bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Serum From Children with Newly Diagnosed Crohn Disease on Primary Cultures of Rat Osteoblasts
Authors: Varghese Samuel , Wyzga Nancy , Griffiths Anne M. , Sylvester Francisco A.
Published: January 2024

Objectives

We propose that Crohn disease (CD) decreases bone formation via circulating inflammatory mediators. We therefore examined the effects of serum from newly diagnosed, untreated children with CD on osteoblasts in culture and the role of interleukin‐6 (IL‐6), a cytokine present in excess in active CD that also has direct effects on bone.

Methods

Bone mineral density was measured by dual x‐ray absorptiometry. Primary cultures of rat osteoblasts were treated with serum from patients with CD and healthy controls. We measured expression of osteoblast proliferation, viability, differentiation markers, and mineralized nodule formation. Neutralizing antibodies were used to inhibit the effects of IL‐6 present in serum.

Results

We studied 24 children with CD (14 male) and 31 controls (15 male). Spine bone mineral density was lower in patients with CD (Z score, −0.8 ± 0.9 vs. 0.0 ± 1.0 for controls;P < 0.05). Nodule formation was markedly decreased in osteoblasts treated with CD serum. However, CD serum did not affect osteoblast proliferation or viability. Expression of proteins characteristic of mature osteoblasts—osteocalcin and alkaline phosphatase—was reduced. Unlike our results in a model of intact bone, neutralization of IL‐6 did not inhibit the effects of CD serum. Addition of IL‐6 to control serum to match serum concentrations in CD had no effect either.

Conclusions

CD serum affects osteoblast function and probably differentiation in vitro, suggesting a mechanism by which CD may affect bone formation. IL‐6 by itself is not sufficient to cause these effects and probably needs a cofactor present in intact bone.
Visceral Pain‐Associated Disability Syndrome: A Descriptive Analysis
Authors: Hyman Paul E. , Bursch Brenda , Sood Manu , Schwankovsky Lenore , Cocjin Jose , Zeltzer Lonnie K.
Published: January 2024

Objective

Pain‐associated disability syndrome (PADS) is a recently defined term that describes patients with chronic pain whose restriction in daily activities appears disproportionately severe for the observable pathology. The aim of this study is to describe the features of a group of pediatric patients with abdominal symptoms fitting this diagnosis.

Methods

To identify factors associated with visceral PADS, we reviewed the records of 40 patients (18 males; age range, 7–21 years) with gastrointestinal symptoms severe enough to prevent school attendance or eating for 2 months or more. These patients, in whom pain was neither feigned nor self‐induced, met the diagnostic criteria for visceral PADS, including failure of usual treatments and lack of a satisfactory organic explanation for the severity of the pain.

Results

The dominant symptom was abdominal pain in 30 patients, regurgitation in 5 patients, nausea in 3 patients, and chest pain in 2 patients. All patients complained of pain or discomfort, and all met symptom‐based criteria for one or more functional gastrointestinal disorder. Disordered sleep was a problem for 39 patients. Factors associated with PADS included learning disabilities, unrealistic goals in a perfectionist, high‐achieving child, early pain experiences, passive or dependent coping style, marital problems in the home, and chronic illness in a parent. All patients had at least two associated factors, and a majority had four or more associated factors. Possible triggering events included an acute febrile illness in 20 patients, school change in 11 patients, trauma in 2 patients, death of a loved one in 2 patients, and sexual abuse in 2 patients. Before diagnosis, all patients underwent extensive negative evaluations. Nearly all patients had mental health evaluations that ruled out eating disorder and psychosis. Medical management had failed, and surgeries worsened symptoms. In a majority of patients, we identified a comorbid psychiatric disorder.

Conclusions

Evaluation of preteens and teens unable to go to school or eat because of unexplained incapacitating symptoms should include queries about factors associated with PADS. To treat PADS, medical and mental health clinicians must recognize pain as having both nociceptive and affective components and address treatment collaboratively. Invasive procedures and surgery reinforce the cycle of arousal and pain and are to be avoided. Age for the onset of PADS in the preteen and early teen years suggests that developmental issues play a role.
The Spectrum of Fatty Liver in Obese Children and The Relationship of Serum Aminotransferases to Severity of Steatosis
Authors: Fishbein Mark H. , Miner Michelle , Mogren Chris , Chalekson Jennifer
Published: January 2024

Objectives

Non‐alcoholic fatty liver disease is an emerging diagnosis in the pediatric population. Previously, ultrasonography and serum aminotransferases have been used to estimate prevalence of the disorder. A lack of concordance has been noted between these two diagnostic tests. To better understand the spectrum of fatty liver in obese children and the relationship of serum aminotransferases to the severity of steatosis, hepatic MRI was used to quantitate fat content.

Methods

Twenty‐two children, ages 6 to 18 years, with obesity (BMI > 95th percentile for age) and hepatomegaly (liver edge more than 2 cm below the right costal margin) underwent hepatic MRI for fat quantitation. Hepatic MRI was performed using a modification of the Dixon method that used a fast gradient echo sequence rather than traditional spin echo. Scan times were sufficiently brief to allow completion within a single breath hold. Serum aminotransferases were obtained within one month of MRI.

Results

Twenty‐one of 22 subjects had an elevated hepatic fat fraction. Seven of 7 subjects with a fat fraction of ≤18% had a normal serum ALT. Twelve of 13 subjects with fat fraction of >18% had an elevated serum ALT. Hepatic fat fraction correlated with serum ALT but did not correlate with age, BMI, or serum AST.

Conclusion

The spectrum of fatty liver is larger than detected by screening for abnormal serum aminotransferases alone. Abnormalities in serum ALT occur exclusively in more severe cases of fatty liver.
Glycine Conjugation of Para‐Aminobenzoic Acid (PABA): A Pilot Study of A Novel Prognostic Test in Acute Liver Failure in Children
Authors: Lebel Sylvie , Nakamachi Yoshiko , Hemming Alan , Verjee Zul , Phillips M. James , Furuya Katryn N.
Published: January 2024

Background

Fulminant hepatic failure (FHF) is associated with high mortality; few patients survive without liver transplantation. It is important to have a sensitive, specific early predictor of outcome to distinguish potential survivors (S) from nonsurvivors (NS).

Objective

Because we had previously shown that glycine conjugation of para‐aminobenzoic acid (PABA) quantitatively reflects liver function in children with chronic liver disease, in this pilot study we wanted to determine whether the measurement of the glycine conjugates of PABA could distinguish S from NS in FHF in comparison with standard prognostic indices.

Methods

Twenty‐four patients were studied: acute severe hepatitis (n = 7), subfulminant hepatic failure (n = 7), and FHF (n = 10). Assessment of King's College criteria, measurement of factor V and VII levels, PABA testing, and transjugular liver biopsies were performed in almost all patients within 48 hours of admission. Serum PABA and its glycine conjugates (para‐aminohippurate (PAHA) and para‐acetamidohippurate (PAAHA)) were measured thirty minutes after oral administration by high‐pressure liquid chromatography. Poor prognostic categories as previously established in the literature were defined as factor V < 0.20U/ml, factor VII < 0.08 U/ml, % necrosis >70%, hippurate ratio = 0%, and PAHA = 0M.

Results

The measurement of PAHA was the best predictor of a poor outcome in patients with acute liver failure with a sensitivity of 92%, and negative predictive value (NPV) of 92% compared with a sensitivity of 54% and a NPV of 63% with King's College criteria.

Conclusion

Measurement of serum PAHA is the best early prognostic marker of death in children who suffer from FHF.
The Clinical Spectrum of Duodenal Polyps in Pediatrics
Authors: Attard T. M. , Abraham S. C. , Cuffari C.
Published: January 2024

Objectives

The aim of this retrospective study was to determine the prevalence, clinical presentation, and histologic subclassification of duodenal polyps identified on endoscopy (EGD) in pediatric patients.

Methods

We performed an 18‐year retrospective study of all pediatric patients (< 21 years) with duodenal polyps diagnosed between 1983 and 2001 at The Johns Hopkins Children's Center. Our analysis includes a formal histologic evaluation of duodenal polyps either biopsied using cold‐forceps or removed by snare cautery.

Results

Duodenal polyps were reported in 22 of 5766 EGDs (0.4%) performed in 16 (M:F; 1:1) patients with a mean (SD) age of 14.1 (5.1) years. Polyps were equal in both the Caucasian and African American population (adjusted ratio 1.2:1). The histologic subtypes included Adenomatous (42%), Brunner's gland hyperplastic (33%), hamartomatous (17%), and heterotopic gastric gland polyps (8%). The most frequent indication for EGD was surveillance in patients with polyposis syndromes; most of these patients were asymptomatic at the time of their EGD. In comparison, the most frequent indication for an EGD in patients without polyposis syndromes was abdominal pain and vomiting.

Conclusions

Duodenal polyps are most frequently encountered in children with polyposis syndromes, most of whom are asymptomatic. In nonsyndromic patients, the most common histologic subtype is Brunner's gland hyperplastic polyp and presenting symptoms include abdominal pain and vomiting.
Homocysteine Prevents Total Parenteral Nutrition (TPN)–Induced Cholestasis Without Changes in Hepatic Oxidative Stress in the Rat
Authors: Belli Dominique C. , Albrecht Robert , La Scala Giorgio C. , Desjeux Jehan‐François , Pelissier Marie‐Agnes
Published: January 2024

Background

The role of oxidative stress in total parenteral nutrition (TPN)–associated cholestasis with liver glutathione depletion was recently shown. The aims of this study were to test the appearance of cholestasis and oxidative stress during TPN, and the hypothesis that reducing oxidative stress with a precursor of glutathione (GSH), homocysteine, would restore bile flow.

Methods

Three groups of rats (weight, 179–278 g) were studied: 1) D/aa group received dextrose and amino acids (3.4 g/d); 2) D/aa/L group received the same amount of amino acids, and lipids were added on an equicaloric basis (50 kcal/d) with a lowered amount of dextrose; and 3) a control group, which received dextrose perfusion and had free access to chow. A subgroup of D/aa/L rats (n = 6) received a TPN solution containing homocysteine. After 5 days of TPN, bile was collected during 2 hours. In liver homogenates, GSH, thiobarbituric acid reactive substances (TBARS), and carbonyl content of proteins (Prot‐CO) were measured to test the level of oxidative stress and hepatic lipid and protein oxidation.

Results

After TPN, bile flow was significantly lower in the D/aa group than in the control group. Addition of lipids further decreased bile flow. Addition of homocysteine to TPN with lipids significantly increased bile flow. Aspartate aminotransferase increased significantly in both TPN groups compared with the control group. γ‐Glutamyl transpeptidase was not different among TPN groups. An increased hepatic lipid oxidation was demonstrated by TBARS level in both TPN groups when compared with the control group. However, the liver GSH contents were not different. Protein oxidation was also significantly increased by TPN. The addition of homocysteine to TPN solution increased bile flow without liver injury or changes of lipid and protein oxidation.

Discussion

This study shows that TPN administered to rats induces a decrease of bile flow and an oxidative stress but that the two changes are not directly correlated. Addition of lipids further impairs bile flow but does not increase the occurrence of liver injury. Consequently, it seems more likely that TPN primarily induces a cholestatic effect that in turn induces an oxidative stress rather than inducing an oxidative stress that leads to cholestasis. However, an association of both mechanisms is not totally excluded.
Bile in the Esophagus: A Factor in the Pathogenesis of Reflux Esophagitis in Children
Authors: Orel Rok , Markovic Sasa
Published: January 2024

Objectives

Bile reflux has been postulated to be an important factor contributing to gastroesophageal reflux disease in adults. The purpose of this study was to investigate its role in children.

Methods

Sixty‐five children with symptoms of gastroesophageal reflux disease were classified on the basis of the endoscopic grade of reflux esophagitis: no esophagitis (n = 26), mild to moderate esophagitis (n = 26), and severe esophagitis (n = 13). Simultaneous 24‐hour esophageal pH and bilirubin monitoring with Bilitec 2000 was performed.

Results

Both bile and acid reflux increased with the severity of esophagitis. The differences between all groups were significant for the percentage of total (P < 0.0005), upright (P < 0.05), and supine time (P < 0.0005) bilirubin absorbance ≥ 0.14, as well as for the percentage of total and supine time pH < 4, and DeMeester score (P < 0.0005). Combined pathologic acid and bile reflux was found in 11% of children with mild esophagitis and in 70% of children with severe esophagitis, while isolated bile reflux was found in 31% and 7.5%, respectively. Combined pH and bilirubin monitoring, compared with ph‐monitoring alone, increased the sensitivity from 56% to 79%, and the accuracy from 69% to 83%.

Conclusions

Both bile and acid reflux increase stepwise with the severity of esophagitis.

Combined acid and bile reflux is associated with severe esophagitis. Isolated acid or bile reflux is usually present in mild esophagitis.

Simultaneous esophageal pH and bilirubin monitoring has a higher sensitivity, as well as predictive values and accuracy than ph monitoring alone.
Urinary NOx:Creatinine Ratios During Gluten Challenge in Children With Celiac Disease
Authors: Koster‐Kamphuis L. , van Straaten E. A. , Kors W. A. , De Schrijver J. E. A. R. , Bovee‐Oudenhoven I. M. Y. , van der Meer R. , Forget P‐Ph.
Published: January 2024

Objectives

Celiac disease is a gluten‐induced small bowel enteropathy. Inflammation is known to be associated with enhanced nitric oxide (NO) production. An increase in urinary nitrate and nitrite (NOx) reflects increased NO production. The urinary NOx:creatinine ratio can be used as an indicator of the endogenous NO production. The aim of the study was to determine whether the urinary NOx:creatinine ratio of celiac disease patients increases during gluten challenge.

Methods

The authors studied 20 patients with unconfirmed celiac disease who had been following a gluten‐free diet for at least 1 year. These patients underwent an 80‐day gluten challenge. Urinary samples were obtained before and 10, 20, 40, and 80 days after starting the gluten challenge. The Griess reagent method was used for measuring urinary NOx.

Results

Gluten challenge confirmed the diagnosis of celiac disease in 15 of 20 patients. The NOx:creatinine ratios (mmol:mmol) of the biopsy‐confirmed celiac disease patients were significantly higher than those of the unconfirmed celiac disease patients (0.67 vs. 0.17 on day 10; 0.78 vs. 0.15 on day 20; 0.85 vs. 0.25 on day 40; and 0.85 vs. 0.17 on day 80).

Conclusions

Gluten challenge resulted in an increased urinary NOx:creatinine ratio in patients with biopsy‐confirmed celiac disease. The NOx:creatinine ratio could be useful for the serial evaluation of disease activity.
Lactobacillus plantarum Inhibits the Intestinal Epithelial Migration of Neutrophils Induced by Enteropathogenic Escherichia coli
Authors: Michail Sonia , Abernathy Frank
Published: January 2024

Background

Lactobacillus plantarum is a Gram‐positive bacillus known for its effect as a probiotic agent. The goal of the study was to determine whether L. plantarum is capable of inhibiting the transepithelial neutrophil migration induced by enteropathogenic Escherichia coli (EPEC).

Methods

Cultured intestinal epithelial T‐84 cell monolayers were rapidly infected with EPEC. L. plantarum or culture supernatants were added to the monolayers before and after the infection. Indium‐labeled neutrophils were added to the basolateral side of inverted monolayers. After 150‐minute incubation, radioactivity of the neutrophils that migrated in the physiologic direction was assayed, and the number of migrating neutrophils was calculated. L. plantarum was also added to the monolayers before and after EPEC infection, and the number of adherent EPEC was determined by plate counting.

Results

EPEC‐induced neutrophil migration and EPEC binding to monolayers were inhibited by viable L. plantarum but only when added to the monolayers before EPEC. Culture supernatants failed to inhibit the neutrophil migration.

Conclusions

These results suggest that L. plantarum is beneficial in inhibiting neutrophil migration induced by EPEC, but only when preincubated with host epithelia. Rather than an indirect effect through a secreted substance produced by the probiotic agent, its effect is direct and requires the presence of the bacterium.
Increased Prevalence of Autoimmune Diseases in First‐Degree Relatives of Patients With Celiac Disease
Authors: Cataldo Francesco , Marino Vincenzo
Published: January 2024

Background

The prevalence of autoimmune disorders is increased in patients with celiac disease (CD), and it is unknown whether their first‐degree relatives also have a high risk of autoimmune disorders.

Methods

To assess the prevalence of autoimmune diseases in first‐degree relatives of CD patients, the authors looked for autoimmune disorders in 225 first‐degree relatives of 66 children with CD (group A) and in 232 first‐degree relatives of 68 healthy children (group B). For both groups, serologic screening for CD was performed through antiendomysium (EMA) and tissue transglutaminase autoantibodies (tTGAA). EMA‐ and tTGAA‐positive subjects were offered an intestinal biopsy. The age at onset of autoimmune diseases was also recorded in group A.

Results

The prevalence of autoimmune disorders was significantly (P = 0.028) higher in group A (11 of 225, 4.8%) than in group B (2 of 232, 0.86%). In relatives of CD patients, the prevalence increased with age (χ2 for trend, 43.5;P < 0.0001). Serologic screening for CD was only positive in group A (15 of 225 subjects). An intestinal biopsy was performed in 13 of these 15 relatives (2 refused biopsy). Eleven of 13 had flat mucosa, with subclinical or silent forms of CD. The prevalence of autoimmune diseases in the EMA‐ and tTGAA‐positive relatives of CD patients was significantly higher (3 of 15, 20%;P = 0.028; odds ratio, 6.3; 95% CI, 1/0.21–1/0.11, 4.9–7.6) than in those who were EMA and tTGAA negative (8/210, 3.8%).

Conclusions

The first‐degree relatives of CD patients have an increased risk of autoimmune diseases, most likely connected with unrecognized subclinical or silent forms of CD.
Rectal Manometry in Patients With Isolated Sacral Agenesis
Authors: Morera Claudio , Nurko Samuel
Published: January 2024

Objective:

The authors evaluated rectal manometry of children with sacral root abnormalities secondary to isolated sacral agenesis.

Methods:

The anorectal manometric recordings of seven patients with isolated sacral agenesis (four with partial agenesis and three with complete agenesis) were retrospectively evaluated and compared with tracings from healthy control subjects. Characteristics of the internal anal sphincter (IAS), the rectoanal inhibitory reflex (RAIR), voluntary external anal squeeze pressure, and threshold of rectal sensation to distension were analyzed. Characteristics of the patients' neurologic function with attention to urinary and fecal continence were obtained by chart review.

Results:

All seven patients had urinary and fecal incontinence. IAS resting pressure was the same in patients and control subjects. In the three patients with total sacral agenesis, IAS relaxation was more complete and lasted longer after balloon distention of the rectum. These patients also had significantly lower voluntary external anal squeeze pressure and blunted sensation of rectal distension.

Conclusions:

Abnormal parasympathetic innervation associated with sacral agenesis is associated with changes in anorectal function. Manometric findings suggest that there is modulation of the RAIR by extrinsic innervation, which may explain the fecal incontinence in these patients.
Long‐Term Follow‐Up of Overweight Children: After Training, After a Single Consultation Session, and Without Treatment
Authors: Reinehr Thomas , Kersting Mathilde , Alexy Ute , Andler Werner
Published: January 2024

Background:

A satisfactory treatment of childhood obesity has not yet been found. An individual consultation session is the usual practice while experts recommend an outpatient training program consisting of a combination of physical exercise, nutrition education, and behavior therapy.

Methods:

We analyzed degree of overweight (SDS‐BMI) after one and two years in overweight children (aged 6‐15 years) who had had a single consultation session (n = 66) and who had finished a one‐year, structured outpatient training program consisting of physical exercise, nutrition education, and behavior therapy (n = 81). Furthermore we collected data on changes in weight for a control group of overweight children not receiving any treatment (n = 100) over the same period of time.

Results:

There was no significant change in the degree of overweight over the period of two years either for the control group or for those having received single consultation. The participants of the training were in mean significantly less overweight than at the beginning of the training (P < 0.001), both after one year (mean change in SDS‐BMI ‐0.38) and after the second year (mean change in SDS‐BMI ‐0.30).

Conclusions:

Overweight children not receiving treatment do not reduce in weight. A single consultation session is not sufficient to achieve weight reduction in children. Weight reduction over at least two years can be achieved in part of the participants of a long‐term, specialized treatment. JPGN 37:72‐74, 2003.
Dietary Nucleotides Modulate Mitochondrial Function of Intestinal Mucosa in Weanling Rats with Chronic Diarrhea
Authors: Arnaud Alexandra , López‐Pedrosa José María , Torres María Isabel , Gil Ángel
Published: January 2024

Background

Chronic diarrhea during early infancy is characterized by intestinal mucosal injury, and as a consequence, the mitochondrial system of oxidation and reduction and energy production is altered. Since dietary nucleotides have been associated with the process of intestinal mucosal repair in rats with chronic diarrhea, the aim of this study was to examine the effects of dietary nucleotides on the functioning of mucosal mitochondria.

Methods

Weanling rats were fed with a semipurified synthetic diet (C) or the same diet in which carbohydrates were substituted by lactose (L), resulting in chronic diarrhea. During recovery, rats were fed with the semipurified synthetic diet (LC) or the same diet supplemented with nucleotides (LN). The activities of adenosine triphosphate synthase (ATPase), cytochrome c oxidase, citrate synthase, and malate dehydrogenase were measured in mitochondria from ileum and colon mucosa.

Results

These enzymatic activities rose in rats with chronic diarrhea, possibly to compensate for the drastic decline in adenosine triphosphate (ATP) synthesis. Dietary nucleotide supplementation allowed normalizing of the activities of ATPase (C: 0.37 ± 0.16 μg/min/mg protein; L: 0.68 ± 0.25 μg/min/mg protein; LC: 0.60 ± 0.20 μg/min/mg protein; LN: 0.42 ± 0.22 μg/min/mg protein), citrate synthase (C: 0.12 ± 0.05 mM/min/mg protein; L: 0.21 ± 0.07 mM/min/mg protein; LC: 0.21 ± 0.06 mM/min/mg protein; LN: 0.12 ± 0.02 mM/min/mg protein), and malate dehydrogenase (C: 0.77 ± 0.48 mM/min/mg protein; L: 3.08 ± 0.85 mM/min/mg protein; LC: 2.11 ± 0.44 mM/min/mg protein; LN: 1.13 ± 0.51 mM/min/mg protein) in the ileum mitochondria of the diarrheic rats. In colonic mucosa, mitochondrial enzymatic activities were restored after eliminating lactose from the diet.

Conclusion

These results suggest that dietary nucleotides promote earlier restoration of the ileal mitochondrial function after chronic diarrhea.
Gastrointestinal Motility and Sensory Abnormalities May Contribute to Food Refusal in Medically Fragile Toddlers
Authors: Zangen Tsili , Ciarla Carla , Zangen Samuel , Di Lorenzo Carlo , Flores Alex F. , Cocjin Jose , Reddy Sarabudla Narasimha , Rowhani Anita , Schwankovsky Lenore , Hyman Paul E.
Published: January 2024

Background

In chronically ill children who refuse to eat, surgery to correct anatomic problems and behavioral treatments to overcome oral aversion often succeed. A few patients fail with standard treatments. The aims of the study were to: 1) investigate motility and gastric sensory abnormalities and 2) describe treatment that was individualized based on pathophysiology in children who failed surgery and behavioral treatments.

Methods

We studied 14 patients (age 1.5–6; mean 2.5; M/F: 7/7). All had a lifelong history of food aversion and retching or vomiting persisting after feeding therapy and fundoplication. All were fed through gastrostomy or gastro‐jejunostomy tubes. We studied esophageal and antroduodenal manometry, and gastric volume threshold for retching. We identified when gastric antral contractions were associated with retching and pain. A multidisciplinary treatment program included a variable combination of continuous post‐pyloric feedings, drugs to decrease visceral pain, drugs for motility disorders, and behavioral, cognitive, and family therapy. We interviewed parents 2–6 months following testing to evaluate symptoms, mode of feeding and emotional health.

Results

We found a motility disorder alone in 2, decreased threshold for retching alone in 5 and both motility and sensory abnormalities in 7. After treatment, 6 of 14 (43%) began eating orally and 80% had improved emotional health. Retching decreased from 15 episodes per day to an average of 1.4 per day (p <0.01).

Conclusions

Upper gastrointestinal motor and/or sensory disorders contributed to reduced quality of life for a majority of children and families with persistent feeding problems. A multidisciplinary approach improved symptoms and problems in these children
Can Pre‐Neoplastic Lesions be Detected in Gastric Biopsies of Children with Helicobacter pylori Infection?
Authors: Guarner Jeannette , Bartlett Jeanine , Whistler Toni , Pierce‐Smith Daphne , Owens Marilyn , Kreh Rachel , Czinn Steven , Gold Benjamin D.
Published: January 2024

Background

Active gastritis, gastric mucosal atrophy and intestinal metaplasia are lesions associated with Helicobacter pylori infection. Atrophy and intestinal metaplasia are only seen in adults.

Objectives

We describe pediatric patients with atrophy and metaplasia, and compare the inflammatory response in these patients to controls.

Methods

As part of a multicenter study of pediatric H. pylori infection, gastric biopsy specimens obtained during diagnostic upper endoscopy of 19 H. pylori‐infected children and 45 uninfected controls were reviewed and graded by using the updated Sydney system. The inflammatory response was characterized using immunohistochemistry for T lymphocytes, B lymphocytes, and macrophages, and TUNEL assay for apoptosis.

Results

Histology of H. pylori‐infected and control biopsy specimens showed active gastritis in 32% and 2% respectively (P = 0.002). Mild intestinal metaplasia was found in 4 H. pylori‐infected children, in two of whom it appeared to be accompanied by atrophy. Specimens from patients with H. pylori infection contained increased numbers of B lymphocytes in lymphoid nodules, and apoptosis in the superficial epithelium and inflammatory cells. T lymphocytes and macrophages appeared in similar numbers in specimens from controls and infected patients.

Conclusions

We describe intestinal metaplasia associated with H. pylori infection in children. Since atrophy usually precedes intestinal metaplasia in adults, we suggest that atrophy exists in children. High numbers of B lymphocytes and apoptosis in the surface epithelium are seen in patients with H. pylori infection and may be related to the development of atrophy and intestinal metaplasia.
Maternal Education and the Incidence and Duration of Breast Feeding: A Prospective Study
Authors: Bertini Giovanna , Perugi Silvia , Dani Carlo , Pezzati Marco , Tronchin Michele , Rubaltelli Firmino F.
Published: January 2024

Introduction

Duration of breast feeding and factors possibly affecting duration were studied in a population of 2174 newborn infants, with gestational age of >37 weeks, who were born in the Department of Obstetrics and Gynaecology at the University of Florence Hospital between November 15, 1997, and November 14, 1998.

Patients and Methods

Nine hundred mothers agreed to participate in the study. Five questionnaires were completed at the end of the 1st, 3rd, 6th, 9th, and 12th postpartum month. These dealt with infant feeding practices, including breast feeding during the previous week. Breast feeding duration was defined as short (1 month); medium‐short (>1 month–<3 months); medium (>3–<6 months); medium‐long (>6–<9 months), and long (>9 months).

Results

The authors found that 76.3%, 64.7%, 42.3%, 26.4%, and 17% of mothers were still breast feeding at 1, 3, 6, 9, and 12 months after delivery, respectively. The multivariate analysis of the correspondence shows that lack of breast feeding is associated with a birth weight of less than 3000 g, a low level of maternal education, and maternal profession as a housewife or blue collar worker in the commercial sector. A period of breast feeding defined as short or medium‐short is associated with mothers who smoke, primiparous mothers, and absence of maternal allergy. The survival curves highlight how the single factor of smoking is an element that leads to a significant difference in the duration of breast feeding. The multiple Cox regression analysis shows a significant negative influence associated with birth weight of less than 3000 g, maternal smoking, and first parity. Above all, among low–birth‐weight infants of mothers who smoke, there is a strong correlation with a shorter duration of breast feeding.

Discussion

There is still a need for programs that support and encourage breast feeding, focusing particularly on mothers with a low level of education who give birth to a low‐weight infant, primiparous mothers, and smokers.
Dietary Nucleotides Accelerate Changes in Intestinal Lymphocyte Maturation in Weanling Mice
Authors: Manzano Manuel , Abadía‐Molina Ana Clara , Olivares Enrique‐García , Gil Angel , Rueda Ricardo
Published: January 2024

Objective

Nucleotides, the building blocks of nucleic acids, are normal components of the mammalian diet. These molecules have been implicated in biologic processes, such as the stimulation of the immunologic response. Nucleotides have also been considered as conditionally essential nutrients for infant formulas. The authors evaluated the influence of dietary nucleotides on the expression of several surface antigens by different intestinal lymphocyte populations in weanling mice.

Methods

Mice at weaning were fed a semipurified diet with or without 3 g/kg of each of the following nucleotides: adenosine monophosphate, cytosine monophosphate, guanosine monophosphate, and uridine monophosphate. Animals were killed at different times (0, 4, 7, 12, and 18 days) after weaning, and lymphocytes from intestinal Peyer's patches, epithelium, and lamina propria were isolated. The expression of different antigens (CD3, CD4, CD8α, CD8β, TCRαβ, TCRγδ, CD5, CD22 and CD45R) was analyzed by flow cytometry.

Results

The expression of these antigens changed parallel to the maturation of the lymphocytes from Peyer's patches, epithelium, and lamina propria. However, developmental changes of expression for most of the antigens occurred sooner in the animals fed the diet supplemented with nucleotides. The expression of T and B antigens was different in the lymphocyte populations analyzed and also changed according to the diet within each population. In general, nucleotides promoted the expression of B‐ and T‐helper cell antigens.

Conclusions

The authors conclude that dietary nucleotides may affect the process of maturation and differentiation of intestinal lymphocytes, which usually takes place at weaning.
Leptin and Cytokines Levels in Children with Failure to Thrive
Authors: Shaoul Ron , Kessel Aharon , Toubi Elias , Lanir Amos , Glazer Oded , Jaffe Michael
Published: January 2024

Background

The majority of cases of failure to thrive (FTT) are non‐organic. Many of these patients present with significant decreased caloric intake. It appears as if the appetite regulation center in the hypothalamus is not attuned to the calorie requirements of the infant.

Objective

Our hypothesis was that some cases of non‐organic FTT might be caused by abnormalities in hunger/satiety control secondary to neuroendocrine or cytokine imbalance. The aim of this study was to investigate which hormonal/cytokine profiles could be assigned to a defined category of FTT, namely organic, psychosocial and idiopathic subgroups.

Study design

34 patients were enrolled and 32 completed the study (12 controls, 12 idiopathic FTT, 5 organic FTT, and 3 psychosocial FTT). Each child was assessed by a pediatric gastroenterologist, dietician, and social worker and underwent appropriate laboratory investigation during which leptin, IL1, IL6 and TNF‐α levels were determined. The Mann‐Whitney U test was used to compare the groups.

Results

IL6 was the only cytokine that showed significant differences between FTT patients (4.06 ± 6.3 pg/ml) and normal controls (0.0 pg/ml (p = 0.028). Leptin values were significantly higher in the normal control group (1632 ± 483 pg/ml) as compared to FTT patients (685 ± 687 pg/ml) (p = 0.001).

Conclusions

Our results indicate that leptin does not play a role in the pathogenesis of anorexia in children with FTT. It is however, possible that IL6 may be an important factor in the etiology of anorexia in patients with FTT.
CARD15 Genotype and Phenotype Analysis in 55 Pediatric Patients With Crohn Disease From Saxony, Germany
Authors: Sun Liping , Roesler Joachim , Rösen‐Wolff Angela , Winkler Ulf , Koch Rainer , Thürigen Anett , Henker Jobst
Published: January 2024

Objectives

Crohn disease is a chronic inflammatory bowel disorder that is caused by environmental and genetic factors. Mutations in the CARD15 gene have been recently identified to be associated with the disease. Until now no genetic study has focused directly on a pediatric population.

Methods

The authors sequenced all 12 exons of the CARD15 gene in 55 pediatric patients with Crohn disease from Saxony. Their average age at onset was 11.2 years (1–17.5 years). The authors also evaluated the genotype‐phenotype relationship in the patients.

Results

Fourteen different polymorphic and/or disease‐related nucleotide alterations have been identified in the patients. Sixty‐five percent of their genomic DNA samples harbored at least one of six mutations within the CARD15 gene, which previously has been identified as being associated with Crohn disease. The authors found that the cytosine insertion mutation 3020insC was significantly more common in their pediatric population than in patients with Crohn disease (26% versus 11% of the alleles) whose results were reported in the literature. The genotype–phenotype analysis showed that the authors' patients with at least one of the six CARD15 disease‐associated mutations had a high risk of inflammation located in the terminal ileum and ascending colon. In 10 of 19 patients with two mutations, intestinal resection surgery was necessary because of stricturing.

Conclusions

In the authors' pediatric patients, the genetic influence on Crohn disease was more pronounced than that reported in any other study, and it strongly affected the clinical phenotype.
Establishing Enteral Feeding in Preterm Infants with Feeding Intolerance: A Randomized Controlled Study of Low‐dose Erythromycin
Authors: Ng Steven Chin‐Yuen , Gomez Joseph Manuel , Rajadurai Victor Samuel , Saw Seang‐Mei , Quak Seng‐Hock
Published: January 2024

Objective

A prospective, double‐blind, randomized, controlled trial was conducted to evaluate the effect of low‐dose erythromycin on the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance.

Methods

Two groups of preterm infants (birth weight ≤ 1500 g) with feeding intolerance were randomized to either low‐dose erythromycin (5 mg/kg every 8 hours) or 5% dextrose placebo, both of which were discontinued 1 week after full enteral feedings were tolerated. The primary outcome variable was the time taken to attain full enteral feedings of at least 130 mL/kg/d.

Results

The gestational age at birth was similar in the two groups (erythromycin, 27.1 ± 1.9 weeks; placebo, 27.5 ± 2.9 weeks). The mean birth weight of the erythromycin group was lower (806.3 ± 215.6 g) than the placebo group (981.4 ± 285.4 g; P = 0.18), and included more infants who were small for gestational age (4/13 = 31% versus 1/11 = 9%; P = 0.224). There was no difference between the two groups with regard to the volume of feedings they were receiving at the time of enrollment. Reduction in symptoms of gastroesophageal reflux was similar in the two groups. 3 of 13 in the erythromycin group and 4 of 11 in the placebo group improved during the study (P = 0.565). The mean time to attain full enteral feedings after enrollment was 24.9 + 2.9 days in the erythromycin group and 30.8 ± 4.1 days in the placebo group, a difference that did not reach statistical significance (P = 0.17).

Conclusions

Low‐dose erythromycin did not reduce the time taken to attain full enteral feedings in preterm infants with very low birth weight and feeding intolerance. Gastroesophageal reflux decreased as a consequence of maturation of the gastrointestinal tract and not because of erythromycin. These preliminary results justify verification in larger multicenter trials.
Increased Levels of Hemostatic Proteins are Independent of Inflammation in Glycogen Storage Disease Type Ia
Authors: Marfaing‐Koka Anne , Wolf Martine , Boyer‐Neumann Catherine , Meyer Dominique , Odievre Michel , Labrune Philippe
Published: January 2024

Objectives

Glycogen storage disease type Ia (GSD‐Ia), a congenital deficiency of hepatic glucose‐6‐phosphatase activity, is often associated with hyperproteinemia. To document the mechanism of hyperproteinemia, the proteins of the hemostatic system were analyzed according to their site of synthesis: hepatocyte, endothelial cell, or both. The role of inflammation was investigated by the measurement of tumor necrosis factor alpha (TNF‐α) and interleukin‐6 (IL‐6) levels in plasma.

Methods

Twenty‐seven patients with GSD‐Ia were evaluated, as were 14 patients with other types of GSD and 30 healthy control subjects. Of the 41 patients with GSD, 15 also had hepatic adenoma (14 patients with GSD‐Ia and 1 with GSD type III).

Results

In patients with GSD‐Ia, there was a two‐fold increase in all hepatocyte‐synthesized proteins (i.e., factor VII, protein C, C4b binding protein) compared with control subjects and patients with other types of GSD. The proteins with mixed endothelial and hepatocyte origin (i.e., antithrombin and protein S) also were significantly increased but to a lesser extent. In contrast, the mean concentration of von Willebrand factor, which is exclusively synthesized in endothelial cells, was normal, as was the concentration of TNF‐α and IL‐6.

Conclusions

These results suggest that the hyperproteinemia of GSD‐Ia (including hemostatic proteins) is attributable to hepatocyte dysfunction and not related to an inflammatory process.
Effects of Highly Purified Eicosapentaenoic Acid on Erythrocyte Fatty Acid Composition and Leukocyte and Colonic Mucosa Leukotriene B4 Production in Children With Ulcerative Colitis
Authors: Shimizu Toshiaki , Fujii Tohru , Suzuki Ryuyo , Igarashi Jun , Ohtsuka Yoshikazu , Nagata Satoru , Yamashiro Yuichiro
Published: January 2024

Background

n‐3 Polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for ulcerative colitis (UC). However, the efficacy of n‐3 PUFAs against UC has not been examined in children. Therefore, the authors investigated the effects of eicosapentaenoic acid (EPA) on fatty acid composition and leukotriene (LT) production in children with UC.

Methods

For 2 months the authors administered highly purified EPA ethyl ester (EPA‐E) (1.8 g/d) to children with UC in remission. Colonic mucosal histology, fatty acid composition of erythrocyte membrane phospholipids, and LTB4 production by leukocytes and colonic mucosa were measured before and 2 months after the initiation of EPA‐E treatment.

Results

No patients relapsed during the study period, and no significant differences were detected in laboratory findings obtained before and 2 months after the initiation of EPA‐E ingestion. There were no significant differences in mucosal histologic scores before and 2 months after EPA‐E treatment. The EPA levels in erythrocyte membranes 2 months after the initiation of EPA‐E treatment were significantly higher than before treatment, but the other fatty acids showed no significant changes. LTB4 production by leukocytes and rectal mucosa after 2 months of EPA‐E treatment was significantly lower than before treatment.

Conclusion

EPA‐E treatment increased the levels of EPA in erythrocytes and decreased LTB4 levels produced by leukocytes and colonic mucosa. To assess the concomitant clinical changes, we should examine the long‐term effects of EPA‐E ingestion on the maintenance of remission in children with UC.
Hyperhomocystinemia in Children With Inflammatory Bowel Disease
Authors: Nakano Emi , Taylor Christopher J. , Chada Lavleen , McGaw Jean , Powers Hilary J.
Published: January 2024

Objectives

Thromboembolism is a significant cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). Plasma total homocysteine (tHcy) is a risk factor for vascular disease and has been implicated as a mediator of thromboembolic events in adults with IBD. The authors studied the link between tHcy and IBD in children, in whom associations may be clearer, and investigated associations with plasma von Willebrand factor antigen, a marker of vascular damage.

Methods

This cross‐sectional study included 43 patients with IBD (27 Crohn disease, 9 ulcerative colitis, and 7 indeterminate colitis) and 46 control subjects from a pediatric gastroenterology clinic. Plasma tHcy, plasma 5‐methyl tetrahydrofolate, red cell folate, plasma vitamin B12, plasma von Willebrand factor antigen, and methylene tetrahydrofolate reductase (MTHFR) genotype (for the C677T mutation) were measured.

Results

Plasma tHcy concentrations were higher in children with IBD than in control subjects, when corrected for age (P < 0.05), and plasma tHcy was negatively correlated with plasma 5 methyl tetrahydrofolate (P < 0.0005). Plasma 5 methyl tetrahydrofolate and age were the main predictors of plasma tHcy. Neither MTHFR genotype nor von Willebrand factor showed any association with any other measure, and there were no differences between children with IBD and control subjects.

Conclusions

Elevated plasma tHcy is a consequence of IBD in children, probably mediated by poor folate status associated with diet or the pathophysiology of the disease.
Assessment of the DQ Heterodimer Test in the Diagnosis of Celiac Disease in the Canary Islands (Spain)
Authors: Peña‐Quintana L. , Torres‐Galván M. J. , Déniz‐Naranjo M. C. , Ortigosa‐Castillo L. , Ramos‐Varela J. C. , Calvo‐Hernández F. , Fiuza‐Pérez M. D. , Rodríguez‐Gallego J. C. , Sánchez‐García F.
Published: January 2024

Background

Celiac disease is a multifactorial disorder of the proximal small intestine associated with a permanent intolerance to gluten. The HLA‐DQ(α1*0501, β1*02) heterodimer is strongly associated with this disease.

Materials and Methods

The authors studied a sample of 354 unrelated Caucasoid individuals: 118 patients with celiac disease and 236 control subjects. All patients and controls subjects were born in Gran Canaria (Canary Islands) at least two generations ago.

The authors typed the HLA‐DQA1 and DQB1 genes by DNA methods. The positive and negative predictive values of the test were studied.

Results

The mean age at diagnosis was 25.4 months, with a statistically significant proportion of females (64.4%, P < 0.002). For DQB1 gene, the susceptibility allele found was DQB1*02 (relative risk [RR] = 7.60, confidence interval [CI]: 5.35–10.78), whereas for the DQA1 gene, the susceptibility alleles found were DQA1*0501 (RR = 2.99, CI: 2.16–4.14) and DQA1*0201 (RR = 1.88, CI: 1.25–2.82). The presence of the DQ(α1*0501, β1*02) heterodimer was strongly associated with the disease (92.4% in the patients group vs. 21.6% in control subjects). HLA‐DQ8 heterodimer was absent in the authors' patients. DQB1*02 homozygous subjects presented a higher relative risk for celiac disease. There was no correlation of DQB1*02 dosage with age at onset below 12 years of age or with gender distribution. Sensitivity, specificity, and the positive and negative predictive values of the test were 92.4%, 78.4%, 68.1%, and 95.4%, respectively.

Conclusions

The presence of the DQ2 (DQA1*0501/DQB1*02) heterodimer is strongly associated with celiac disease in the population studied by the authors. The value of this test derives from its ability to exclude disease when a negative result occurs.
Tests to Assess Symptoms of Gastroesophageal Reflux in Infants and Children
Authors: Orenstein Susan R.
Published: January 2024

In studying antireflux medications, we may use tests for assessing symptoms of gastroesophageal reflux to establish or confirm a diagnosis of reflux disease and to evaluate whether study subjects are improving with therapy. Symptom assessment questionnaires need to be validated, results need to be reproducible, and the outcome variables measured need to be clinically relevant. Other outcomes for clinical trials include measures of esophagitis: histologic (morphometric) measures in infants and endoscopic and histologic visualization in older children. Intraesophageal pH monitoring studies may be useful for obtaining pharmacodynamic data.
Current Regulatory Policies Regarding Pediatric Indications and Exclusivity
Authors: Rodriguez William J. , Roberts Rosemary , Murphy Dianne
Published: January 2024

Pediatric studies have resulted in changes in the dose of many medications given to children and an increased awareness of safety issues. An additional 6 months of pediatric exclusivity legislated under the Food and Drug Administration (FDA) Modernization Act of 1997 for pediatric studies undertaken in response to written requests from the FDA have stimulated the conduct of a large number of studies.