bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiserum to Tumor Necrosis Factor and Failure to Prevent Murine Colitis
Authors: Olson Allan D. , DelBuono Elizabeth A , Bitar Khalil N. , Remick Daniel G.
Published: January 2024

Summary: Cytokines regulate many aspects of disease and have been implicated as mediators of the inflammatory reactions in patients with both ulcerative (UC) and Crohn's colitis. We examined the local and systemic appearance of tumor necrosis factor (TNF) and interleukin 6 (IL‐6) in an experimental animal model of inflammatory bowel disease. Colitis was induced in CBA/J mice by adding dextran sulfate sodium (DSS), 5% (wt/vol), to their water. DSS‐induced colitis is a reproducible animal model for evaluating the role of cytokines in the pathology of colitis. Animals were weighed daily, and stools were checked for the presence of blood. Groups of mice were killed daily, blood samples were taken for measurement of plasma cytokine levels, and colonic samples were taken for histology and measurement of TNF and IL‐6 bioactivity. Mice fed DSS developed colitis with bloody diarrhea, weight loss, and colonic inflammation by days 5–9. Histologic examination of the colons showed focal crypt destruction and ulceration. In mice with DSS‐induced colitis no TNF was detectable in colonic tissue extracts or in plasma. In contrast, plasma IL‐6 was detectable from days 4 to 9 and was detectable in colonic tissue in only a few (two of four) terminally ill animals on day 9. Animals were injected with a neutralizing, polyclonal anti‐TNF antiserum that maintained high in vivo neutralizing titers for ≥ 48 h. This anti‐TNF antiserum failed to block or modify the severity of colitis induced by DSS. Failure to detect local or systemic TNF and failure to prevent colonic inflammation with anti‐TNF antiserum showed that TNF is not an inflammatory mediator in DSS‐induced murine colitis.
Leukotriene B4 and C4 Metabolism in Small Intestine Mucosa of Children with Celiac Disease
Authors: Shimizu Toshiaki , Beijer Eva , Strandvik Birgitta
Published: January 2024

Summary: The enhanced generation of cicosanoids, including leukotriencs (LTs), may be involved in the patho‐physiology of small intestine mucosal injury in patients with celiac disease. We investigated the metabolism of LTB4 and LTC4 by small intestine mucosa in patients with celiac disease by incubating biopsics of small intestine mucosa from patients and healthy subjects in media containing LTB4 and LTC4 and measuring the changes in LTB4 and cysteinyl LT concentrations in the incubation media. There was no significant degradation of LTB4 during a 60‐min incubation of the small intestine mucosa from either children with celiac disease or controls. LTC4 was metabolized to LTD4 and LTE4 in a time‐dependent manner by the small intestine mucosa of both patients and controls. However, the decreases in LTC4 and the increases in LTD4 and LTE4 by the intestinal mucosa from patients with celiac disease occurred more slowly than the changes observed in control experiments. Reduced catabolism of LTC4 in the small intestine mucosa due to villous atrophy may contribute to increased levels of LTC4 and may play an important role in the pathophysiology of celiac disease.
Artificial Formula Induces Precocious Maturation of the Small Intestine of Artificially Reared Suckling Rats
Authors: Dvorak Bohuslav , McWilliam Debra L. , Williams Catherine S. , Dominguez Jessica A. , Machen Nancy W. , McCuskey Robert S. , Philipps Anthony F.
Published: January 2024

Background

The artificially reared rat model was used successfully to study the effect of nutrition during the early postnatal period on growth and development of the neonate. Overgrowth and morphologic changes of the gastrointestinal tract are known consequences of artificial rearing. The major goal of our study was to elucidate whether artificial rearing–enhanced gut development is caused by artificial diet or by gastrostomy and the artificial rearing technique itself.

Methods

Suckling rats at day 8 of age underwent intragastric cannulation and were machine fed either a cow's milk–based artificial rat's milk substitute or pooled rat's milk for 4 days. Dam‐fed littermates served as a control.

Results

Body growth did not differ in the three experimental groups. In rats receiving rat's milk substitute, small intestinal wet weight was approximately 60% greater than in rats fed rat's milk or control rats. Additionally, the entire small intestine was approximately 20% longer in the rat's milk substitute group. Morphologically, rat's milk substitute–fed pups demonstrated significantly greater intestinal villus length and crypt depth compared with rat's milk–fed or control rats. Jejunum and midjejunum of the rat's milk and control groups did not differ in these parameters. Intestinal sucrase activity of rat's milk substitute–fed rats was significantly elevated compared with rat's milk–fed rats or control animals.

Conclusions

These results indicate that cow's milk–based formula, not gastrostomy or artificial feeding technique, is a principal cause of the small intestine overgrowth and precocious maturation of some intestinal functions observed in artificially reared sucklings.
A Single Food Bolus Stimulates Albumin Synthesis in Growing Piglets
Authors: de Meer Kees , Smolders Hedwig C. , Meesterburrie Jan , de Sain‐van der Velden Monique , Voorbij Hieronymus A.M. , Okken Albert , Reijngoud Dirk‐Jan , Kulik Wim
Published: January 2024

Background

A stable isotope tracer method to quantify the synthesis of proteins of hepatic origin in response to feeding is described. The response of albumin synthesis on one mixed meal in a piglet model was investigated and the intragastric and intravenous administration modes of 13C‐valine were compared.

Methods

The fasting and postprandial fractional synthesis rates (FSRs) of albumin in 15 piglets were measured while infusion rates of 13C‐valine were changed in anticipation of the increased appearance of the tracee after a single liquid food bolus (30 mL/kg infant formula). 13C‐valine enrichments in albumin hydrolysates at regular time intervals were determined with gas chromatography–combustion isotope ratio mass spectrometry.

Results

The intravenous mode (n = 8) showed constant plasma α‐ketoisovalerate tracer‐to‐tracee ratios (coefficient of variation range: 1–8%), and a 27% increase in albumin FSR after the food bolus (mean FSR ± standard error [SE]: fasting 14.4% ± 1.6% vs. postprandial 18.3% ± 2.2% per day;P < 0.005). In the intragastric mode (n = 7), albumin FSR calculated from the mean precursor values increased 32% after feeding (fasting 14.6% ± 1.5% vs. postprandial 19.3% ± 1.6% per day;P = 0.005), despite absence of constant α‐ketoisovalerate enrichment (coefficient of variation range: 15–31%). The FSRs were not significantly different between both infusion modes.

Conclusions

A mixed food bolus increases albumin FSR in growing piglets by approximately 30%, irrespective of the tracer administration route. The concept of anticipated precursor steady state is applicable to study changes of hepatic protein synthesis after a single meal. The intragastric mode of tracer administration can be applied as a less invasive method to measure tissue specific protein synthesis in children.
α1‐Antitrypsin Deficiency–Associated Liver Disease Progresses Slowly in Some Children
Authors: Volpert Diana , Molleston Jean P. , Perlmutter David H.
Published: January 2024

Background

A prospective nationwide screening study initiated more than 20 years ago in Sweden has shown that clinically significant liver disease develops in only 10% to 15% of α1‐antitrypsin (AT)–deficient children. This study provides information about 85% to 90% of those children, many of whom had elevated serum transaminases in infancy but have no evidence of liver injury by age 18 years. However, there is relatively limited information about the course of α1‐AT–deficient children who have cirrhosis or portal hypertension. Based on several anecdotal experiences, we have been impressed by the relatively slow progression and stable course of the liver disease in some of these children.

Methods

We reviewed the course of patients with homozygous PIZZ α1‐antitrypsin deficiency seen at this institution since establishing a patient database 16 years ago.

Results

Of 44 patients with α1‐AT deficiency, 17 had cirrhosis, portal hypertension, or both. Nine of the 17 patients with cirrhosis or portal hypertension had a prolonged, relatively uneventful course for at least 4 years after the diagnosis of cirrhosis or portal hypertension. Two of these patients eventually underwent liver transplantation, but seven are leading relatively healthy lives for up to 23 years while carrying a diagnosis of severe α1‐AT deficiency–associated liver disease. Patients with the prolonged stable course could be distinguished from those with a rapidly progressive course on the basis of overall life functioning but not on the basis of any other more conventional clinical or biochemical criteria.

Conclusions

These data provide further evidence for the variable severity of liver disease associated with α1‐AT deficiency and indicate that some patients have chronic, slowly progressing or nonprogressing cirrhosis.
Randomized, Double‐Blind, Placebo‐Controlled Pilot Trial of Megestrol Acetate in Malnourished Children With Cystic Fibrosis
Authors: Marchand Valerie , Baker Susan S. , Stark Tracy J. , Baker Robert D.
Published: January 2024

Background

Undernutrition is common in patients with cystic fibrosis (CF). Nutritional rehabilitation has been shown to improve linear growth, pulmonary function, well‐being, and resistance to infection in this population. The purpose of this study was to determine whether the administration of megestrol acetate (MA) induces weight gain in malnourished patients with CF, and to assess the composition of weight gain.

Methods

In a randomized, placebo‐controlled, double‐blind, crossover study, 12 children with CF received MA (10 mg/kg/d) or placebo for 12 weeks, followed by a 12‐week washout period, then the alternative treatment. Anthropometrics, caloric intake, and clinical assessment were obtained every 6 weeks; pulmonary function tests, biochemistry, hematology, cortisol, growth hormone, insulin, C‐peptide, insulin‐like growth factor‐1, insulin‐like growth factor binding protein‐3, and dual‐energy x‐ray absorptiometry scans were obtained every 12 weeks.

Results

Six children did not complete the study, three for reasons unrelated to the study, two because they developed diabetes while receiving MA, and one who had glucose intolerance while receiving the placebo. Average weight gain was 3.05 kg in the MA group and 0.3 kg in the placebo group. The change in weight z score was +0.76 in the MA group and −0.05 in the placebo group. The change in height z score was −0.06 in the MA group and +0.06 in the placebo group. Lean body mass and body fat increased by 1507 g and 1192 g respectively in the MA group. Pulmonary function tests improved in the MA group; serum cortisol levels decreased. Side effects included glucosuria, insomnia, hyperactivity, and irritability.

Conclusions

Weight, body fat, and lean body mass increased and pulmonary function improved in the children with CF given MA. Adrenal suppression, glucose intolerance, and diabetes are side effects.
Prevalence of Celiac Disease in Down Syndrome in the United States
Authors: Zachor Ditza A. , Mroczek‐Musulman Elizabeth , Brown Pamela
Published: January 2024

Background

Numerous studies in Europe have documented a high prevalence of celiac disease in Down syndrome. This study was undertaken to estimate the prevalence of celiac disease in Down syndrome in the southeastern United States.

Methods

Seventy‐five patients with Down syndrome were screened using immunoglobulin (Ig)A‐anti antiendomysium antibodies, IgA‐antigliadin antibodies, and total IgA level. When either antiendomysium or antigliadin antibodies produced positive findings, patients were referred to a pediatric gastroenterologist for consideration of a duodenal biopsy.

Results

Thirteen percent (10/75) were positive for antiendomysium antibodies. Half of these patients were also positive for antigliadin antibodies. Six of 10 patients positive for antiendomysium antibodies underwent intestinal biopsy. Changes consistent with celiac disease were documented in five. Histologic findings ranged from focal to total villous atrophy. None had IgA deficiency.

Conclusions

There was a high prevalence of positivity to antiendomysium antibody in Down syndrome. Antiendomysium antibody was a more sensitive screening test than antigliadin antibody. The prevalence of celiac disease in Down syndrome in the southeastern United States was 1 in 14 cases. Screening with antiendomysium antibody and IgA for all children with Down syndrome is recommended, even if there are no gastrointestinal symptoms.
Cutaneous Application of Vegetable Oil as a Coadjutant in the Nutritional Management of Preterm Infants
Authors: Soriano Cláudio Rodrigo , Martinez Francisco Eulógio , Jorge Salim Moysés
Published: January 2024

Background

The cutaneous application of vegetable oil as a therapeutic practice and dietary coadjuvant has been described mainly in adult patients at risk for essential fatty acid deficiency. In the current study, the effects of cutaneous soybean oil application on somatic growth and plasma linoleic and arachidonic acid levels were examined in enterally fed preterm newborns.

Methods

Sixty consecutive preterm infants were chosen from patients admitted to the nursery. Infants were randomly assigned to one of two groups: the oil group, which was treated cutaneously with soybean oil, or the control group, which received no cutaneous treatment.

Results

After 30 days, a significant increase in anthropometric parameters was observed in infants who received cutaneous oil, mainly in infants small for gestational age. An increase in linoleic acid level and a decrease in arachidonic acid level were seen in both groups but do not justify the difference found in growth rates in the control and oil groups.

Conclusions

Preterm infants treated cutaneously with soy oil showed better somatic growth than the control group. The factors leading to the present results, especially the response of the infants who were small for gestational age merit further evaluation.
North American Indian Cirrhosis in Children: A Review of 30 Cases
Authors: Drouin Eric , Russo Pierre , Tuchweber Beatriz , Mitchell Grant , Rasquin‐Weber Andrée
Published: January 2024

Background

North American Indian childhood cirrhosis (NAIC) is a distinct, rapidly evolving form of familial cholestasis found in aboriginal children from northwestern Quebec. This is a retrospective review of the 30 patients treated in Quebec since the discovery of NAIC in 1970.

Methods

The clinical records and histologic samples from 30 patients were reviewed. Extensive metabolic, biochemical, viral, genetic, and radiologic studies were performed in most patients.

Results

Genetic analysis suggests autosomal recessive inheritance and a carrier frequency of 10% in this population. Gene mapping studies showed that the NAIC gene is located on chromosome 16q22. Typically, patients have neonatal cholestatic jaundice (70%) or hepatosplenomegaly (20%) with resolution of clinical jaundice by age 1 year but persistent direct hyperbilirubinemia. Portal hypertension was documented in 29 patients (91%). Variceal bleeding (15 patients, 50%) occurred as early as age 10 months. Surgical portosystemic shunting was performed in 13 of these 15 patients (87%); 4 (31%) rebled after 1 to 5 years. Fourteen patients died (47%). In 10 (71%), liver disease was the cause. Four children died of liver failure before liver transplantation became available. In transplanted livers, no recurrence of NAIC was observed after 1 to 10 years. Recognized infectious, metabolic, toxic, autoimmune, and obstructive causes of cirrhosis have been eliminated. The histologic features of NAIC show early bile duct proliferation and rapid development of portal fibrosis and biliary cirrhosis, suggesting a cholangiopathic phenomenon.

Conclusion

Together with gene mapping studies showing that the NAIC gene is different from those of other familial cholestases, these observations suggest that NAIC is a distinct entity that could be classified as “progressive familial cholangiopathy.”
Measurement of Total Body Water in Children Using Bioelectrical Impedance: A Comparison of Several Prediction Equations
Authors: Beertema Wieske , van Hezewijk Marjan , Kester Arnold , Forget Pierre‐Philippe , van Kreel Bernard
Published: January 2024

Background

Body composition evaluation by bioelectrical impedance analysis in children makes use of different group‐specific population‐derived equations. The present study was conducted to attempt to validate the use of population‐independent physical model–derived equations in children.

Methods

The validity of bioelectrical impedance analysis for the measurement of total body water in children was evaluated by comparing results of two physical model–derived and two population‐derived equations with those of deuterium dilution as reference method in a group of 38 heterogeneous children.

Results

Means ± standard deviation (in liters) for total body water measured with deuterium dilution and the physical model 1–derived equation were 18.4 ± 4.7 L and 18.1 ± 4.4 L, respectively. This difference is not significant, whereas significant differences were found for all other tested equations. Significant smaller absolute differences between the model 1 equation and deuterium reference results were found when compared with the results of the other three tested equations.

Conclusion

When compared with results of the reference deuterium method the physical model 1–derived equation was the only one that provided reliable total body water results by bioelectrical impedance analysis in children.
Smaller Volume, Thickened Formulas in the Management of Gastroesophageal Reflux in Thriving Infants
Authors: Khoshoo Vikram , Ross Gerald , Brown Shannan , Edell Dean
Published: January 2024

Background

The effect of smaller volume, thickened formulas on gastroesophageal reflux is not clear.

Methods

The frequency of gastroesophageal reflux and duration of acid pH in the esophagus were determined in six thriving infants using extended esophageal pH monitoring.

Results

There was a significant reduction in frequency of emesis and gastroesophageal reflux but not the duration of acid pH in the esophagus with the use of infant formula thickened with rice cereal to provide a nutritionally appropriate intake in a smaller volume.

Conclusions

Thickening of formula with rice cereal in a nutritionally balanced form and smaller volume may be an appropriate strategy for reducing frequency of emesis and gastroesophageal reflux in thriving infants.
Autoimmune Hepatitis as a Late Complication of Liver Transplantation
Authors: Hernandez Hector M. , Kovarik Paula , Whitington Peter F. , Alonso Estella M.
Published: January 2024

Background

The development of de novo autoimmune hepatitis as a long‐term complication after liver transplantation has been recently reported. The authors describe five liver allograft recipients who developed chronic hepatitis associated with autoimmune features.

Methods

Five of 155 liver transplant recipients at risk (2.5%) developed this particular form of graft dysfunction. The authors review the clinical records, liver histology, therapy, and outcome of these five patients.

Results

Patients included two boys and three girls. Median age at transplantation was 3.5 years (range, 0.5–14 years), median age at presentation was 9 years (range, 2–17 years), and median interval after transplantation was 5.1 years (range, 1.5–9 years). Indications for liver transplant included biliary atresia in four patients and primary sclerosing cholangitis in one patient. At the time of presentation, all patients were receiving cyclosporine as their primary immunosuppressive agent. Only one patient had a history of rejection, which had resolved. All patients presented with increased transaminase levels, and one had a mildly elevated conjugated bilirubin level. Only one patient had constitutional complaints. Acute and chronic rejection, viral hepatitis, vascular insufficiency, and biliary tract obstruction were excluded. Antinuclear antibody levels were elevated in four patients (titer range, 1:160–1:640), one of whom also had positive antismooth muscle antibody (titer 1:80) results. The fifth patient had an elevated serum total protein level. Histologic analysis of liver biopsy samples from the five patients showed findings consistent with chronic autoimmune hepatitis. All patients were treated with standard therapy for autoimmune hepatitis, which included daily steroids and azathioprine. Cyclosporine doses were reduced in three patients and eliminated in two. All patients responded with normalization (n = 2) or improvement (n = 3) of liver transaminases within the first 3 months of therapy. Histologic analysis of the 3‐month follow‐up liver biopsy was normal (n = 2) or showed improvement in inflammation (n = 2). Two patients developed acute allograft rejection within 6 to 12 months after discontinuation or reduction in cyclosporine.

Conclusions

Autoimmune hepatitis occurs after liver transplantation in patients without a previous history of autoimmune hepatitis. The risk of developing autoimmune hepatitis appears to be greater in children after liver transplantation than in the general pediatric population. Standard therapy for autoimmune hepatitis is effective.
Helicobacter pylori and Meckel's Diverticula
Authors: Finn Laura S. , Christie Dennis L.
Published: January 2024

Background

Helicobacter pylori is known to infect only gastric mucosa and is strongly associated with gastroduodenal ulceration. The authors studied whether H. pylori colonizes the gastric mucosa of Meckel's diverticula, and determined its relationship to “gastritis” and bleeding.

Methods

A 10‐year retrospective review identified 45 children with Meckel's diverticulum. Hematoxylin–eosin and Diff‐Quik stains were used to assess the presence and severity of gastritis, and to highlight organisms in the resected diverticula. Cases with organisms were then studied with antibodies specific for H. pylori using immunoperoxidase methods.

Results

Twenty‐eight children, 7 months to 12.6 years of age, had lower gastrointestinal hemorrhage caused by Meckel's diverticulum and had positive radionuclide scans. All had acid‐secreting mucosa in their diverticula, and ulceration. “Chronic gastritis” and eosinophilia were constant findings; “acute gastritis” was present in four patients. Twenty specimens exhibited lymphoid follicles in the gastric mucosa. Seventeen patients with Meckel's diverticula (age range, 1 month–14.7 years) who presented with acute abdominal pain associated with intussusception were used for comparison. Acid‐secreting gastric mucosa was seen in four patients. H. pylori was identified in only one of the 45 patients; this patient had ulceration and moderate “acute gastritis.”

Conclusions

H. pylori does not colonize a substantial number of children who have ulcerated and bleeding Meckel's diverticulum in the presence of acid‐secreting mucosa. Although H. pylori is a notable cause of ulceration, the authors confirm that ulceration is possible in its absence, and alternative mechanisms of ulceration are important. The presence of lymphoid follicles in Meckel's diverticula, unlike gastric biopsies, is not associated with H. pylori.
Survival of Rotavirus Antibody Activity Derived From Bovine Colostrum After Passage Through the Human Gastrointestinal Tract
Authors: Pacyna Janina , Siwek Kasia , Terry Sandra J. , Roberton Elizabeth S. , Johnson Ronald B. , Davidson Geoffrey P.
Published: January 2024

Background

Rotavirus is a major cause of infectious diarrhea in infants and young children. Several studies have shown that hyperimmune bovine colostrum, derived from cows immunized with rotavirus, can prevent rotavirus diarrhea when given passively. The objective of this study was to determine whether colostral antibody activity survived transit through the gut by measuring the level of rotavirus antibody activity in the feces.

Methods

Hyperimmune colostrum containing different levels of rotavirus antibody was administered to 105 children attending nine Adelaide childcare centres. Subjects were asked to drink 100 ml of whole milk supplemented with colostrum 3 times a day, for a period of 6 days. Stool samples were collected from the subjects before, during , and after consumption of the study product. Rotavirus activity was determined using a novel virus reduction enzyme‐linked immunosorbent assay (ELISA) and a virus neutralization assay.

Results

Rotavirus antibody activity was detected in 521 (86%) of 602 fecal specimens obtained during the study using the virus reduction ELISA. The antibody activity was detected as early as 8 hours after ingestion of hyperimmune colostrum and up to 72 hours after consumption had ceased. There was a strong relation (r = 0.81) between the titer of rotavirus antibody administered to subjects and the level of antibody activity detected in the feces.

Conclusions

The results show that antirotavirus activity survived passage through the gut. Therefore, passive immunotherapy may be used to prevent or treat infectious diseases that affect the entire length of the gastrointestinal tract.
Successful Immune Response to a Recombinant Hepatitis B Vaccine in Children After Liver Transplantation
Authors: Duca Pablo , Del Pont Jose Marco , D'Agostino Daniel
Published: January 2024

Background

Patients who undergo liver transplantation require multifaceted general care, and vaccination has a fundamental role before and after transplantation. The purpose of this study was to provide a prospective evaluation of the immunogenicity of the recombinant vaccine (RV) against Hepatitis B in pediatric patients with liver transplants (TxH) who for different reasons did not receive a pretransplantation vaccine.

Methods

From June 1996 to December 1999, 47 pediatric patients with liver transplants were vaccinated with RV. Patients older than 1 year of age, in stable condition, and 6 months post‐transplantation were included. The vaccination scheme was 0–1 and 6 months, intramuscular 10 μg in less than 30 kg body weight, and 20 μg in more than 30 kg body weight. The nonresponder patients were vaccinated with a booster dose and a double dose 1 to 6 months after the last dose. Responders to titer HBs Ab enzyme immunoassay (EIA) <10 UI/ml were defined as nonresponders, to titer between 10–100 UI/ml as responders, and to higher titer of 100 UI/ml as high responders.

Results

The following data were obtained from the 47 patients: mean ± standard deviation (SD) age at vaccination was 10.76 ± 5.96 years old and the mean ± SD post‐transplant time at the beginning of vaccination was 3.56 ± 2.19 years. Thirty‐three of 47 patients (70%) responded to doses according to body weight, and 14 (30%) did not respond, necessitating a booster dose after which 7 responded (50%). The global seroconversion was 85%. There was not a significant responder cyclosporine concentration dosage (154 vs. 150 ng/ml) difference between responders and nonresponders. Sixty‐six percent (8 of 12) of patients receiving a triple immunosuppressive scheme (cyclosporine, steroids, and Azathioprine) had a positive response, while 84% (16 of 19) receiving a double scheme (cyclosporine and steroids) and 100% (16 of 16) receiving monotherapy with cyclosporine had a positive response. By comparing a triple scheme with monotherapy, the Fisher exact test found a P < 0.01. Incidence of adverse effects (local pain) was 2.63%.

Conclusion

Immunization with RV was well‐tolerated with acceptable seroconversion and safety in recipients after liver transplantation, particularly in those undergoing cyclosporine monotherapy. The population studied showed better results than did other populations of immunosuppressed patients.
Fecal Calprotectin as a Measure of Disease Activity in Childhood Inflammatory Bowel Disease
Authors: Bunn Susan K. , Bisset W. Michael , Main Margaret J.C. , Golden Barbara E.
Published: January 2024

Background

Calprotectin is an abundant neutrophil protein that is extremely stable in feces. The aim of this study was to assess the effectiveness of fecal calprotectin as a noninvasive measure of disease activity in childhood inflammatory bowel disease (IBD) by comparison to a modified Lloyd‐Still and Green score and laboratory inflammatory indices.

Methods

Spot fecal samples from 37 children with IBD and 31 control children were sent by ordinary mail to the laboratory. Fecal calprotectin concentration was measured by an in‐house enzyme linked immunosorbent assay (ELISA). A modified Lloyd‐Still & Green score (mLSS) was calculated for each child with IBD within 10 days of obtaining the fecal sample.

Results

Compared with control values (median, range) (2.1, 0.5–6.3 mg/L), fecal calprotectin was increased in 16 children with ulcerative colitis, (11.5, 0.6–272.5 mg/L, P < 0.001) and in 21 children with Crohn disease, (14.0, 0.7–59.7 mg/L, P < 0.001). Twelve “moderately affected” children (mLSS of 35–65) had higher fecal calprotectin concentrations (22.2, 2.7–141.7 mg/L) than 25 “mildly affected” children (mLSS > 65), (10.3, 0.6–272.5 mg/L, P = 0.002). For the total IBD group, fecal calprotectin concentration correlated negatively with the mLSS (r = ‐ 0.61, P < 0.001). It also correlated negatively with serum albumin concentration (r = ‐ 0.49, P = 0.002) and positively with erythrocyte sedimentation rate (r = 0.40, P = 0.01).

Conclusions

Fecal calprotectin seems to reflect bowel inflammation in children with IBD. As a simple, safe, noninvasive test, it has the potential to reduce the number of invasive investigations performed in these children.
Gastroesophageal Endoscopic Findings and Gastrointestinal Symptoms in Preterm Neonates With and Without Perinatal Indomethacin Exposure
Authors: Ojala Riitta , Ruuska Tarja , Karikoski Riitta , Ikonen R. Sami , Tammela Outi
Published: January 2024

Background

The aim of this study was to investigate whether perinatal indomethacin treatment has effects on the development of esophageal and gastric lesions in preterm infants and to evaluate other potential etiologic factors behind these lesions.

Methods

Sixty‐nine infants were born at less than 33 weeks' gestation. Forty‐five of these infants underwent treatment with perinatal indomethacin (study group) and 24 did not (control group). All underwent upper gastrointestinal tract endoscopy and biopsy during the neonatal period. The correlation between gastrointestinal symptoms, abnormal endoscopic findings, and the factors correlating with the development of esophageal and gastric mucosal lesions was evaluated.

Results

Abnormal endoscopic findings were equally common in the study group (77.8%) and in controls (83.3%). There was no dependence between gastrointestinal symptoms and endoscopic findings because only 15 infants (21.7%) were symptomatic before endoscopy. The interval between endoscopy and the last perinatal indomethacin dose correlated significantly with abnormal esophageal findings and gastric mucosal lesions. Shorter duration of enteral feeding before endoscopy correlated with greater risk of abnormal esophageal findings. Older gestational age and need of ventilator treatment at the time of endoscopy remained the risk factors associated with abnormal gastric findings.

Conclusions

Esophageal and gastric lesions diagnosed by endoscopy correlate poorly with the gastrointestinal symptoms of patients. Short duration of enteral feeding seems to be correlated with an increased risk of esophageal mucosal lesions, increasing gestational age and ventilator treatment with gastric mucosal lesions, and perinatal indomethacin with esophageal and gastric mucosal lesions in preterm infants. Ventilator‐treated preterm infants not receiving enteral nutrition and patients with indomethacin exposure might benefit from ulcer prophylaxis.
Assessment of Hepatic Function in Cystic Fibrosis by Lidocaine Metabolism
Authors: Gremse David A. , Sindel Lawrence J. , Hoff Charles J. , Wells David J. , Boerth Robert C.
Published: January 2024

Background

To determine hepatic drug metabolism in patients with cystic fibrosis, as measured by monoethylglycinexylidide formation after lidocaine injection and indocyanine green (ICG) clearance.

Methods

The following study is a case–control study, which included 19 patients with cystic fibrosis and 13 control subjects. Serum monoethylglycinexylidide concentration was measured after intravenous injection of 1 mg/kg (maximum, 50 mg) lidocaine. Indocyanine green (0.5 mg/kg) was injected concomitantly, and absorbance (805 nm) of serum was measured over time to determine its volume of distribution, serum half‐life, and hepatic blood flow.

Results

Monoethylglycinexylidide formation was decreased in patients with cystic fibrosis compared with controls (39.4 ± 16.9 μg/L versus 70.3 ± 45.7 μg/L, mean ± SD , respectively, P < 0.02). Indocyanine green half‐life (4.6 ± 2.7 min versus 3.0 ± 1.0 min), volume of distribution (8.6 ± 5.5 L versus 8.3 ± 3.4 L), and hepatic blood flow (10.9 ± 5.9 ml · kg−1 · min−1 versus 7.4 ± 2.0 ml · kg−1 · min−1) were similar in both groups.

Conclusion

Monoethylglycinexylidide formation after lidocaine injection is impaired in patients with cystic fibrosis. This impairment may have clinical implications when using hepatically metabolized medications in patients with cystic fibrosis.
Saccharomyces boulardii Does Not Stimulate Mucosal Hyperplasia after Intestinal Resection in the Rat
Authors: Kollman Kathryn A. , Goulet Olivier , Vanderhoof Jon A.
Published: January 2024

Background

Polyamines have been shown to be important regulators of the intestinal adaptation process after massive bowel resection. Saccharomyces boulardii is yeast that has the ability to synthesize polyamines. Therefore, S. boulardii may be useful in the treatment of short bowel syndrome.

Methods

Twenty 150‐g male Sprague‐Dawley rats were subjected to 80% jejunoileal resection. Another 20 animals received transection and closure and served as pair fed controls. One half of the resected rats and one half of the controls were given S. boulardii 25 mg/day.

Results

After 2 weeks, mucosal mass (mg/cm bowel) did not differ between treated and non‐treated animals despite the presence of a marked resection effect. Mucosal DNA, protein, and sucrase activity likewise did not differ. Subsequently, the experiment was repeated four times the original dose (100 mg/day) and found comparable results. In the proximal bowel, mucosal mass was 92 ± 6 mg/cm in treated animals versus 107 ± 8 mg/cm in untreated rats. In the distal small bowel, comparable values were 85 ± 5 mg/cm and 88 ± 4 mg/cm. Again, mucosal DNA, protein, and sucrase activity levels paralleled these results.

Conclusions

Although S. boulardii may stimulate polyamine synthesis, it does not seem to be helpful in augmenting gut adaptation in this animal model of short bowel syndrome.
Delayed Gastric Emptying and Gastroesophageal Reflux: A Pathophysiologic Relationship
Authors: Estevão‐Costa José , Campos Miguel , Dias Jorge Amil , Trindade Eunice , Medina Ana Maria , Carvalho José Luis
Published: January 2024

Background

Delayed gastric emptying (DGE) is frequent in patients with gastroesophageal reflux (GER), but its pathophysiologic role has not yet been established. To identify a relationship between DGE and GER, we assessed whether DGE increases esophageal acid exposure and the related importance of possible mechanisms.

Methods

Thirty pediatric patients with pathological GER were divided according to gastric emptying scintigraphy into a DGE group (n = 14) and normal‐emptying group (n = 16). The esophageal pH‐monitoring parameters of the two groups were compared with respect to the individual variation between postprandial and fasting periods.

Results

Patients with DGE had less total acid exposure than did those with normal emptying, but patients in both groups had a pathological fraction of time when pH was below 4 in both the postprandial (median: 18 vs. 27.6;P = 0.49) and fasting (8.5 vs. 23.9;P = 0.01) periods. Patients in the normal‐emptying group had similar fraction of time when pH was below 4 in the postprandial and fasting periods. However, patients in the group with DGE had a fraction of time when pH was below 4 in the postprandial period that was almost double that presented in fasting period (postprandial to fasting ratio: 2.11:0.90;P = 0.002). The postprandial to fasting ratio for episodes per hour was similar in the two groups (1.81 vs. 1.79;P = 0.62). Patients with DGE had a significantly higher frequency of long episodes in the postprandial period than did those with normal emptying (62.5% vs. 38.2%;P = 0.04). The occurrence of the longest episode in the postprandial period was also significantly higher for patients with DGE (57.1% vs. 6.2%;P = 0.003).

Conclusions

DGE seems to accentuate postprandial reflux by increasing the volume of refluxate per episode of reflux through an underlying incompetent lower esophageal sphincter.
Gas Production by Feces of Infants
Authors: Jiang Tianan , Suarez Fabrizis L. , Levitt Michael D. , Nelson Steven E. , Ziegler Ekhard E.
Published: January 2024

Background

Intestinal gas is thought to be the cause abdominal discomfort in infants. Little is known about the type and amount of gas produced by the infant's colonic microflora and whether diet influences gas formation.

Methods

Fresh stool specimens were collected from 10 breast‐fed infants, 5 infants fed a soy‐based formula, and 3 infants fed a milk‐based formula at approximately 1, 2, and 3 months of age. Feces were incubated anaerobically for 4 hours at 37°C followed by quantitation of hydrogen (H 2 ), methane (CH 4 ), carbon dioxide (CO 2 ), hydrogen sulfide (H 2 S), methanethiol (CH 3 SH), and dimethyl sulfide (CH 3 SCH 3 ) in the head‐space.

Results

H 2 was produced in greater amounts by breast‐fed infants than by infants in either formula group, presumably the consequence of incomplete absorption of breast milk oligosaccharides. CH 4 was produced in greater amounts by infants fed soy formula than by infants on other diets. CO 2 was produced in similar amounts by infants in all feeding groups. Production of CH 3 SH was conspicuously low by feces of breast‐fed infants and production of H 2 S was high by soy‐formula–fed infants. CH 3 SCH 3 was not detected. Only modest changes with age were observed and there was no relation between gas production and stool consistency, although stools were more likely to be malodorous when concentrations of H 2 S and/or CH 3 SH were high.

Conclusions

Gas release by infant feces is strongly influenced by an infant's diet. Of particular interest are differences in production of the highly toxic sulfur gases, H 2 S and CH 3 SH, because of the role that these gases may play in certain intestinal disorders of infants.
Intestinal and Systemic Infection, HIV, and Mortality in Zambian Children With Persistent Diarrhea and Malnutrition
Authors: Amadi Beatrice , Kelly Paul , Mwiya Mwiya , Mulwazi Elvin , Sianongo Sandie , Changwe Francis , Thomson Michael , Hachungula Justina , Watuka Angela , Walker‐Smith John , Chintu Chifumbe
Published: January 2024

Background

Persistent diarrhea–malnutrition syndrome is a complex of infection and immune failure that involves protein, calorie and micronutrient depletion, and metabolic disturbances. We report an analysis of the impact of HIV infection on infectious disease, clinical presentation, and mortality in Zambian children with persistent diarrhea and malnutrition.

Methods

Two hundred children (94 boys and 106 girls, 6–24 months old) were examined on admission to the malnutrition ward of University Teaching Hospital in Lusaka, Zambia. There was then 1 month of follow‐up.

Results

Antibodies to HIV were found in 108 of the children (54%). The common intestinal infections (Cryptosporidium parvum [26%] and nontyphoid Salmonella spp [18%]), septicemia (17%), and pulmonary tuberculosis confirmed by gastric lavage (13.5%) were not significantly more common in HIV‐seropositive than in HIV‐seronegative children. HIV‐seropositive children were more likely to have marasmus whereas HIV‐seronegative children were more likely to have kwashiorkor. Weight‐for‐age z scores at nadir (postedema) were lower in HIV‐seropositive children (median, ‐4.4; interquartile range [IQR], −5.0 to −3.8) than in HIV‐seronegative children (median, −3.7; IQR, ‐4.2 to ‐3.1;P < 0.0001). Height‐for‐age and weight‐for‐height z scores and mid‐upper arm circumference showed a similar difference. Of the 200 children, 39 (19.5%) died within 28 days; cryptosporidiosis and marasmus were the only independent predictors of death.

Conclusions

Although intestinal and systemic infections did not differ for HIV‐seropositive and HIV‐seronegative children, HIV influenced nutritional states of all children. Cryptosporidiosis and marasmus were associated with higher mortality.
Extent of Intestinal Damage in the Developing Chick Embryo After Repetitive Hypoxia Under Normoxic or Hyperoxic Conditions
Authors: Van Golde Jolanda , Tibboel Dick , Okazaki Tadaharu , Blanco Carlos E.
Published: January 2024

Background

Episodes of hypoxia and reperfusion play an important role in the development of intestinal damage during perinatal development. The aim of this study was to investigate the histopathology of the intestine in the developing chick embryo after exposure to repetitive hypoxia and recovery under two different conditions: normoxic and hyperoxic (60% O 2 ).

Methods

Chick embryos were exposed to 5 minutes of hypoxia. This was repeated six times with a recovery period of 15 minutes under normoxic conditions (21% O 2 ) for chick embryos in test group 1 (TG1) and under hyperoxic conditions (100% O 2 ) for chick embryos in test group 2 (TG2), from day 11 until day 20. Chick embryos that recovered under hyperoxic conditions (100% O 2 ) were previously incubated under hyperoxic conditions (60% O 2 for 24 hours). Histologic evaluation of the ileum was performed at different times after the interventions (2, 4, 8, 16, and 24 hours).

Results

In both test groups, only chick embryos older than 19 days showed intestinal damage. Intestinal histology on day 19 showed vasodilation of villus capillaries (10% in TG1 and 15% in TG2), necrosis in the top of the villi (29% in TG1 and 30% in TG2), and necrosis with preservation of base of the crypts (2% in TG1) and transmucosal necrosis (2% in TG2).

Conclusions

Significant histologic changes, compared with the control group, were only found in chick embryos that were studied 2 hours after the interventions. Furthermore, recovery under hyperoxic conditions did not cause more intestinal damage compared with recovery under normoxic conditions.
13 C Mixed Triglyceride Breath Test: A Noninvasive Method to Assess Lipase Activity in Children
Authors: van Dijk‐van Aalst Kristal , Van Den Driessche Mieke , van der Schoor Sophie , Schiffelers Sandra , van't Westeinde Tanneke , Ghoos Yvo , Veereman‐Wauters Gigi
Published: January 2024

Background

Results from the 13 C mixed triglyceride (MTG) breath test correlate with duodenal lipase activity in adults. This noninvasive test is a potential screening and diagnostic tool for children with fat malabsorption. The aim of this study was to adapt the methodology of the MTG breath test to study test meals and sampling methods and to define normal values for healthy children of all age groups; premature and full‐term infants have similar pancreatic lipase deficiencies.

Methods

After parental consent was obtained, 12 premature infants (< 37 weeks gestation and with body weights > 2 kg), 12 full‐term infants (1–6 months old), 20 children (3–10 years old), and 20 teenagers (11–17 years old) were tested. All children were thriving well, had no gastrointestinal or respiratory problems, and had not received any medication that contained natural 13 C. For the premature and full‐term infants, a formula was prepared that had a low and stable natural 13 C content mixed with 100 mg 13 C‐labeled MTG (1,3‐distearyl, 2‐[ 13 C‐carboxyl] octanoyl glycerol) and 1 g polyethylene‐glycol 3350. The best accepted test meal for children over 3 years old was a slice of white bread with 5 g butter and 15 g chocolate paste, mixed with 250 mg 13 C‐labeled MTG, and a glass of 100 mL whole‐fat milk. Children over 3 years old were able to blow through a straw in a vacutainer for collecting the breath samples. In children under 3 years old, expired air was collected by aspirating breath via a nasal prong. Carbon dioxide production was calculated according to weight, age, and sex.

Results

For healthy pediatric control participants, the mean values for cumulative excretion of 13 CO 2 as a percentage of the administered dose after 6 hours were 23.9 ± 5.2% in premature infants, 31.9 ± 7.7% in full‐term infants, 32.5 ± 5.3% in children, and 28.0 ± 5.4% in teenagers. The mean value for healthy adults is 35.6% with a lower reference limit of 22.8%.

Conclusions

Age‐specific test meals and breath‐sampling techniques for the MTG breath test were defined. The mean values for different age groups may serve as guidelines for normal values in the pediatric population. The cumulative values for expired 13 CO 2 were above the lower limit for adults, which suggests that preduodenal lipases compensates for pancreatic lipase deficiency in premature and full‐term infants.
Cisapride Plasma Levels and Corrected QT Interval in Infants Undergoing Routine Polysomnography
Authors: Benatar A. , Feenstra A. , Decraene T. , Vandenplas Y.
Published: January 2024

Background

Reported QTc prolongation associated with cardiac arrhythmia in a small number of children undergoing cisapride therapy and lack of pharmacokinetic correlation provided the impetus for this prospective study. The authors evaluated the relation between cisapride plasma concentrations, the electrocardiographic QT interval, and cardiac rhythm in infants undergoing routine 8‐hour polysomnography.

Methods

A total of 211 infants were enrolled: 84 (17 born prematurely) undergoing cisapride therapy for at least 4 days for suspected gastroesophageal reflux and 127 controls (10 born prematurely), aged between 1 week and 13.5 months. Infants underwent continuous bipolar limb lead I recording during routine 8‐hour polysomnography. QT intervals and heart rate were measured at hourly intervals. The morning after polysomnography, 12‐lead electrocardiography was performed (1 hour after cisapride administration). Cisapride plasma concentrations were determined immediately before and 1 to 2 hours after administration. Serum electrolyte concentrations were measured.

Results

The administered cisapride dose ranged from 0.35 to 1.55 (mean, 0.81, median 0.79) mg · kg −1 · d −1 . Cisapride plasma concentrations were significantly higher in infants younger than 3 months of age. Cisapride‐treated infants younger than 3 months of age had longer QTc intervals compared with age‐matched controls. Heart rate was similar for cisapride‐treated and control infants. No arrhythmia or atrioventricular conduction abnormalities were observed.

Conclusions

At comparable doses of cisapride and comparable plasma concentrations, the QTc was significantly higher in infants younger than 3 months of age. This confirms age‐dependent cisapride pharmacokinetics in the first 10 to 12 weeks strongly correlated with changes in body weight and may also suggest an altered ability of infants younger than 3 months of age to metabolize cisapride. The clinical significance and risk of the increased QTc interval is unclear. Cisapride should be judiciously prescribed in infants younger than the age of 3 months and electrocardiography should be performed before and during therapy.