bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmunity in Diarrhoeal Disease
Authors: Unsworth D. J. , Walker‐Smith J. A.
Published: January 2024

Evidence for autoimmunity in diarrhoeal disease is reviewed. Firstly, coeliac disease (CD) is considered. The incidence of tissue‐reactive autoantibodies in both adults and children with CD (68% and 65%, respectively) is higher than the incidence of these autoantibodies in controls (6% in normal adults, and 14% and 9% in disease controls drawn respectively from adult and child populations). The Rr an‐tireticulin antibody, when present, was found to disappear after several weeks on a gluten‐free diet, but in contrast, other autoantibodies persisted. Secondly, a case is argued for a new disease category, namely “autoimmune enteropathy.” Seven cases are reviewed in which patients presented with protracted diarrhoea, a small intestinal enteropathy which failed to heal during periods of total parenteral nutrition, and evidence of a predisposition to autoimmunity (namely, the presence of high titre autoantibodies including one specific for gut epithelium, and/or the presence of associated diseases regarded to be autoimmune). Thirdly, evidence for autoimmunity in inflammatory bowel disease is reviewed and includes discussion of serum goblet cell antibodies and of circulating T cells which participate in antibody‐dependent cellular cytotoxicity in vitro using colonic epithelial cells as targets. Finally, an unusual child is described who presented with chronic diarrhoea and a flat small intestinal mucosa, who responded to gluten withdrawal but who later relapsed spontaneously during a strict gluten‐free diet. Her mucosa healed only after a period of total parenteral nutrition and treatment with oral steroids. This child'S enteropathy was also associated with thyrotoxicosis and a microscopic colitis.
Comparison of In Vitro Jejunal Uptake of L‐Valine and L‐Lysine in the Rat During Maturation
Authors: Younoszai M. Kabir , Smith Carolyn , Finch Michael H.
Published: January 2024

The maturational characteristics and patterns of absorption of the neutral amino acid L‐valine were compared with those of the basic amino acid L‐lysine using in vitro preparations of everted sacs obtained from the jejunum of suckling (2 weeks old), weanling (3 weeks old), and adolescent (6 weeks old) rats. Absorption rates determined as net transport into sac fluid and mucosal uptake ($mUmol/h/g protein or weight of mucosal scrapings) for both valine and lysine were greater in the suckling than in the weanling or adolescent rats. This appeared to be true for both the carrier‐mediated and the diffusive processes for absorption, determined from the relationship between the observed absorption rates and the corresponding mucosal incubation medium amino acid concentrations. The major decline in rate of absorption occurred before the period of weaning. Between the period of suckling and adolescence the carrier‐mediated absorption decreased by 55% for valine and by 90% for lysine, suggesting that during maturation of the jejunum the number of the carrier macromolecules responsible for absorption of valine and lysine per unit protein or weight of mucosa decreases with increasing age.
The Steatocrit
Authors: Colombo C. , Maiavacca R. , Ronchi M. , Consalvo E. , Amoretti M. , Giunta A.
Published: January 2024

Steatocrit was determined through microcentrifugation of fecal homogenate from 110 pediatric controls and 107 patients with cystic fibrosis (CF). For 74 CF patients, steatocrit was determined in the same fecal material collected to determine a tat balance. In controls, steatocrit value was 0.7 ‐ 1.0%, which was significantly lower than values found in CF patients with a coefficient of fat excretion <10% of intake (1.7 ± 1.2%). Significantly increased values were found in CF patients with a coefficient of fat excretion ranging between 10 and 25% of intake (4.7 ± 1.7%) and in those whose coefficient of fat excretion was >25% of intake (11.3 + 4.3%). In the 74 CF patients, steatocrit was directly correlated to the coefficient of fat excretion (r 0.93: P < 0.001). We performed steatocrit several times in the course of the 1st year of life in 33 infants with CF diagnosed by means of CF screening. Values obtained at the time of diagnosis, before starting enzymatic therapy, were relatively high: they showed a progressive decrease when, using steatocrit as a guide, the dose of pancreatic enzymes had been increased. The normalization of steatocrit values was accompanied by a better growth rate in the majority of these infants, confirming the importance of an optimal early correction of pancreatic insufficiency. We propose that this simple semiquantitative test can be usefully performed for the frequent monitoring of fat absorption and for checking the response to enzymatic therapy in patients with CF.
Familial Neonatal Hemochromatosis with Survival
Authors: Colletti Richard B. , Clemmons Jackson J. W.
Published: January 2024

We report two sisters with neonatal hemochromatosis (NHC), including the first documented survivor. Characterized by excessive parenchymal iron in liver, pancreas, heart, and other organs, but little iron in the spleen, bone marrow, or other sites of the reticuloendothelial system, NHC is rarely reported and has been uniformly fatal. The first infant (case 1) presented with neonatal hypoglycemia, coagulopathy, and mild hyperbilirubinemia; she rapidly deteriorated and died of multisystem failure. Autopsy showed cirrhosis. Her sister (case 2) presented similarly; liver biopsy showed giant cell hepatitis, which is consistent with idiopathic neonatal hepatitis (INHP). However, iron staining revealed that case 1 had extensive iron deposits in the liver, pancreas, heart, thymus, and bone, but none in bone marrow or spleen. Case 2 had grade 4 liver iron staining, normal bone marrow iron, elevated serum ferritin and transferrin saturation, and HLA‐A3 haplotype. At 16 months of age, the growth, development, and serum measures of iron status in case 2 were normal; liver biopsy showed fibrosis, negative iron staining, and normal tissue iron concentration. NHC is compatible with survival, has clinicopathologic features that overlap with INHP, and may frequently be misdiagnosed as INHP. A prospective study is needed to determine the incidence and natural history of NHC a disorder that may be more common than is currently recognized.
Endoscopic Sclerotherapy for Varices in Children
Authors: Sarin S. K. , Misra S. P. , Singal A. K. , Thorat V. , Broor S. L.
Published: January 2024

Thirty‐one children with variceal bleeding due to portal hypertension (extrahepatic obstruction 19, non‐cirrhotic portal fibrosis five, and cirrhosis of liver seven patients) were treated with endoscopic sclerotherapy with absolute alcohol. Acute variceal bleeding was successfully controlled in 10 patients by emergency sclerotherapy. A 3 weekly schedule of sclerotherapy could achieve obliteration of varices in all the patients. The mean (SD) number of sclerotherapy courses and the time required for variceal cradication was 4.5 × 1.7 and 14.4 × 3.9 weeks, respectively. During a mean follow‐up of 23.3 × 11.4 months, variceal recurrence was seen in three (9.7%) patients, two with cirrhosis and one with noncirrhotic portal fibrosis. Recurrence was not seen in any patient with extrahepatic obstruction. Five (16.1%) patients had a rebleed that could be controlled with emergency selerotherapy. Esophageal stricture developed in four (12.9%) patients and could be dilated easily in all of them. The other complications of sclerotherapy included retrosternal pain, dysphagia, and fever; these were mild and short lasting. Survival in patients with extrahepatic obstruction and noncirrhotic portal fibrosis was 100%. The only death was in a cirrhotic, who died due to terminal hepatic failure. In conclusion, endoscopic sclerotherapy can be recommended as a safe and effective treatment in children for the control of acute variceal bleeding and for variceal obliteration.
Feeding Gastrostomy in Neurologically Impaired Children
Authors: Langer Jacob C. , Wesson David E. , Ein Sigmund H. , Filler Robert M. , Shandling Barry , Superina Riccardo A. , Papa Moshe
Published: January 2024

Some authors recommend a routine “protective” antireflux procedure (ARP) in neurologically impaired children undergoing feeding gastrostomy (FG). Over 4 years, we performed FG in 107 neurologically impaired children aged 1 month to 16 years. Ninety‐eight had preoperative radiological assessment for gastroesophageal reflux (GER), which was documented in 44, of whom 33 had FG plus ARP and II had FG alone. Seven of the 11 subsequently developed symptomatic GER and 5 of them had a secondary ARP. Of the 54 children with no demonstrable GER preoperatively. 3 children underwent FG plus ARP. The remaining 51 had FG alone. There was one postoperative death. Of the 50 surviving patients. 22 developed symptomatic GER and 17 of these had a subsequent ARP. Mean follow‐up of 20.0 months showed that the risk of developing GER after FG alone was not influenced by age, sex, indication for FG, underlying diagnosis, or method of gastrostomy. There was no significant difference in mortality and early morbidity between patients undergoing FG alone and those having FG with simultaneous or subsequent ARP. Only 44% of our patients in whom GER was not demonstrated initially developed symptomatic GER followed FG alone. This incidence does not justify a routine “protective” ARP.
Serum Levels of Immunoreactive Trypsin During Development
Authors: Colombo Carla , Maiavacca Rita , Ronchi Mariangela , Bottani Paolo , Stripparo Luciana , Corbetta Carlo , Sereni Lucia Piceni
Published: January 2024

In order to obtain additional information on serum pancreatic enzyme levels during development, we have measured immunoreactive trypsin (IRT), immunoreactive lipase (IRL), and total amylase in paired fetal and maternal sera. Samples were obtained during early gestation (14–21 week of gestation) and at the time of normal delivery. IRT levels were lower in maternal sera as compared to paired fetal and neonatal (p < 0.005); conversely, IRL and amylase, although present in measurable concentrations, were significantly lower in fetal and neonatal sera than in the maternal (p < 0.001). We also serially monitored serum pancreatic enzyme levels in a group of premature infants during the first 10 days of life. Concentrations of IRT showed a significant increase over time (p < 0.05) and those of IRL remained stable while amylase levels decreased sharply, suggesting possible maternal origin of this enzyme. Serum concentrations of the three pancreatic enzymes in newborns at term (second day of life) were higher than in infants aged 0.5–6 months; however, only IRT levels were above the normal range for adults. Beyond the neonatal period, IRT levels were stable and comparable to adults, whereas amylase and IRL levels were very low in infants younger than 6 months and increased significantly with age (p < 0.001). These data seem to indicate that “physiologic hypertrypsinemia” occurs early during development and may be accentuated by postnatal events. They provide an indirect indication of both early fetal production of trypsinogen and possible placental transfer of pancreatic enzymes from the maternal circulation. The overall results would suggest that only beyond the neonatal period can determination of serum pancreatic enzyme levels be used as an indirect index of their asynchronous development.
Endoscopic Sclerotherapy of Esophageal Varices in Infants and Children
Authors: Thapa Babu R. , Mehta Saroj
Published: January 2024

Thirty children, aged 7 months to 13 years, with bleeding esophageal varices were managed by endo‐scopic sclerotherapy (EST). Of these children, 73.3% had extrahepatic portal vein obstruction (EHPVO), 16.6% had cirrhosis of the liver, and 10% had noncirrhotic portal fibrosis. EST was done with fiberoptic pediatric upper gastrointestinal endoscopes and a flexible sclerotherapy needle under sedation with intravenous diazepam and pentazocine. The sclerosants used were ethoxysclerol 1% and absolute alcohol. Ten injections were given to control active variceal bleeding, and 145 injections were given on planned basis at 2–3‐week interval. An average of five injections was required to obliterate the esophageal varices. In 90% of cases, an avariceal state was achieved; 10% had decreased size and number of varices. Emergency EST was effective to control bleeding in all sessions. Complications, including retrosternal discomfort, esophageal ulceration, stricture formation, and aspiration pneumonia, occurred in 60, 20, 20, and 6.6% of cases, respectively; complications were managed conservatively. Strictures were dilated with Eder‐Puestow's olive dilators. Recurrence of esophageal varices, gastric varices, and rebleeding was seen in 13.3, 13.3, and 10% of cases, respectively. Shunt surgery was performed in 13.3% cases, who had developed gastric varices and were having EHPVO.
Acceptability, Tolerance, and Nutritional Value of a Rice‐Based Infant Formula
Authors: Gastañaduy Arturo , Cordano Angel , Graham George G.
Published: January 2024

An infant formula based on high protein rice flour, with added lysine and threonine, was evaluated in recovering malnourished infants. Acceptability, tolerance, and the digestibility of most major nutrients (energy 93.9 ± 0.7%, fat 96.9 ± 0.3%, carbohydrate 96.8 ± 0.6% of intake) were excellent. Digestibility of protein, as with all rice products, was moderately low (80.1 ± 3.3%), but its high biological value made N retention equal to that from casein. Plasma‐free amino acids were consistent with the low essential/total amino acids ratio found in cereals, with slower absorption, and with the possibility that leucine was the first‐limiting amino acid. Absorptions of Ca, Mg, PO4, and Zn were considered satisfactory. Energy costs of weight gain and the estimated percentage N in the weight gained during 14 days were comparable to those attained with the highest quality cow's milk‐derived formulas in children of similar ages and nutritional status.
Neuronal Intestinal Dysplasia
Authors: Simpser Edwin , Kahn Ellen , Kenigsberg Kenneth , Duffy Lynn , Markowitz James , Daum Fredric
Published: January 2024

Neuronal intestinal dysplasia (NID) clinically resembles Hirschsprung's disease but is characterized by hyperplasia rather than aganglionosis of the intramural plexus. Surgical intervention is common. We report the 5‐year follow‐up of an infant with the mixed form of NID managed medically and a method by which NID can be quantified historically. Hyperganglionosis was determined by counting the number of ganglia per high‐power field and the number of ganglion cells per ganglia from at least two biopsy specimens. The patient's biopsies and biopsies from “normal” and “inflamed” patients were compared. Normals contained 0.68 ± 0.28 (X ± SD) ganglia per high‐power field and 2.16 ± 0.31 ganglion cells per ganglion. The inflamed biopsies were similar, 0.69 ± 0.38 ganglia per high‐power field and 2.63 ± 0.40 ganglion cells per ganglion. The patient's initial rectal biopsy revealed 7.6 ganglia per high‐power field and 3.8 ganglion cells per ganglion. Management of the patient included saline colonic irrigations and hyperalimentation with gradual reinstitution of breast‐feeding. Clinical improvement was associated with normalization of manometry and biopsy findings, a phenomenon not documented previously in the literature. Irrigations were stopped at age 9 months, and the child is now asymptomatic.
Insulin‐Like Growth Factors I and II and Their Binding Proteins in Human Milk
Authors: Donovan Sharon M. , Hintz Raymond L. , Rosenfeld Ron G.
Published: January 2024

Summary: Insulin‐like growth factors (IGF‐I and ‐II) are peptide growth factors that contribute to the growth‐promoting properties of human milk. IGFs in extra cellular fluids are associated with high‐affinity binding proteins (IGFBPs). In this study, IGF‐I and ‐II, and IGFBPs in human milk were characterized, and the stability of the IGFs and IGFBPs to heat treatment was investigated. IGF‐I and ‐II were quantified by radioimmunoassays of acid‐chromatographed samples, and IGFBPs were characterized using Western ligand blotting. The concentration (mean ± SD) of IGF‐I in human milk was 1.5 ± 0.5 μg/L, compared to 2.7 ± 0.7 μg/L for IGF‐II. Heat treatment did not significantly affect either IGF‐I or ‐II content. Human milk contains a single, nonglycosylated, IGFBP, with an apparent Mr of 31 k, which was immunoprecititable by an antibody to IGFBP‐2. Stability of the IGFBP to heat treatment was assessed and was not significantly affected by heat treatment. Therefore, both IGF‐I and ‐II, and the IGFBP in human milk appear to be stable under heat treatment conditions routinely used for processing banked human milk.
Short Stature as the Primary Manifestation of Monosymptomatic Celiac Disease
Authors: Bonamico M. , Sciré G. , Mariani P. , Pasquino A. M. , Triglione P. , Scaccia S. , Ballati G. , Boscherini B.
Published: January 2024

It is generally accepted that celiac disease (CD) must always be taken into consideration when dealing with children manifesting growth failure. It is therefore important to have laboratory tests capable of detecting patients who should undergo intestinal biopsy. Auxological and endocrine parameters, bone age, some nutritional indices (hemoglobin, serum iron, calcium, total protein, and albumin), and anti‐gliadin antibodies (AGA) IgA and IgG and 1‐h blood xylose levels were evaluated in 49 children of short stature. On the basis of the intestinal biopsy, 29 (59.1%) patients affected by CD were found. When patients with atrophic and normal intestinal mucosa were compared, significant differences in the frequency of pathological values of hemoglobinemia, serum iron, AGA, and 1‐h blood xylose levels were found, whereas no difference was observed in the levels of serum calcium, total protein, and albumin. Bone age was delayed in 81% of the celiac patients and in 47% of the controls. In particular, AGAs were found in 27 of 29 celiac patients and in three control subjects who showed a low level of one of the two antibodies. The results of our study demonstrate that AGA (IgA and IgG), together with 1‐h blood xylose, hemoglobinemia, serum iron, and family history of CD determination, are extremely useful for screening patients of short stature. This type of screening cannot, however, replace the intestinal biopsy because such tests cannot be completely sensitive and specific.
Gastrointestinal Priming Prior to Full Enteral Nutrition in Very Low Birth Weight Infants
Authors: Meetze William H. , Valentine Christina , McGuigan James E. , Conlon Michael , Sacks Nancy , Neu Josef
Published: January 2024

Priming of the gastrointestinal (GI) tract with low‐volume feedings before giving full enteral feedings to very premature, high‐risk infants is a controversial practice. We designed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain, improve tolerance of subsequent feedings, enhance nutritional status, and increase serum concentration of gastrin, a hormone trophic for intestinal growth. Infants were randomly assigned to receive total parenteral nutrition (TPN) alone (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life. Full‐strength premature infant formula was used for priming. Both groups received the same total nutrition. Beginning on day 15, feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20, where they were maintained until day 30. After day 30, the feedings were modified according to the infants' condition. The groups did not differ in birth weight, gestational age, or 5‐min Apgar scores. GI‐primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study. There was no significant difference in weight gain. GI priming improves tolerance of feedings, accelerates rate of rise of serum gastrin during the first weeks of life, and does not increase the risk of feeding complications when compared to TPN alone. This may lead to more rapid maturation of the GI tract in primed infants.
Iron Absorption and Incorporation into Red Blood Cells by Very Low Birth Weight Infants
Authors: Ehrenkranz Richard A. , Gettner Patricia A. , Nelli Catherine M. , Sherwonit Elaine A. , Williams Joanne E. , Pearson Howard A. , Ting Bill T. G. , Janghorbani Morteza
Published: January 2024

Measurements of iron absorption and incorporation into RBCs were obtained with the stable isotope 58Fe, administered as a reference dose, in 11 premature infants with birth weights between 780 and 1,520 g and gestational ages between 24 and 33 weeks. Each study included a timed stool and urine collection, nasogastric tube administration of a single dose of about 228 μmlg of 58Fe/kg of body weight (as FeSO4, with 10 mg/kg of vitamin C) between feedings, and blood samples before 58Fe (day 1) and then 2 weeks (day 15) later. Gastrointestinal absorption of the 58Fe dose as measured by fecal isotope balance was 41.6 ± 17.6% (mean ± SD). However, only 12.0 ± 9.6% of the 58Fe dose (28.7 ± 22.3% of the absorbed 58Fe dose) was incorporated into RBCs on day 15. 58Fe absorption and 58Fe incorporation into RBCs on day 15 were significantly correlated with the hemoglobin concentration and reticulocyte count on day 1. Transfusion history did not affect 58Fe absorption or 58Fe incorporation into RBCs. We conclude that concurrent measurement of 58Fe absorption with fecal monitoring and of 58Fe incorporation into RBCs permits a better understanding of the fate of iron ingested by premature infants than either measurement alone.
Plasma Amino Acid Response to Ingestion of L‐Amino Acids and Whole Protein
Authors: Gropper Sareen S. , Gropper Daniel M. , Acosta Phyllis B.
Published: January 2024

The effect of whole protein and L‐amino acid ingestion on plasma amino acid concentrations was investigated in 10 men. Each subject ingested equivalent amounts of amino acids as cottage cheese (session 1), an L‐amino acid mixture (session 2), and cottage cheese and L‐amino acids (session 3). Postprandial changes from baseline were larger for essential versus nonessential amino acids in each session. Higher and more rapid rises followed by more rapid declines in individual plasma amino acid concentrations were observed after ingestion of L‐amino acids alone or with whole protein than after ingestion of an equivalent amount of amino acids as whole protein. Individuals receiving the majority of their essential amino acid and nitrogen needs from elemental products may need, for example, to consume them more frequently or after consumption of other foods in an effort to slow down absorption rates.
Iron Nutrition and Growth of Breast‐ and Formula‐Fed Infants During the First 9 Months of Life
Authors: Haschke Ferdinand , Vanura Hanns , Male Christoph , Owen George , Pietschnig Beate , Schuster Ernst , Krobath Evelyn , Huemer Christian
Published: January 2024

Feeding of iron (Fe)‐fortified (12–15 mg/L) infant formulas is an effective and convenient means to protect infants from Fe deficiency. To study lower levels of Fe fortification of infant formulas (3 or 6 mg/L) compared with those currently in use, we compared Fe intake and Fe nutritional status of three groups of healthy, term infants between 90 and 274 days of age. One group received an Fe‐fortified whey‐predominant formula (3 mg/ L) and the second group received the same formula with a higher Fe level (6 mg/L). A comparison group was breast‐fed at least until 274 days of age. All infants received infant foods and cereals according to European Community recommendations. Mean Fe intake of infants fed formula fortified with 3 mg/L was significantly lower at 183 and 274 days of age (p < 0.05) than that of infants fed formula fortified with 6 mg/L. None of the infants fed the formula fortified with 3 mg/L met the recommended daily allowance value (10 mg) for infants between 6 and 12 months of age. Hemoglobin, hematocrit, mean corpuscular volume, free erythrocyte protoporphyrin, and serum ferritin levels were similar in the formula‐fed groups; none of the infants had depleted Fe stores (ferritin < 10 μg/L) at 183 and 274 days of age. Thirteen percent of breast‐fed infants had depleted Fe stores at 183 days of age, but only 3% were depleted at 273 days of age, when Fe‐fortified beikost was already part of the diet. No influence of Fe nutritional status was found on zinc and copper nutritional status or on growth. We conclude that regular consumption of an infant formula fortified with 3 mg Fe/L, a level substantially below present recommendations, prevents healthy, term infants from developing Fe deficiency during the first 6 months of life. It is preferable that infants 6 months of age and older receive an Fe‐fortified formula and a judicious selection of beikost to ensure an adequate dietary intake of Fe.
Down's Syndrome and Celiac Disease
Authors: Zubillaga P. , Vitoria J. C. , Arrieta A. , Echaniz P. , Garcia‐Masdevall M. D.
Published: January 2024

The association between Down's syndrome (DS) and autoimmune diseases has long been recognized. However, its relationship to celiac disease (CD) has only recently been reported, and a clear‐cut association remains to be fully established. We have studied the prevalence of CD in a random sample of 70 individuals with DS. IgA anti‐gliadin antibodies (IgA AGAs) were determined in all and found to be positive in nine (13%). In eight, anti‐endomysium antibodies (AEAs) were investigated, and jejunal biopsies were performed. AEAs were positive in two, and three had flat intestinal mucosa. The class I and II human leukocyte antigens of two patients with CD were determined. Results were as follows: A2/B8 B39/DR1 DR3/DQW1 DQW 2 in one case and A2 A28/B44 B17/DR4 DR5/DQW3 in the other. This implies a 43% prevalence of CD in DS, which is well above that previously found by us in our population (0.62/1,000 live births). We conclude that the association between DS and CD is not fortuitous and suggest that the determination of such serologic markers as IgA AGA and AEA should be part of health assessment in DS patients.
Increased in Vitro Intestinal Permeability in Suckling Rats Exposed to Cow Milk During Lactation
Authors: Arvola Taina , Isolauri Erika , Rantala Immo , Kaila Minna , Majamaa Heli , Virtanen Elina , Arvilommi Heikki
Published: January 2024

Specific mucosal barrier functions of the gut develop in the newborn to combat the constant challenge of foreign antigens. To determine whether exposure to cow milk antigens interferes with this maturational process, jejunal permeability to macromolecules and the activation of immune mechanisms were studied in preweaning rats. At the age of 14 days, rat pups were divided into three feeding groups. Controls (n = 18) remained on normal maternal milk; group CM (n = 27) additionally received a daily gavage feed of cow milk; and in group D (n = 23), cow milk was given to dams. At 21 days, when “gut closure” normally occurs, intestinal in vitro absorption of horseradish peroxidase in its intact form was significantly higher in group CM and in group D than in controls (F = 5.6; p = 0.006): group CM: mean, 37.8 ng/h/cm2; 95% confidence interval (CI), 19.4–73.6; group D: mean, 26.9 ng/h/cm2; 95% CI, 8.2–88.2; controls: mean, 4.0 ng/h/cm2; 95% CI, 1.2–13.9. In association with increased jejunal permeability, there was enhanced jejunal eosinophilic infiltration in group CM. In group D, the number of specific antibody‐secreting cells in peripheral blood against β‐lactoglobulin was significantly higher than in group CM and controls. These data indicate that there is a critical period in development when feeding cow milk antigens delays gut closure. They further suggest that mucosal barrier function is impaired due to a local hypersensitivity reaction to cow milk antigens, irrespective of the protection of maternal milk or maternal antigen processing.
Gastroesophageal Reflux and Bronchial Asthma
Authors: Tucci Fabio , Resti Massimo , Fontana Rossana , Novembre Elio , Lami Caterina Adami , Vierucci Alberto
Published: January 2024

We evaluated the prevalence of gastroesophageal reflux in 36 children, 22 (61.2%) male and 14 (38.8%) female (median age, 75.5 months; range, 18–178), with noncontrolled asthma by means of prolonged (22–24 h) esophageal pH monitoring. None of the children had gastrointestinal symptoms suggesting gastroesophageal reflux. Atopy was seen in 21 of 36 (58.3%) patients. Pathological gastroesophageal reflux was present in 27 (75%) children. All patients were given cisapride (0.2 mg/ kg q.i.d.) for 3 months. A clinical and pharmacological score was determined, and a second pH‐metric study was made at the end of the follow‐up period. The following pH‐metric parameters were evaluated: the total percentage of time pH was <4, the number of reflux episodes, the number of reflux episodes lasting >5 min, the length of the longest single reflux episode, and the percentage of time the esophageal pH was <4 during sleep. The study was completed in 11 of 27 children. The percentage of time that esophageal pH was <4 improved in nine of 11 (81.8%) patients (p = 0.013). The percentage of time that esophageal pH was <4 during sleep showed the most significant decrease (p = 0.002) after treatment. Improvement in both clinical and pharmacological scores was highly significant (p < 0.0001) in 19 of 27 patients, eight of whom did not want to repeat the pH study. We conclude therefore that gastroesophageal reflux is frequently associated with noncontrolled asthma and that medical therapy for reflux may improve the further course of respiratory disease.
Duodenal and Esophageal Manometry in Total Colonic Aganglionosis
Authors: Faure Ch , Ategbo S. , Ferreira G. C. , Cargill G. , Bellaiche M. , Boige N. , Viarme F. , Aigrain Y. , Cézard J. ‐P. , Navarro J.
Published: January 2024

SummaryEleven children with total colonic aganglionosis were studied by esophageal and duodenal manometry. They were separated into two groups: group 1, with ileal involvement, and group 2, without ileal involvement. The results of the digestive motility studies were compared with the extent of ileal involvement of the aganglionosis and with the amount of artificial nutritional support required. All children showed abnormalities on both esophageal and duodenal manometry, suggesting complete digestive tract motility involvement. Recent advances in understanding Hirschsprung's disease and manometrical abnormalities suggest a primary motility disorder in children with total colonic aganglionosis.
Identification of Gliadin Presence in Pharmaceutical Products
Authors: Miletic Ivanka Dj. , Miletic Vojislav D. , Sattely‐Miller Elizabeth A. , Schiffman Susan S.
Published: January 2024

Celiac disease is characterized by hypersensitivity to the alcohol‐soluble wheat proteins called gliadins. Total avoidance of gliadin is the lifelong treatment for such patients. However, wheat gliadins are often present as impurities in industrial starch commonly used in the preparation of different pharmaceutical products. Therefore, some drugs might contain gliadin, which can be dangerous for sensitive patients if taken in large amounts or used permanently. The purpose of this study was to develop a sensitive, reliable assay that is specific for the detection of gliadins in pharmaceutical products. Gliadins were extracted here using sodium dodecyl sulfate rather than 70% ethyl alcohol, which has been the traditional solvent. This gliadin extract was utilized in a dot‐blot assay that incorporated an antigliadin antibody developed in rabbit and labeled with peroxidase. 4‐Chloro‐1‐naphthol was used as a peroxidase‐specific substrate. Isolated wheat gliadin was used as the positive control. Dilution experiments showed that the lower level of sensitivity for the assay was in the range of 0.0045 mg/ml of gliadin, which is a concentration level lower than that suggested for a gluten‐free diet. The assay developed here revealed that 71.2% of 59 prescription and nonprescription drugs tested contained gliadin in the amount detected by our dot‐blot assay. The prescription drugs tested were among the top 50 most frequently dispensed in U.S. community pharmacies. The nonprescription drugs were among those that constitute the largest sales in the United States. The results showed that the simple dot‐blot assay developed here can be used for pharmaceutical testing performed either by hospital laboratories or by patients themselves.
Fatty Acid Composition of Plasma and Red Blood Cell Phospholipids in Preterm Infants from 2 Weeks to 6 Months Postpartum
Authors: Luukkainen Päivi , Salo Matti K. , Janas Martti , Nikkari Tapio
Published: January 2024

The purpose of this study was to follow the long‐chain polyunsaturated fatty acid (LCP) status in initially human milk‐fed preterm infants from 2 weeks to 6 months postpartum. Twenty‐two infants aged 27–33 weeks of gestation at birth who had a birthweight of 710–2525 g were fed human milk for ≥4 weeks. After discharge from the hospital, they were either human milk‐fed or formula‐fed according to their mothers' decision: 10 were fully breast‐fed for 6 months and 12 were formula‐fed after discharge at 1–2 months. The formula fat contained 20% 18:2n‐6 and 3% 18:3n‐3 but was devoid of long‐chain polyunsaturated fatty acids (LCP). Blood samples were taken at 2 weeks, 3 months, and 6 months postpartum. Percentage fatty acid compositions in red blood cell (RBC) and plasma total phospholipids were analyzed by capillary gas liquid chromatography. In formula‐fed infants, the change from human milk to formula resulted in a significant rise in plasma and RBC l8:2n‐6 and 18:3n‐3 and a decrease in plasma 20:4n‐6. Interestingly, RBC20:4n‐6 remained constant in both groups, even after 4–5 months of formula feeding. In the formula‐fed group, RBC 22:5n‐6 showed an increasing trend. The largest changes were seen in 22:6n‐3; in the formula‐fed group, il decreased in both plasma and RBC, whereas in the human milk‐fed group, it showed an increasing trend. At 6 month, RBC 22:6n‐3 was twice as high in the human milk‐fed group [7.70% (95% CI 6.17–9.22)] than in the formula‐fed group [3.80% (3.36–4.24)]. The relative birthweight correlated positively with RBC 20:4n‐6 and 22:6n‐3 in both groups at 3 months. In conclusion, in initially human milk‐fed preterm infants, formula feeding resulted in a rapid and significant decrease in plasma and RBC 22:6n‐3 and plasma 20:4n‐6 but not in RBC 20:4n‐6. Relative birthweight was associated with RBC 20:4n‐6 and 22:6n‐3 levels up to 3 months, showing the importance of intrauterine nutrition on LCP status.
Lactic Acid Bacteria in the Treatment of Acute Rotavirus Gastroenteritis
Authors: Majamaa Heli , Isolauri Erika , Saxelin Maija , Vesikari Timo
Published: January 2024

We compared different lactic acid bacteria for their effect on the immune response to rotavirus in children with acute rotavirus gastroenteritis. After initial oral rehydration, 49 children aged 6 to 35 months with rotavirus gastroenteritis randomly received cither Lactobacillus casei subsp. casei strain GG (LGG), L. casei subsp. rhamnosus (Lactophilus), or a combination of Streptococcus thermophilus and L. delbriickii subsp. bulgaricus (Yalacta) twice daily for 5 days. Serum antibodies to rotavirus, total number of immunoglobulin‐secrcting cells (ISC), and specific antibody‐secreting cells (sASC) to rotavirus were measured at the acute stage and at convalescence. The mean (SD) duration of diarrhea was 1.8 (0.8) days in children who received LGG, 2.8 (1.2) days in those receiving Lactophilus, and 2.6 (1.4) days in those receiving Yalacta (F = 3.3, p = 0.04). The ISC response was comparable in the three study groups, but the rotavirus‐specific immune responses were different. LGG therapy was associated with an enhancement of IgA sASC to rotavirus and serum IgA antibody level at convalescent stage. We conclude that certain strains of lactic acid bacteria, particularly LGG, promote serum and intestinal immune responses to rotavirus, and thus may be important in establishing immunity against rotavirus reinfections
Estimation of Arachidonic Acid Synthesis in Full Term Neonates Using Natural Variation of 13C Content
Authors: Demmelmair Hans , Schenck Ursula v. , Behrendt Eva , Sauerwald Thorsten , Koletzko Berthold
Published: January 2024

Neonates need arachidonic acid (AA) for their growing tissues, but it is unknown to what extent they can synthesize AA from dietary linoleic acid (LA). We studied infantile AA synthesis by using different natural 13C amounts in dietary fats. The diets of four infants ages 18 ± 4 days (mean ± SD) with newly diagnosed phenylketonuria were changed from breast milk or formula to a phenylalanine‐free diet with corn oil as the only fat source. Compared with most dietary fats in Europe derived from C3 plants, corn oil LA has a higher 13C content. We determined the 13C content of LA and AA in 0.25–0.5 ml serum before and for 3–4 days after the diet change with gas chromatography combustion isotope ratio mass spectrometry (GC‐IRMS). Baseline δ 13C values were ‐ 31.5 ± 1.1%0 (mean ± SD) for serum LA and ‐ 30.1 ± 1.2%0 for AA. The corn oil diet induced changes of δ 13C values over baseline in LA of 8.9 ± 1.0 on day 1 and 12.7 ± 0.7 on day 4, respectively. The changes of AA δ 13C values were 0.5 ± 0.7 and 2.7 ± 0.7 on days 1 and 4. We conclude that reproducible detection of differences in δ 13C values of fatty acids in small samples of infantile serum, induced by dietary variation of natural 13C amounts, is feasible with GC‐IRMS. Since the corn oil diet did not contain AA, the observed change of AA δ 13C shows active endogenous AA synthesis in full‐term neonates. Using a simplified isotopic balance calculation, we estimate that an average 23% of plasma AA on study day 4 originates from infantile LA conversion.
Tracer Kinetic Studies on a Methionine‐Supplemented Soy‐Based Infant Formula Using 1‐13C‐ and 15N‐Methionine as Tracers
Authors: Radke Michael , Heine Willi , Wutzke Klaus D. , Leitzmann Peter , Walther Frank
Published: January 2024

A tracer‐kinetic study using 1‐13C‐ and 15N‐labeled L‐methionine was conducted in order to measure the retention rate of free methionine added to commercially‐produced soy‐based infant formulas. Twelve male infants, fed on a soy formula, received a single‐pulse labeling by oral administration of L‐1‐13C‐methionine (5 mg/kg) and L‐15N‐methionine (10mg/kg). The abundance of expired 13C‐labeled CO2 was measured up to 7 h after administration at 15‐, 30‐, and 60‐min intervals. Additionally, enrichment of total 15N and 15N in urinary ammonia were determined up to 48 h after administration. Retention rates of the labeled carboxyl group amounted to an average of 91.2% (SD 4.1) of the intake. A similar retention rate was measured for the 15N‐label of methionine (90.0%, SD 4.3). The data point at the efficacy of methionine supplementation of soy‐based infant formulas.
TIA1 and Mast Cell Tryptase in Food Allergy of Children: Increase of Intraepithelial Lymphocytes Expressing TIA1 Associates With Allergy
Authors: Augustin Merja , Karttunen Tuomo J. , Kokkonen Jorma
Published: January 2024

Background

Variability of symptoms and signs make the diagnosis of children's food allergy (FA) difficult. In addition, mechanisms and antigens involved vary with age. In young infants, cow's milk protein allergy is associated with an increase of cytotoxic intraepithelial lymphocytes (IELs) expressing T‐cell–restricted intracellular antigen (TIA1). In the current study, the significance of TIA1 in FA in older children of mainly preschool and school age was analyzed and the findings correlated the with a detailed clinical, endoscopic, and histopathologic analysis.

Methods

The subjects of this study were 66 children (mean age, 7.9 years; range, 1–15), including 27 with untreated and 15 with treated FA, and 24 control subjects. The morphology of duodenal and antral biopsy specimens was evaluated, and the proportion of TIA1‐positive IELs was counted from immunostained sections. Quantification of mast cells with immunostaining for mast cell tryptase (MCT) was completed, with the estimation of diffuse extracellular staining considered to indicate degranulation.

Results

Patients with untreated FA showed an increase in the total number of TIA1‐positive cells and IELs and of the TIA1/IEL ratio. The number of mast cells in duodenal mucosa was decreased in children with FA, but no association with degranulation was observed. Endoscopic abnormalities were common in FA, but conventional histopathology showed no informative differences.

Conclusions

The significant increase of TIA1‐positive IELs in duodenal tissue specimens is associated with FA. The cytotoxicity of T lymphocytes seems to play a role in the pathogenesis of gastrointestinal FA. Activation and mechanisms of action should be studied further.
In Vitro Availability of Calcium, Iron, and Zinc from First‐Age Infant Formulae and Human Milk
Authors: Bosscher Douwina , Van Caillie‐Bertrand Micheline , Robberecht Harry , Van Dyck Kristien , Van Cauwenbergh Rudy , Deelstra Hendrik
Published: January 2024

Background

Variation in the bioavailability of calcium (Ca), iron (Fe), and zinc (Zn) occurs because of interactions of food components in the gastrointestinal microenvironment. Bioavailability is preferably determined by in vivo tests, but these are expensive, labor‐intensive, time consuming, and often unethical. As an alternative, in vitro methods can be used to predict bioavailability of nutrients from foodstuffs.

Methods

A continuous‐flow dialysis model with preliminary intraluminal digestive phase, adapted to the gastrointestinal conditions of infants younger than 6 months, was used. Human milk was the reference standard. Ca, Fe, and Zn content of samples and dialysates after digestion were analyzed by atomic absorption spectrometry.

Results

Ca availability is similar in human milk (13.1% ± 0.8%), whey (13.3% ± 1.2%), and soy‐based formulae (13.0% ± 1.2%;P > 0.05), and higher in casein‐predominant formula (21.2% ± 0.6%;P < 0.05). Availability of Fe is highest in human milk (8.12% ± 0.27%;P < 0.05). Fe availability in whey (1.28% ± 0.28%) and soy formulae (1.48% ± 0.28%) is similar (P > 0.05), but availability is lower in casein‐predominant formula (0.48% ± 0.22%;P < 0.05). Zn availability is also highest in human milk (13.1% ± 0.7%;P < 0.05). However, Zn availability is similar in whey (6.7% ± 0.6%) and casein formulae (8.5% ± 1.6%;P > 0.05), but lower in soy formula (2.3% ± 0.4%;P < 0.05).

Conclusions

Our observations are in agreement with previous data from in vivo studies in term infants. This in vitro procedure is an inexpensive, simple, rapid, and reliable method that predicts the bioavailability of Ca, Fe, and Zn in foods.
A Prospective Study of Endoscopic Esophageal Variceal Ligation Using a Multiband Ligator
Authors: McKiernan Patrick J. , Beath Susan V. , Davison Suzanne M.
Published: January 2024

Background

Endoscopic variceal band ligation (EVL) is the preferred method of treating variceal hemorrhage in adults. The need to reinsert the endoscope after reloading for each varix ligation has been a drawback. The Saeed multiband ligator allows ligation of multiple varices during a single insertion. The multibander has not been used previously in children.

Methods

Twenty‐eight consecutive children were referred to a pediatric liver unit because of esophageal variceal bleeding from 1998 to 2000. Endoscopic variceal band ligation was performed at initial endoscopy and repeated monthly until varices were obliterated or were too small to ligate.

Results

Results are expressed as median (range). Age at EVL was 11 years (3 months to 16 years) and weight 30 kg (5.4–63 kg). Portal hypertension was caused by cirrhosis in 15 children. Endoscopic variceal band ligation was performed on 66 occasions with 4 bands applied per session. Ten children had active bleeding at initial endoscopy and all responded to EVL. Interval bleeding developed in 2 children before variceal ablation. Varices were obliterated in 26 of 28 patients after 2 sessions. During the 21‐month follow‐up (2 months to 3 years), six children have undergone elective liver transplantation and three have had mesoportal bypass procedures. Rebleeding developed in 2 of 26; 1 from recurrent esophageal varices that responded to repeat EVL and 1 from gastric varices. Following variceal ablation, 2‐year actuarial variceal recurrence risk was 40%.

Conclusions

Endoscopic variceal ligation is highly effective in obliterating esophageal varices in children. The use of a multibander device for endoscopic variceal ligation is technically feasible and safe even in small children, and its use results in more rapid ablation of esophageal varices.
Total and Segmental Colonic Transit Time and Anorectal Manometry in Children With Chronic Idiopathic Constipation
Authors: Gutiérrez Carolina , Marco Alfredo , Nogales Angel , Tebar Roque
Published: January 2024

Background

Constipation is a frequent symptom in pediatric clinical practice, although the underlying pathogenesis is not fully understood. Estimating the colonic transit time may help identify subgroups of patients with different physiopathologic mechanisms.

Methods

Thirty children with normal bowel habits and 38 children with chronic idiopathic constipation, aged 2 to 14 years, were studied. The total and segmental colonic transit times were estimated by administering multiple radiopaque markers for 6 days and performing a single abdominal radiograph on day 7. Anorectal function was evaluated using manometry with an Arhan probe.

Results

The observed upper reference values were 19.02 hours for the right colon, 19 hours for the left colon, 32 hours for the rectosigmoid colon, and 45.7 hours for the total colon. Fifty percent of the children with chronic idiopathic constipation had colonic transit times within reference values, whereas 37% had left colonic and rectosigmoid delays and 13% had global delay in all colonic segments (colonic inertia). Paradoxic anal contraction was observed in 64% of the constipated children with distal delay but in none of the subjects with colonic inertia.

Conclusions

Estimating colonic transit time is a simple and noninvasive technique for classifying patients with constipation. Colonic inertia may be a manifestation of global motility dysfunction. Children with delayed distal colonic transits are more likely to have abnormal defecation dynamics.
Ileal Cytokine Dysregulation in Experimental Necrotizing Enterocolitis Is Reduced by Epidermal Growth Factor
Authors: Halpern Melissa D. , Dominguez Jessica A. , Dvorakova Katerina , Holubec Hana , Williams Catherine S. , Meza Yolanda G. , Ruth Miriam C. , Dvorak Bohuslav
Published: January 2024

Background

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin‐18 and interleukin‐12 are up‐regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin‐18, interleukin‐12 and/or antiinflammatory interleukin‐10.

Methods

Newborn rats were artificially fed with either growth‐factor–free rat milk substitute (RMS) or RMS supplemented with 500 ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold stress. Cytokine expression and localization were assessed using reverse‐transcription real‐time polymerase chain reaction and immunohistology/confocal microscopy.

Results

Enteral administration of EGF (RMS + EGF) decreased overproduction of interleukin‐18 and increased interleukin‐10 production in the ileum. Furthermore, increased interleukin‐10 production was associated with up‐regulation of the transcription factor Sp1 in RMS + EGF rats.

Conclusions

These data suggest that EGF may reduce NEC via increased interleukin‐10 and decreased interleukin‐18 and that EGF‐mediated up‐regulation of Sp1 may account for the increased interleukin‐10.