Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3.

A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.

[Clinico-endoscopic spectrum of gastritis associated with Helicobacter pylori in pediatrics]. / El espectro clínico-endoscopico de la gastritis asociada a Helicobacter pylori en pediatría.

In order to gain further knowledge about the clinical and endoscopic features of chronic gastritis (CG) associated with Helicobacter pylori (H py) we retrospectively analyzed 81 pediatric cases. All were biopsy-proven. The cases were divided in two groups: Group (1988-1992) included 21 cases. These represented the early stage of clinical recognition of the disease. Group 2(1993-1995) comprised 60 cases and represents the stage in which the disease was mandatory. Mean number of cases/year was 4.2 and 20 for group 1 and 2, respectively. Recurrent abdominal pain (RAP) was the most frequent clinical symptom (74/81; 91%), followed by upper digestive tract hemorrhage (UDTG) (34/81; 41.9%). The combination gastroesophageal reflux (GER) and esophagitis (E) was found in 52/81 (64.2%) of the children. Endoscopically, granularity of the mucosa was more frequently found in cases with RAP (47/74), GER (28/36) and E, while a smooth mucosa predominated in patients with UDTH (23/34). Our findings strongly suggest that symptomatic CG with H py in children expresses peculiar clinical and endoscopic features. Since RAP was present in 91% of the cases it appears adequate to include this disease in the differential diagnosis of it. These clinical manifestations have not been previously linked to CG with H py. Better understanding of the clinical and endoscopic spectrum of CG with H py results in adequate treatments and possibly prevention of gastric (and esophageal) diseases found in adults.

[Antibodies against smooth muscle in the detection and follow-up of the celiac disease patient]. / Anticuerpos antimúsculo liso en la detección y seguimiento del enfermo celiaco.

The presence of smooth muscle antibodies (SMA) as determined by indirect immunofluorescence was investigated in the serum of 40 patients, 36 out of which were children. Group I included patients having celiac disease (diagnosed by three biopsies). 7/7 (Group Ia) showed no SMA on gluten-free diet while antibodies were present after challenge. 4/6 (Group Ib) were positive also after challenge (these had not had previous determination). Group II was composed by patients presumed to have celiac disease for they had only one biopsy showing grade IV villous atrophy. 5 patients were of recent diagnosis (group IIa) and showed SMA. 4/5 (Group IIb) who admitted not to had been able to follow the gluten-free diet were also positive for SMA. 6/6 (Group IIc) patients on strict gluten-free diet and showing good clinical response had no detectable SMA. Group III included relatives of patients having celiac disease. 5/6 with SMA showed pathologic small bowel biopsies; only 1/4 with no SMA had mucosal alterations. It is concluded that the presence of serum SMA can be considered a useful marker in the follow-up of cases of celiac disease already diagnosed and to investigate presumed cases of such disease.

[Focal atrophy with stellate scars in children with chronic gastritis associated to Helicobacter pylori. Is this early atrophic gastritis?]. / Atrofia focal con "cicatrices estrelladas" en niños con gastritis crónica asociada con Helicobacter pylori. Gastritis atrófica inicial?

BACKGROUND: Atrophic gastritis has not been described in children in the setting of Helicobacter Pylori infection. METHODS: Gastric biopsies of six children (7 to 11 years old) with history of HpCG and recent therapeutic eradication of H. Pylori, were reviewed. In the 6 H. Pylori was documented with histology, culture, direct visualization and/or serology before treatment. Cases were compared with five biopsies of age-matched patients showing none of the above-mentioned clinical data. All the biopsies were formalin-fixed, paraffin embedded and stained with hematoxilin-eosin, Masson trichrome and reticulin stain. RESULTS: The biopsies of the six treated patients showed variable-in-size stellate-shaped spots of glandular loss replaced by dense connective tissue with few inflammatory cells. The fibrous tissue showed a central area of scarring and radially oriented spikes extending to adjacent interglandular tissue, more evident with the Masson trichrome stain. Density of inflammatory cells in the lamina propria was variable. H. Pylori organisms were consistently absent. On the reticulin stain the atrophic areas showed coarser and compacted reticulin. Stellate scars were not present in the five controls. CONCLUSIONS: Small foci with fibrous scars may be found in children with long standing HpCG, perhaps as an early sequel of it. We hypothesize that if the chronic gastritis-gastric atrophy process is a continuum, these stellate scars may be representing the very beginning of the multifocal atrophic gastritis usually seen in adult patients.

Assessment of the Sydney System in Helicobacter pylori-associated gastritis in children.

OBJECTIVE: The aim of our study was to establish the usefulness of the Sydney System in grading H. pylori-associated chronic gastritis in biopsies from pediatric patients. STUDY DESIGN: Fifteen children (average age: 10.8 years) with histologically-proven gastritis were studied. Classification and grading of gastritis were performed according to the analogue visual scales described in the updated version of the Sydney System. A chart was specially designed to record the morphological grading in this study. Altogether, we studied 79 gastric biopsies. RESULTS: Neutrophilic infiltrates were absent in 27 biopsies, mild in 35, and moderate in 17. This feature was not marked in any of the biopsies. Mononuclear infiltrates were mild in 38 biopsies, moderate in 36, and marked in 5. Density of H. pylori was mild in 39 biopsies, moderate in 27, and marked in 2. In three post-treatment biopsies belonging to the same patient, no H. pylori was observed. Additional 8 biopsies (7 from the body and 1 from the antrum) showed no H. pylori, although organisms were simultaneously present in other stomach sites. Lymphoid follicles were present in 19/79 biopsies. Intestinal metaplasia was not seen on slides stained with hematoxylin-eosin (HE). However, the Alcian blue-PAS stain revealed isolated positive cells in 8 out of 15 patients. None of the gastric biopsies showed mucosal atrophy. CONCLUSION: The results show that the Sydney System is applicable for pediatric patients in case of H. pylori-associated gastritis. However, the number of biopsies recommended in the Sydney System seems excessive for this age group.

[Toxocariasis with liver involvement]. / Toxocariasis con afectación Hepática.

We are reporting 16 cases of toxocariasis found in a two year period. Mean age was 2 years and 9 months. Sex distribution was 1:1. Thirteen (81%) children presented pica, 8 (50%) had pets at home, 10 (62.5%) presented anemia and long standing fever, and all eosinophilic leukocytosis. Fundoscopy was normal in all. Toxocara antibodies (Through ELISA) were increased in all of them. High resolution ultrasonography revealed hypoechoic areas in the liver in 50% of the cases. Therapeutic response was good, the clinical signs and symptoms disappearing at the end of treatment. The eosinophilic leukocytosis, ELISA serum positivity for toxocara and ultrasound findings persisted approximately for a year. Toxocariasis is a common parasitosis in our setting. It must be regarded as the first diagnosis when confronted with eosinophilic leukocytosis and abnormal liver findings by ultrasound.

Omeprazole-associated changes in the gastric mucosa of children.

AIMS: To describe histological findings in gastric mucosa biopsy specimens of children treated with proton-pump inhibitors (PPIs) for different periods of time. METHODS: Biopsy specimens from 12 children (aged 8 months to 15 years) treated with PPIs and 8 controls were processed for paraffin embedding and stained with H&E as well as inmmunohistochemically for sialyl-Tn antigen. RESULTS: The main changes were related to parietal cells which showed brisk cytoplasmic eosinophilia, apical cytoplasmic protrusions to dilated glands, cytoplasmic and nuclear hypertrophy, dilated intracytoplasmic canaliculi, binucleation and multinucleation. The intracellular canaliculi surface showed strong immunohistochemical reaction for sialyl-Tn antigen, apparently a marker for this structure. Some of the patients were biopsied after a short period of oral or intravenously administered omeprazole; the changes may therefore occur rapidly. CONCLUSIONS: PPIs induce the same changes in the gastric mucosa of children as in adults, but the number of nuclei is increased. These effects have not been reported previously in this age group. It is suggested that the changes result from a combination of effects of PPIs and gastrin release.

Expression of cytokeratins 7 and 20 in Helicobacter pylori-associated chronic gastritis in children.

Helicobacter pylori gastric infection induces structural changes in the gastric epithelium. Among them, variations in the expression of cytokeratins have been reported in adult patients. In the present study, we describe the expression of CK7 and CK20 in gastric samples taken from the antrum in three groups of pediatric patients: (A) Helicobacter pylori-associated chronic gastritis (mean age: 11.4 years); (B) previous H. pylori chronic gastritis patients (mean age: 9.4 years); and (C) controls (mean age: 8.8 years). In all, the presence of sulfomucins was assessed with Alcian blue-periodic acid-Schiff pH 1.0. Immunoreactivity was graded as absent (0), weak (1+), moderate (2+), or intense (3+), in accordance with the intensity of the staining, and its distribution as focal or diffuse. CK7 reactivity was 2+ either focal or diffuse in all group A biopsies. The reactivity was more evident in the cells at the neck of the glands, in the areas with more inflammatory infiltrates, decorating long vertical segments of epithelium. In groups B and C, CK7 reactivity was also focal and 1+ at the cells of the necks of the glands. However, group B presented longer vertical segments of positive cells as compared to group C, and shorter than those of group A. The deeper glandular structures were focally 1+ in both groups. CK20 expression was comparable in all three groups, depicting a 2+ diffuse reactivity at the surface epithelium and interposed pits with absence or focal reactivity at the neck and coiled gland areas. Ki-67 immunostaining paralleled that of the CK7. Staining for sulfated mucosubstances was positive in two of five cases of groups A and B, and in none of the cases of group C. We conclude that: (1) the long segments of CK7-positive glandular necks in H. pylori cases most probably indicate intense regenerative activity during active inflammation; (2) eradication of H. pylori does not warrant ad integrum restitution since long segments of Ki-67+, CK7+ cells at the germinative compartment of the glands (as well as cells with sulfomucins) were still recognizable in ex- H. pylori patients; (3) finally, differing from what happens in adults, children somehow manage to maintain fully differentiated CK20+ superficial epithelium while the H. pylori is in action.

Presence of human papillomavirus in extrahepatic biliary atresia.

BACKGROUND: In a previous study the human papillomavirus DNA was detected in seven cases of so-called idiopathic neonatal giant cell hepatitis by using nested polymerase chain reaction. The purpose of the present study was to study the prevalence and possible common causes of human papillomavirus-associated idiopathic neonatal giant cell hepatitis and extrahepatic biliary atresia. METHODS: Formalin-fixed, paraffin-embedded archival tissues obtained in 18 cases of extrahepatic biliary atresia were studied for human papillomavirus DNA by nested polymerase chain reaction. In addition, in situ hybridization was performed on tissue obtained in 6 cases. RESULTS: Tissue in 16 of the 18 cases studied showed amplified human papillomavirus DNA, whereas no human papillomavirus was amplified in any of 30 control samples. Main human papillomaviruses detected were types 6 and 18. Punctate intranuclear positive signals were detected in the hepatocytes after in situ hybridization for human papillomavirus DNA. CONCLUSIONS: The high prevalence of human papillomavirus DNA in liver tissue in cases of extrahepatic biliary atresia suggests a strong correlation between this disorder and idiopathic neonatal giant cell hepatitis. It further suggests that this virus may be one of the causative agents in extrahepatic biliary atresia and may represent part of the spectrum of lesions associated with neonatal human papillomavirus-induced hepatic damage.

[Intestinal parasites in two periurban populations in La Plata, Argentina]. / Enteroparasitosis en dos poblaciones periurbanas de La Plata, Argentina.

The prevalence of intestinal parasites was studied in two urban neighborhoods with different socioeconomic conditions in La Plata, Argentina. Age, sex, and environmental factors were considered. One hundred and one hundred one children up to 14 years old were examined by coproparasitologic analysis. Giardia lamblia was the most frequent species. Overall prevalences (73.0% and 54.4%), frequencies of polyparasitism (45.0% and 14.8%), and prevalences of helminthic infection (48.0% and 12.7%) were highest in the population having significantly inferior sanitary and environmental conditions. A correlation with age was observed. It is necessary to apply management practices for the control of enteroparasitoses, in accordance with the corresponding characteristics of the environmental and sociocultural ecosistem.

Prevalence of intestinal parasitosis within three population groups in La Plata, Argentina.

The prevalence of intestinal parasites was studied as a function of socioeconomic conditions within La Plata, Argentina. Age, sex, and environmental factors were considered. Thus, from each of three areas within the city - the first a 'marginal' zone, the second a lower-income suburb, the third a middle-income urban district - 100,101, and 91 children up to 14 years old, respectively, were examined for intestinal parasites. Giardia lamblia was the most frequent species found. The respective prevalences of intestinal parasites overall (73, 54.4, and 35.1%), of polyparasitism (61.6, 27.2, and 12.5%), and of helminthic infection (32, 10.9, and 0.0%) were the highest within the population group having significantly inferior sanitary and environmental conditions. A positive statistical association between the prevalence of intestinal parasitosis and age was observed in all three of the neighborhoods. We also noted a correspondence between the frequency of such infections and school attendance in the two suburban districts. Management practices in accordance with the specific characteristics of an urban environmental and sociocultural ecosystem are thus important for the control of intestinal-parasite infection within municipal populations.

PIP: The prevalence of intestinal parasites, as a function of socioeconomic conditions, was investigated in 3 urban population groups in La Plata, Argentina. 100 children under 14 years of age from a marginal settlement, 101 children from a lower-income suburb, and 91 children from a middle-income district were enrolled. The overall prevalences of intestinal parasites in these 3 groups were 73%, 54.4%, and 35.1%, respectively. Polyparasitism was present in 61.6%, 27.2%, and 12.5%, respectively, while helminthic infection rates were 32%, 10.9%, and 0.0%. Giardia lamblia was the most frequently identified species. These findings confirmed the hypothesized inverse relationship between intestinal parasitosis and socioeconomic conditions. The marginal zone with the highest rates of parasitic disease was characterized by a lack of running water in the homes, outdoor garbage disposal, primitive latrines, and dirt floors. Parasite prevalence increased with age, and with school attendance rates, in the 2 suburban communities. These findings suggest a need for multidisciplinary sanitation programs and community education to reduce parasite transmission through food, water, and soil, in accordance with the environmental and sociocultural characteristics of each municipal ecosystem.

El espectro clinico-endoscopico de la gastritis asociada a Helicobacter pylori en pediatria / Endoscopic spectrum of gastritis associated with Helicobacter pylori in pediatrics

Con el objeto de analizar el espectro clinico y endoscópico de la enfermedad "gastritis crónica asociada a Helicobacter pylory (H py)" realizamos el estudio retrospectivo de 81 casos pediátricos. En todos la biopsia gástrica fue positiva. La población se dividió en dos periódos: el grupo 1 (1988-1992) incluyó 21 casos y representó la etapa inicial del reconocimiento clínico de la enfermedad. El grupo 2 (1993-1995) incluyó 60 casos representó el periódo en que la enfermedad era buscada en forma activa en la endoscopía. El número promedio de casos que se registraron en el período 1 y 2 correspondió a 4.2 y 20 casos/año, respectivamente. El exámen conjunto de ambos períodos reveló que los signos clínicos más frecuentes fueron el dolor abdominal recurrente (DAR) (74/81; 91 por ciento) y la hemorragia digestiva alta (HDA) (34/81; 41.9 por ciento). La combinación de reflujo gastro-esofágico (RGE) y esofagitis ("E") se presentó en 52/81 (64.2 por ciento) de la población estudiada. El hallazgo de mucosa granular en la endoscopía fue más común en los casos con DAR (47/74), RGE (28/36) y "E"(14/16), mientras que la mucosa lisa predominó en los pacientes con HDA (23/34). Concluímos que la infección gástrica asociada a H py en la población pediátrica estudiada mostró un espectro clínico endoscópico peculiar. EL DAR fue referido como síntoma principal en el 91 por ciento de los casos. Consideramos que este hecho sustenta la inclusión de la gastritis por H py entre las posibles etiologías del DAR. Un hecho notable fue la estrecha asociación de RGE y "E" con la gastritis crónica por H py. Un mejor conocimiento del espectro clínico y endoscópico de la gastritis crónica con H py redundar en tratamiento adecuados y, posiblemente en la prevención de las enfermedades gástricas (y esofágicas) de los pacientes adultos.

Atrofia focal con cicatrices estrelladas en niños con gastritis crónica asociada con Helicobacter pylori. Gastritis atrófica inicial? / Focal atrophy with stellate scars in children with chronic gastritis associated to Helicobacter pylori. Is this early atrophic gastritis?

Background: Atrophic gastritis has not been described in children in the setting of Helicobacter pylori infection. Methods: Gastric biopsies of six children (7 to 11 years old) with history of HpCG and recent therapeutic eradication of H. pylori, were reviewed. In the 6 H. pylori was documented with histology, culture, direct visualization and/or serology before treatment. Cases were compared with five biopsies of age-matched patients showing none of the above-mentioned clinical data. All the biopsies were formalin-fixed, paraffin embedded and stained with hematoxilin-eosin, Masson trichrome and reticulin stain. Results: The biopsies of the six treated patients showed variable-in-size stellate-shaped spots of glandular loss replaced by dense connective tissue with few inflammatory cells. The fibrous tissue showed a central area of scaring and radially oriented spikes extending to adjacent interglandular tissue, more evident with the Masson trichrome stain. Density of inflammatory cells in the lamina propria was variable. H. pylori organisms were consistently absent. On the reticulin stain the atrophic areas showed coarser and compacted reticulin. Stellate scars were not present in the five controls. Conclusions: Small foci with fibrous scars may be found in children with long standing HpCG, perhaps as an early sequel of it. We hypothesize that if the chronic gastritis-gastric atrophy process is a continuum, these stellate scars may be representing the very beginning of the multifocal atrophic gastritis usually seen in adult patients.

Evaluación de la utilidad del sistema Sydney en la gastritis asociada a Helicobacter pylori en niños / Assessment of the Sydney system in Helicobacter pylori associated gastritis in children

Objetivo: Establecer la utilidad de la escaa visual del "Sistema Sydney"actualizado (Ssa) para calificar las biopsias con gastritis crónica en la edad pediátrica. Material y métodos: Se analizaron 79 biopsias gástricas de 15 pacientes con gastritis crónica asociada con H. Pylori. Se obtuvieron biopsias de antro y cuerpo de todos los pacientes, y en 13 series de biopsias de 11 pacientes (dos con dos series), se realizaron cinco biopsias siguiendo la propuesta del Ssa: dos del antro a 2-3 cm proximales al piloro (una de la curvatura menor y otro de la curvatura mayor), dos del cuerpo a 8 cm del cardias (una de la curvatura menor y otro de la curvatura mayor), y una de la incisura angularis. La presencia de sulfomucinas se detectó mediante la coloración de azul Alcian-PAS a pH 1,0, preferentemente en las muestras de la incisura angularis. En cada muestra se calificó la densidad de H. pylori, infiltrados de neutrófilos y células mononucleadas, atrofia y metaplasia intestinal como: normal (ausencia), leve moderada o marcada, y se determinó la presencia o no de folículos linfóides. Resultados: Diez pacientes fueron mujeres y cinco, varones; la edad osciló entre 2 y 16 años (promedio: 10.8 años). Los principales síntomas de presentación fueron dolor abdominal recurrente (10 casos), hemorragia gastrointestinal (4 casos), pirosis (2 casos), vómitos y anemia (uno cada uno). Un paciente tenía hipertensión portal. En los 15 pacientes, se efectuaron en total 79 biopsias. La evaluación de esas muestras siguiendo la escala de analogía visual del Ssa mostró las siguientes calificaciones morfológicas: no hubo infiltrados de neutrófilos en 27 biopsias; fueron leves en 35 y moderados en 17. No se halló ninguna biopsia con marcada cantidad de neutrófilos. Los infiltrados mononucleares fueron leves en 38 biopsias, moderados en 36, y abundantes en 5. La densidad de H. pylori fue considerada leve en 39 biopsias, moderada en 27 y marcada en dos. En tres biopsias postratamiento del mismo paciente (caso 8) no se encontró H. pylori. Otras ocho biopsias (7 del cuerpo y una del antro) revelaron ausencia de H. pylori, aunque los gérmenes estuvieron presentes simultáneamente en otros sitios del estómago...

Virus papiloma humano, hepatitis gigantocelular neonatal y atresia de vias biliares / Human papillomavirus, neonatal giant cell hepatitis and biliary duct atresia

En trabajos previos hemos relatado el reconocimiento de la presencia de ADN del HPV en casos de hepatitis gigantocelular neonatal idiopática (HGNI) y atresia de vías biliares (AVB) en material de archivo usando la técnica de PCR. A fin de investigar una posible transmisión vertical estudiamos la presencia de ADN del HPV en hisopados cervicales de madres así como un tejido hepático fijado en formol e incluído en parafina, de 3 lactantes con HGNI y 4 con AVB mediante la técnica de nested-PCR. En dos casos los extendidos cervicales presentaron coilocitos, compatibles con infección por HPV. Excepto en uno el parto fué por vía vaginal en todos. Todos los lactantes eran del sexo masculino. En todos los casos se demostró amplificación del ADN del HPV, siendo concordante los tipos en los lactantes y sus madres. Aunque este es un grupo pequeño los hallazgos están de acuerdo con nuestros datos previos. La presencia del mismo tipo de HPV en el hígado de los lactantes y en hisopados de sus madres es otro argumento que apoya la posibilidad de una transmisión vertical del virus.