bluuebunny/crossref_metadata_2025 huggingface dataset:
Cow's Milk Protein‐Sensitive Enteropathy
Authors: de Sousa Salazar J. , da Silva Aires , Pereira Virginia M. , Soares J. , Ramalho Magalhães P.
Published: February 2024

Intestinal biopsy is an essential procedure in the diagnosis of cow's milk protein‐sensitive enteropathy. The number and timing of biopsies, however, is still controversial. Twenty‐two infants who were clinically suspected of having cow's milk protein intolerance were put on a milk‐free diet, during which they all improved. In the first 14 infants (Group I), milk withdrawal lasted 6‐8 weeks; in the following 8 infants (Group II), milk withdrawal lasted 3.5‐4 months. At the end of the withdrawal period, each patient was submitted to an oral lactose tolerance test and then to a first jejunal biopsy, followed by a cow's milk challenge, and a second biopsy (1‐2 days later). None of the infants showed evidence of lactose intolerance, but they all reacted adversely to milk reintroduction. In Group I, the distribution of mucosae from grade 0 (normal) to III was almost the same before and after challenge (p > 0.5); this is considered to be due to the severe mucosal damage still present in prechallenge biopsies. In Group II, however, a significant difference was found in the distribution of mucosae before and after challenge (p < 0.05), and a deterioration could be observed in each case after challenge. Intraepithelial lymphocyte counts and mitotic index determinations before and after milk reintroduction were of no diagnostic value in either group. It is suggested that the diagnosis of cow's milk protein‐sensitive enteropathy may rely on two biopsies, the first after a period of 3.5‐4 months on milk‐free diet and the second following milk challenge.
Transfer of Orally or Intravenously Administered Proteins to the Milk of the Lactating Rat
Authors: Telemo E. , Weström B. , Dahl G. , Karlsson B.
Published: February 2024

Lactating rats were given a test solution containing various marker proteins via oral or intravenous routes. Using immunoprecipitation methods for the detection of ovalbumin (OvA), bovine serum albumin (BSA), and bovine gammaglobulins (BIgG) and radioimmunoassay for the analysis of β‐lactoglobulin (β‐LG), these proteins could be found in the blood serum and the milk of the rat 6 h after administration. A specific distribution pattern between the serum and the milk was observed for each protein. The results show that orally fed dietary proteins are able to cross the gut of the lactating rat and can be found in the serum and the milk. It was also observed that oral feeding of the proteins resulted in relatively greater concentrations in the milk than did intravenous administration. This very early presentation to the young of antigenic macromolecules derived from the mother's diet might be of importance for the development of a proper immunological response to common food antigens.
Trypsin‐Binding Immunoglobulin G in Cystic Fibrosis, Allergic, and Normal Children
Authors: Laroche D. , Jezequel M. , Travert G.
Published: February 2024

Summary: Using a simple and sensitive radioassay, we have determined the frequency of trypsin‐binding (TB) immunoglobulin G (IgG) as a function of age in cystic fibrosis (CF) patients, in allergic patients, and in control subjects. These IgGs appear during the 1st years of life. Their frequency is maximum between 3 and 20 years of age and decreases during adulthood. In allergic children TBIgG appears later than in CF children and the maximum frequency (32%) is intermediate between those observed in CF and in control children (66 and 19.6%, respectively). We suggest that an endogenous form of trypsin is involved in the phenomenon.
Relationships Between Pulmonary Function and Plasma Fatty Acid Levels in Cystic Fibrosis Patients
Authors: Gibson Robert A. , Teubner Jillian K. , Haines Kay , Cooper David M. , Davidson Geoffrey P.
Published: February 2024

Summary: Nineteen patients with cystic fibrosis (CF) were studied to determine whether plasma fatty acids correlated with severity of their lung disease as assessed by pulmonary function testing. Results were compared with 19 normal subjects of similar age and sex. Linoleic acid content of all lipid fractions was significantly lower in CF patients than controls including cholesterol ester fraction (CF 31%, control 50%, p < 0.001), triglyceride fraction (7.6 to 16.6%, p < 0.001), and phospholipid fraction (13.9 to 21.7%, p < 0.001). Mean 20:3ω9/20:4ω6 ratio for CF patients was higher in all lipid classes and was suggestive of essential fatty acid deficiency. Correlations were found to exist between most pulmonary function parameters and fatty acids of plasma phospholipids but not any other lipid class. Positive correlations were found between all ventilatory tests and total ω3 polyunsaturated fatty acids and also 22:5ω3 and 22:6ω3. There was no correlation between total saturated fatty acids, total monounsaturates, total ω6 fatty acids, or triene/tetraene ratios and pulmonary function. Positive correlations were found between pulmonary function parameters and certain ω6 polyunsaturates including 20:4 and 22:4 but not 18:2.
Intestinal Barrier to Intact Horseradish Peroxidase in Experimental Secretory Diarrhea
Authors: Heyman M. , Dumontier A. M. , Desjeux J. F.
Published: February 2024

Summary: Intestinal permeability to intact horseradish peroxidase (HRP, MW 40,000) was assessed during the acute phase of secretory diarrhea. Secretion was either induced in ligated loops of rabbit jejunum with cholera toxin or mimicked in vitro with db‐cAMP, 8Br‐cGMP, or theophylline in isolated fragments of rabbit jejunum mounted in Ussing chambers. Although intestinal electrolyte secretion was obtained under these conditions, as shown by the rises in short‐circuit current and potential difference, jejunal permeability to HRP did not change. These results suggest that, throughout the time course of secretory diarrhea, no change occurs in the functional ability of the jejunal epithelium to protect the organism against massive intact protein penetration.
Chronic Hepatitis Associated with Epstein‐Barr Virus Infection in an Infant
Authors: Tanaka Kazuhiko , Shimada Morimi , Sasahara Akiko , Yamamoto Hisashi , Naruto Toshiyuki , Tomida Yasunobu
Published: February 2024

Summary: A 1‐year‐old infant girl had a chronic illness characterized by persistent intermittent fever, thrombocytopenia, granulocytopenia, and marked hepatosplenomegaly. Histological findings on liver biopsy 307 days after the onset of her illness disclosed marked mononuclear cell infiltration and moderate fibrosis in the portal and perilobular areas. Interferon‐therapy induced no clinical and laboratory improvement, whereas the patient's clinical and biochemical findings responded to prednisone. Although these findings suggested a possible autoimmune mechanism, there were no significant findings in extensive immunological and serological tests consistent with autoimmune disease. The profile of antibodies to Epstein‐Barr virus (EBV)‐specific antigens in the patient demonstrated that this prolonged atypical illness was the result of persistent EBV infection.
Congenital Hepatic Fibrosis and Cerebral Aneurysm in a 32‐Year‐Old Woman
Authors: King Kerry , Genta Robert M. , Giannella Ralph A. , Weesner Robert E.
Published: February 2024

Summary: Congenital hepatic fibrosis has been associated with a number of visceral abnormalities, but only rarely with cerebral aneurysms. We report a case of a 32‐year‐old woman with congenital hepatic fibrosis and a subarachnoid hemorrhage secondary to a ruptured cerebral aneurysm. A review of the literature reveals only two previous reports of such an association and both were also associated with polycystic kidney disease. Our patient is unique in that she does not have polycystic kidney disease but rather medullary sponge kidney.
Niemann‐Pick Variant Lipidosis Presenting as “Neonatal Hepatitis”
Authors: Semeraro Lucille A. , Riely Caroline A. , Kolodny Edwin H. , Dickerson G. Richard , Gryboski Joyce D.
Published: February 2024

Summary: Neonatal hepatitis is a nonspecific term that may include a variety of disease entities. Two patients are presented who developed jaundice in the neonatal period and progressive hepatosplenomegaly. The infants were initially felt to have “neonatal hepatitis” but were subsequently found to have Niemann‐Pick disease. Biochemical investigation revealed normal levels of sphingomyelinase activity in leukocytes and liver but diminished levels in cultured skin fibroblasts, compatible with Niemann‐Pick type C.
Lactulose‐Rhamnose Intestinal Permeability in Children With Cystic Fibrosis
Authors: Leclercq‐Foucart J. , Forget P. P. , Van Cutsem J. L.
Published: February 2024

The lactulose‐rhamnose intestinal permeability test was performed in 10 cystic fibrosis (CF) children. Urine was collected for 5 h after oral intake of the test solution. A single thin‐layer chromatography followed by densitometry was used for the measurement of lactulose and rhamnose concentrations in the urine specimens. The excretion of each molecule was expressed as the percentage of the orally administered dose excreted and the lactulose‐rhamnose ratio was the ratio of the percentage quantities of each probe molecule excreted. The mean lactulose‐rhamnose excretion ratio in CF patients and controls was 0.16 and 0.038, respectively (p < 0.001). The mean 5‐h lactulose excretion was 2% and 0.28% in CF patients and control subjects, respectively (p < 0.001). The mean 5‐h rhamnose excretion was 12.8% and 7.6% in CF patients and control subjects (p < 0.05). We conclude that CF patients have an increased intestinal permeability to lactulose and rhamnose. Further studies are needed in order to elucidate the mechanisms involved as well as the eventual nutritional implications.
Comparison of Serum Fibronectin, Prealbumin, and Albumin Concentrations During Nutritional Repletion in Protein‐Calorie Malnourished Infants
Authors: Yoder Mervin C. , Anderson Donald C. , Gopalakrishna G. S. , Douglas Steven D. , Polin Richard A.
Published: February 2024

Anthropometric measurements and serum fibronectin, prealbumin, and albumin concentrations were determined on admission and during the hospitalization of 20 noninfected infants with protein‐calorie malnutrition. Serum fibronectin concentrations were significantly decreased on admission but increased to greater than normal serum values in 2 weeks. During this same interval, serum prealbumin values rose from significantly decreased to normal levels. Serum albumin concentrations and anthropometric measurements were not significantly elevated above admission levels until the fourth week of nutritional support. Serum fibronectin and prealbumin concentrations may serve as indices of the short‐term efficacy of nutritional support in noninfected infants with protein‐calorie malnutrition.
Intralipid Effects on Preterm Neonate Serum
Authors: Etzioni A. , Meshulam T. , Zeltzer M. , Benderly A. , Merzbach D. , Sujov P.
Published: February 2024

The effects of Intralipid (IL) administration of preterm infants have been investigated. For this purpose, adult neutrophils were stimulated by infant sera collected before and after IL treatment. A definite decrease (p < 0.0005) in chemoattractant capacity of zymosan‐activated serum was observed after IL. On the other hand, no difference in the opsinizing abilities of untreated versus treated sera could be demonstrated by measuring the chemiluminescence responses to serum‐opsonized zymosan. This study emphasized the need of caution in the use of IL treatment for preterm infants.
Sclerosing Cholangitis and Ulcerative Colitis in a Mother and Her Son
Authors: Silber Gary H. , Finegold Milton J. , Wagner Milton L. , Klish William J.
Published: February 2024

We present two cases, a 32‐year‐old mother and her 10‐year‐old son, both of whom had ulcerative colitis and sclerosing cholangitis. The mother had radiologic as well as pathologic evidence of both diseases, while the child's disease was demonstrated pathologically. A review of the literature indicates the rarity of sclerosing cholangitis in childhood, with no reported instances of a parent‐child affliction. The hypothesis that there is a genetic component to the development of sclerosing cholangitis may be supported by this family.
Neonatal Hepatitis
Authors: Chang Mei‐Hwei , Hsu Hey‐Chi , Lee Chin‐Yun , Wang Tso‐Ren , Kao Chuan‐Liang
Published: February 2024

Fifty‐six patients with moderate to severe neonatal hepatitis were followed for 12 to 78 months. Two died from causes other than hepatitis itself and were free from liver disease at the time of death. Of the remaining 54 patients, seven died of hepatitis, two are living with chronic liver disease and psychomotor retardation, and 45 are living without liver disease. High peak bilirubin levels and liver histologic findings of periportal fibrosis, moderate to severe portal inflammation, and/or diffuse giant cell transformation appear to be major factors predictive for poor outcome. Cytomegalovirus (CMV) infection was a common associated infection. Evidence of CMV infection was found in 22 (49%) of the 45 patients studied. Three of them died, and one is still living with cirrhosis of the liver. Metabolic disorders such as alpha‐1‐antitrypsin deficiency, galaclosemia, and aminoaciduria and/or aminoacidemia were carefully screened but were not found in these cases. A fatal case had a sibling who had died of a similar disease course. Chinese infants may have metabolic and familial cholestasis diseases requiring further investigation.
Continuous 24‐Hour Esophageal pH Monitoring in 285 Asymptomatic Infants 0–15 Months Old
Authors: Vandenplas Yvan , Sacré‐Smits Liliane
Published: February 2024

A continuous 24‐h esophageal pH monitoring was performed in 283 asymptomatic infants between 5 days and 15 months old. Several parameters (reflux index, duration of the longest reflux episode, number of reflux episodes in 24 h, number of reflux episodes >5 min in 24 h) were studied in different groups of infants according to their age: 5–15 days old, 24–37 days old, 3.5–4.5 months old, 5.5–6.5 months old, 7.5–8.5 months old, 14–16 months old. For all parameters we obtained statistically significant different results in infants younger and older than 4 months. The 24‐h esophageal pH monitoring is an investigation technique in physiological circumstances in order to establish normal ranges for gastroesophageal reflux in asymptomatic infants.
Alpha and Gamma Tocopherols in Pooled Mature Human Milk After Storage
Authors: Moffatt Paula A. , Lammi‐Keefe Carol J. , Ferris Ann M. , Jensen Robert G.
Published: February 2024

The α‐and ‐γ‐tocopherols in pooled stored human milk were determined. Storage times and temperatures were t = 0 (up to 2 h after start of pool collection); t = 8 h (25°, 4°C); t = 24 h (25°, 4°, – 11°C); and t = 72 h, 1, 4, 8, and 16 weeks (‐11°, −20°, −70°C). Lipids were extracted with a modified Folch procedure and tocopherols were analyzed with high‐performance liquid chromatography. There were no significant differences in α‐or γ‐tocopherol at any time or temperature. Therefore, mothers, milk bank operators, and researchers can be assured of the stability of tocopherol in human milk stored under the conditions of this study.
Methane Production in Patients with Cystic Fibrosis
Authors: Bujanover Y. , Peled Y. , Blau H. , Yahav J. , Katzenelson D. , Gilat T.
Published: February 2024

Methane production was studied in 28 cystic fibrosis patients aged 3–16 years and in 290 healthy children. The percentages of methane producers in the cystic fibrosis and control groups were 60.7 and 20.6%, respectively. In the patient group there was no difference between methane producers and nonproducers with respect to the degree of malabsorption or the administration of pancreatic supplements or antibiotics. We hypothesize that the high proportion of methane producers in cystic fibrosis patients may be associated with the presence of specific substrate(s) (glycoprotein?) in their intestinal contents. Changes of the intestinal microenvironment may favor the development of a methanogenic flora.
Effects of Nutritional Recuperation on E‐Rosetting Lymphocytes and in Vitro Response to Thymosin in Malnourished Children
Authors: Cruz Jose R. , Chew Francisco , Fernandez Raul A. , Torun Benjamin , Goldstein Allan L. , Keusch Gerald T.
Published: February 2024

The percentage of peripheral blood lymphocytes forming rosettes with sheep erythrocytes (E‐rosettes) was determined at admission to the INCAP Clinical Center in eight acutely malnourished Guatemalan children, and again after 14 and 28–30 days of nutritional therapy. While the mean percentage of E‐rosettes increased during therapy, the change (from 35.6 ± 10% to 43.3 ± 19%) did not reach statistical significance because of the variable response of different subjects. At each time period, however, in vitro incubation with the thymic factor, thymosin fraction 5, significantly increased the percentage of E‐rosetting lymphocytes. The presence of thymosin responsive cells in circulation after 1 month of optimal nutritional support indicates that immature T‐lymphocytes can persist in circulation in patients with severe malnutrition, even after clinical improvement. Thus, neither the percentage of E‐rosettes in peripheral blood nor their response to in vitro incubation with thymosin correlated with anthropometric measures of nutritional status in individual patients. This suggests that other nutritional or nonnutritional factors may be important modulating influences on T‐lymphocytes, and that prospective studies with thymic factor administration are warranted.
15N Tracer Kinetic Studies on the Validity of Various 15N Tracer Substances for Determining Whole‐Body Protein Parameters in Very Small Preterm Infants
Authors: Plath C. , Heine W. , Wutzke K. D. , Krienke L. , Töwe J. , Massute G. , Windischmann C.
Published: February 2024

Reliable 15N tracer substances for tracer kinetic determination of whole‐body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post‐conceptual age was 32.2 ± 0.8 weeks, and their body weight was 1670 ± 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]‐ glycine (Ib). In a second group of three infants with a post conceptual age of 15N‐labeled 32.0 ± 1.0 weeks and a body weight of 1,907 ± 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three‐pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 ± 3.1 g kg‐1 d‐1 (Ia), 16.2 ± 2.5 g kg‐1 d‐1 (Ib), and 10.8 ± 3.0 g kg‐1 d‐1 (II). We were able to demonstrate an over‐estimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N‐labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole‐body protein parameters in very small preterm infants.
Morphometric and Functional Studies of Proximal and Distal Colon in Young and Adult Rats Yigael Finkel and Lars Larsson
Authors: Finkel Yigael , Larsson Lars
Published: February 2024

Net sodium and fluid absorption in the colon is higher in young than in adult rats. The mechanism behind the high absorption in young rats is not well understood. In this study, we investigated the structural and functional properties of the proximal and the distal colon in 20− and 40‐day‐old rats. The surface area of the mucosa along the luminal surface of the gut in relation to the mucosal volume (surface density) was determined by morphometry. Net sodium and water absorption was determined by in vivo perfusion experiments. The surface density of the mucosa was greater in the proximal than in the distal colon in both 20− and 40‐day‐old rats. No developmental change in the surface density of the mucosa occurred between 20 and 40 days of age, however, in either the proximal or distal colon. Net sodium and fluid absorption per unit of weight were higher in both segments in 20− than in 40‐day‐old rats, and higher in the distal than in the proximal colon in 40‐day‐old rats. We conclude that other factors than the absorptive area are responsible for the decrease in the net colonic sodium and fluid absorption observed during late postnatal development and for the differences in sodium net absorption between the proximal and distal colon in 40‐day‐old rats.
Levels of Immunoreactive Insulin, Neurotensin, and Bombesin in Porcine Colostrum and Milk
Authors: Weström B. R. , Ekman R. , Svendsen L. , Svendsen J. , Karlsson B. W.
Published: February 2024

High concentrations of insulin (411 ± 214 μU/ml), neurotensin‐like (265 ± 72 pg/ml), and bombesin‐like immunoreactivities (1995 ± 288 pg/ml) were detected in porcine colostrum using radioimmunoassay, as compared to the levels found in sow blood serum at farrowing (5 μU/ml, <12 pg/ml, and 17 pg/ml, respectively). After 72 h of lactation, the levels of insulin and neurotensin‐like immunoreactivities had decreased to 28 ± 17 μU/ml and 89 ± 23 pg/ml, respectively, while the bombesin‐like activity remained constant. Characterization with reversed‐phase high performance liquid chromatography showed that the insulin immunoreactivity eluted at the same position as the insulin standard, while the elution patterns of the neurotensin‐like and bombesin‐like immunoreactivities (eluted in three separate peaks) did not correspond to that of their respective standards. The biological function of the peptide hormones in colostrum/milk may be as triggers of the developmental changes taking place in the nursing neonate, especially in the gastrointestinal tract.
A Study of Liver HBV DNA During Follow‐Up of Acute Viral Hepatitis in Children
Authors: Marconi Massimo , Scotto Jacques , Laliam Malika , Hadchouel Michelle , Dazza Marie‐Christine , Larouzé Bernard
Published: February 2024

Twenty‐nine children with acute icteric hepatitis were classified as follows after serological tests for the agents of viral hepatitis: hepatitis B 17 patients, hepatitis A 3 patients, hepatitis A + B 1 patient, possible non‐A, non‐B hepatitis 8 patients. In four of these cases, hepatitis A or non‐A, non‐B occurred in chronic HBsAg carriers. Hepatitis B virus (HBV) DNA was present in the initial serum of 15 of the 18 patients with acute hepatitis B. About 1 year after onset, HBsAg and HBV DNA were absent in 17 of them (16 of whom developed anti‐HBs) and the remaining patient became a chronic HBsAg carrier without HBV DNA in his serum. At the same time, liver biopsy samples from all 29 patients were available for HBV DNA investigation. HBV DNA sequences in the liver were never found in any patient, neither under free form nor integrated into the cellular genome. The absence of HBV DNA integration in any of the liver samples taken about 1 year after the acute phase of hepatitis B suggests that such integration is either unlikely or is transitory during the symptomatic period.
Enzyme‐Linked Immunosorbent Assay for Apolipoprotein B on Dried Blood Spot Derived from Newborn Infant
Authors: Ohta Takao , Migita Masahiro , Yasutake Toshiaki , Matsuda Ichiro
Published: February 2024

Hypercholesterolemia is a risk factor for atherosclerotic cardiovascular disease, and early diagnosis and treatment should be given attention. We developed a simple and sensitive enzyme‐linked immunosorbent assay (ELISA) for apolipoprotein B (apoB) on a dried blood spot (DBS). The specificity of this assay was investigated by constructing curves for other proteins. The crossreactivity was negligible. The mean intra‐ and intercoefficients of variation were 5.2 and 7.8%, respectively. We used phosphate buffer with Triton X‐100 for extracting apoB on DBS. The elution of apoB was stable up to 30 days after bleeding. The correlation between plasma and DBS apoB was r = 0.94, p < 0.005, n = 55.

Using this method, we screened 2,500 babies between 5 and 7 days of age. The mean ± SD of DBS apoB was 75 ± 15 U. Seven hypercholesterolemic neonates were detected. Family studies of these neonates disclosed one definite and two suspected heterozygotes for familial hypercholesterolemia. Four other neonates showed no related familial background. This ELISA method for assaying apoB should prove to be a useful tool for large mass screening for hypercholesterolemia, particularly in the newborn.
Predictive Value of Intraepithelial Lymphocyte Counts in Childhood Coeliac Disease
Authors: Taylor C. J.
Published: February 2024

To evaluate the use of intraepithelial lymphocyte (IEL) counts in identifying coeliac disease in childhood the jejunal histology from 116 children initially diagnosed as coeliac was reviewed. The diagnosis had been based on a characteristic mucosal abnormality and an apparent response to gluten exclusion. Lymphocyte counts were performed by one observer on the presenting biopsy and tissue samples obtained before and after a supervised gluten challenge. Results were expressed as IELs/100 enterocytes. On challenge 49% of patients failed to show histological deterioration with only one late relapse on 2 year follow‐up. Reappraisal of these cases suggested alternate diagnoses, of which cow's milk protein intolerance (CMPI) (16%) and postenteritis malabsorption (20%) were the most common. In confirmed coeliacs IEL counts were high at diagnosis (67 ± 16) (mean ± SD), fell on diet (28 ±13), and rose on challenge (64 ± 20). These changes were significant (p < 0.01 using paired t test). Raised IEL counts at diagnosis were also found in patients with CMPI and giardiasis but a significant fall on diet only occurred in CMPI patients (p < 0.05). Only patients showing mucosal relapse, i.e., confirmed coeliacs, showed a significant increase in lELs postgluten challenge compared with counts on a gluten‐free diet. Although an increase in lELs showed good correlation with mucosal relapse on challenge, a high count at diagnosis was of insufficient specificity to obviate the need for gluten challenge.
Immunohistochemical Findings in the Intestine of IgA‐Deficient Persons
Authors: Klemola Timo
Published: February 2024

We studied jejunal biopsy specimens of 13 IgA‐deficient persons (IgAdp) and 12 controls. Four Ig‐Adp had celiac disease, in the others the jejunal mucosa appeared normal. Monoclonal antibodies and the peroxidase technique were used to identify T lymphocytes, T‐lymphocyte subsets, HLA‐DR antigens, and IgE‐containing cells in the lamina propria and epithelium. Intraepithelial lymphocytes (IEL); goblet cells; and IgA‐, IgG‐, and IgM‐containing cells were counted in paraffin sections. Both IgAdp with normal jejunal structure and IgAd celiacs on gluten‐free diet (p < 0.001 and p < 0.01 versus controls, respectively) had decreased numbers of IgA‐containing cells, and an increased number of IgM‐containing cells (p < 0.01) was noted in the IgAdp with normal jejunal structure. The IgAdp with normal intestines had increased numbers of intraepithelial lymphocytes (mean 57 cells/mm versus 33 in controls, p < 0.01) and so did the IgAd celiacs after gluten challenge (mean 74, p < 0.001). The HLA‐DR antibody stained the epithelial cells of the IgAd celiacs differently from those of controls and IgAdp with normal intestines: the whole cytoplasm was never stained in the celiacs, but in six of 12 controls (p < 0.05) and during gluten challenge, the crypt cells of the IgAd celiacs showed strong staining, never seen in a normal intestine (p < 0.05 compared with prechallenge specimens). The increase in IEL number in the jejunal mucosa of IgAdp probably indicates ineffective antigen exclusion.
Effect of Infusion of Bile Salts into the Mesenteric Artery in Situ on Jejunal Mucosal Transport Function in Dogs
Authors: Berant Moshe , Diamond Eric , Alon Uri , Mordochovitz Daniel
Published: February 2024

We studied the effects of increased circulating levels of bile salts on jejunal mucosal function in dogs. In situ luminal perfusion of a 30‐cm proximal jejunal segment was performed while deoxycholate, cholate, tauro‐deoxycholate, or taurocholate solutions were directly added to the mesenteric arterial supply, reaching the intestinal wall at successive concentrations of 5, 8, 12, and 22 μmol/L. The transport rates of water, sodium, glucose, fructose, glycine, and lysine were measured. The mucosa of the experimental loop was assayed for ATPase activity, and examined by light and electron microscopy. Deoxycholate at 8 μM in the blood supply of the perfused jejunal segment was associated with a significant (p < 0.02) reduction in the absorption rates of water, sodium, glucose, and glycine, and inhibition of mucosal Na+,K+ ‐ATPase. The absorption of fructose and lysine, and brush border enzyme activities, were not affected. Cholate had a similar effect at 12 μM. There were no obvious histological alterations, but electron microscopy showed swelling of mitochondria in the enterocytes. The reduction in mucosal transport, the inhibition of mucosal Na+,K + ‐ATPase, and the mitochondrial swelling were reversed after discontinuation of the bile salt infusion. The taurine conjugates at 22 μM depressed transport of water and sodium only, and did not inhibit Na, K + ‐ATPase. Our study indicates that increased circulating concentrations of unconjugated bile salts, particularly deoxycholate, may impair Na+, K + ‐ATPase‐related jejunal mucosal function.
Unresponsive Enteropathy Associated with Circulating Enterocyte Autoantibodies in a Boy with Common Variable Hypogammaglobulinemia and Type I Diabetes
Authors: Catassi Carlo , Mirakian Rita , Natalini Giuliana , Sbarbati Andrea , Cinti Saverio , Coppa Giovanni V. , Giorgi Pier Luigi
Published: February 2024

A 13‐year‐old boy with common variable hypogammaglobulinemia and type I diabetes developed a severe enteropathy that proved to be unresponsive to any treatment, including total parenteral nutrition. No evidence of known etiologies of malabsorption and/or secretory diarrhea was found in this subject. A high titer of complement‐fixing enterocyte autoantibody was persistently found in the patient's serum. These features suggest that the enteropathy of this primarily immunodeficient subject had an autoimmune origin. A cycle of cyclophosphamide failed to show any amelioration of the diarrhea or a significant decrease in the autoantibody titer.
Trypsin‐Binding Immunoglobulin G and Associated Antigen in Cystic Fibrosis
Authors: Blandin Céline , Laroche Dominique , Lemonnier Françoise , Pasquet Catherine , Travert Georges
Published: February 2024

Trypsin‐binding immunoglobulin G (TBIgG) is found in the sera of a high proportion of patients with cystic fibrosis. We previously reported that TBIgG preferentially binds human cationic trypsin rather than trypsin from other animal species. Binding affinity is enhanced by complex formation with bovine pancreatic trypsin inhibitor, which is known to induce characteristic conformational modifications in the active site region of the trypsin molecule. To identify the human trypsin‐like antigen associated with TBIgG, we have studied the effects of conformational changes of cationic trypsin induced by limited proteolysis based on competitive binding studies. It is shown that the most likely TBIgG‐related self‐antigen is an 11,000‐dalton fragment that is a cleavage product of the complex formed by trypsin and α1‐protease inhibitor. This result emphasizes the occurrence of circulating trypsinogen activation and is interpreted to be a consequence of the protease‐antiprotease imbalance, which has been well documented by previous investigators in cystic fibrosis and also in other lung diseases associated with an inflammatory state.
Gastroesophageal Reflux Associated with Respiratory Abnormalities During Sleep
Authors: Sacré Liliane , Vandenplas Yvan
Published: February 2024

To determine whether gastroesophageal reflux (GER) might be a factor in the pathogenesis of apnea in certain infants, we analyzed the frequency of prolonged central apnea (>15 s) and of numerous irregularly repeated short apneas (5‐15 s) (“respiratory dysfunction”) in infants with an apparent life‐threatening event (ALTE) (group 1, n = 62), in control infants (group 2, n = 387), and in infants with GER pathologic findings (group 3, n = 60). Finally, the incidence of GER was analyzed in 76 infants with a respiratory dysfunction during sleep (group 4). Gastroesophageal reflux was investigated using 24‐h esophageal pH monitoring; respiration during sleep was investigated by polysomnography. The pH monitoring data and results of sleep investigation were analyzed in a double‐blind study. A great number of infants who had an ALTE appeared to suffer from GER (42%, 26 of 62 infants), especially if the ALTE occurred while the infant was awake (52%, 14 of 27 infants). In the control infants, pH monitoring data were abnormal in 8.5%; respiratory dysfunction was observed in 5%. In those with a respiratory dysfunction, GER was detected in 75% (15 of 20 infants). In those with GER, respiratory dysfunction was observed in 45% (15 of 33 infants). In groups 3 and 4, respiratory dysfunction was associated with abnormal pH data in 40‐43%. If, in the infants with a respiratory dysfunction, the GER pathologic symptoms were treated efficiently (normalization of pH data), respiratory dysfunction disappeared in 92%. If GER was resistant to therapy, respiratory dysfunction persisted in 81% (13 of 16 infants). Results failed to show any causal relationship between prolonged apnea and GER. We conclude that GER in infancy is often associated with a typical breathing pattern during sleep characterized by multiple irregularly repeated short apneas. The recognition of this breathing pattern in (control) infants screened for risk of sudden infant death syndrome should result in GER investigations. We recommend studying GER in all infants with an ALTE.
Area Under pH 4
Authors: Vandenplas Y. , Franckx‐Goossens A. , Pipeleers‐Marichal M. , Derde M. P. , Sacré‐Smits L.
Published: February 2024

Twenty‐four‐hour continuous esophageal pH monitoring has become the preferred test to quantify acid gastroesophageal reflux. Agreement has been achieved that acid gastric content reflux into the esophagus constitutes a major cause of reflux esophagitis; we therefore calculated the “area under pH 4” (A) in 560 consecutive pH monitorings in infants 1‐12 months old and related this parameter (A) to the reflux index (RI): RI < 10%: A 185 ± 295 (mean ± 1 SD); RI 10‐19%: A 1,046 ± 1,206; RI 20‐29%: A 1,967 ± 2,038; RI 30‐39%: A 3,307 ± 2,955; RI > 40%: A 7,977 ± 7,227. A higher RI is associated with a greater area under pH 4 (p < 0.001); the high SD obtained in each group, however, illustrates the great variability in surface (or acidity of the reflux episodes) in all groups. Esophagoscopy and biopsy were performed in 112 infants (20%). Specificity in the prediction of (mild) esophagitis was higher for the area under pH 4 (88%) compared with the RI (50%). The sensitivity of both parameters was comparable (96 versus 93%). Our results strongly suggest that in young infants, the acidity of the reflux episodes (the area under pH 4) is a determining factor in the prediction of esophagitis. These data need to be confirmed by more studies before general application of this parameter can be advised.
Effects of Topical Anesthetic Agents on Campylobacter pylori
Authors: Czinn Steven J. , Carr Howard S. , Speck William T.
Published: February 2024

The susceptibility of Campylobacter pylori was determined for the two topical anesthetic agents commonly used prior to gastroscopy. Campylobacter pylori proved to be extremely sensitive to the anti‐infective activity of benzocaine, the active ingredient in most commonly used topical anesthetic agents, with minimum inhibitory concentrations of 0.14 mg/ml. However, lidocaine‐containing agents did not interfere with the growth of this microorganism. Specifically, in patients with histologic evidence of C. pylori, the bacterium was recovered from significantly more patients anesthetized with lidocaine than with benzocaine. Thus, the use of benzocaine‐containing topical anesthetic agents limits recovery of Campylobacter pylori from clinical specimens and might account for the low colonization rates reported in some recent publications (1‐4,8).
Lymphangioendothelioma of the Liver in a Neonate
Authors: Peters M. E. , Gilbert‐Barness E. F. , Rao B. , Odell G. B.
Published: February 2024

The case report describes the clinical features, imaging findings, and pathology of a lymphangioendothelioma that almost entirely replaced the liver parenchyma in a neonate. No other organs were involved.
Metabolic Etiologies of Cyclic or Recurrent Vomiting
Authors: Korson Mark
Published: February 2024

Treatable metabolic diseases are infrequently considered in the differential diagnosis of a child with cyclic or recurrent vomiting. Helpful clues in a complete medical history can heighten a clinician's suspicion about a metabolic etiology, as can the presence of certain symptom complexes or biochemical features. A rational approach to investigation is discussed using routine laboratory tests as a first‐line screen. More definitive testing is indicated when screening results are abnormal or when the patient's history is particularly suggestive. Until test results become available, patients in whom a metabolic etiology cannot be ruled out should be treated as if they have an inborn error, in parallel with other conventional therapies, to avoid complications that are often preventable.
Psychophysiologic Treatment of Cyclic Vomiting
Authors: Magagna Jeanne
Published: February 2024

Cyclic vomiting (CV) presents a crisis not only to the identified patient but also to the entire family, who often feel like helpless victims of the effects of the vomiting cycles. This often creates despair, depression, and anger about the vomiting continuing indefinitely. If the child can be given effective medication and the family can be helped with the emotional burden surrounding the illness, the frequency and severity of CV tends to diminish. This article explores ways of lessening the psychologic and social effects of the cyclical vomiting through a multidisciplinary treatment plan for the family that involves the pediatrician, school, psychotherapist, and family as effective therapeutic agents. The child needs to be helped to express feelings which he or she cannot put into words. The article describes dramatic play involving symbolization of the illness, creation of metaphors in stories and drawings for the dilemmas surrounding CV and family therapy in which unnamed stresses are given consideration. Through this treatment, health and hope are promoted within each family member.
T Cells of the Colonic Mucosa in Patients With Infantile Colitis
Authors: Örmälä Timo , Rintala Risto , Savilahti Erkki
Published: February 2024

Background

Infantile colitis is a heterogeneous group of disorders, including enterocolitis complicating Hirschsprung disease, allergic colitis, inflammatory bowel disease, and Behçet syndrome. There are limited data concerning the immune responses induced by the inflammation of the intestine in young infants.

Methods

Twenty‐four colonic biopsy specimens from 12 infantile colitis patients and 12 age‐matched control patients were studied by immunohistologic methods. The authors compared the T cells, their subsets expressing the surface antigens CD8 and CD4, and T‐cell receptors αβ and δγ, and densities of mononuclear and epithelial cells expressing human leukocyte antigen class II antigens.

Results

The density of CD3+ intraepithelial lymphocytes (IELs) in the large intestinal specimens was significantly higher (P = 0.036) in colitis patients than in the control group. The majority of the CD3+ IELs were CD8+‐expressing cells, and only a minority were CD4+ cells in both groups. T‐cell receptors αβ+ (P = 0.023) and δγ+ (P = 0.027) IELs were observed significantly more frequently in colitis patients than in the control group. In surface epithelium, δ non–disulphide‐linked type T‐cell receptor (δTCS1) IELs were found strikingly more frequently (P = 0.001) in the specimens taken from the colitis patients. Also, the density of the δTCS1+ cells in crypts of the large intestine was significantly higher in colitis patients than in the control patients (P = 0.047).

Conclusions

A significant increase of CD3+ lymphocytes in the colonic epithelium of the patients with infantile colitis was noted. This increase involved both T‐cell receptor αβ‐positive and δγ‐positive IELs. The finding of this study supports the proposal that intraluminal antigens, either microbial or food derived, are important in the pathogenesis of colitis in young infants.
Intravenous Omeprazole in Children: Pharmacokinetics and Effect on 24‐Hour Intragastric pH
Authors: Faure C. , Michaud L. , Shaghaghi E. Khan , Popon M. , Turck D. , Navarro J. , Jacqz‐Aigrain E.
Published: February 2024

Background

Omeprazole is a proton pump inhibitor, acting selectively on the gastric parietal cell H+K+‐adenosine triphosphatase. Data on the intravenous route are limited in children and not available in infants.

Objective

This study was designed to determine the pharmacokinetics and the optimal dosage of intravenous omeprazole in patients younger than 30 months of age.

Methods

Nine children (three girls), aged 4.5 to 27 months, with normal liver and renal functions requiring intravenous omeprazole were studied. After enrollment in the study and randomization, omeprazole was administered once daily, at 8 am, as a 1‐hour infusion. Group 1, consisting of the first four patients, received 20 mg/1.73 m2, and group 2, consisting of the following five patients, received 40 mg/1.73 m2. At day 3, a 24‐hour intragastric pH and a pharmacokinetic study of omeprazole were performed. Plasma concentrations were measured by high‐performance liquid chromatography.

Results

Patients in group 2 had a significantly higher median pH (6.99 vs. 3.35;P = 0.01) and percent of monitored time with gastric pH >4 than children given 20 mg/1.73 m2 (90.6% vs. 44.8%;P < 0.01). Four had a pH more than 4 during more than 90% of the time versus none of the patients of group 1. The plasma concentration versus time curves showed rapid elimination of the drug. The median area under the curve of omeprazole was 0.78 μg · mL−1 · h−1 (range, 0.55–1.64 μg · mL−1 · h−1) and 3.95 μg · mL−1 · h−1 (range, 1.9–4.9 μg · mL−1 · h−1), respectively, in groups 1 and 2 (P < 0.05). Systemic clearance was not different between the two groups: median values were 0.68 and 0.42 L · kg−1 · h−1 (P = 0.22).

Conclusions

In critical situations, intravenous administration of omeprazole may be required in infants. The authors demonstrate that the dose of 20 mg/1.73 m2 is not effective in maintaining 24‐hour gastric pH of more than 4 and that a dose of 40 mg/1.73 m2 is required.
Safety of Lansoprazole in the Treatment of Gastroesophageal Reflux Disease in Children
Authors: Tolia Vasundhara , Fitzgerald Joseph , Hassall Eric , Huang Bidan , Pilmer Betsy , Kane Robert
Published: February 2024

Objectives:

To evaluate the safety of lansoprazole in children between 1 and 11 years of age.

Methods:

In a phase I/II, open‐label, multicenter (11 sites) study, children with symptomatic gastroesophageal reflux disease (GERD), erosive esophagitis (≥grade 2), and/or esophageal pH < 4 for > 4.2% of the 24‐hour period were assigned, on the basis of body weight, to lansoprazole 15 mg (≤30 kg) or 30 mg (>30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Safety for all study participants was monitored by adverse event reports and laboratory evaluations.

Results:

Sixty‐six children were enrolled in the study and were included in the safety analysis. Throughout the treatment period, no child discontinued therapy because of an adverse event and no. clinically significant changes in laboratory values were observed. Three of the 32 children (9%) who received lansoprazole 15 mg once daily (mean exposure 50.3 days) and 6 of the 34 children (18%) who received the 30 mg once‐daily dose (mean exposure 49.4 days) experienced one or more treatment‐related adverse events before any dose increase. The three children in the lansoprazole 15 mg treatment group were treated with doses of 0.6 mg to 1.2 mg/kg/day; those in the lansoprazole 30 mg treatment group were treated with doses of 0.7 mg to 0.9 mg/kg/day. Only one child experienced a new treatment‐related adverse event after an increase in lansoprazole dose to 1.3 mg/kg/day. Treatment‐related events experienced by two or more children were: constipation (lansoprazole 15 mg QD, two children; lansoprazole 30 mg QD, one child), and headache (lansoprazole 30 mg QD, two children). Mean fasting serum gastrin levels were significantly increased from 58.0 pg/mL at baseline to 112.4 pg/mL at week 2 and 121.9 pg/mL at the final visit (P ≤ 0.001 for each comparison). However, the median fasting serum gastrin levels at the week 2 and the final visit were within the normal range (25‐111 pg/mL).

Conclusion:

Lansoprazole, when administered on the basis of body weight in children between 1 and 11 years of age, is safe and well‐tolerated.
Comparison of Longstanding Pediatric‐Onset and Adult‐Onset Crohn's Disease
Authors: Freeman Hugh J.
Published: February 2024

Introduction:

Limited information is available on the characteristics of longstanding Crohn's disease with onset in childhood or adolescence.

Materials and Methods:

In this retrospective study, 224 patients with pediatric‐onset Crohn's disease were compared to a group of patients with disease diagnosed as adults.

Results:

More than 50% of the patients in the pediatric‐onset group were followed for more than a decade, with a mean follow‐up of 12.2 years. There were 96 male (42.9%) and 128 female (57.1%) patients. Most had disease diagnosed in adolescence. The female predominance, similar to adult‐onset disease, was noted only among patients with disease diagnosed in adolescence (13–19 years), not in childhood. Disease most often involved both ileum and colon (128 of 224; 57.1%). Isolated ileal or colonic disease was less common. Upper gastrointestinal tract disease was present in 42 of 224 (18.8%) patients. The incidence of strictures (28.6%) and penetrating complications (46.4%) was similar to that of adults followed for the same period of time.

Conclusion:

In pediatric‐onset Crohn's disease, female‐predominance emerges during adolescence. Pediatric‐onset disease is more extensive than adult‐onset disease. When followed for an extended period of time, it has high rates of disease complexity, with strictures and penetrating complications similar to adult‐onset disease.