bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Quantitative Epstein‐Barr Virus Polymerase Chain Reaction and Preemptive Immunosuppression Reduction in Pediatric Liver Transplantation: A Preliminary Experience
Authors: Kogan‐Liberman Debora , Burroughs Margaret , Emre Sukru , Moscona Anne , Shneider Benjamin L.
Published: January 2024

Background

Risk factors for the development of posttransplant lymphoproliferative disease (PTLD), a major cause of morbidity and mortality after pediatric liver transplantation, are primary Epstein‐Barr virus (EBV) infection and intensity of immunosuppression. The authors assessed monitoring of EBV replication and preemptive immunosuppression reduction in pediatric liver transplant recipients.

Methods

The authors prospectively followed monthly EBV‐quantitative competitive polymerase chain reaction to measure EBV replication in 23 patients who underwent liver transplant between July 1997 and November 1998. Preemptive immunosuppression reduction was instituted for significant EBV replication. Patients were followed up for at least 1 year and divided in two groups for analysis (group 1, pretransplant seronegative for EBV [13 patients]; group 2, seropositive for EBV [10 patients]).

Results

In group 1, 9 of 13 patients had positive polymerase chain reaction results at a mean time of 22.4 weeks after transplantation. All but one of these patients were asymptomatic. In seven of nine patients, preemptive immunosuppression reduction was undertaken without development of PTLD or rejection. In two of nine patients, immunosuppression could not be continuously reduced, and both patients experienced low‐grade and medically responsive PTLD. In no patient in group 2 did an EBV‐positive viral load or PTLD develop.

Conclusions

Prospective longitudinal measurement of EBV by quantitative competitive polymerase chain reaction permits early detection of asymptomatic viral replication. Subsequent preemptive reduction of immunosuppression may prevent the progression to PTLD.
Percutaneous Endoscopic Gastrostomy and Gastrojejunostomy in Psychomotor Retarded Subjects: A Follow‐Up Covering 106 Patient Years
Authors: Mathus‐Vliegen E. M. H. , Koning H. , Taminiau J. A. J. M. , Moorman‐Voestermans C. G. M.
Published: January 2024

Background

Whether psychomotor retarded persons should be treated by percutaneous endoscopic gastrostomy (PEG) or by surgical gastrostomy combined with an antireflux procedure is controversial. Therefore, the authors investigated the feasibility of a PEG and enteral feeding in these patients.

Methods

Patients referred from specialized institutions for a PEG placement were assessed extensively by a multidisciplinary team. When considered eligible, age and general condition determined the choice of treatment under general anesthesia (group 1) or conscious sedation (group 2). Patients were followed up after 1 and 7 days, 4 and 12 weeks, and thereafter every 6 to 12 weeks. Data were collected prospectively over a period of 5 years until gastrostomy removal, death, or arrival at the censory date, 6 months after PEG placement. The endpoints were 1) to evaluate the procedure and its complications; 2) to discover barriers that impeded adequate nutrition; and 3) to explore the appropriateness of the choice of PEG or percutaneous endoscopic gastrojejunostomy (PEJ).

Results

The procedure was successful in 95% of patients, in every patient in group 1 (35/35; median age, 4.1 years) and in 20 of 23 patients (87%) in group 2 (median age, 22.0 years). There were no procedure‐related deaths and no 30‐day mortality. Major complications changed from procedure‐related problems in the short term (5.4%) to tube‐related problems in the long‐term (24.1%). Nausea and vomiting interfered with adequate feeding mainly in young children, but dietary adjustments alleviated the symptoms and ensured an adequate intake. The choice of a PEG was incorrect in four patients: surgery was needed twice and two PEGs had to be converted into a PEJ. All seven primarily indicated PEJs seemed justified and of temporary need in five.

Conclusions

In severely disabled patients, a PEG and adequate enteral nutrition is feasible in the setting of a multidisciplinary approach and protocol‐wise follow‐up. Yet, anatomic deformities and restricted pulmonary function rendered the procedure more difficult. In cases with obvious aspiration or gastroesophageal reflux, a PEJ combined with acid suppression and prokinetic drugs may be tried before surgery.
Effect of Insulinlike Growth Factor‐1 Treatment in Children With Cystic Fibrosis
Authors: Bucuvalas John C. , Chernausek Steven D. , Alfaro Mary Pat , Krug Susan K. , Ritschel Wolfgang , Wilmott Robert W.
Published: January 2024

Objectives

Malnutrition is common in cystic fibrosis (CF) and adversely affects survival. Because insulinlike growth factor‐1 (IGF‐1) has insulinlike effects in terms of carbohydrate metabolism and is growth promoting, the authors hypothesized that its use would increase linear growth rate and decrease insulin requirements in children with CF.

Methods

The authors used a double‐blind placebo‐controlled crossover design. Seven prepubertal children aged 9.6 to 13 years (5 boys and 2 girls) were treated with placebo or IGF‐1 for 6 months. After a 6‐month washout period, patients received the alternative therapy for 6 months. The primary outcome measure was linear growth rate. Secondary outcome measures were changes in body mass index, body composition determined by dual energy x‐ray absorptiometry, forced expiratory volume (FEV 1 ), and the blood glucose/insulin ratio.

Results

The mean height z score at baseline was −1.5 ± 0.8. At entry, the mean serum IGF‐1 level was 124 ± 25 ng/mL (normal range, 110–771 ng/mL). With treatment, mean serum IGF‐1 levels increased twofold to threefold for all patients. The half‐life for IGF‐1 was 10.3 hours. We observed no significant difference in linear growth rate, weight gain, rate of accretion of lean body mass, or mean FEV 1 during treatment with IGF‐1 compared with placebo. The glucose/insulin ratio, an indirect index of insulin sensitivity, was significantly increased with IGF‐1 treatment compared with placebo (P < 0.02). No adverse events related to IGF‐1 were detected.

Conclusions

Treatment with IGF‐1 for 6 months did not promote linear growth in prepubertal children with CF. However, the glucose/insulin ratio was increased without changing blood glucose levels with IGF‐1 treatment suggesting increased insulin sensitivity.
Effect of IGF‐Rich Colostrum on Bowel Adaptation in Neonatal Piglets With Short Bowel Syndrome
Authors: Heemskerk V. H. , van Heurn L. W. E. , Farla P. , Buurman W. A. , Piersma F. , ter Riet G. , Heineman E.
Published: January 2024

Background

Insulin‐like growth factor 1 (IGF‐1), a polypeptide growth factor with mitogenic effects on intestinal epithelial crypt cells occurs naturally in high concentrations in colostrum. The hypothesis for this study was that colostrum rich in IGF‐1 could promote small bowel adaptation in neonatal piglets with short bowel syndrome.

Methods

Twenty‐four piglets, aged 7 days, underwent 75% small bowel resection and were fed 525 kJ · kg −1 · d −1 (125 kcal) of colostrum‐based formula (Rs + ) or placebo formula (Rs − ). Immunoglobulin G (IgG) accounted for 35% of the protein and was compensated with casein and whey protein in the control feed. The piglets were weighed daily and killed 28 days after surgery. Bowel samples were taken at surgery and at death.

Results

Relative body‐weight increase did not differ between the Rs + and Rs − group (84% ± 9% vs. 90% ± 12%, P = 0.83). There was a significant relative increase in crypt depth in the Rs − compared with the Rs + group (201% ± 15% vs. 147% ± 17%, P = 0.02) and total protein (mg/cm bowel) (482 ± 51 vs. 278 ± 46, P = 0.008). Increase in villus length, DNA/RNA content, and mitotic index did not differ between groups.

Conclusion

Colostrum supplement rich in IGF‐1 has no benefits over protein‐enriched feed with respect to growth and bowel adaptation in neonatal piglets with short bowel syndrome.
An Analysis of Published Trials of Interferon Monotherapy in Children With Chronic Hepatitis C
Authors: Jacobson Karen R. , Murray Karen , Zellos Aglaia , Schwarz Kathleen B.
Published: January 2024

Background

Although no therapeutic regimen has received Food and Drug Administration approval for treating children with chronic hepatitis C viral infection (CHC), there have been a number of pediatric interferon‐α (IFN‐α) trials. The purpose of this study was to perform a critical review of these trials to determine 1) end‐of‐treatment (ETR) and sustained‐response (SR) rates, 2) predictors of response to therapy, and 3) safety of and tolerance to IFN‐α in children with CHC.

Methods

Relevant studies in the English‐language medical literature and abstracts (January 1990 through November 2000) were identified by searching for manuscripts that contained the key words “children,” “hepatitis C,” and “interferon.” Trials were considered eligible for inclusion in this analysis if criteria for treatment included positive serum polymerase chain reaction for hepatitis C virus RNA (HCV PCR).

Results

Twenty published manuscripts of the use of IFN‐α in children with CHC were found, of which 12 met our inclusion criteria. Twenty‐two abstracts, of which seven met our inclusion criteria, were identified. In the 19 included trials, 366 treated and 105 untreated children were observed; five countries were represented. Average ETR was 54% (0%–91%) and average SR was 36% (0%–73%). The SR in children with genotype 1 was 27% versus 70% for nongenotype 1 (P = 0.001). Five of 105 (5%) untreated controls exhibited spontaneous viral clearance.

Conclusions

To date, there is no published large‐scale, multicenter, prospective, placebo‐controlled randomized trial of the use of IFN‐α in children with CHC. The data in this review suggest that IFN‐α in children with CHC does have reasonable efficacy and safety. This review highlights the need for a more systematic design of future pediatric CHC trials. Ideally, such trials would be large scale, prospective, and controlled, and would include HCV genotype and viral load, histology, quality of life measures, and systematic recording of adverse events and of effects of therapy on growth and development.
Serum Biotinidase Activity in Children With Chronic Liver Disease and Its Clinical Significance
Authors: Pabuçcuoğlu Aysun , Aydoğdu Sema , Baş Meral
Published: January 2024

Background

Biotinidase is the enzyme responsible for liberating the vitamin biotin from biocytin and dietary protein–bound vitamin. Individuals lacking biotinidase activity become biotin deficient. Because the liver is the major source of plasma biotinidase, chronic liver diseases can lead to decreased serum biotinidase activity and biotin deficiency. The aim of this study is to determine serum biotinidase activity values in children with chronic liver disease and to investigate the relation among enzyme activity, certain liver function tests, and degree of liver damage.

Method

In this study, using a spectrophotometric method, biotinidase activity was determined in sera from 62 children with chronic liver diseases (median age, 9.73 years; range, 8 months to 18 years) and from 27 healthy controls. Diagnoses of the patient group were as follows: noncirrhotic chronic hepatitis B virus infection (n = 12), metabolic liver diseases (n = 16), autoimmune hepatitis (n = 6), intrahepatic and extrahepatic cholestasis (n = 14), fulminant hepatitis (n = 5), cryptogenic cirrhosis n = 5), prehepatic portal hypertension (n = 4). Meanwhile, serum albumin, total bilirubin, alkaline phosphatase, alanine aminotransferase, and γ‐glutamyltransferase concentrations and prothrombine time were determined for each patient and the results were correlated with serum biotinidase activity.

Results

There was significant difference between mean enzyme activity of the controls (7.6 ± 1.2 nmol · min −1 · mL −1 ) and of all patients with chronic liver disease (6.3 ± 2.5 nmol · min −1 · mL −1 ) (P < 0.05). Serum biotinidase activity in patients with noncirrhotic chronic liver diseases (chronic viral hepatitis, prehepatic portal hypertension, glycogen storage disease, Gaucher disease) was within the normal ranges. However, serum biotinidase activity in patients with cirrhosis and Wilson disease was significantly less than that of the control group (P < 0.05). The lowest enzyme activities were detected in patients with fulminant hepatitis.

Conclusion

In this study, serum biotinidase activity was significantly lower in patients with cirrhosis, particularly in the patients with decompensated cirrhosis and fulminant hepatitis who exhibited no clinical symptoms related to biotin deficiency. The decreased serum biotinidase activity in chronic liver diseases was associated with severe impairment of hepatocellular function.
Children's Knowledge, Anticipatory Anxiety, Procedural Distress, and Recall of Esophagogastroduodenoscopy
Authors: Claar Robyn Lewis , Walker Lynn S. , Barnard John A.
Published: January 2024

Background

This study evaluates the relations among children's knowledge of esophagogastroduodenoscopy (EGD) and anticipatory anxiety, procedural distress, and the nature of postprocedural recall and evaluations.

Methods

One hundred patients, aged 8 to 17 years, completed self‐report measures of knowledge and anxiety before EGD. Parents completed a self‐report measure assessing how they prepared their children. Nurses and trained observers completed observational ratings of distress. Children's recall and evaluation of the procedure were assessed by self‐report 1 hour after the procedure and by telephone that evening.

Results

Most children knew about the major components of EGD. Children with greater knowledge experienced less distress and reported that they would be less anxious and upset when undergoing future EGDs. Children with greater anticipatory anxiety exhibited more procedural distress. Children's distress varied by the phase of the procedure. Children who were more distressed during intravenous line insertion experienced greater distress during esophageal intubation and the endoscopic examination. Approximately 20% of patients reported at least some memory of the procedure even at the end of the day. Children with greater recall reported greater aversion and a more negative attitude toward future EGDs.

Conclusions

This study provides information about children's distress during EGD and the effects of conscious sedation on patients' memories and attitudes toward future procedures. The study indicates that preparation before EGD may reduce patient distress.
Modeling 13C Breath Curves to Determine Site and Extent of Starch Digestion and Fermentation in Infants
Authors: Christian Martin T. , Amarri Sergio , Franchini Fabio , Preston Tom , Morrison Douglas J. , Dodson Brian , Edwards Christine A. , Weaver Lawrence T.
Published: January 2024

Background

The colon salvages energy from starch, especially when the capacity of the small intestine to digest it is limited. The aim of this study was to determine the site and relative extent of starch digestion and fermentation in infants.

Methods

Thirteen infants (10 male and 3 female infants), median age 11.8 months (range, 7.6–22.7 months), were fed a starchy breakfast containing 13C‐labeled wheat flour after an overnight fast. Duplicate breath samples were obtained before breakfast and every 30 minutes for 12 hours. Breath 13CO2 enrichment was measured using isotope ratio mass spectrometry, and results were expressed as percentage dose recovered (PDR) for each 30 minutes. The PDR data were analyzed and mathematically modeled assuming either a constant estimate of CO2 production rate or adjusted for physical activity.

Results

Mean ± SD cumulative 13C PDR (cPDR) at 12 hours was 21.3% ± 8.4% for unadjusted data and 26.5% ± 11.6% for adjusted data. A composite model of two curves fit significantly better than a single curve. Modeling allowed estimation of cPDRs of small intestine (17.5% ± 6.5% and 22.7% ± 9.3% for unadjusted and adjusted data, respectively) and colon (4.6% ± 2.9% and 6.3% ± 5.4%).

Conclusions

Modeling of 13CO2 enrichment curves after ingestion of 13C‐enriched wheat flour is an attractive means to estimate the contribution of the upper and lower gut to starch digestion and fermentation.
Omeprozole Therapy in Pediatric Patients After Liver and Intestinal Transplantation
Authors: Kaufman Stuart S. , Lyden Elizabeth Ruby , Brown Cindy R. , Davis Carolyn K. , Andersen Deborah A. , Olsen Keith M. , Bergman Kimberly L. , Horslen Simon P. , Sudan Debra L. , Fox Ira J. , Shaw Byers W. , Langnas Alan N.
Published: January 2024

Background

Proton pump inhibitors such as omeprazole are increasingly used to prevent stress‐related gastric bleeding in critically ill patients. In this investigation, the acid‐suppressive potency of omeprazole was assessed in one at‐risk group, pediatric patients undergoing liver or intestinal transplantation, or both.

Methods

Twenty‐two patients ranging in age from 0.9 to 108 months (23.8 ± 6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver allografts) transplantation. Omeprazole was delivered in bicarbonate suspension through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every 12 hours. Gastric pH monitoring was performed approximately 2 days later.

Results

For the entire group, mean gastric pH equaled 6.1 ± 0.3, the same in recipients of isolated liver and intestinal allografts. Twelve of the 22 patients demonstrated a discontinuous omeprazole effect, that is, dissipation of acid reduction before the next dose. Five of the 12 patients with discontinuous omeprazole effect had mean gastric pH of less than 5 (3.9 ± 0.4). In 4 of these 5, the omeprazole dosing interval was shortened to every 8 or every 6 hours, resulting in an increase in mean pH to 6.6 ± 0.2 (P < 0.01). In the remaining 10 of 22 patients, acid suppression was uninterrupted until the next dose. No patient experienced bleeding attributable to gastric erosion.

Conclusion

Omeprazole suspended in sodium bicarbonate is an effective acid‐suppressing agent in pediatric recipients of liver or intestinal transplant, or both. A dosage of 0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8 hours is required to assure maximal acid suppression in all.
Infliximab as a Novel Therapy for Pediatric Ulcerative Colitis
Authors: Mamula Petar , Markowitz Jonathan E. , Brown Kurt A. , Hurd Linda B. , Piccoli David A. , Baldassano Robert N.
Published: January 2024

Objectives

The role of infliximab (anti–tumor necrosis factor α antibody) therapy in ulcerative colitis (UC) is not well defined. There are only two reports published describing its use in UC. The authors describe their experience with open‐label use of infliximab in children with moderate to severe UC.

Methods

The authors collected data on all consecutive pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia until July 2001. The primary measured outcome was clinical response at 2 days and 2 weeks after infliximab infusion, as measured by the Lichtiger colitis activity index (LCAI) score and the Physician Global Assessment (PGA). Tolerance of the infusions and adverse events were recorded.

Results

Nine patients qualified for clinical response analysis. The median Lichtiger colitis activity index score decreased from 11 before the infusion to 1 at 2 days and 2 weeks after the infusion, respectively (P = 0.01 for 2 days and 2 weeks). Seven of nine (77%) patients had decreased activity of their disease measured by the Physician Global Assessment. Corticosteroid therapy was discontinued in six (66%) patients. An infusion reaction developed (generalized pruritus and facial flushing) in two patients and an elevated anti‐nuclear antibody (ANA) titer of 1:1280 developed in one patient.

Conclusion

Infliximab is associated with short‐term clinical improvement in children and adolescents with moderate to severe UC.
Effects of Nutritional Rehabilitation on Intestinal Function and on CD4 Cell Number in Children With HIV
Authors: Guarino Alfredo , Spagnuolo Maria Immacolata , Giacomet Vania , Canani Roberto Berni , Bruzzese Eugenia , Giaquinto Carlo , Roggero Paola , Plebani Anna , Gattinara Guido Castelli
Published: January 2024

Background

A complex interplay of malnutrition, intestinal dysfunction, and immune impairment increases the progression of human immunodeficiency virus (HIV) disease in children. The authors tested the hypothesis that nutritional support improves intestinal and immune functions in children infected with human immunodeficiency virus (HIV).

Methods

A questionnaire was circulated through reference centers for pediatric HIV infection to evaluate the effects of nutritional rehabilitation, total parenteral nutrition (TPN) and enteral nutrition (EN), in children. Information included changes in body weight, CD4 cell numbers, and intestinal absorption—as judged by the xylose load—before and after clinical nutritional support and the outcome of children.

Results

Sixty‐two children underwent nutritional support: 46 received TPN and 16 received EN. All but three had full‐blown acquired immunodeficiency syndrome, and all were severely malnourished. Baseline clinical conditions were worse in children receiving TPN than in those receiving EN. Intestinal dysfunction was detected in all children who received xylose oral load. A significant increase in CD4 cell count, xylose levels, and body weight followed EN. A similar pattern was observed after TPN, but none of the parameters significantly changed. Twenty‐seven children who received TPN and three who received EN eventually died. Fourteen who received TPN and eight who received EN were shifted to oral feeding, and five who received TPN and five who received EN continued with clinical nutritional support at the end of the observation period.

Conclusions

Nutritional intervention may restore intestinal absorption and increase CD4 cell numbers. The efficacy of nutritional intervention is enhanced if provided before a terminal stage of HIV infection. These data provide evidence of a close association among nutritional condition, intestinal absorption, and immune impairment.
Treatment of Childhood Encopresis: A Randomized Trial Comparing Three Treatment Protocols
Authors: Borowitz Stephen M. , Cox Daniel J. , Sutphen James L. , Kovatchev Boris
Published: January 2024

Objectives

To compare short‐ and long‐term effectiveness of three additive treatment protocols in children experiencing chronic encopresis.

Methods

Children, 6 to 15 years of age, who experienced at least weekly fecal soiling for 6 months or longer were eligible for the study. Children were randomly assigned to a group that received intensive medical therapy (IMT), a group that received intensive medical therapy plus a behavior management program called enhanced toilet training (ETT), or a group that received intensive medical therapy with enhanced toilet training and external anal sphincter electromyographic biofeedback (BF). Data concerning toileting habits were collected for 14 consecutive days before an initial visit, and at 3, 6, and 12 months after initiation of therapy. All data were collected using a computerized voice‐mail system that telephoned the families each day. At 12 months, children were classified as significantly improved (reduction in soiling, P < 0.001) or cured (<one fecal accident in 2 weeks).

Results

Eighty‐seven children participated in the study, 72 boys and 15 girls. Mean age at enrollment was 8.6 ± 2.0 years, and mean duration of symptoms was 58.2 ± 38.5 months. At 12 months, the cure rates for the IMM, ETT, and BF groups were 36, 48, and 39, respectively (not significant). The improvement rates for these three groups were 45, 78, and 54, respectively (P < 0.05). These results were very stable over time (r > 0.90, P < 0.001 in each case). Response to treatment during the first 2 weeks of therapy was highly predictive of outcome at 3, 6, and 12 months (P < 0.0001). Children in the ETT group used less laxative medication (P < 0.04) and required fewer treatment contacts (P = 0.08) than children in the IMM group. All three treatments resulted in significant increases in daily bowel movements passed in the toilet and self‐initiated toileting, and resulted in decreases in average daily soiling at 3, 6, and 12 months (P < 0.05).

Conclusions

Enhanced toilet training is somewhat more effective in treating childhood encopresis than either intensive medical therapy or anal sphincter biofeedback therapy. Although similar total cure rates at 1 year can be expected with these three forms of therapy, enhanced toilet training results in statistically significant decreases in the daily frequency of soiling for the greatest number of children.
Trophic Effect of Multiple Growth Factors in Amniotic Fluid or Human Milk on Cultured Human Fetal Small Intestinal Cells
Authors: Hirai Chie , Ichiba Hiroyuki , Saito Mika , Shintaku Haruo , Yamano Tsunekazu , Kusuda Satoshi
Published: January 2024

Objectives

To evaluate the role of growth factors in amniotic fluid and in human milk on gastrointestinal adaptation of the fetus and very low‐birth‐weight infants, the effects of these fluids and multiple growth factors were investigated in a human fetal small intestinal cell line (FHs 74 Int).

Methods

After FHs 74 Int cells were incubated with amniotic fluid, human milk, or recombinant growth factors, growth‐promoting activity was measured by [3H]‐thymidine incorporation into cells.

Results

Incubating cells with amniotic fluid or human milk promoted growth dose dependently. Genistein almost completely inhibited growth‐promoting activity in amniotic fluid P = 0.002), and growth was partially inhibited by antibodies against epidermal growth factor (EGF) (P = 0.047), insulin‐like growth factor‐1 (IGF‐1, P = 0.047), or fibroblast growth factor (FGF, P = 0.014). This activity in human milk was inhibited almost completely by genistein (P h 0.0001) and partially inhibited by antibodies against EGF (P = 0.036), IGF‐1 (P = 0.009), FGF (P = 0.004), hepatocyte growth factor (HGF, P = 0.001), or transforming growth factor‐α (TGF‐α, P = 0.001). Although recombinant EGF, IGF‐1, FGF, HGF, and TGF‐α elicited a synergistic trophic response on cultured cells, the response was much less than with amniotic fluid or with human milk.

Conclusion

In aminiotic fluid and in human milk, EGF, IGF‐1, FGF, HGF, and TGF‐α have a strong trophic effect on immature intestinal cells and may be involved in perinatal gastrointestinal adaptation.
Supplementation of Infant Formula With the Probiotic Lactobacillus reuteri and Zinc: Impact on Enteric Infection and Nutrition in Infant Rhesus Monkeys
Authors: Kelleher Shannon L. , Casas Ivan , Carbajal Noris , Lönnerdal Bo
Published: January 2024

Gut colonization by Lactobacillus reuteri may have beneficial effects on infant health or capacity to resist infectious disease. Zinc supplementation has also been proposed to increase infants' resistance to disease; however, many studies have yielded conflicting results.

Objectives

To study effects of probiotic supplementation of infant formula (with or without supplemental zinc) on nutritional status, gut colonization and the ability to resist gastrointestinal infection in an infant rhesus monkey model.

Methods

Infant monkeys were fed control infant formula (5 mg Zn/L), control formula with L. reuteri or control formula with L. reuteri and supplemental zinc (15 mg Zn/L) from birth to 4 months. Growth, nutritional status, mineral absorption, intestinal colonization and frequency and severity of enteropathogenic Escherichia coli‐induced gastroenteritis were monitored.

Results

Gastrointestinal L. reuteri colonization was achieved and was associated with increased ileal villous surface area and improved hematocrit, with no adverse effects on growth or nutritional indices. Fortification to 15 mg Zn/L reduced plasma copper, erythrocyte Cu/Zn‐superoxide dismutase, hemoglobin, and iron absorption. Infants fed L. reuteri‐supplemented formula had reduced diarrhea severity throughout the study period and recovered more rapidly from acute diarrhea than the other groups.

Conclusion

L. reuteri‐supplementation of infant formula is safe, improves iron status and decreases diarrhea severity in infant rhesus monkeys and thus may help protect formula‐fed human infants from infection and nutritional deficiencies.
Immunoreactive Ghrelin in Human Cord Blood: Relation to Anthropometry, Leptin, and Growth Hormone
Authors: Chanoine Jean‐Pierre , Yeung Louisa PK , Wong Alfred CK , Birmingham Carl Laird
Published: January 2024

Background

Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone–secreting and orexigenic properties. Leptin is secreted mainly by the adipocyte, plays a major role in energy balance, and reflects fat mass in infants as well as adults. Leptin and ghrelin central effects are mediated, at least partly, through the neuropeptide Y/Y1 receptor pathway in the hypothalamus.

Methods

We determined whether ghrelin is also present in the fetus and investigated its relationship to leptin, growth hormone, birth weight, and calf and abdominal circumferences in 90 full‐term neonates.

Results

Immunoreactive ghrelin was detected in all cord samples (mean ± SD, 187 ± 88 pmol/L; range, 66—594 pmol/L). In contrast to leptin, ghrelin concentrations of boys and girls were not statistically different. In female neonates, ghrelin is inversely correlated with anthropometric measures. In male neonates, ghrelin is positively correlated with leptin and negatively with growth hormone.

Conclusion

The presence of significant ghrelin concentrations in all neonates before the first feeding is intriguing. Unlike the fairly constant concentrations and effects of leptin over the short term, the wide variability of ghrelin concentrations observed in newborns raises the possibility that ghrelin secretion causes short‐term changes in feeding behavior. We suggest that ghrelin may play a physiologic role in the initiation of feeding.
Clinical Response to Amino Acid‐Based Formula in Neurologically Impaired Children With Refractory Esophagitis
Authors: Miele Erasmo , Staiano Annamaria , Tozzi Arturo , Auricchio Renata , Paparo Francesco , Troncone Riccardo
Published: January 2024

Objective

Chronic gastrointestinal symptoms and histologic changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux disease (GERD) may be improved by the use of elemental formulas. The aim of our study was to evaluate the efficacy of a dietary trial in neurologically impaired children unresponsive to medical and surgical therapy for GERD.

Methods

Nine children (three boys and six girls; median age, 44 months; range, 13–180 months) affected by cerebral palsy associated with severe mental retardation and with long‐standing history of GERD were fed the elemental formula, Neocate, for a minimum of 4 weeks. Before and after the dietary trial, each child underwent endoscopy with esophageal biopsy and a cellobiose/mannitol sugar permeability test. The diagnosis of GERD was based on the microscopic changes of the esophagus.

Results

Before the dietary trial, according to conventional histologic criteria, esophagitis was considered moderate in seven children and mild in two. Five of nine patients also had abnormal sugar permeability test results. During and after the dietary trial, seven of nine patients experienced resolution of their long‐term symptom complaints. Furthermore, after the dietary trial, both endoscopic (P < 0.01) and histologic (P < 0.05) findings significantly improved. At 6‐month follow‐up, progressive reintroduction of individual dietary proteins, except for cow's milk protein, did not cause reappearance of the symptoms.

Conclusions

In neurologically impaired children unresponsive to conventional antireflux treatments, a course of a highly restricted diet with an amino acid–based formula may bring an immediate and sustained, endoscopically and histologically proven improvement in long‐standing gastrointestinal symptoms and esophagitis.
Childhood Gastroesophageal Reflux Symptoms in Adult Patients
Authors: Waring J. Patrick , Feiler Michael J. , Hunter John G. , Smith C. Daniel , Gold Benjamin D.
Published: January 2024

Objectives

Gastroesophageal reflux (GER) and its esophageal (esophagitis, Barrett's esophagus) and extraesophageal (asthma, laryngeal disease) disease manifestations (GERD) are increasing common problems in children and adults. There are virtually no published longitudinal outcome studies that describe the natural history of childhood‐onset GER throughout a person's lifetime. The aim of this study was to compare the frequency of recalled childhood reflux symptoms in adult patients currently with and without GER symptoms.

Methods

Four hundred adult patients were classified as refluxers (225 patients; 57%), nonrefluxers (154 patients; 38%), and those who claimed to not know if they had reflux (21 patients; 5%; excluded from analysis). Subjects were given a questionnaire asking them to recall childhood symptoms attributed to GER. Of the 225 refluxers, 141 (63%) recalled at least one childhood symptom, compared with 54 of the 154 nonrefluxers (35%) (P < 0.001).

Conclusions

Adult refluxers were more likely to recall having developed GER symptoms at an earlier age, beginning at infancy and developing statistically significant GER compared with nonrefluxers after age 11. Adults suffering from GER were far more likely than nonrefluxers to recall having experienced GER symptoms during childhood. Well‐designed, population‐based epidemiologic studies are needed to more accurately assess the extent of GER in the overall population and the extent of its impact on health care in the United States.
Lactase Deficiency: Not More Common in Pediatric Patients With Inflammatory Bowel Disease Than In Patients With Chronic Abdominal Pain
Authors: Pfefferkorn Marian D. , Fitzgerald Joseph F. , Croffie Joseph M. , Gupta Sandeep K. , Corkins Mark R. , Molleston Jean P.
Published: January 2024

Objective

Lactase deficiency is commonly found in adults with inflammatory bowel disease (IBD). Our aim was to determine its prevalence in children with IBD.

Methods

We conducted a retrospective and descriptive analysis of patients with symptomatic IBD whose mucosal lactase activity was measured on duodenal biopsies obtained during gastrointestinal endoscopic evaluations. Age‐ and gender‐matched controls were chosen randomly from a group with chronic abdominal pain.

Results

One hundred twelve patients with IBD were identified from January 1994 to December 2000. Seventy‐nine (71%) had Crohn disease, and 33 (29%) had ulcerative colitis. Forty‐five (40%) of all IBD patients (29 with Crohn disease and 16 with ulcerative colitis) had low lactase activity levels (< 15 μM/min/gm). The prevalence of lactase deficiency in patients with IBD was 37% (38 of 103) in white patients and 78% (7 of 9) in blacks. Thirty‐four of 112 controls (30%) had lactase deficiency. IBD patients were more likely to be lactase deficient than the controls, but the difference was not statistically significant (P = 0.162). Normal duodenal histology was found in 67% of lactase‐deficient IBD patients compared with 82% in lactase‐sufficient IBD patients. The frequency of duodenal inflammation did not differ significantly between lactase‐deficient and ‐sufficient patients with IBD (P = 0.068).

Conclusions

More than one third of pediatric patients with IBD have lactase deficiency, which is not significantly different from non‐IBD patients with chronic abdominal pain. The majority of lactase‐deficient patients with IBD have normal duodenal biopsy results. Lactase activity from small bowel biopsy specimens can be measured at the time of initial endoscopy. Reevaluation, either by small bowel biopsy or the breath hydrogen test, may then be considered during follow‐up of symptomatic patients.
Diagnosis and Management of MNGIE Syndrome in Children: Case Report and Review of the Literature
Authors: Teitelbaum J. E. , Berde C. B. , Nurko S. , Buonomo C. , Perez‐Atayde A. R. , Fox V. L.
Published: January 2024

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare disorder that presents in childhood; however, marked delay in diagnosis is common. We report a case and review the literature describing the typical features that should alert pediatricians to the diagnosis. We also describe a novel management strategy for providing symptomatic relief.
Azathioprine Metabolite Measurements in the Treatment of Autoimmune Hepatitis in Pediatric Patients: A Preliminary Report
Authors: Rumbo Carolina , Emerick Karan M. , Emre Sukru , Shneider Benjamin L.
Published: January 2024

Potential adverse effects of azathioprine (AZA), such as neutropenia and hepatotoxicity, make its use in autoimmune hepatitis (AIH) problematic.

Objective

To determine longitudinal AZA metabolite levels in a cohort of children with AIH, correlate them with therapeutic effects, medication‐induced toxicity and adherence.

Methods

From January 2000 to January 2002, 122 blood samples from 30 pediatric patients with AIH were prospectively analyzed. Ten patients had previously been treated with AZA (mean dose of 1.3mg/kg/day) for an average of 30 months. At the outset, 24 patients were taking steroids and 10 had cirrhosis/hypersplenism. Routine biochemical studies, 6‐thioguanine (6‐TG) and 6‐methylmercaptopurine (6‐MMP) levels were assessed every 8 weeks. Red blood cell thiopurine methyltransferase (TPMT) enzyme activity was determined in each patient. AZA dose was adjusted to achieve a target 6‐TG level 235‐450 pmoles per 8 × 108 RBC.

Results

8/10 patients who had previously been treated with standard doses of AZA had 6‐TG below target levels. Increasing AZA mean dose by 50% in those patients resulted in 6/10 patients in target range; ALT levels and steroid requirements were reduced. AZA dosing was safely increased in patients with cirrhosis/hypersplenism. In spite of normal TPMT levels, 64% of patients did not make measurable concentrations of 6‐MMP. Inappropriately low 6‐TG levels revealed non‐adherence in 5 patients. Two patients were identified with AZA hepatotoxicity.

Conclusion

AZA metabolite testing in children with AIH is useful in identifying medication toxicity and non‐adherence. AZA dose escalation is safe and may be required in order to achieve 6‐TG target levels described for inflammatory bowel disease.
Growth Slowing After Acute Helicobacter pylori Infection Is Age‐Dependent
Authors: Passaro Douglas J. , Taylor David N. , Gilman Robert H. , Cabrera Lilia , Parsonnet Julie
Published: January 2024

Objective

Most Helicobacter pylori infections occur during childhood, but the health effects of childhood infection are poorly understood. We investigated whether growth decreases in the 2 months after acute H. pylori seroconversion.

Methods

We performed a nested case‐control study among children 6 months to 12 years of age in a community on the outskirts of Lima, Peru. Health interviews were completed daily. Anthropometric measurements were taken monthly. Sera were collected every 4 months and tested for H. pylori immunoglobulin G. Two‐month height and weight gains of seroconverters were compared with gains of sex, age, and size‐matched seronegative controls.

Results

In the 2 months after H. pylori infection, 26 seroconverters gained a median of 24% less weight than 26 matched controls (interquartile range, 63% less to 21% more). In multivariate analysis, H. pylori infection attenuated weight gain only among children aged 2 years or older. This decrease was not explained by increased diarrhea.

Conclusions

H. pylori seroconversion is associated with a slowing of weight gain in children aged 2 years or older. Reasons for this finding merit additional study.
Effect of Lactobacillus GG and Breast‐feeding in the Prevention of Rotavirus Nosocomial Infection
Authors: Mastretta Emmanuele , Longo Patrizia , Laccisaglia Anna , Balbo Luciano , Russo Roberto , Mazzaccara Alfonso , Gianino Paola
Published: January 2024

Background

Rotavirus is one of the leading etiologic agents of nosocomial infections among children. The development of preventive measures is therefore important. The efficacy of Lactobacillus GG in the treatment of rotavirus infection has been reported in literature, but there is only one recent study about its effectiveness in prevention of infection. The role of breast‐feeding in the prevention of rotavirus infection is still debated. The aim of our study was to assess the efficacy of Lactobacillus GG and breast‐feeding in the prevention of nosocomial rotavirus infections.

Methods

In a randomized, placebo‐controlled, double‐blind study, 220 children aged 1 to 18 months hospitalized from December 1999 to May 2000, received Lactobacillus GG (n = 114) at a dose of 1010 colony‐forming units or a comparable placebo (n = 106) every day of their hospital stay. Rotavirus testing on stool samples was performed for every patient on admission, during hospitalization, and after discharge.

Results

The total incidence of nosocomial rotavirus infections was 27.7% (61 of 220 patients). The attack rate of rotavirus infections among the patients who received probiotic was 25.4% (29 of 114 patients), while for the placebo group it was 30.2% (32 of 106 patients). The difference is not significant (P = 0.432). Forty‐seven of 220 infants (21.4%) were breast‐fed, and 173 of 220 (78.6%) were non–breast‐fed. The attack rate of rotavirus infections among breast‐fed infants was 10.6% (5 of 47 infants), while for non–breast‐fed infants it was 32.4% (56 of 173 infants). The difference is significant (P = 0.003).

Conclusion

In our study, Lactobacillus GG was ineffective in preventing nosocomial rotavirus infections, whereas breast‐feeding was effective.
Congenital Maltase‐Glucoamylase Deficiency Associated With Lactase and Sucrase Deficiencies
Authors: Nichols Buford L. , Avery Stephen E. , Karnsakul Wikrom , Jahoor Farook , Sen Partha , Swallow Dallas M. , Luginbuehl Ursula , Hahn Dagmar , Sterchi Erwin E.
Published: January 2024

Background

Multiple enzyme deficiencies have been reported in some cases of congenital glucoamylase, sucrase, or lactase deficiency. Here we describe such a case and the investigations that we have made to determine the cause of this deficiency.

Methods and Results

A 2.5 month‐old infant, admitted with congenital lactase deficiency, failed to gain weight on a glucose oligomer formula (Nutramigen®). Jejunal mucosal biopsy at 4 and 12 months revealed normal histology with decreased maltase‐glucoamylase, sucrase‐isomaltase, and lactase‐phlorizin hydrolase activities. Testing with a 13C‐starch/breath 13CO2 loading test confirmed proximal starch malabsorption. Sequencing of maltase‐glucoamylase cDNA revealed homozygosity for a nucleotide change (C1673T) in the infant, which causes an amino acid substitution (S542L) 12 amino acids after the N‐terminal catalytic aspartic acid. The introduction of this mutation into “wildtype” N‐terminus maltase‐glucoamylase cDNA was not associated with obvious loss of maltase‐glucoamylase enzyme activities when expressed in COS 1 cells and this amino‐acid change was subsequently found in other people. Sequencing of the promoter region revealed no nucleotide changes. Maltase‐glucoamylase, lactase, and sucrase‐isomaltase were each normally synthesized and processed in organ culture.

Conclusions

The lack of evidence for a causal nucleotide change in the maltase‐glucoamylase gene in this patient, and the concomitant low levels of lactase and sucrase activity, suggest that the depletion of mucosal maltase‐glucoamylase activity and starch digestion was caused by shared, pleiotropic regulatory factors.
Endoscopic Retrograde Cholangiopancreatography in Children and Adolescents
Authors: Pfau Patrick R. , Chelimsky Gisela G. , Kinnard Margaret F. , Sivak Michael V. , Wong Richard C. K. , Isenberg Gerard A. , Gurumurthy Priya , Chak Amitabh
Published: January 2024

Objectives

Endoscopic retrograde cholangiopancreatography (ERCP) is becoming a more frequently used diagnostic and therapeutic tool in children. We sought to determine the indications, feasibility, safety, and effect on patient management of ERCP in pediatric patients of varying age.

Methods

All ERCPs performed during a 4‐year period in patients aged 18 years or less at an academic hospital were retrospectively reviewed. The indications, type of anesthesia administered, type of duodenoscope used, diagnostic findings, therapeutic interventions, complication rate, and effect on management were compared between children (age 0–12 years) and adolescents (age 13–18 years).

Results

A total of 53 procedures were performed in 43 patients whose median age was 13.5 years. ERCP was successful in 50 of 53 cases (94%) with a complication rate of 6%. Endoscopic therapy was provided in 24 of 53 cases (45%). Compared with adolescents (n = 28), children (n = 25) were more likely to receive general anesthesia (96% vs. 29%;P < 0.001) and undergo ERCP with a pediatric duodenoscope (0% vs. 40%). ERCP affected management in 73% of cases, equally in both groups.

Conclusion

ERCP is a successful and safe diagnostic and therapeutic modality in a variety of pancreatobiliary disorders that directly affects management in children of all ages.
Gastric Polyps and Nodules in Children Receiving Long‐Term Omeprazole Therapy
Authors: Pashankar Dinesh S. , Israel David M.
Published: January 2024

Objective

Multiple gastric polyps have been reported to occur in adults receiving omeprazole therapy. There are little published data in children. We report our experience in monitoring the gross and histologic appearance of the stomach in children receiving long‐term omeprazole therapy.

Methods

This was a retrospective review of the charts of children who received omeprazole for more than 6 months for reflux esophagitis between 1989 and 1998. All patients had repeated endoscopic examinations until healing of the esophagitis was confirmed and then annually thereafter. At endoscopy, gastric mucosal swellings were classified as polyps or nodules based on histology.

Results

Thirty‐one children had long‐term endoscopic follow‐up while receiving omeprazole. Seven of 31 children had gastric polyps and/or nodules, noted between 10 and 48 months (mean = 28 months) of omeprazole therapy. Four had nodules only, one had a sessile hyperplastic polyp, and two had both a polyp (one hyperplastic and one fundic gland polyp) and nodules. All lesions were found in the gastric body. Nodules in four of the six children disappeared spontaneously while the children continued to receive omeprazole. The polyps persisted. There were no dysplastic changes in the gastric mucosa or polyps in any of the patients. There were no significant differences between the 7 children with and the 24 without polyps/nodules with respect to age, gastrin concentrations, or dose and duration of omeprazole therapy.

Conclusions

Gastric polyps and nodules may be found in children receiving long‐term omeprazole therapy. The gastric changes in our patients were benign during the mean observation period of 31 months.