bluuebunny/crossref_metadata_2025 huggingface dataset:
IFN‐γ Enhances Macromolecular Transport Across Peyer's Patches in Suckling Rats: Implications for Natural Immune Responses to Dietary Antigens Early in Life
Authors: Sütas Yelda , Autio Soile , Rantala Immo , Isolauri Erika
Published: February 2024

Background:

The capacity to generate (interferon‐gamma) IFN‐γ, a potent immunoregulatory and inflammatory cytokine, is low in neonates and deficient in patients with food allergy.

Methods:

We investigated the effect of IFN‐γ on antigen transport in the gut. In experiment I rat pups were randomized into two groups at the age of 14 days i.e., before gut maturation: Group IFN was given intraperitoneally recombinant rat IFN‐γ on days 14, 16, 18, 20. In experiment II, rats were randomized into two groups at the age of 26 days, i.e., after gut maturation: Group IFN received the IFN‐γ treatment on days 26, 28, 30, 32. Controls in both experiments received sterile saline. The absorption of horseradish peroxidase (HRP) across jejunal segments with and without Peyer's patches was studied in Ussing chambers on days 21 and 33 for experiments I and II, respectively.

Results:

In experiment I, the absorption of intact HRP across both types of segments was significantly increased in Group IFN compared to controls. The mean (95% confidence interval) rate of degraded HRP absorption across patch‐containing segments in Group IFN was significantly greater than in controls, 4420 (3162‐6179) ng · h‐1 · cm‐2 in comparison to 1550 (633‐3790) ng · h‐1 · cm‐2; F = 8.96, p = 0.009.

Conclusion:

IFN‐γ increases macromolecular transport before gut maturation particularly across Peyer's patches. This Peyer's patch‐targeted effect can be important eliciting mucosal immune responses against dietary antigens early in life and aiding their immune exclusion.
Orally Administered Iodinated Recombinant Human Insulin‐like Growth Factor‐I (125I‐rhIGF‐I) Is Poorly Absorbed by the Newborn Piglet
Authors: Donovan Sharon M. , Chao Jane Chen‐Jui , Zijlstra Ruurd T. , Odle Jack
Published: February 2024

Background:

The purpose of the current study was to determine the degree to which milk‐borne insulin‐like growth factor‐I (IGF‐I) is absorbed.

Methods:

Cesarean‐derived piglets were fitted with umbilical arterial and venous catheters within 2 h of birth and were administered formula containing 21.7 ± 1.8 μCi of iodinated recombinant human IGF‐1 (125I‐rhIGF‐I) by orgogastric gavage. Blood samples were taken before administration of the 125I‐rhIGF‐I (t0) and for 4 h postgavage. Plasma was obtained by centrifugation and total and trichloroacetic acid precipitable radioacitivity were determined. Immunoreactive 125I‐rhIGF‐I was assessed using a polyclonal antibody to human IGF‐I. Four hours after feeding, intestines were removed, divided into 13 segments, and flushed with saline. Radioactivity within the small intestinal lumen and wall were measured.

Results:

Radioactivity in portal blood was higher than t0 at all times points (p < 0.05), whereas arterial radioactivity did not differ from t0 until 30 min postgavage. On average 18‐20% of total radioactivity in both portal and arterial blood was acid‐precipitable, with the proportion decreasing over time (p < 0.001). Immunoprecipitable radioactivity averaged 3‐5% of the total radioactivity and was higher in portal than arterial blood (p < 0.05). Based on a plasma volume of 0.062 ± 0.005 L and a baseline plasma IGF‐I concentration of 1.81 ± 0.56 nmol/L, absorbed 125I‐rhIGF‐I represented 0.205% of the total plasma IFG‐I pool, whereas 14% of the dose was associated with the lining of the intestine.

Conclusions:

Absorption of orally administered IGF‐I does not contribute significantly to circulating IGF‐I.
Fecal Bacterial Enzyme Activities in Infants Increase with Age and Adoption of Adult‐Type Diet
Authors: Mykkänen H. , Tikka J. , Pitkänen T. , Hänninen O.
Published: February 2024

Background:

The present study was conducted to determine the effects of age and diet (breast milk, milk formula, weaning diet) on the activities of some bacterial enzymes in fecal samples collected from 3‐ to 24‐month‐old infants. These bacterial enzymes may generate toxic, mutagenic, or carcinogenic metabolites from plant glycosides (β‐glucuronidase, β‐glucosidase) or from urea (urease).

Methods:

The subjects were 68 healthy children ages 3 (n = 20), 6 (n = 20), 12 (n = 17), and 24 (n = 11) months. None of the children had been given any antibiotics during 4 weeks before collection of the fecal samples. Health status, bowel habits, and food consumption of the children were determined by interview of one of the parents using a structured questionnaire. A spot fecal sample from each child was collected.

Results:

The activities of β‐glucuronidase and β‐glucosidase increased from 0.52 and 1.17 nmol/min × mg protein (at 3 months) to 1.41 and 2.38 nmol/min × mg protein (at 2 years), respectively. However, at 2 years of age, the children had not yet reached the levels reported in earlier studies on adult populations. Urease activity increased from 4.18 nmol/min × mg protein (at 3 months) to 19.0 nmol/min × mg protein (at 2 years), reaching by 12 months of age the level observed in adults. Breast feeding as such had no consistent effect on fecal bacterial enzyme activities. β‐Glucuronidase and β‐glucosidase were higher in those 6‐ and 12‐month‐old children who consumed more meat, fish, sausages, or eggs.

Conclusions:

It can be concluded that the fecal enzyme activities in the gastrointestinal tract increase and that their profile changes with age and adoption of adult‐type diet. It remains open, however, whether these changes are caused by the normal physiological aging process or by stepwise introduction of new foods to the diet.
Acceptability, Safety, and Digestibility of Spray‐Dried Bovine Serum Added to Diets of Recovering Malnourished Children
Authors: Lembcke Jorge L. , Peerson Janet M. , Brown Kenneth H.
Published: February 2024

Background

Specially collected, spray‐dried bovine and porcine blood plasma have been incorporated previously in feeds of weanling farm animals, resulting in increased dietary intakes and greater rates of weight gain than observed in control animals. Before conducting similar trials in human populations, preliminary studies have been completed to assess the acceptability, safety, and digestibility of processed animal plasma in young children.

Methods

Masked study diets were provided sequentially to each of ten young, Peruvian children recovering from severe protein‐energy malnutrition during three randomly ordered 7‐day dietary periods. The control diet was prepared from rice, milk, vegetable oil, and sugar; the two study diets included spray‐dried, bovine serum concentrate to replace either 25% or 50% of the milk protein of the control diet. Urine and faces were collected quantitatively during the last four days of each diet period to assess stool weight, apparent absorption of macronutrients, and retention of nitrogen.

Results

All children consumed the entire amounts offered of each of the diets. The mean number of daily bowel movements and mean apparent absorption and retention of nitrogen and mean apparent absorption of carbohydrate were similar for each diet. Fractional absorption of dietary lipid and of total energy increased significantly in relation to the amount of bovine serum concentrate in the diet, although this might be explained by the simultaneous replacement of milk fat with additional vegetable oil.

Conclusions

Each of the diets was well accepted by the study children, and there was no evidence of any adverse effects of bovine serum concentrate.
Colonic Structural and Ion Transport Abnormalities in Suckling Rabbits Infected with Escherichia coli K12
Authors: O'Loughlin Edward V. , Zhe Li , Buret Andre , Bell Cameron , Robins‐Browne Roy M. , Elliott Elizabeth J.
Published: February 2024

Background

Escherichia coli K12 is a laboratory strain considered nonpathogenic. The purpose of this study was to examine the effect of E. coli K12 infection on colonic structure and function.

Methods

Suckling rabbits were infected at 10 days of age with 6 × 109 CFU E. coli by intragastric inoculation and were examined 4 to 5 days later. Segments of ileum and proximal and distal colon were removed for light and electron microscopy, and NaCl transport was examined in vitro under short‐circuited conditions in Ussing chambers.

Results

Infection did not cause weight loss or diarrhea. Colonic mucosa was inflamed with infiltration by polymorpho‐nuclear neutrophils mainly in the lamina propria. The proximal and distal colon exhibited reduced Na+ absorption. The proximal colon also showed increased Cl‐ secretion; the ileum was unaffected.

Conclusions

Infection with E. coli K12 disrupts the epithelium and alters ion transport in the colon, probably as a result of mucosal inflammation. The changes indicate that nonpathogenic E. coli have the potential to cause intestinal disease.
Abnormal Expression of Brush‐Border Membrane Transporters in the Duodenal Mucosa of Two Patients with Microvillus Inclusion Disease
Authors: Michail Sonia , Collins James F. , Xu Hua , Kaufman Stuart , Vanderhoof Jon , Ghishan Fayez K.
Published: February 2024

Background:

Microvillus inclusion disease is a congenital disorder characterized by secretory diarrhea. Patients demonstrate villus atrophy, loss of microvilli, and internalized inclusions of microvilli within the cytoplasm of small intestinal enterocytes. The exact molecular defect in these patients is not known. Two infants are described in this report with microvillus inclusion disease. Case 1 was a 3‐month‐old boy who developed secretory diarrhea shortly after birth. Case 2 was a 9‐month‐old boy who had abrupt onset diarrhea at 2 weeks of age resulting in weight loss and dehydration. Light microscopy revealed total villus atrophy with minimal crypt hyperplasia, and electron microscopic examination revealed variably shortened microvilli and cytoplasmic microvillus inclusions in both patients.

Methods:

Poly (A)+ RNA was purified from duodenal biopsies and RT‐PCR reactions were performed. Normal human intestinal RNA was used as a positive control. Primers specific for human NHE‐1, NHE‐2, NHE‐3 (2 sets), sodium‐glucose transporter (SGLT1), and β‐actin were used.

Results:

Results showed that NHE‐1 and β‐actin cDNAs amplified to similar levels in both patient and control samples. However, the expression of NHE‐2 and SGLT1 was much higher in the control sample than in the patient samples. Additionally, NHE‐3 mRNA was not detected in the patient samples using two sets of NHE‐3 specific primers.

Conclusions:

The patients with microvillus inclusion disease have defects in apical but not basolateral membrane transport systems, and these defects are related to the pathogenesis of the disease.
Evaluation of Serology, 13C‐Urea Breath Test, and Polymerase Chain Reaction of Stool Samples to Detect Helicobacter pylori in Bangladeshi Children
Authors: Casswall Thomas H. , Nilsson Hans‐Olof , Bergström Mats , Aleljung Pär , Wadström Torkel , Dahlström Anders K. , Albert M. John , Sarker Shafiqul A.
Published: February 2024

Background:

Serologic methods to detect Helicobacter pylori in infants, especially in developing countries, may be limited because of decreased immune response caused by malnutrition. The true prevalence may therefore be underestimated in this age group. Urea breath test is considered to be a good screening method in children but is expensive and therefore is not suitable for screening in developing countries. Simple, inexpensive, and accurate noninvasive methods to detect H. pylori in infants and young children are needed.

Methods:

Enzyme immunoassay (EIA) and immunoblot (IB) serologic analyses, 13C‐urea breath test (UBT), and immunomagnetic separation‐polymerase chain reaction (IMS‐PCR) were performed on stool specimens, to detect H. pylori in 68 children between 4 and 24 months of age (mean, 11.5 months) in an endemic area in Bangladesh and the results compared.

Results:

The occurrence of H. pylori was 57% (n = 39) using only UBT, 60% (n = 41) using only IMS‐PCR, and 78% (n = 53) using UBT and IMS‐PCR together. The concordance between UBT and IMS‐PCR results was 62%. Immunoblot was positive in only 9% (n = 6). Results in all 68 children were negative using EIA.

Discussion:

The prevalence of H. pylori infection in this peri‐urban community and age group was high. Only serologic methods seem to be unsatisfactory for screening of H. pylori infection in infants and may not reflect the true prevalence. Immunomagnetic separation‐PCR is a simple and rapid method for detection of H. pylori in stool and is an attractive method for analysis of colonization in infants. However, it may reflect a different stage of disease than UBT. Further studies are needed to clarify this.
Dietary Lipid Composition Modifies Intestinal Morphology and Nutrient Transport in Young Rats
Authors: Perin Nilza , Jarocka‐Cyrta Elizabeth , Keelan Monika , Clandinin Tom , Thomson Alan
Published: February 2024

Background:

Varying lipid content of the diet of pregnant and nursing dams results in alterations in sugar and lipid uptake into the intestine of their suckling offspring. In this study, we wished to determine whether the same alterations in dietary lipid result in adaptation of intestinal transport in postweaning rats.

Methods:

During nursing, the dams were fed the same diet that their offspring were fed for 3 more weeks after weaning. These semipurified diets contained: 1) 15.8% of total fatty acids (w/w) as 18:2n‐6 and an n6/n3 ratio of 7.3:1; 2) a diet with 17.6% of total fatty acids as 18:2n‐6 and an n6/n3 ratio of 4:1; 3) a diet with 16.2% of total fatty acids as 18:2n‐6 and 1.2% arachidonic acid (AA); 4) a diet with 16.8% of total fatty acids at 18:2n‐6, 1.2% AA and 0.7% docosahexaenoic acid (DHA); and 5) a diet with 16.0% of total fatty acids as 18:2n‐6 and 0.7% as DHA. The in vitro uptake of D‐glucose, D‐fructose, medium‐ or long‐chain fatty acids and cholesterol was assessed in 6‐week‐old rats.

Results:

Feeding AA increased the Vmax for jejunal and ileal uptake of glucose, compared with the high n6/n3 diet. This effect was prevented by adding DHA to the AA diet. The low n6/n3 fatty acid ratio diet decreased uptake of fructose as compared with the high n6/n3 diet, and the increased uptake of fructose with DHA was prevented by adding AA. The incremental change in free energy associated with uptake of medium chain‐length fatty acids was lower in the jejunum of animals fed AA plus DHA as compared with the other diet groups. Jejunal uptake of 18:0 was lower for animals fed DHA or AA plus DHA, as compared with AA alone; ileal rate of uptake of long‐chain fatty acids was unaffected by diet.

Conclusions:

The intestine of young rats modifies its intestinal morphology and adapts its nutrient transport in response to variations in dietary lipids. In postweaning rats, the potentially undesirable effect of one fatty acid on nutrient uptake may be countered by adding a select second fatty acid to the diet.
Lymphocyte Subset Profile of Young Healthy Children Residing in a Rural Area: Possible Role of Recurrent Gastrointestinal Infections
Authors: Granot Esther , Rabinowitz Ruth , Schlesinger Michael
Published: February 2024

Background:

Lymphocyte subsets in healthy children are currently characterized by age‐related standards. Because antigenic stimuli play a role in maturation of the immune system after birth, there is a question of whether cellular immune development differs in infants whose living conditions entail extensive antigenic exposure and infants growing up in a more protected environment.

Methods:

Peripheral blood lymphocyte subsets were studied in two populations of children of similar age and nutritional status; children belonging to a rural population residing in proximity with farm animals and children from an economically privileged urban population. In each population, children studied included a group with an acute diarrheal episode and a healthy control group.

Results:

Among rural population children, 65% had experienced at least one episode of gastroenteritis within the previous 3‐month‐period, compared with less than 10% of urban population children. In the rural population group 15% had experienced two or more episodes of gastroenteritis. The proportion of helper T cells was similar in rural population and urban population children. Among helper T cells, the proportion of CD29+ “memory” cells of the total CD4+ helper T cells was more than two times higher than those in rural population children. The proportion of CD8 cells was higher in rural population children than in urban population children, and the proportion of natural killer cells, CD56+ and CD57+, was two to three times higher in rural population children. Within each population, peripheral blood lymphocyte subsets did not differ between the healthy control group and those with acute diarrhea.

Conclusions:

In young children exposure to environmental pathogens and specifically to gastrointestinal antigenic stimuli is a major factor affecting development of the cellular immune response. Young children who have experienced enhanced infectious exposure have a peripheral blood lymphocyte profile similar to that of adults.
Epidemiology of Altered Intestinal Permeability to Lactulose and Mannitol in Guatemalan Infants
Authors: Goto Keiko , Chew Francisco , Torún Benjamin , Peerson Janet M. , Brown Kenneth H.
Published: February 2024

Background:

Subclinical alterations of small intestinal function have been reported frequently in tropical countries. Studies of small intestinal permeability to lactulose and mannitol were therefore completed in Guatemalan infants from a low‐income, periurban community to assess the prevalence of altered intestinal function and the factors associated with this condition.

Methods:

Two hundred studies were successfully completed in 158 infants who had been free of diarrhea for at least 1 week before the day of study. Urinary concentrations of lactulose and mannitol during the 5‐hour period after ingestion of 400 mg/kg body weight of lactulose and 100 mg/kg body weight of mannitol were measured by gas‐liquid chromatography and compared by age group, feeding practices, anthropometric indexes, and serum iron and zinc concentrations.

Results:

The overall prevalence of altered intestinal permeability (defined as a ratio of urinary recovery of lactulose to mannitol [L/M] ≥0.07) was 30%. The urinary L/M recovery ratio was positively associated with age; low weight for age; and, in infants less than 6 months of age, non‐breast‐feeding. Children with serum iron concentrations less than 7.16 µM/l (40 µg/dl) had higher median L/M ratios (L/M = 0.068; 95% confidence interval [CI], 0.054, 0.085) than those with iron levels higher than this cutoff (L/M = 0.052; CI = 0.046, 0.058; p = 0.038). The median urinary L/M recovery ratio in 10 currently asymptomatic infants who had diarrhea during the week before testing (0.087; CI = 0.49, 0.154) was higher than that in children who had been free from diarrhea for at least 1 week (0.052; CI = 0.048, 0.056; p = 0.01).

Conclusion:

Age, feeding practices, low weight‐for‐age, low serum iron concentration, and recent diarrhea were all associated with altered intestinal function in this group of Guatemalan infants.
Helicobacter pylori and Nonulcer Dyspepsia in Childhood: Clinical Pattern, Diagnostic Techniques, and Bacterial Strains
Authors: Rutigliano Vincenzo , Ierardi Enzo , Francavilla Ruggiero , Castellaneta Stefania , Margiotta Marcella , Amoruso Annacinzia , Marrazza Elisa , Traversa Andrea , Panella Carmine , Rigillo Nicola , Francavilla Antonio
Published: February 2024

Background:

This is a report of the results of a multicenter study performed in children with dyspepsia from five pediatric centers in Puglia, a region in southern Italy. In the study, clinical features of Helicobacter pylori infection, the reliability of diagnostic techniques, and the involvement of bacterial strains were examined.

Methods:

Fifty‐three outpatients with dyspepsia enrolled in our study and compiled a diary recording clinical symptoms in patients before they underwent the following diagnostic techniques: endoscopy, biopsy for histologic analysis, rapid urease test, 13C urea breath test, serology specific for immunoglobulin (Ig) G and anti‐CagA and VacA.

Results:

H. pylori showed a prevalence of 30.2% (n = 16). Histologic positivity was seen in all patients at the antral level (H. pylori‐associated chronic gastritis). In the gastric body, bacterial chronic active gastritis was present only in six patients (H. pylori‐associated chronic pangastritis). Clinical evaluation showed a significant difference in favor of subjects positive for H. pylori only for epigastric burning and/or pain (p < 0.001). The comparison of results of diagnostic tests, using histology as the gold standard, showed sensitivity and specificity of more than 93% for 13C urea breath test and more than 85% for rapid urease test and serology. Anti‐CagA antibodies were found in 64.3% and anti‐VacA antibodies in 42.8% of H. pylori‐positive patients.

Conclusions:

H. pylori prevalence in children with dyspepsia from the geographic area studied in comparable with that found in other developed countries. Approximately 50% of the studied patients were infected by cytotoxic strains. The urea breath test was the most reliable noninvasive diagnostic tool and is suitable for routine use, although endoscopy with histologic assessment remains the definitive investigation and is particularly important in patients with positive serology for CagA and VacA. Finally, the frequency of aggressive strains in our region seems to affect the clinical pattern; this emphasizes the importance of definitive diagnosis in children and offers a new role for serology.
Growth Hormone Stimulates, Through Tyrosine Kinase, Ion Transport and Proliferation in Human Intestinal Cells
Authors: Canani Roberto Berni , Bisceglia Massimo , Bruzzese Eugenia , Mallardo Giuseppe , Guarino Alfredo
Published: February 2024

Background:

Growth hormone (GH) stimulates intestinal growth and differentiation and promotes water and ion absorption in the rat intestine. Epidermal growth factor has similar effects, which involve tyrosine kinase activity. The effects of growth hormone on ion transport and cell growth and the role of tyrosine kinase in these effects were examined in a human‐derived intestinal cell line (Caco‐2).

Methods:

For transport study, electrical parameters were measured in human intestinal Caco‐2 cell monolayers mounted in Ussing chambers. Cell growth was monitored by counting and 3H‐thymidine incorporation in the presence and absence of growth hormone. The role of tyrosine kinase was investigated by using its specific inhibitor genistein.

Results:

The addition of growth hormone induced a rapid, Cl‐‐dependent, decrease in short‐circuit current without affecting tissue conductance, which is consistent with an anion‐absorptive effect. Incubation with growth hormone increased cell count by 85% and 3H‐thymidine incorporation by 64% versus the count in control specimens. The absorptive and trophic effects of growth hormone were dose‐dependent, and the maximum effective concentration was identical for each effect. Genistein blocked and growth effect on ion transport and cell growth.

Conclusions:

Growth hormone stimulates ion absorption and cell growth in human enterocytes. Both effects result from a direct growth hormone‐enterocyte interaction, and both require tyrosine kinase activity. Growth hormone may have therapeutic potential in intestinal diseases characterized by epithelial atrophy and loss of water and electrolytes.
Gastroesophageal Reflux and Respiratory Phenomena in Infants: Status of the Intraluminal Impedance Technique
Authors: Wenzl Tobias G. , Silny Jiri , Schenke Simone , Peschgens Thomas , Heimann Gerhard , Skopnik Heino
Published: February 2024

Background:

The coincidence of recurrent respiratory symptoms and gastroesophageal reflux (GER) is a well‐known phenomenon in infants. Twenty‐four‐hour pH metry is the presumed gold standard of diagnostic tools for this symptom complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be detected. Gastroesophageal reflux with an esophageal pH in the physiological range (pH 5‐6.8) may represent many cases of clinically relevant GER unrecognized by pH metry. In this study the intraluminal multiple electrical impedance (IMP) procedure for complete registration of GER was compared with pH metry for its diagnostic value in the presence of respiratory symptoms.

Methods:

Twenty‐two infants with recurrent regurgitation or pulmonary problems were investigated simultaneously with IMP, pH metry, and polygraphy during two feeding periods. Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded, among other parameters.

Results:

Three hundred sixty‐four occurrences of GER were detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances were accompanied by a decrease of oxygen saturation of more than 10% of the initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16 reflux episodes were recognized by IMP only. After software‐aided preselection, 165 instances of apnea were visually validated, 49 of which were accompanied by GER. Thirty‐eight (77.6%) of these were exclusively recorded by IMP.

Conclusions:

The use of pH metry alone cannot detect most GER incidents accompanied by respiratory symptoms and therefore does not appear to be suitable for this approach. The pH‐independent IMP technique promises to be a reliable tool for presumably GER‐associated respiratory symptoms.
Nonspecific Esophageal Motility Disorders in Children Without Gastroesophageal Reflux
Authors: Rosario Jorge A. , Medow Marvin S. , Halata Michael S. , Bostwick Howard E. , Newman Leonard J. , Schwarz Steven M. , Berezin Stuart H.
Published: February 2024

Background:

Nonspecific esophageal motility disorders (NEMDs) have been identified in up to 50% of adults with noncardiac chest pain or dysphagia. This study sought to determine the incidence of NEMDs in children with upper gastrointestinal tract symptoms and to evaluate the clinical course of pediatric patients with these manometric abnormalities.

Methods:

The study involved 154 children aged 4 to 18 years (mean age, 11.6 ± 2.6 years [SE]) who had upper gastrointestinal, swallowing‐related symptoms. The children were evaluated by 24‐hour intraesophageal pH monitoring, esophageal manometry, and esophagogastroduodenoscopy.

Results:

Gastroesophageal reflux (GER) was diagnosed by pH study in 109 (71%) of 154 patients, and examination of biopsy specimens demonstrated esophagitis in 70 children with GER. Results of esophageal manometry were abnormal in 30 (67%) of 45 children without GER. A variety of motility disorders were diagnosed in 17 of the patients without GER, whereas NEMDs were diagnosed in the remaining 13 children (mean age, 10.6 ± 2.7 years; 10 boys, 3 girls). Patients with GER showed normal esophageal wave propagation; however, mean lower esophageal sphincter pressure was significantly lower in patients with GER than in children with NEMDs. The children with NEMDs exhibited a diverse array of symptoms, including esophageal food impaction in 4 of the 13 patients. During a 36.2 ± 4.3‐month follow‐up period, no correlation was found between therapeutic intervention and clinical course in the 13 patients with NEMDs. Symptomatic improvement occurred in 6 of 13 patients, including 3 children for whom no pharmacologic therapy was prescribed.

Conclusions:

These data indicate that NEMDs represent a common group of esophageal manometric abnormalities in children with upper gastrointestinal tract symptoms and without GER. Food impaction appears to be a relatively frequent complication, and NEMDs should be considered in children who have this finding.
Propranolol in Prevention of Portal Hypertensive Hemorrhage in Children: A Pilot Study
Authors: Shashidhar Harohalli , Langhans Nancy , Grand Richard J.
Published: February 2024

Background:

Data regarding the use of propranolol in the prevention of portal hypertensive hemorrhage in pediatric patients are limited despite its widespread use in adults with cirrhosis. The purpose of this study was to evaluate safety and efficacy of propranolol in the management of portal hypertension in the pediatric population.

Methods:

Medical information was retrieved from the records of 21 children with portal hypertension who received propranolol either before or after an episode of gastrointestinal bleeding. Data collected included diagnosis, type of portal hypertension, age at initiation of therapy, bleeding episodes before and during propranolol therapy, degree of reduction of heart rate, adherence, and adverse effects.

Results:

Fourteen of 21 patients did not experience portal hypertensive bleeding while receiving propranolol. Of the seven patients who had bleeding episodes, two had failed to adhere to the medication regimen, and four were receiving doses of less than 1 mg/kg per day. Only one of the four patients who experienced bleeding before initiation of therapy also bled while receiving propranolol, and two of the three patients who had a heart rate reduction of less than 25% each experienced a bleeding episode. Side effects were minimal and did not necessitate discontinuation of therapy in any patient.

Conclusions:

Propranolol was well tolerated with minimal side effects in our patients with portal hypertension. Adherence and adequacy of dosage (>1 mg/kg per day, more than twice daily dose frequency) are important determinants of efficacy. A reduction in heart rate of less than 25% may be associated with suboptimal efficacy.
Percutaneous Endoscopic Gastrostomy for Continuous Feeding in Children with Chronic Cholestasis
Authors: Duché Mathieu , Habès Dalila , Lababidi Abdullraman , Chardot Christophe , Wenz Joelle , Bernard Olivier
Published: February 2024

Background:

Malnutrition associated with chronic cholestasis in children often requires continuous enteral feeding through a nasogastric tube, which may be poorly tolerated.

Method:

Percutaneous endoscopic gastrostomy was performed in five children (age range, 20 months to 13 years) with severe cholestasis (Alagille syndrome in four; biliary atresia in one) and severe malnutrition (mean weight, ‐2.6 standard deviations; mean height, ‐2.7 standard deviations) who were awaiting liver transplantation. The pull‐through technique was used in patients under general anesthesia, and the button was set within 2 months.

Results:

Minor wound infection required antibiotic therapy in one patient. In the four children with Alagille syndrome, enteral feeding by means of percutaneous endoscopic gastrostomy was used until liver transplantation for a mean period of 14 months with a mean weight gain of 350 g/mo and a mean height gain of 0.53 cm/mo. Seventeen months to 3 years, 3 months after liver transplantation, all four children were alive and in good clinical condition with normal readings in liver function tests. The technique had to be discontinued in the child with biliary atresia because of secondary occurrence of ascites, gastric intolerance, and refractory wound infection.

Conclusion:

Percutaneous endoscopic gastrostomy may be a valuable alternative to nasogastric tube for nutritional support in children with cholestasis and mild portal hypertension.
Amelioration of Ischemia‐Reperfusion Injury in Rat Intestine by Pentoxifylline‐Mediated Inhibition of Xanthine Oxidase
Authors: Hammerman Cathy , Goldschmidt Doris , Caplan Michael S. , Kaplan Michael , Schimmel Michael S. , Eidelman Arthur I. , Branski David , Hochman Ayala
Published: February 2024

Background:

Intestinal ischemia‐reperfusion (IR) injury results in cell destruction, which may be mediated by the generation of reactive oxygen species, potentially toxic metabolites of xanthine oxidase. Pentoxifylline (PTX) possesses a variety of biochemical and antioxidant properties that can improve capillary flow and tissue oxygenation. Because of these combined effects, it has been hypothesized that pentoxifylline would protect against intestinal IR.

Methods:

Young adult rats were randomly assigned to one of four experimental groups: IR/Placebo (n = 12) in which superior and inferior mesenteric arteries were clamped for 45 minutes and then reopened; IR/PTX (n = 11) in which IR was induced as in the Placebo group, but with 25 mg/kg PTX at 0, 30, and 60 minutes; No IR/Placebo (n = 12); and No IR/PTX (n = 6) in which placebo and PTX were applied with no IR. Blood and intestinal samples were taken for serial thiobarbituric acid‐reducing substances (TBARS; index of lipid peroxidation), for xanthine oxidase‐xanthine dehydrogenase ratios, glutathione, myeloperoxidase, and histopathology.

Results:

Animals in the IR/PTX group had lower TBARS and the least severe histopathologic injury. Xanthine oxidase‐xanthine dehydrogenase ratios were elevated only in IR/Placebo (0.67 ± 0.22 vs. 0.45 ± 0.14 in IR/PTX; 0.42 ± 0.22 in No IR/Placebo; and 0.40 ± 0.11 in No IR/PTX; p = 0.0009). Reduced glutathione was diminished in IR/PTX animals (38.9 ± 1.35 vs. 46.1 ± 7.0 in IR/Placebo; 41.1 ± 2.5 in No IR/Placebo; 43.6 ± 1.0 in No IR/PTX; p = 0.048). No differences were recorded in myeloperoxidase levels among groups.

Conclusions:

Pentoxifylline ameliorates histopathologic signs of injury and decreases lipid peroxidation (TBARS). Normal xanthine oxidase‐xanthine dehydrogenase ratios in the treated compared with IR‐only animals imply that the protective effect of PTX is at least partially mediated through inhibition of xanthine oxidase.
Dietary Intake of Austrian Diabetic Children 10 to 14 Years of Age
Authors: Schober Edith , Langergraber Barbara , Rupprecht Gabriele , Rami Birgit
Published: February 2024

Background:

The dietary intake of 63 children with insulin‐dependent diabetes mellitus (IDDM; age 10 to 14 years) was weighed by dietitians for 2 days during a summer camp for youth with diabetes. Data were analyzed for the content of macronutrients with the help of a computer database program.

Methods:

The dietary intake of children with diabetes was compared with that of healthy Austrian school children and with the current nutritional recommendations for children with IDDM.

Results:

The mean intake of carbohydrate did not meet the recommended level, whereas sucrose, fiber, and protein intake approximated the recommendations. The total consumption of fat and cholesterol, however, exceeded the recommended values. The nutritional intake of Austrian children with IDDM was similar to that of healthy children of the same age and thus reflected regional dietary habits.

Conclusion:

Dietary educational measures on a national basis are needed to change harmful local eating patterns.
Triglyceride Oxidation in Cystic Fibrosis: A Comparison Between Different 13C‐Labeled Tracer Substances
Authors: Wutzke Klaus D. , Radke Michael , Breuel Katja , Gurk Steffen , Lafrenz Jan‐D. , Heine Willi E.
Published: February 2024

Background:

For indirect evaluation of pancreatic lipase activity in cystic fibrosis, different 13C‐labeled triglycerides may be used.

Methods:

Triglyceride oxidation in patients with cystic fibrosis was investigated after administration of different 13C‐labeled triglycerides by comparing 13CO2 breath exhalation. In the comparative study, five patients with cystic fibrosis (age, 8‐15 years; body weight, 22.5‐39.8 kg) were treated with Pangrol (individual dosages: 1‐3 capsules per morning meal; Berlin‐Chemie, Berlin, Germany). [1,1,1‐13C3]Glyceryl tripalmitate and [1,1,1‐13C3]glyceryl trioleate were administered as a single oral pulse at 8:00 A.M. (dosage, 4 mg/kg each) with the standard diet Fresubin (dosage, 10 ml/kg; Fresenius, Bad Homburg, Germany). Alternately, the same subjects were given the synthetic mixed triglyceride 1,3‐distearyl, 2[13C]octanoyl glycerol (dosage, 12.5 mg/kg) contained in the standard diet Nutri‐Mix (dosage, 10 ml/kg; Nutricia, Zoetemeer, The Netherlands). Breath samples were taken in 15‐ and 30‐minute intervals over 8 hours. The 13CO2 enrichment was measured by continuous‐flow isotope ratio mass spectrometry.

Results:

After administration of the 13C‐labeled tripalmitin‐triolein mixture and the mixed triglyceride, mean maximum 13CO2 enrichments were 4.70 and 7.37 δ over baseline, occurring at 7.0 and 3.5 hours, respectively. The corresponding percentage cumulative 13CO2 exhalations were 12.25% and 29.19%, respectively, and differed significantly in the five paired subjects (p = 0.003).

Conclusions:

After using different 13C‐labeled triglycerides the resultant 13CO2 exhalation reflected the triglyceride hydrolysis and subsequent oxidation. It is concluded that the different cumulative 13CO2 exhalations were mainly caused by the rate‐limiting step of triglyceride hydrolysis to free fatty acids and 2‐monoglycerides and by fat deposition. Noninvasive 13C breath tests using different 13C‐labeled triglycerides can be used for evaluation of pancreatic lipase activity before and during enzyme supplementation.
Constipation in School‐Aged Children at Public Schools in Rio de Janeiro, Brazil
Authors: de Araújo Sant' Anna Ana Maria Guilhon , Calçado Antonio Celso
Published: February 2024

Background:

Constipation in childhood is a significant problem worldwide; however, understanding of its epidemiology is limited. Some investigators in the United States have estimated the prevalence of constipation to be 1.2% to 8.0% in the general population. In Brazil, some have found a prevalence of up to 36%.

Methods:

This cross‐sectional, descriptive, observational prevalence study included 391 pupils (age range, 8‐10 years) who were attending three public education centers in Rio de Janeiro. The prevalence of constipation, associated symptoms, and dietary fiber intake were evaluated by questionnaire. A child was considered to be constipated when he or she reported difficulty in defecating two or more times per week. The children were divided into constipated and nonconstipated groups, and the presence of fecal soiling, blood in the feces, and shape of the feces were assessed.

Results:

Twenty‐eight percent of the children were constipated. There was no significant difference between the sexes. Blood in the stools was significantly more frequently reported by the constipated children (p < 0.01). There was no significant difference in the prevalence and frequency of fecal soiling or in the stool shape between the constipated and nonconstipated children (p > 0.1). Fiber content in the diet ranged from 3.4 to 4.8 g per day, which is below the range recommended.

Conclusions:

The prevalence of constipation in Rio de Janeiro is similar to the rates reported in all of Brazil and in a recent study from the United Kingdom but is much higher than that in the United States. In addition, the school menu was found to contain inadequate dietary fiber content.
Macronutrient and Energy Intakes in Young Children Fed Milk Products Containing Different Quantities and Qualities of Fat and Protein
Authors: Svahn Johan C. E. , Axelsson Irene E. M. , Räihaä Niels C. R.
Published: February 2024

Background:

Milk is the major source of protein and saturated fats in the diet after infancy. In the present study, the effects of different fat and protein quantity as well as fat quality in milk and dairy products on nutrient intake and growth in young children were determined.

Methods:

Thirty‐eight healthy children were randomly assigned to one of four feeding groups at 12 months of age: 1) Low‐fat milk (1.0 g fat/dl, 3.3 g protein/dl); 2) standard‐fat milk (3.5 g fat/dl, 3.3 g protein/dl); 3) partially vegetable fat and protein‐reduced milk (3.5 g fat/dl, 50% vegetable; 2.2 g protein/dl); and 4) full‐vegetable‐fat milk (3.5 g fat/dl, 100% vegetable; 3.0 g protein/dl). Nutrient intake and growth were measured at 12, 15, and 18 months.

Results:

The protein intake was significantly reduced with the protein‐reduced milks. The intake of saturated fat was significantly lower with low‐fat milk (11% of energy) or milks containing vegetable fat (13%) than in standard‐fat milk (19.6%). However, the total fat intake was below 30% of energy in low‐fat milk, whereas the total fat intake remained more than 30% in the other groups. Energy intake and growth were similar in all groups.

Conclusions:

A modified milk with reduced protein content for young children results in protein intakes closer to recommendations. A modified milk with either 50% or 100% vegetable fat and dairy products with low milk fat and high vegetable fat content results in intakes of total and saturated fats closer to international recommendations, compared with standard or low‐fat milk and dairy products.
Differing Patterns of Transforming Growth Factor‐β Expression in Normal Intestinal Mucosa and in Active Celiac Disease
Authors: Lionetti Paolo , Pazzaglia Anna , Moriondo Maria , Azzari Chiara , Resti Massimo , Amorosi Andrea , Vierucci Alberto
Published: February 2024

Background:

Growth‐inhibitory autocrine polypeptides such as transforming growth factor (TGF)‐β may play a role in the control of normal epithelial cell proliferation and differentiation. In addition, TGF‐β has a central role in extracellular matrix homeostasis and regulates the immune response at the local level. In this study immunohistochemistry was used to examine the pattern of TGF‐β protein distribution and quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) to determine levels of TGF‐β messenger RNA expression in normal intestinal mucosa and in the flat mucosa of children with celiac disease.

Methods:

Small intestinal biopsies were performed in children with active celiac disease and in histologically normal control subjects. Frozen sections were single stained using an anti‐TGF‐β monoclonal antibody and were double stained for TGF‐β and T cell, macrophages, and the activation marker CD25. Total RNA was extracted from frozen specimens and competitive quantitative RT‐PCR performed for TGF‐β mRNA using internal synthetic standard RNA.

Results:

In normal intestinal mucosa, by immunohistochemistry, TGF‐β expression was most prominent in the villous tip epithelium, whereas in the lamina propria, weak immunoreactivity was present. The celiac mucosa showed weak and patchy epithelial TGF‐β immunoreactivity. In contrast, an intense staining positivity was present in the lamina propria localized mostly in the subepithelial region where T cells, macrophages, and CD25+ cells were detected by double staining. By quantitative RT‐PCR, levels of TGF‐β mRNA transcripts appeared to be increased in celiac intestinal mucosa compared with that in control subjects, although the difference did not reach statistical significance.

Conclusions:

These observations suggest that TGF‐β expression is associated with differentiated enterocyte function. In celiac disease the lower TGF‐β epithelial cell expression could be a consequence of the preponderance of a less differentiated epithelial cell phenotype also present in the surface epithelium. In contrast, the prominent TGF‐β positivity of the subepithelial lamina propria suggests an association with the local immune and inflammatory response, as well as a potential role of these peptides in mesenchymal‐epithelial cell interaction.
13C and H2 Breath Tests to Study Extent and Site of Starch Digestion in Children with Cystic Fibrosis
Authors: Amarri Sergio , Harding Marilyn , Coward W. Andrew , Evans T. John , Weaver Lawrence T.
Published: February 2024

Background:

Starch is an important source of energy for children with cystic fibrosis, but little is known about their capacity to digest it.

Methods:

A 13C breath test was used to measure starch digestion and oxidation in 16 children with cystic fibrosis (median [range] age, 7.9 [4‐15] years; 7 girls, 9 boys) and 5 normal healthy control subjects (median age, 8.3 [7‐13] years; 3 girls, 2 boys). A test meal of 13C flour and lactulose was consumed and breath samples were obtained half‐hourly thereafter for 6 hours to measure 13C enrichment by isotope ratio mass spectrometry and H2 by electrochemistry. The test was repeated on 10 children with cystic fibrosis when they were taking pancreatic supplements.

Results:

The median (range) cumulative percentage 13C dose recovery (cPDR), was 35% (18‐52%) in control subjects, 18% (9‐33%) in children with cystic fibrosis without enzymes, and 29% (22‐51%) in those with pancreatic supplements. cPDR differed significantly between healthy control subjects and children with cystic fibrosis without enzymes (p = 0.01) and between children with cystic fibrosis with and without enzymes (p < 0.0001), but there was no difference between control subjects and children with cystic fibrosis taking enzymes (p = 0.5). Eight children with cystic fibrosis had a cPDR within control range, and in six there was a second peak in 13CO2 enrichment coincident with an increase in H2.

Conclusions:

Starch digestion and oxidation are diminished in children with cystic fibrosis, but pancreatic enzymes restored them to near normal levels. A second peak in 13CO2 enrichment, suggestive of colonic starch fermentation was absent in healthy children, but present in some children with cystic fibrosis and abolished by pancreatic enzymes.
Individualized Protein Fortification of Human Milk for Preterm Infants: Comparison of Ultrafiltrated Human Milk Protein and a Bovine Whey Fortifier
Authors: Polberger Staffan , Räihä Niels C. R. , Juvonen Pekka , Moro Guido E. , Minoli Iolanda , Warm Amiel
Published: February 2024

Background:

To improve the nutritional management of preterm infants, a new individualized human milk fortification system based on presupplementation milk protein analyses was evaluated.

Methods:

In an open, prospective, randomized multicenter study, 32 healthy preterm infants (birth weights, 920‐1750 g) were enrolled at a mean of 21 days of age (range, 9‐36 days) when tolerating exclusive enteral feedings of 150 ml/kg per day. All infants were fed human milk and were randomly allocated to fortification with a bovine whey protein fortifier (n = 16) or ultrafiltrated human milk protein (n = 16). All human milk was analyzed for protein content before fortification with the goal of a daily protein intake of 3.5 g/kg. During the study period (mean, 24 days) daily aliquots of the fortified milk were obtained for subsequent analyses of the protein content.

Results:

Both fortifiers were well tolerated, and growth gain in weight, length, and head circumference, as well as final preprandial concentrations of serum urea, transthyretin, transferrin, and albumin were similar in both groups. The ultimate estimated protein intake was equivalent in both groups (mean 3.1 ± 0.1 g/kg per day). Serum amino acid profiles were similar in both feeding groups, except for threonine (significantly higher in the bovine fortifier group) and proline and ornithine (significantly higher in the human milk protein group).

Conclusions:

Protein analyses of the milk before individual fortification provides a new tool for an individualized feeding system of the preterm infant. The bovine whey protein fortifier attained biochemical and growth results similar to those found in infants fed human milk protein exclusively with the corresponding protein intakes.