bluuebunny/crossref_metadata_2025 huggingface dataset:
Etiology and Epidemiology of Persistent Diarrhea in Northeastern Brazil
Authors: Fang Guodong D. , Lima Aldo A. M. , Martins Ceci V. , Nataro James P. , Guerrant Richard L.
Published: January 2024

With the improved therapy for acute diarrhea, persistent diarrhea (> 14 days) is emerging as a major problem in developing countries. However, the etiologies and pathogenesis of persistent diarrhea remain poorly understood. We conducted a prospective case‐control study in children <3 years old presenting to the hospital with persistent diarrhea in Fortaleza, Brazil. Over the study period (August 1988 to March 1991), 56 children seen with persistent diarrhea, 52 children seen with acute diarrhea, and 42 controls attending the same hospital/clinic for illnesses other than diarrhea were enrolled. A potential pathogen was found in 91% of children with persistent diarrhea and 90% of those with acute diarrhea versus 45% of controls (both p‘s < 0.01). Thirty‐four percent of persistent (19/56) and 38% of acute (20/52) diarrhea cases versus 2% (1/42) of controls (both p’s < 0.01) had multiple pathogens. Enteroaggregative Escherichia coli (EAggEC) were found in 68% (38/56) of children with persistent diarrhea versus 31% (13/42) of controls (p < 0.01) and in 46% (24/52) of those with acute diarrhea. Furthermore, when the EAggEC were subdivided into aggregative adherence (AA) gene probe positive (18/56; 32%) and negative (20/56; 36%), both subgroups were still significantly different from controls [6/42 (14%) and 7/42 (17%), respectively; both p‘s < 0.05]. EAggEC were the sole pathogen in 17 of 56 (30%) of patients with persistent diarrhea [vs. 11/94 (11.7%) in those with acute diarrhea and controls; p < 0.01], and AA gene probe‐positive EAggEC were the sole pathogen in 20% of children with persistent diarrhea, whereas only 6% of those with acute diarrhea and 7% of controls had AA probe‐positive E. coli (persistent diarrhea vs. acute diarrhea and controls; p < 0.03) Cryptosporidia were found in 25% (14/56) of children with persistent diarrhea (vs. 5% of controls; p < 0.02). Of 32 children with persistent diarrhea who had quantitative small bowel cultures, 13 (41%) had ≥ 104/ml EAggEC (2 had AA probe‐positive EAggEC) in the upper small bowel. Of 10 EAggEC isolated from the small bowel of seven patients with persistent diarrhea, 6 significantly colonized and caused diarrhea in the rabbit‐reversible ileal tie model. Both AA gene probe‐positive and AA gene probe‐negative EAggEC and Cryptosporidium are important potential pathogens in young children with persistent diarrhea and warrant further study to improve our understanding of their pathogenesis and control.
Effect of a Fermented Infant Formula Containing Viable Bifidobacteria on the Fecal Flora Composition and pH of Healthy Full‐Term Infants
Authors: Langhendries J. P. , Detry J. , Van Hees J. , Lamboray J. M. , Darimont J. , Mozin M. J. , Secretin M. C. , Senterre J.
Published: January 2024

We assessed the growth, tolerance, and acceptability as well as fecal flora composition and stool pH of 20 healthy full‐term infants fed with a fermented whey‐adapted infant formula containing viable bifidobacteria (106/g of powder) during the first 2 months of life. This fermented infant formula, first biologically acidified by Streptococcus thermophilus and Lactobacillus helveticus, was compared to a whey‐adapted, nonacidified, low‐phosphate infant formula in a double‐blind, randomized controlled study. The results were compared to a control group (n = 14) of fully breast‐fed infants. The fermented whey‐adapted formula containing viable bifidobacteria induced a prevalence of colonization with bifidobacteria at 1 month of age similar to that of breast‐fed infants (12/20 versus 8/14) but significantly higher than in the group fed the standard infant formula (4/20). The mean bacterial count of bifidobacteria was similar in all colonized infants; however, fecal pH was significantly lower in the breast‐fed infants than in the nonacidified bottle‐fed infants. This kind of infant formula was well tolerated and promoted a normal growth during the first 2 months.
Plasma Endothelin‐1 Levels of Children with Cirrhosis
Authors: Nozue Tomio , Kobayashi Akio , Uemasu Fujio , Takagi Yasuo , Endoh Hiroomi , Sako Akiko
Published: January 2024

We measured plasma concentration of endothelin‐1 in three children with Byler's disease, five with biliary atresia after portoenterostomy, and nine controls. No patients had ascites or hepatorenal syndrome. Plasma endothelin‐1 levels were significantly higher in patients with Byler's disease than in the controls (5.19 ± 0.90 versus 1.81 ± 0.19 pg/ml, respectively; p < 0.01), but were normal in operated biliary atresia. Urinary concentrations of N‐acetyl‐β‐L‐glucosaminidase (NAG) were significantly higher in the patients with Byler's disease than in controls. Plasma endothelin‐1 level correlated significantly with serum concentration of bile acid (r = 0.91; p < 0.01) and urinary concentration of NAG (r = 0.92; p < 0.01). We conclude that plasma endothelin‐1 levels are high in patients with severe biliary cirrhosis and that endothelin‐1 may partially contribute to development of renal injury in cirrhosis.
Effects of Dietary Supplementation with Fructooligosaccharides on Colonic Microbiota Populations and Epithelial Cell Proliferation in Neonatal Pigs
Authors: Howard Michael D. , Gordon Dennis T. , Pace Lanny W. , Garleb Keith A. , Kerley Monty S.
Published: January 2024

Two experiments were conducted with neonatal pigs to determine the effects of feeding fructooligosaccharides on cecal and colonic microbiota, proliferation of cecal and colonic epithelial mucosa, and short‐chain fatty acid concentrations in the cecum. Experiment 1 consisted of feeding neonatal pigs diets containing either 0 or 3 g fructooligosaccharides/L of formula for 15 days and then examining the large intestine for changes in cecal and proximal colonic microbiota; cecal pH; short‐chain fatty acid concentrations; morphology of cecal, proximal, and distal colonic epithelial mucosa; gross necropsy; and his‐topathology. Supplementation with fructooligosaccharides (FOS) did not alter cell counts of viable bifidobac‐teria organisms or total anaerobic microbiota, cecal pH, or concentrations of short‐chain fatty acids. Cecal mu‐cosal cell density and labeled cells increased with FOS consumption. Proximal colonic mucosal crypt height, leading edge, labeled cells, proliferation zone, and labeling index increased with FOS consumption. Distal colonic mucosal crypt height, leading edge, cell density, labeling index, and labeled cells increased with FOS consumption. Gross necropsy and histopathology found no significant lesions. In Experiment 2, neonatal pigs were fed diets containing either 0 or 3 g fructooligosaccharides/L of formula for 6 days. Fecal samples were collected on the first full day of feeding and on days 3 and 6 after initiation of feeding. On days 1 and 3, concentrations of bifidobacteria were similar between diets; however, on day 6, pigs consuming FOS tended to have greater numbers of bifidobacteria (p = 0.08). These data suggest dietary consumption of FOS will enhance bifidobacteria populations and prevent colonic epithelial mucosa atrophy in neonates fed an elemental diet.
The Association of Syndromic Paucity of the Interlobular Bile Ducts and Congenital Mechanical Obstruction of the Small Intestine
Authors: Chiu Hsiu‐Hui , Chang Mei‐Hwei , Chen Chi‐Long , Hsu Hong‐Yuan , Ni Yen‐Hsuan
Published: January 2024

Three patients with congenital mechanical intestinal obstruction and features of syndromic paucity of the interlobular bile ducts (SPILBD) are presented. Two of them have siblings with syndromic paucity of the interlobular bile ducts. Two patients had jejunoileal atresia, while the other had a meconium plug with intestinal perforation. All subjects underwent surgery for intestinal ob‐ struction within the first 24 h of life. Progressive disappearance of the bile ductules was observed in one case. We believe that an insult such as vascular insufficiency to both bile ductal epithelium and the small intestine may be the cause of this congenital disorder.
The Three‐Week‐Old Piglet as a Model Animal for Studying Protein Digestion in Human Infants
Authors: Darragh Alison J. , Moughan Paul J.
Published: January 2024

Summary: The piglet was evaluated as a model animal for studying the digestion of high‐quality proteins in human infants. Three‐week‐old male piglets (n = 6) and 3‐month‐old male human infants (n = 6) were fed a bovine‐milk‐based formula over a 17‐day experimental period comprising 7 days' adaptation followed by a 10‐day fecal collection period. The piglets and infants were given 345‐g liquid formula/kg body weight/day and 170‐g liquid formula/kg body weight/day, respectively, which equated to similar dry matter intakes per unit stomach volume (0.923 g dry matter/cm3/day). Both the piglets and infants were individually bottle‐fed the reconstituted milk formula (12.2% dry matter) at similar meal frequencies. Small but statistically significant differences (p < 0.01) were found for the apparent fecal digestibility (mean ± overall SE) of dietary dry matter (98.8 versus 97.4% ± 0.13%), organic matter (99.0 versus 97.7% ± 0.12%), and total nitrogen (97.5 versus 94.5% ± 0.36%) between the piglets and infants. The fecal digestibilities for most of the amino acids were not significantly different (p > 0.05) between the species. The digestion of protein appeared to be similar in the two species. The study provides support for using the piglet as a model animal for studying protein digestion in human infants.
Hyperplasia of the Muscularis Propria in Response to Massive Intestinal Resection in Rat
Authors: Scott R. B. , Sheehan A. , Chin B. C. , Tan D. T. M.
Published: January 2024

Summary: Adaptation of the muscularis propria to intestinal resection is not well studied. Growing, 150− to 200‐g Sprague‐Dawley rats were divided into a resected group (R), which had 75% of the jejunoileum removed; a sham‐resected group (SR); and a group of untreated controls (C). Food intake and weight gain were documented. Animals were killed on days 0, 10, 20, 30, or 40 (n = 14 animals for each day in each group). Small‐intestinal length and jejunal circumference, wet weight/cm, thickness of the muscle layers, muscle morphometry, mg protein, and μg DNA per cm of the muscularis propria were measured. R rats had an initially greater food intake than SR or C animals, but the rate of weight gain was not different between groups. There was no significant increase in length of the residual intestine in R animals during the postoperative adaptive period, but circumference was significantly increased in R compared with SR or C animals. Wet weight/cm, mg protein, and μg DNA per cm of the muscularis propria were significantly greater in R compared with SR or C animals, but there was no change in thickness of the smooth‐muscle layers in R versus SR or C rats. The number of cross‐sectioned circular smooth‐muscle cells/mm2 and the ratio of mg protein/μg DNA/cm length of muscularis propria were not different in R compared with SR or C animals. Intestinal resection resulted in a significant increase in circumference but not length of the residual intestine. A significant increase in the mass/cm, with no change in the number of cross‐sectioned circular smooth‐muscle cells/mm2 or in mg protein/μg DNA/cm of the muscularis propria, indicates that the adaptive response of muscularis propria is characterized by hyperplasia. This response potentially confers benefit to the organ and animal as a whole as a mechanism that permits structural and functional adaptation of the muscularis propria to resection.
Relationship of Interleukin‐1 Receptor Antagonist to Mucosal Inflammation in Inflammatory Bowel Disease
Authors: Hyams Jeffrey S. , Fitzgerald John E. , Wyzga Nancy , Muller Richard , Treem William R. , Justinich Christopher J. , Kreutzer Donald L.
Published: January 2024

Summary: Previous work has suggested that the interleu‐kin‐1 (IL‐1) receptor antagonist, IL‐Ira, may regulate mucosal inflammation in inflammatory bowel disease. The present study assessed the relationship of mucosal IL‐Ira levels to histologic severity of inflammation and the related proinflammatory cytokines IL‐1β and IL‐6 in children with inflammatory bowel disease. Colonic biopsy specimens from 29 patients with ulcerative colitis, 27 with Crohn's disease, and 24 noninflammatory control subjects were assayed for IL‐Ira, IL‐1β, and IL‐6 by enzyme‐linked immunosorbent assay. Histologic activity was graded as none, mild, moderate, or severe. Mucosal IL‐1β levels, but not IL‐lra levels, were significantly elevated in moderate/severely inflamed biopsies from patients with either ulcerative colitis (p < 0.01) or Crohn's disease (p < 0.001) compared with those with none/mild inflammation. The mucosal molar ratio of IL‐lra/IL‐1β was significantly lower for moderate/severe inflammation compared with none/mild inflammation for patients with ulcerative colitis (p < 0.05) and Crohn's disease (p < 0.01). The mucosal IL‐lra/IL‐1β ratio was similar in controls to none/mild inflamed biopsies from subjects with either ulcerative colitis or Crohn's disease. Our observations suggest that increasing mucosal inflammation in inflammatory bowel disease in children is associated with a decrease in the “normal” effective IL‐lra/IL‐1β ratio in which IL‐lra predominates. The importance of this abnormality to the pathogencsis of inflammatory bowel disease awaits further study.
A Multicenter Long‐Term Safety and Efficacy Trial of Preterm Formula Supplemented with Long‐Chain Polyunsaturated Fatty Acids
Authors: Vanderhoof Jon , Gross Steven , Hegyi Thomas ,   Multicenter Study Group
Published: January 2024

Background

The tissue accretion of long‐chain polyunsaturated fatty acids is compromised in infants born prematurely. Human milk contains long‐chain polyunsaturated fatty acids, but most preterm infant formulas do not. The long‐term effects of preterm formula supplemented with arachidonic acid and docosahexaenoic acid, in proportions typical of those in human milk, were therefore investigated.

Methods

In this double‐blind, randomized study, 288 preterm infants received experimental formula (n = 77), unsupplemented (control) formula (n = 78), or human milk (n = 133) until 48 weeks postconceptional age (PCA). Term formula, without supplemental long‐chain polyunsaturated fatty acids, was administered from 48 to 92 weeks PCA to formula‐fed infants and to infants weaned from human milk. Anthropometric and fatty acid data were assessed by using analysis of variance.

Results

At 92 weeks PCA, no statistically significant anthropometric measurement differences were found except for midarm circumference, which was smaller in human milk–fed infants than in those fed formula. Phospholipid concentrations were similar in the experimental and human milk–fed groups, and docosahexaenoic acid levels were significantly greater than in the control group. The types and incidences of adverse events were similar among the feeding groups.

Conclusions

The results of this study demonstrate the efficacy and long‐term safety of preterm formula supplemented with long‐chain polyunsaturated fatty acids.
Liver Abnormalities During Growth Hormone Treatment
Authors: Salerno Mariacarolina , Di Maio Salvatore , Ferri Pasqualina , Lettiero Teresa , Di Maria Federica , Vajro Pietro
Published: January 2024

Background

Occasional and transient increase in liver enzymes is reported during growth hormone (GH) treatment in girls with Turner syndrome (TS).

Methods

Retrospectively, the specific role of GH treatment on liver and muscular enzymes was evaluated in 78 patients (48 boys; age range 4.0–20.8 years) affected by GH deficiency (GHD) who had been treated with GH for at least 1 year (range: 1–15 years). All patients had normal serum levels of liver and muscular enzymes before GH therapy was started.

Results

A clinically asymptomatic and mild increase in serum transaminase levels was observed in 6 of 78 patients with GHD during GH treatment; 3 (3.8%) of the patients showed an isolated, transitory and self‐limiting increase in serum liver transaminase levels which was noticed 6 to 12 months after GH treatment was started, and normalized spontaneously within 3 to 6 months, without stopping the therapy. Three additional patients showed a transitory mild increase both in aspartate aminotransferase (AST) and creatine phosphokinase (CK) which also normalized spontaneously within 3 to 6 months. The increase in transaminase levels was not related to the brand of GH preparations nor to the dosage administered.

Conclusions

A mild, transient, self‐limiting increase in serum transaminase may occur during GH treatment. Concomitant determination of CK serum levels may quickly differentiate muscular from hepatic hypertransaminasemia. Except for persistent cases, this condition does not generally require further investigations.
Unusual Early Presentation of Gilbert Syndrome in Pediatric Recipients of Liver Transplantation
Authors: Vajro Pietro , DeVincenzo Anna , Lucariello Stefania , Migliaro Fiorella , Sokal Etienne , Bernard Olivier , Vilei Teresa , Muraca Maurizio
Published: January 2024

Background

Gilbert syndrome as a rule becomes manifest in adolescence or in early adulthood; it may be transferred by the donor to orthotopic liver transplant (OLT) recipients.

Methods

We examined the frequency of Gilbert syndrome in 46 OLT pediatric recipients who had a follow‐up of 1 year or more. Diagnostic criteria included unexplained chronic or recurrent unconjugated hyperbilirubinemia; its increase after reduced caloric intake plus prolonged fasting, without changes of the proportion of conjugated bilirubin; and high relative amounts of serum unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide.

Results

Of the 46 patients, 42 had normal bilirubin values. Only four otherwise healthy OLT recipients showed hyperbilirubinemia and normal conjugated fractions. Liver donors had been four men. Hyperbilirubinemia persisted with a fluctuating pattern for the whole follow‐up after OLT in all. Total bilirubin level in blood samples obtained after reduced caloric intake and prolonged fasting became notably higher than basal values, whereas the proportion of conjugated bilirubin remained stable. High relative amounts of unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide were found. Finally, DNA from liver donors' lymphocytes was available for one jaundiced and two nonjaundiced patients: tests for abnormalities in the promoter region of the gene for the enzyme bilirubin uridine diphospho‐glucuronosyltransferase were in agreement with a diagnosis of GS in the former one.

Conclusions

Gilbert syndrome may have an unusual early presentation in pediatric OLT recipients.
Risk Factors for Severe Esophageal and Gastric Lesions in Term Neonates: A Case–Control Study
Authors: Benhamou Pierre‐Henri , Francoual Christine , Glangeaud Marie‐Christine , Barette Antoinette , Dupont Christophe , Bréart Gerard ,   Groupe Francophone d'Hépato‐Gastroentérologie et Nutrition Pédiatrique
Published: January 2024

Background

The purpose of this multicenter case–control study was to search for causes and risk factors related to the severe upper digestive tract lesions often seen in neonates.

Methods

Case patients were full‐term neonates with endoscopically confirmed severe bleeding or ulcerative lesions of the esophagus and/or stomach. Matched control subjects were the next infant born in the same maternity unit who met the same criteria and had no clinical abnormality (and, for ethical reasons, no endoscopy). The analysis was based on 137 case–control pairs and considered data showing the mothers' medical and obstetric background, the infants' clinical status and laboratory results, feeding details, and the State and Trait Anxiety Inventory (STAI) questionnaire, which was used to assess the anxiety of the mothers.

Results

Cases and controls did not differ in any demographic or social factors. Antacid and anti‐ulcer drugs were used significantly more frequently during the last month of pregnancy by case mothers than by control mothers (28% and 10%, respectively;P < 0.001). Mode of delivery was similar. Case infants more frequently experienced cardiac deceleration during labor and delivery (28% and 12.9%;P = 0.003). Breast‐feeding at birth was less frequent for case infants (36% and 49%;P = 0.05). The mean trait anxiety scores did not differ between the two groups, but the mean state anxiety score was higher in case mothers. Multivariate logistic regression found that three factors were independently and significantly associated with esophageal and gastric lesions: use of antacid and antiulcer treatments (odds ratio [OR], 3.9;P < 0.001), cardiac deceleration (OR, 2.2;P = 0.03), and breast‐feeding (OR, 0.5;P = 0.02).

Conclusions

Antacid drug use by mothers during the last month of pregnancy was associated with esophageal and gastric lesions. Breast‐feeding may play a protective role against severe lesions in neonates.
Celiac Disease in a Chilean Population Carrying Amerindian Traits
Authors: Araya Magdalena , Mondragón Alexandra , Pérez‐Bravo Francisco , Roessler Jose Luis , Alarcón Teresa , Ríos Gloria , Bergenfreid Carmen
Published: January 2024

Background

Although clinical manifestations of celiac disease may change throughout life, clinical, histologic, immunologic, and genetic studies show that there are incomplete forms of this condition, making it difficult to define the disease at a given moment. Because there is no information published in the Latin American‐Amerindian population, this study was conducted to assess relations between these parameters in Chileans with celiac disease and their first‐degree relatives.

Methods

Sixty‐two persons with confirmed celiac disease (mean age, 17.9 ± 5.1 years; 78.3% females) and 126 relatives (mean age, 27.9 ± 17.2 years; 65.1% females) were evaluated. Clinical manifestations, antiendomysial antibodies (EMAs), and human leukocyte antigen (HLA) haplotypes were studied in patients. Additionally, jejunal biopsy specimens were assessed (light microscopy) in EMA‐positive (EMA+) relatives.

Results

Of the patients, 24.1% adhered to a strict gluten‐free diet; 26% were oligosymptomatic, and none were malnourished; 45% were EMA+; 13.8% who ingested gluten were EMA‐negative (EMA−); one patient consuming a strict gluten‐free diet was EMA+. The DQA1*0501 allele was present in the highest frequency (48%, P < 0.0005), whereas combinations of DQ8 were predominant. Of the relatives, 4.8% were EMA+; they had a significantly higher frequency of diarrhea, weight loss, and anorexia (P < 0.03); and all had abnormal histology in biopsy specimens.

Conclusions

After childhood, celiac disease is oligosymptomatic and is often unrecognized by patients. Disease in 13.8% of patients and in 4.8% relatives appeared as incomplete forms of celiac disease. Predominance of DQ8 HLA haplotypes reflects the genetic Spanish‐Mapuche heritage of this population.
Posttransplantation Lymphoproliferative Disorder: Endoscopic Findings
Authors: O'Connor Judith A. , Cogley Catherine , Burton Mark , Lancaster‐Weiss Kristen , Cordle Richard A.
Published: January 2024

Background

posttransplantation lymphoproliferative disorder (PTLD) may manifest a variety of nonspecific symptoms and must be suspected in the patient who undergoes solid organ transplantation. Common sites of occurrence include the gastrointestinal tract, the central nervous system, and lymphoid tissue of the oral pharynx, mediastinum, and mesentery. The large incidence of gastrointestinal involvement provides an opportunity for endoscopic diagnosis. This is the description of a characteristic endoscopic finding in patients who have undergone liver transplantation who are under evaluation for suspected PTLD.

Methods

During a 2‐year period, 27 liver transplantations were performed in 24 pediatric patients. Fourteen patients underwent endoscopic evaluation. Indications for endoscopy included abdominal pain, vomiting, hematemesis, irritability, growth failure, anemia, occult blood loss, and suspected PTLD. Biopsy specimens were obtained from any endoscopically detected abnormality and from the duodenum, gastric antrum, esophagus, terminal ileum, cecum, and rectum. Specimens with suspected PTLD were evaluated with Epstein–Barr virus latent membrane stain.

Results

Six patients were found to have a characteristic lesion, which was raised, rubbery, and erythematous, with a central ulceration. Lesions were singular or multiple and ranged from 5 to 15 mm in diameter. Microscopic evaluation revealed a monotonous proliferation of lymphocytes. All specimens were positive for Epstein–Barr virus latent membrane protein stain. Stains for cytomegalovirus were negative. Biopsy specimens from the eight patients without identified characteristic lesions were negative for PTLD.

Conclusions

Panendoscopy is a useful tool for the diagnosis and treatment of gastrointestinal PTLD. Endoscopy is easily accomplished, may provide an instantaneous result if the characteristic lesion is identified, and provides tissue for disease classification. Patients with unexplained gastrointestinal signs or symptoms should undergo panendoscopy for suspected PTLD.
Tissue Transglutaminase Is the Target in Both Rodent and Primate Tissues for Celiac Disease–Specific Autoantibodies
Authors: Korponay–Szabó Ilma R. , Sulkanen Satu , Halttunen Tuula , Maurano Francesco , Rossi Mauro , Mazzarella Giuseppe , Laurila Kaija , Troncone Riccardo , Mäki Markku
Published: January 2024

Background

Endomysial antibodies have recently been shown to react with tissue transglutaminase. This study was undertaken to investigate whether the tissue distribution of transglutaminase is also compatible with reticulin, jejunal, and fibroblast autoantibody binding patterns.

Methods

Sera from patients with and without celiac disease, monoclonal tissue transglutaminase antibodies, and sera from mice parenterally immunized against commercially available tissue transglutaminase, transglutaminase complexed with gliadin, or gliadin were used in indirect immunofluorescence and double‐staining studies using both rodent and primate tissues as substrates. Also, antibody competition, affinity chromatography, and potassium thiocyanate extraction studies were undertaken.

Results

Tissue transglutaminase antibody binding patterns were identical with the extracellular binding patterns seen with celiac patient sera. Human umbilical cord–derived fibroblasts exhibited both cytoplasmic and extracellular matrix staining. Double staining with patients' sera and tissue transglutaminase antibodies showed complete overlapping. Tissue transglutaminase effectively absorbed reticulin‐endomysial antibodies from celiac sera, and patients' sera blocked the staining of the monoclonal tissue transglutaminase antibodies. Potassium thiocyanate extraction abolished the staining patterns, but they were elicited again after readdition of tissue transglutaminase.

Conclusions

Reticulin, endomysial, and jejunal antibodies detect transglutaminase in both rodent and primate tissues, indicating that these tissue autoantibodies are identical.
Percutaneous Liver Biopsy in Children: Impact of Ultrasonography and Spring‐Loaded Biopsy Needles
Authors: Scheimann Ann O. , Barrios Jose M. , Al‐Tawil Youhanna S. , Gray Krista M. , Gilger Mark A.
Published: January 2024

Background

Percutaneous liver biopsy is a valued tool of pediatric hepatology. Recent advances in technology have incorporated spring‐loaded biopsy needles and ultrasonography in percutaneous liver biopsy.

Methods

To determine the frequency of complications after liver biopsy and whether variables such as needle selections (Jamshidi, Monopty, or ASAP) and ultrasound guidance could predict complications, medical records were retrospectively reviewed of all patients who underwent percutaneous liver biopsy during a 7‐year period. Available data were collected from 123 patients who had undergone a total of 249 percutaneous liver biopsies. All patients with evidence of mild clotting abnormalities (8.83%) received platelets, cryoprecipitate, or fresh‐frozen plasma.

Results

There was a 6.83% incidence of overall complications, and a 2.4% incidence of major complications. The mortality rate was 0.4%. Ultrasound localization did not diminish the risk of bleeding during biopsy. There was no significant difference in the change of hematocrit between the aspiration (Jamshidi) and spring‐loaded (Monopty) needles. However, in patients less than 5 years of age, the change of hematocrit was significantly higher (P < 0.05) with the 15‐or 18‐gauge ASAP needle (Microvasive, Quincy, MA, U.S.A.) than with either the Jamshidi (Allegience Healthcare, Columbia, MD, U.S.A.) or Monopty (Bard Technologies, Covington, GA, U.S.A.) needles.

Conclusion

Percutaneous liver biopsy is safe, using either aspiration or spring‐loaded needles. Ultrasound guidance may not be helpful except in patients who underwent segmental liver transplantation.
Impact of Early Dietary Intake and Blood Lipid Composition of Long‐Chain Polyunsaturated Fatty Acids on Later Visual Development
Authors: Hoffman Dennis R. , Birch Eileen E. , Birch David G. , Uauy Ricardo , Castañeda Yolanda S. , Lapus Maia G. , Wheaton Dianna H.
Published: January 2024

Background

In contrast to human milk, current infant formulas in the United States do not contain ω3 and ω6 long‐chain polyunsaturated fatty acids. This may lead to suboptimal blood lipid fatty acid profiles and to a measurable diminution of visual function in developing term infants. The need for docosahexaenoic acid and arachidonic acid supplementation in the infant diet was evaluated in a double‐blind, randomized clinical trial.

Methods

Healthy term infants were randomized to diets of (1) commercial formula, (2) docosahexaenoic acid–enriched formula (0.35% of total fatty acids), or (3) docosahexaenoic acid– (0.36%) and arachidonic acid– (0.72%) enriched formula. Eighty‐seven infants completed the 17‐week nutritional trial, and 58 were observed until 52 weeks of life. A reference group was exclusively breast fed for at least 17 weeks (n = 29). Outcome measures included electroretinographic responses, visual evoked potentials, and blood fatty acid analysis in infants at birth and at 6, 17, and 52 weeks of age.

Results

Commercial formula‐fed infants had 30% to 50% lower content of docosahexaenoic acid in total red blood cell lipids during the 17‐week feeding trial compared with breast‐fed infants. Significant differences persisted at the 1‐year follow‐up. Arachidonic acid content was consistently reduced in the commercial formula group by 15% to 20%. Infants fed long‐chain polyunsaturated fatty acid–enriched formulas had docosahexaenoic acid and arachidonic acid blood lipid profiles resembling those of human milk‐fed infants. Infants receiving this enriched formula had more mature electroretinographic responses than commercial formula‐fed infants at 6 weeks of age. Human milk‐fed and docosahexaenoic acid‐enriched formula‐fed infants had better visual acuity than commercial formula‐fed infants at both 17 and 52 weeks of age. Early (17‐week) fatty acid profiles in blood lipids were correlated with later (52‐week) visual function development in study infants.

Conclusions

Results from this clinical trial demonstrate that long‐chain polyunsaturated fatty acid supplementation of formula in term infants produces blood lipid fatty acid profiles that are similar to those observed in breast‐fed infants. This supplementation leads to better visual function later in life (i.e., 1 year of age) than that shown by infants fed commercial formula.
Randomized, Placebo‐Controlled, Clinical Trial of Hyperimmunized Chicken Egg Yolk Immunoglobulin in Children With Rotavirus Diarrhea
Authors: Sarker Shafiqul A. , Casswall Thomas H. , Juneja Lekh R. , Hoq Enamul , Hossain Iqbal , Fuchs George J. , Hammarström Lennart
Published: January 2024

Background

Hyperimmunized bovine colostrum containing antibodies has been shown to be effective in the treatment of rotavirus diarrhea. Antibodies derived from eggs of immunized hens may be a less expensive and more practical alternative. In this study, children with proven rotavirus diarrhea were treated with immunoglobulin extracted from eggs of chicken immunized with human rotavirus strains.

Methods

In a randomized, double‐blind study, 79 children with known rotavirus diarrhea were assigned to receive either 10 g hyperimmune egg yolk (HEY) daily in four equally divided doses for 4 days (HEY group) or a similar preparation obtained from nonimmunized chicken (placebo group). The daily stool frequency and amount, oral rehydration solution (ORS) intake, and presence of rotavirus in the stool were monitored for 4 days.

Results

In the HEY‐treated group. there was significant reduction in stool output (in grams per kilogram per day; HEY vs. placebo; 87 ± 59 vs. 120 ± 75, P = 0.03), and significant reduction of ORS intake (in milliliters per kilogram per day) (HEY vs. placebo; 84 ± 46 vs. 122 ± 72, P = 0.008) on day 1 and clearance of virus on day 4 (HEY vs. placebo; 73% vs. 46%, P = 0.02). There was, however, no difference in diarrheal duration between the groups.

Conclusions

Treatment with HEY against four human rotavirus strains resulted in modest improvement of diarrhea associated with earlier clearance of rotavirus from stools. These results indicate an encouraging role of HEY in the treatment of rotavirus‐induced diarrhea in children. Further studies are needed to optimize the dose and neutralization titer and thus improve the efficacy of egg yolk immunoglobulin IgY derived from immunized hens.
Interferon‐α Treatment of Chronic Hepatitis C in Children with Hemophilia
Authors: Ko Jae Sung , Choe Yon Ho , Kim Eun Joo , Lee Eun Hee , Jang Ja‐June , Seo Jeong Kee
Published: January 2024

Background

In children with hemophilia, hepatitis C virus (HCV) is the major cause of chronic liver disease. In this study, long‐term efficacy of interferon‐α was studied to determine the factors that predict a sustained response to interferon therapy in young children with hemophilia who have chronic hepatitis C.

Methods

Seventeen Korean children with hemophilia and chronic hepatitis C were treated with 3.7 million units/m2 of interferon‐α2a three times weekly for 6 months. Liver biopsy, pretreatment serum HCV RNA quantitation with competitive reverse transcription assay, and HCV genotyping with reverse hybridization assay were performed.

Results

Hepatitis C virus genotypes 1a, 1b, and 2a were found in three (18%), five (29%), and six (35%) patients, respectively. Interferon‐α was well tolerated, and the frequency of bleeding did not increase. Of the 17 patients, 7 (41%) had a sustained response for 3 years after the end of therapy. Patients with a sustained response had lower pretreatment serum HCV RNA levels. One (13%) of eight patients with genotype 1 and five (83%) of six with genotype 2 had a sustained response (P < 0.05).

Conclusions

Interferon‐α treatment of chronic hepatitis C in children with hemophilia was safe and effective in producing sustained responses. The pretreatment serum HCV RNA level and viral genotype may be predictive factors for sustained response to interferon therapy.
Clinical Correlations in Infants in the Neonatal Intensive Care Unit With Varying Severity of Gastroesophageal Reflux
Authors: Khalaf M. Nabeel , Porat Rachel , Brodsky Nancy L. , Bhandari Vineet
Published: January 2024

Background

Gastroesophageal reflux (GER) is frequently a benign condition in infancy with spontaneous resolution. In the neonatal intensive care unit (NICU), however, it can add to neonatal morbidity if not adequately diagnosed and treated. The objective of the current study was to analyze factors associated with GER in infants in the NICU and correlate them with the severity of the disease.

Methods

All infants in the NICU (n = 150; born November 1994 through April 1999) who were evaluated by a five‐channel pH study to rule out GER were included in the study. Infants were grouped as normal, with a reflux index (RI) of less than 6 (n = 66); mild, with RI of 6 to 14 (n = 42); and severe, with RI of more than 14 (n = 42). Maternal and neonatal data were obtained. Clinical GER was defined as the presence of feeding problems (significant gastric residue or emesis) and medical improvement with antireflux measures and medications.

Results

There was no difference in birth weight, gestational age; incidence of patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, or chronic lung disease; and treatment with aminophylline or caffeine among the groups. Infants with mild and severe GER (RI 6–14 and >14) had significantly more clinical GER than the normal group (P = 0.0001). Additionally, infants with RI more than 14 had significantly more respiratory distress syndrome, lower hematocrits at the time of study and longer length of stay than those with no or mild GER (P = 0.02).

Conclusion

Infants with severe GER had lower hematocrits despite receiving more blood transfusions and iron therapy. Infants with severe GER also had prolonged hospital stays. Early diagnosis and aggressive management of GER may decrease neonatal morbidity and result in earlier discharge from the NICU.
Gastrostomy as a Decompression Technique in Children With Chronic Gastrointestinal Obstruction
Authors: Michaud Laurent , Guimber Dominique , Carpentier Bénédicte , Sfeir Rony , Lambilliotte Anne , Mazingue Françoise , Gottrand Frédéric , Turck Dominique
Published: January 2024

Background

Percutaneous or surgical insertion of gastrostomy tubes for feeding children has been well described. However, there is no report of percutaneous gastrostomy for chronic decompression in children with chronic gastrointestinal obstruction. The objective of this study was to evaluate this technique.

Methods

Eighteen gastrostomies were performed for gastrointestinal decompression in children. The patients ranged in age from 2 to 125 months (median: 15.5), and all had prolonged hospital stays for severe disease: severe gastroparesis and/or duodenal dysmotility (n = 8), duodenal stenosis (n = 2), chronic intestinal pseudo‐obstruction (n = 4), enterocolitis (n = 2), and metastatic abdominal carcinomatosis (n = 2). The duration of symptoms before gastrostomy placement ranged from 0.5 to 44 months (median: 2), with major symptoms including epigastric pain, early satiety, nausea, vomiting, and bloating.

Results

The goals of gastric decompression and removal of the nasogastric tube were achieved in all patients, and all had significant relief of both nausea and emesis. Oral intake of liquids and soft foods was possible in 17 of 18 of the children. The tubes were kept in place for a median of 22.5 months (range, 2–73). There was neither long‐term morbidity nor mortality associated with the presence of the tube. Seventeen patients returned home with gastric decompression and cyclic parenteral nutrition, two of them for terminal care. Six patients died. In all patients, gastrostomy was used throughout and did not contribute to the death of the patients. For seven children, tubes were removed because of resolution of small bowel or gastric outlet obstruction.

Conclusions

Gastrostomy is an efficient and well‐tolerated method of achieving long‐term gastric decompression in children with abdominal obstruction not amenable to surgery and/or resistant to medical treatment.
Efficacy of Long‐Term Treatment With Thalidomide in Children and Young Adults With Crohn Disease: Preliminary Results
Authors: Facchini Sergio , Candusso Manila , Martelossi Stefano , Liubich Mario , Panfili Elisabetta , Ventura Alessandro
Published: January 2024

Background

Several proinflammatory cytokines are involved in the pathogenesis of inflammatory bowel diseases. A significant role has been given to tumor necrosis factor α (TNF‐α) as a guide proinflammatory cytokine. Thalidomide selectively reduces TNF‐α production by inflammatory cells. The aim of the study was to assess the efficacy of thalidomide to induce and maintain remission in refractory Crohn disease.

Methods

The decision to administer thalidomide was made on the basis of patient intolerance or resistance to conventional medical treatment or as the last medical resort before surgical intervention. Only 5 of 96 patients with inflammatory bowel disease satisfied these criteria. All five patients had Crohn disease (male; mean age, 17 years). Thalidomide was administered at night at a dose of 1.5–2 mg/kg/day. The Pediatric Crohn Disease Activity Index, modified Harvey‐Bradshaw scores, and steroids reduction were used to assess clinical response.

Results

Disease activity decreased consistently in four patients with a reduction of mean Pediatric Crohn Disease Activity Index from 36,9 to 2,5 and the mean Harvey‐Bradshaw from 8.5 to 0.75 after 3 months of treatment. Steroid treatment (mean dose, 35 mg/day before treatment) was tapered and then discontinued, in four patients, within 1–3 months. Four patients are in remission after 19–24 months of treatment. The fifth patient discontinued thalidomide after 1 week because of distal paresthesia.

Conclusion

Thalidomide seems to be an effective and safe treatment in patients with refractory Crohn disease. This is the first report of long‐term use of thalidomide in refractory Crohn disease in pediatric patients.
Outcome of Early Hepatic Portoenterostomy for Biliary Atresia
Authors: Volpert Diana , White Fran , Finegold Milton J. , Molleston Jean , DeBaun Michael , Perlmutter David H.
Published: January 2024

Background

The outcome of the hepatic portoenterostomy (Kasai) procedure for biliary atresia is improved when it is performed before 90 days of age. However, it is not known whether intervention before 30 days is better than intervention between 30 and 90 days.

Methods

The authors reviewed the records of all patients seen by the Pediatric Gastroenterology Service at St. Louis Children's Hospital from 1984–1999 to ascertain the outcome of patients who underwent Kasai procedure before or after 30 days of age.

Results

Of 92 patients with biliary atresia treated at St. Louis Children's Hospital over 15 years, 9 underwent the Kasai procedure before 30 days of age. Liver transplantation was necessary in 77.8% of these patients at a mean age of 11.0 ± 4.26 months, as compared with 53.4% at 32.14 ± 7.14 months for the remainder of the patients who underwent the procedure after 30 days of age.

Conclusions

Although these data suggest that outcomes are worse for patients who undergo the procedure before 30 days of age, they may reflect a difference in the pathogenesis of biliary atresia that brings it to clinical attention earlier and may provide further evidence that biliary atresia is a phenotype for a number of distinct underlying disease processes.
Absence of Toll‐Like Receptor 4 Explains Endotoxin Hyporesponsiveness in Human Intestinal Epithelium
Authors: Naik Sandhia , Kelly Eric J. , Meijer Lisa , Pettersson Sven , Sanderson Ian R.
Published: January 2024

Background

The Toll protein in Drosophila regulates dorsal ventral patterning during embryogenesis, and participates in antibacterial and antifungal host defense. Mammalian homologues are termed Toll‐like receptors and, to date, nine have been cloned (TLR1–9) in humans. They are characterized by extracellular leucine‐rich repeats and a cytoplasmic domain similar to the interleukin 1 receptor. Both TLR2 and TLR4 recognize various bacterial cell wall components including lipopolysaccharide (LPS). This results in the activation of the NFκB pathway. Peripheral blood mononuclear cells (PBMCs) express both TLR2 and TLR4. The authors hypothesized that the expression of TLR 2 and TLR4 in human intestinal epithelial cells differs from PBMCs because of the abundance of LPS in the intestinal lumen.

Methods

Epithelial cells were isolated from Caco‐2 cells, fetal gut explants, and small bowel resection specimens using Hanks/ethylenediamine tetraacetic acid solution. PBMCs were used as positive controls. Ribonucleic acid (RNA) was isolated using the TRIzol method. Standard reverse transcription–polymerase chain reaction examined TLR2 and TLR4 messenger RNA (mRNA) expression. NFκB expression was determined using a luciferase reporter assay.

Results

TLR2 mRNA was highly expressed in PBMCs and was present in all human intestinal epithelial cells. TLR4 mRNA was detected only in PBMCs. TLR4 is not present in epithelium from children with inflammatory bowel disease. In Caco‐2 cells, significant NFκB activation in response to LPS occurred only in the presence of TLR4 introduced by complementary deoxyribonucleic acid transfection.

Conclusion

Absence of TLR4 is associated with endotoxin hyporesponsiveness of intestinal epithelial cells. TLR4 is not directly involved in inflammation of the intestinal epithelium. Although TLR2 is normally present in the epithelial cell, it plays a limited role in inflammation. It may be activated during conditions in which bacterial cell wall concentrations within the intestine are pathologically high.
Does Cisapride Influence Cardiac Rhythm? Results of a United States Multicenter, Double‐Blind, Placebo‐Controlled Pediatric Study
Authors: Levy Joseph , Hayes Constance , Kern Jeffrey , Harris Jennifer , Flores Alex , Hyams Jeffrey , Murray Robert , Tolia Vasundhara
Published: January 2024

Background

Major concerns about serious cardiac side effects underlie the recent decision by the FDA and Janssen Pharmaceutica (Titusville, NJ) to make cisapride available only through a limited access program.

Concerns have grown despite the fact that most instances of prolonged QTc and other ventricular arrhythmias occurred while the drug was used concomitantly with contraindicated drugs. This study sought to analyze electrocardiograms (ECGs) from a multicenter pediatric study and to identify abnormalities in QTc interval associated with cisapride use.

Methods

Children between 6 months and 4 years of age were enrolled if they manifested symptoms of gastroesophageal reflux not responding to medical therapy for at least 6 weeks. In 49 subjects, ECGs obtained before and after randomization to receive 0.2 mg/kg dose three times daily or placebo were reviewed independently and blindly by two pediatric cardiologists. Placebo and active drug groups were compared for QTc and for change in QTc from baseline values after 3 to 8 weeks of treatment.

Results

Mean QTc among patients taking the drug was 408 ± 18 ms. None was higher than 450 ms. Change between baseline and subsequent QTc at 3 to 8 weeks of treatment was 2 ± 20 ms.

Conclusions

In our study group of children without underlying cardiac disease or electrolyte imbalance, cisapride was found to have no significant effect on cardiac electrical function compared with placebo. These results are consistent with the drug's record of exceedingly infrequent cardiac events. Because the availability of this prokinetic is threatened, its safety and the safety and efficacy of alternative treatment options (including surgery) should be studied further.