooligosaccharides in Formula‐Fed Term Infants
Authors: Moro G. , Minoli I. , Mosca M. , Fanaro S. , Jelinek J. , Stahl B. , Boehm G.
Published: January 2024

Background

Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine. In this study, the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low‐molecular‐weight galactooligosaccharides and high‐molecular‐weight fructooligosaccharides was analyzed in 90 term infants.

Methods

Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides. In the control formula, maltodextrin was used as placebo. At study day 1 and study day 28, the fecal species, colony forming units (cfu) and pH were measured and stool characteristics, growth, and side effects were recorded.

Results

At study day 1, the median number of Bifidobacteria did not differ among the groups (0.4 g/dL group, mean [interquartile range] 8.5 [1.9] cfu/g; 0.8 g/dL group, 7.7 [6.1] cfu/g; and the placebo group, 8.8 [6.1] cfu/g) (figures in square brackets are interquartile range). At the end of the 28‐day feeding period, the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas (the 0.4 g/dL group, 9.3 [4.9] cfu/g; the 0.8 g/dL group, 9.7 [0.8] cfu/g) versus the placebo group (7.2 [4.9] cfu/g, P < 0.001). This effect was dose dependent (0.4 g/dL versus 0.8 g/dL, P < 0.01). The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas (versus placebo, P < 0.001), but there was no statistically significant difference between the group fed formula with 0.4 g/dL oligosaccharides and the group fed formula with 0.8 g/dL oligosaccharides. The dosage of supplement significantly influenced the change in fecal pH (P < 0.05) (placebo, pH 5.5–6.1; 0.4 g/dL formula, pH 5.48–5.44; 0.8 g/dL formula, pH 5.54–5.19). Slight changes in the stool frequency resulted in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 (P < 0.01). Supplementation had a significant dose‐dependent influence on stool consistency (0.8 g/dL versus placebo, P < 0.0001; 0.8 g/dL versus 0.4 g/dL, P < 0.01). Supplementation had no influence on the incidence of side effects (crying, regurgitation, vomiting) or growth.

Conclusions

These data indicate that supplementation of a term infant's formula with a mixture of galacto‐ and fructooligosaccharides has a dose‐dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation.
Reactive Nitrogen Species Modulate the Effects of Rhein, an Active Component of Senna Laxatives, on Human Epithelium In Vitro
Authors: Raimondi Francesco , Santoro Pasquale , Maiuri Luigi , Londei Marco , Annunziata Simona , Ciccimarra Filippo , Rubino Armido
Published: January 2024

Background

Senna laxatives are used worldwide. However, their misuse can lead to chronic mucosal inflammation with the accumulation of pigment‐laden leukocytes and may cause colon cells to undergo apoptosis. This study explores the mechanisms by which rhein, an active component of senna, acts on a human intestinal cell line to induce ion secretion, apoptosis, and indirect chemotaxis of polymorphonuclear leukocytes.

Methods

Human colonic adenocarcinoma (CaCo‐2) monolayer cells, in the presence or in the absence of rhein, were used to monitor the production of reactive nitrogen species using the Griess reaction. Modified Ussing chambers were used to study electrolyte secretion. The capacity to recruit human polymorphonuclear leukocytes was evaluated using masked well chemotaxis chambers. Rhein‐induced apoptosis was investigated by counting apoptotic nuclei stained with Hoechst 33258 dye.

Results

Rhein caused a dose‐dependent increase in short‐circuit current that was abolished in chloride‐free bathing buffer or by preincubating with 100 μmol/L NG‐nitro‐L‐arginine (L‐NAME) methyl ester. The concentration that maximally stimulated intestinal secretion, 50 μmol/L rhein, induced nitrate production. Supernatants obtained from CaCo‐2 cultures after incubation with 50 μmol/L rhein stimulated a time‐dependent polymorphonuclear leukocytes chemotaxis that was significantly decreased with 100 μmol/L L‐NAME, whereas rhein per se was not active. Neutralizing antibodies anti–interleukin‐8 (IL‐8) and anti‐ENA78 also inhibited chemotaxis. Overnight rhein incubation produced an increased number of apoptotic cells in the culture supernatant that was significantly decreased by preincubation with 100 μmol/L L‐NAME. Light‐degraded rhein had no effects on CaCo‐2 monolayers.

Conclusions

The integrity of rhein is crucial to generating nitric oxide, which mediates, with different time courses, ion secretion, chemotaxis, and apoptosis of human‐derived cells.
Management of Esophageal Strictures in Children With Recessive Dystrophic Epidermolysis Bullosa
Authors: Castillo Ricardo O. , Davies Yinka K. , Lin Yuan‐Chi , Garcia Manuel , Young Harvey
Published: January 2024

Background

Recessive dystrophic epidermolysis bullosa is a rare, genetically transmitted skin disorder characterized by blister formation and scarring in response to minor trauma. One of the most debilitating features of the disease is the development of esophageal strictures, which produces profound dysphagia, exacerbating an already highly compromised nutritional status common to these patients. Due to the extreme fragility of epithelial surfaces, the optimal therapeutic approach to esophageal strictures in this setting has not been established.

Methods

We have developed an approach to treatment of esophageal strictures in children with epidermolysis bullosa combining upper endoscopy using small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted balloon dilatation. We report our experience using this technique in 22 children who have undergone a total of 109 dilatations.

Results

Upper endoscopy, endotracheal intubation, and balloon dilatation were well tolerated by even very young children with epidermolysis bullosa. Dysphagia was markedly reduced post‐procedure, permitting resumption of normal diet for age, including solids, within six hours of the procedure. Post‐procedure recovery has been rapid and does not require admission to the hospital. Complications have been infrequent, minor, and limited to the first year of our experience. The mean interval between dilatations for all children is 11 months. All children have gained weight, and have not required steroids or phenytoin.

Conclusions

Balloon dilatation is a safe and effective therapy for esophageal strictures in children with recessive dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal intubation are well tolerated by these children. This approach should be considered as primary therapy in this clinical setting.
Neonatal Hypoxia in the Rat: Effects on Exocrine Pancreatic Development
Authors: Lee Ping C. , Struve Mark , Lewis Suzan M. , Raff Hershel
Published: January 2024

Background

Glucocorticoids profoundly affect pancreatic development during the suckling period. Increases in circulating glucocorticoids during exposure to hypoxia may alter the normal pattern of pancreatic enzyme development.

Methods

Rats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35 days of age (weaned at day 21).

Results

Hypoxia in neonatal rats (0–7 days) led to decreased pancreatic weight, and trypsin, lipase, and amylase activity compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to 35 days of age had decreased lipase activity but no change in other pancreatic parameters. Two weeks after hypoxia (0–7 days) pups were returned to normoxia, and their body weights remained smaller than the age‐matched, previously normoxic controls. Pancreatic enzyme activities were decreased in the group recovering from hypoxia compared with controls. Recovery of enzyme activities was observed 3 weeks after hypoxic rats were returned to normoxia. Normoxic pups were given dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7‐day olds. Dexamethasone administration led to decreased body weight, but increased pancreatic weight and enzyme activity compared with normoxic, age‐matched controls.

Conclusions

Hypoxia in newborn rats delays the maturation of pancreatic exocrine enzymes. The mechanism is not related to increased serum glucocorticoids.
Helicobacter pylori Infection in Asymptomatic Children: Impact of Epidemiologic Factors on Accuracy of Diagnostic Tests
Authors: Malaty Hoda M. , Haveman Teresa , Graham David Y. , Fraley J. Kennard
Published: January 2024

Background

Childhood is a time of high risk for acquiring H. pylori infection. Accurate information on the epidemiology of the infection requires accurate diagnostic tests.

Objective

To study the epidemiologic factors that influence the accuracy of diagnostic tests among asymptomatic children.

Methods

Two rapid, noninvasive assays (FlexSure® whole‐blood test and OraSure® saliva test) were evaluated using the 13C‐urea breath test (13C‐UBT) as the gold standard. The three diagnostic tests were conducted in children from 10 licensed day care centers from various locations in Houston, Texas. Demographic information and socioeconomic factors evaluated included age, gender, ethnicity, and crowded living conditions in each center. The three tests were conducted on each child on the same day. We examined the effect of epidemiologic factors on the sensitivity, the specificity, and the positive and negative predictive values of both tests.

Results

Thirty‐two percent of the 243 asymptomatic children who participated in the study tested positive for H. pylori using 13C‐UBT. Among all the children, the sensitivities of FlexSure and OraSure were 47% (95% confidence interval, 35–57%) and 65% (95% confidence interval, 54–73%), respectively. Both tests had greater than 95% specificity. Positive and negative predictive values for FlexSure were 86% and 80%, respectively, and 98% and 86% for OraSure. Among children attending the more crowded day care centers, the sensitivities of FlexSure and OraSure were 40% and 63%, respectively, compared with 100% sensitivity for FlexSure and 80% sensitivity for OraSure among children attending the less‐crowded centers. FlexSure and OraSure tests had the highest sensitivities among the 6‐to 10‐year‐olds. Ethnicity had no effect on the sensitivity or the specificity of either test.

Conclusion

Epidemiologic factors influenced the accuracy of serologic tests for diagnosing H. pylori infection in children. The lowest sensitivities of both tests were among children who attended the more crowded centers and among the youngest and oldest age groups, reflecting an increased proportion of recent infections. The strategy for choosing a diagnostic test for H. pylori infection in children varies based on the epidemiologic characteristics of the studied population.
Tyrosinemia I, A Model For Human Diseases Mediated By 2‐Oxoacid‐Utilizing Dioxygenases: Hepatotoxin Suppression By NTBC Does Not Normalize Hepatic Collagen Metabolism
Authors: Hanauske‐Abel Hartmut M. , Popowicz Anthony , Remotti Helen , Newfield Ron S. , Levy Joseph
Published: January 2024

Objectives

Medical treatment of tyrosinemia I relies on the herbicide NTBC [Orfadin™ 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐cyclohexane‐1,3‐dione], an inhibitor of plant and mammalian 2‐oxoacid‐utilizing dioxygenases with a collective catalytic cycle (`HAG' mechanism). We hypothesize that NTBC‐treated tyrosinemia I is a human model for the pathogenic role of two major enzymes in this class, 4‐hydroxyphenylpyruvate dioxygenase (4‐HPPD; EC 1.13.11.27) and prolyl 4‐hydroxylase (P4‐H; E.C. 1.14.11.2), essential for tyrosine and collagen metabolism, respectively.

Methods

In a patient with established tyrosinemia I, we monitored the in vivo activities of 4‐HPPD and P4‐H via five biomarkers before and during NTBC medication. Hypothesis testing at the molecular level was performed by computational modeling of NTBC binding to the crystal structure‐derived active site of 4‐HPPD, and then relating these findings to our experimental results and to known P4‐H data.

Results

NTBC rapidly normalized the biomarkers for 4‐HPPD activity. However, those for P4‐H activity remained uniformly elevated after one hundred days on NTBC, the PIIINP biomarker even increasing above its grossly abnormal, initial level. This selective enzyme inhibition despite a collective catalytic cycle is attributed to the conformation of NTBC, which only fits the active site of 4‐HPPD, as confirmed by its crystal structure.

Conclusions

Normalization of hepatic collagen formation, highly desirable in all fibrotic liver diseases, is not achieved by NTBC in tyrosinemia I. By establishing the molecular cause for this failure, our results also establish a rational approach to identify inhibitors that achieve that goal, either by joint 4‐HPPD / P‐4H inhibition, or by inhibition of only P‐4H.
Mechanisms of Gastroesophageal Reflux and Gastroesophageal Reflux Disease
Authors: Vandenplas Yvan , Hassall Eric
Published: January 2024

Gastroesophageal reflux is a physiological phenomenon, occurring with different severity and duration in different individuals. Reflux disease occurs when this normal event results in the occurrence of symptoms/signs or complications. The pathophysiology of gastroesophageal reflux is complex and diverse, since it is influenced by factors that are genetic, environmental (e.g., diet smoking), anatomic, hormonal, and neurogenic. However, many mechanisms remain incompletely understood. Future research should focus on a better understanding of the physiology of the upper and lower esophageal sphincters, and of gastric motility. The afferent and efferent neural pathways and neuropharmacologic mediators of transient lower esophageal sphincter relaxations and gastric dysmotility require further study. The role of anatomic malformations such as hiatal hernia in children has been underestimated.

While therapeutic possibilities are greater in number and largely improved, the outcomes of some treatments are far from satisfactory in many cases. In addition to development of new forms of treatment, research should address better use of currently available medical and surgical treatments.
Esophageal Acid Clearance: More Volume‐Dependent Than Motility‐Dependent in Healthy Piglets
Authors: Vicente Yvone , da Rocha Cecilia , Hernandez‐Peredo Guillermo , Madero Rosario , Tovar Juan A.
Published: January 2024

Background/aims

The present study investigates manometrically in healthy piglets whether esophageal clearance after distension with different volumes of acid is volume‐dependent.

Methods

Sedated, non‐intubated piglets (n = 22) underwent stationary manometry of the esophagus with a 4‐probe perfused assembly after successive injection of 1, 2, and 3 mL of saline and acid. Simultaneous pH metering allowed assessment of acid clearance. Wave features and clearance times after saline and acid were compared by paired non‐parametric tests and Friedman analysis of variance. The linearity of the relationships between the clearance times and the volumes of acid infused were tested after square root transformations by one‐way ANOVA repeated measures. The significance level was set atP< 0.05.

Results

The motor response was identical after distension with saline and acid except for the largest amount of acid used, which elicited more waves during the first 5 minutes after infusion. Time elapsed until regaining pH4 was longer after higher amounts of acid, but not significantly, whereas that necessary to regain baseline pH was significantly longer after such challenge. Esophageal motility was practically identical after 1 and 2 mL of acid, but it was slightly less effective in the first minute after the 3 mL challenge. There was a linear correlation between clearance times and volumes of acid infused.

Conclusions

Up to a certain volume, the motor responses of the healthy esophagus to distension with neutral or acid fluids were similar. Acid clearance was more a function of the amount of acid present than of the motor response elicited by its presence. Only when the amount of acid was large, esophageal motor response was worse than that elicited after equivalent volumes of neutral fluid. The present evidence suggests that long episodes of reflux in pH tracings might reflect large volumes of refluxate as well as disturbed motor function.
Parenteral Amino Acids Increase Albumin and Skeletal Muscle Protein Fractional Synthetic Rates in Premature Newborn Minipigs
Authors: Hellstern Gerald , Kaempf‐Rotzoll Daisy , Linderkamp Otwin , Langhans Klaus‐Dieter , Rating Dietz
Published: January 2024

Objectives

Early administration of parenteral amino acids increases whole body nitrogen retention in premature infants. Tracer kinetic studies suggest an increase in whole body protein synthesis as a possible mechanism for this increase in nitrogen retention. However, the effect of early parenteral amino acids on synthesis of specific proteins remains uncertain. Using premature newborn minipigs as a model for human premature newborns, we investigated the effects of parenterally administered amino acids on albumin and skeletal muscle protein fractional synthetic rates.

Methods

Fifteen Yucatan minipigs were delivered by cesarean section 6 days before the mean expected delivery date (day 106 of gestation; expected gestation, 111–113 days) and randomized to two groups immediately after birth: 7 piglets received a mixture of amino acids (0.4 g · kg−1 · h−1) and glucose (0.8 g · kg−1 · h−1) for 5 hours, and 8 piglets (control group) received glucose only. All piglets received a continuous primed infusion of 1‐[13C]valine. Arterial plasma free 13C‐valine enrichment was measured by gas chromatography/mass spectrometry, and protein synthetic rates were determined by measuring incorporation of 13C‐valine into albumin and skeletal muscle protein using gas chromatography/combustion/isotope ratio mass spectrometry.

Results

Administration of amino acids increased albumin (87.0% ± 42.1% [mean ± SD] vs. 37.6% ± 6.8% per 24 hours;P < 0.05) and skeletal muscle fractional synthetic rates (11.60% ± 6.9% vs. 6.5% ± 1.5% per 24 hours;P < 0.05).

Conclusion

We conclude that parenteral amino acids increase albumin and skeletal muscle fractional synthetic rates in premature piglets on the first day of life.
Assay of Tracheal Pepsin as a Marker of Reflux Aspiration
Authors: Krishnan Usha , Mitchell John D. , Messina Isabella , Day Andrew S. , Bohane Timothy D.
Published: January 2024

Objectives

Aspiration of gastric contents is a relatively common cause of acute and chronic pulmonary disease. However, a reliable method of diagnosing recurrent aspiration is currently lacking. The aim of this study was to determine whether the presence of gastric pepsin in tracheal aspirates of infants and children might be used as a reliable marker of the microaspiration of refluxed gastric contents.

Methods

Ninety‐eight children undergoing general anesthesia and tracheal intubation participated in the study. Sixty‐four of 98 children underwent endoscopy for clinically significant gastroesophageal reflux. Thirty‐four children from routine operative lists were nonreflux controls. These two groups were further subdivided based on the presence or absence of associated respiratory symptoms. After endotracheal intubation, tracheal aspirates were obtained and subsequently assayed for gastric pepsin using a fluoroscein isothiocyanate casein.

Results

Pepsin was detected in 7 of 27 children with reflux symptoms alone and in 7 of 8 of those with chronic respiratory symptoms. In addition, pepsin was present in 31 of 37 children with a history of both reflux and chronic respiratory symptoms. Tracheal pepsin was not detected in any of the 26 children without gastroesophageal reflux or respiratory symptoms. Tracheal pepsin was found significantly more frequently in children with reflux symptoms than in those without, particularly in children with both reflux and respiratory problems.

Conclusion

Tracheal pepsin assay as a reliable marker of gastroesophageal reflux aspiration.
Terminal Ileum Intubation in Pediatric Colonoscopy and Diagnostic Value of Conventional Small Bowel Contrast Radiography in Pediatric Inflammatory Bowel Disease
Authors: Batres L. Arturo , Maller Eric S. , Ruchelli Eduardo , Mahboubi Soroosh , Baldassano Robert N.
Published: January 2024

Background

Small bowel contrast radiography is often suggested as the first diagnostic tool in evaluating pediatric inflammatory bowel disease. The purpose of this study was to determine the sensitivity and specificity of small bowel radiography compared with terminal ileal biopsies in diagnosing pediatric inflammatory bowel disease, and to determine the success rate and safety of terminal ileum intubation during pediatric colonoscopy.

Methods

We retrospectively reviewed the records of 164 subjects who had colonoscopies with terminal ileal biopsies between 1994 and 1996. Small bowel contrast radiography was performed in 84 subjects within two weeks of the colonoscopy. We also reviewed all the colonoscopy reports from the years 1994 to 1996 and 1999 to 2000 to determine the percentage of terminal ileal intubation.

Results

Eighty‐four subjects with small bowel contrast radiography and terminal ileal biopsies were reviewed. Using small bowel radiography as a screening test for the diagnosis of terminal ileum inflammatory bowel disease resulted in a sensitivity of 45% (17/37) and a specificity of 96% (17/19). Between the years 1994 and 1996 the percentage of pediatric colonoscopies that resulted in terminal ileal intubation was 21.5%; between the years 1999 and 2000 the percentage increased to 65.6%.

Conclusions

A normal small bowel radiography alone should not be used to rule out pediatric inflammatory bowel disease when the symptoms suggest it. Colonoscopy with terminal ileal intubation is feasible and safe; it should be attempted in all children with symptoms consistent with inflammatory bowel disease.
Fibrosing Colonopathy Revealing Cystic Fibrosis In A Neonate Before Any Pancreatic Enzyme Supplementation
Authors: Serban Daniela Elena , Florescu Petre , Miu Nicolae
Published: January 2024

Although its pathogenesis remains still unknown, fibrosing colonopathy (FCP) is considered to be the result of prolonged treatment by high doses of pancreatic enzyme preparations, in a small proportion of patients who present with cystic fibrosis (CF). We present the case of a newborn with meconium ileus (treated by conservative measures), in which, at the age of 3 weeks, the features of intestinal obstruction made necessary the removal of 15 cm of the proximal large intestine. Macroscopical and especially microscopical appearances typical for FCP were found, despite the absence of any enzymatic treatment. These findings raised the suspicion of CF, which was confirmed 4 weeks later at necropsy by the presence of characteristic pancreatic lesions. This case and another similar report in the literature suggest that the mechanism of FCP must be linked with the disease itself, at least in some patients. Thus, for us, FCP is not a “closed subject” and we sustain the importance of continuing studies, which will shed light on its etiopathogenesis.
Acute Gastric Perforation after Acid Ingestion
Authors: Gün Feryal , Abbasoğlu Latif , Çelik Alaaddin
Published: January 2024

Gastric outlet obstruction is a common late result after acid ingestion; early complications, such as gastric necrosis or perforations are unusual. This is a report of a patient with the history of strong acid ingestion who underwent total gastrectomy due to perforation and extensive necrosis of the stomach.
Drug Reaction To Ursodeoxycholic Acid: Lichenoid Drug Eruption In An Infant Using Ursodeoxycholic Acid For Neonatal Hepatitis
Authors: Büyükgebiz Benal , Arslan Nur , Oztürk Yeşim , Soyal Cüneyt , Lebe Banu
Published: January 2024

Lichenoid drug eruptions are skin reactions associated with a number of drugs and chemicals. They are rare in infants. We report here an infant who presented with neonatal hepatitis and who was being treated with ursodeoxycholic acid. The infant developed lichenoid skin eruptions in the third week of the therapy. The lesions have resolved two months after the discontinuation of the drug. To our knowledge, this is the first infant case of lichenoid drug eruption associated with ursodeoxycholic acid.