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1.
J Crohns Colitis ; 16(2): 216-223, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-34379117

RESUMEN

BACKGROUND: Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. METHODS: Patients aged <17 years, enrolled in a Canadian nationwide inception cohort study, were included. Baseline demographic and IBD phenotypic features were compared between SA and Caucasian children. Longitudinal outcomes through 18 months of follow-up were compared matched by propensity scores. RESULTS: Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2-14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p <0.001]. Additionally, a greater proportion of SA CD patients present with colonic-only disease [colonic-only CD/UC/IBD-U in SAs 67% vs 57% for Caucasians, p = 0.001], and among those with CD, colonic CD in SAs 31% vs 23% in Caucasians, p = 0.20]. Perianal fistulising disease was also numerically more common in SAs (14 [27%] vs 64 [18%], p = 0.06]. Adjusting for differences in phenotypic presentation, anti-tumour necrosis factor [TNF] exposure, and time to initiation was similar, and two-thirds of children, whether anti-TNF exposed or naïve, were in corticosteroid-free clinical remission at 18 months irrespective of ethnicity. CONCLUSIONS: The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adolescente , Canadá/epidemiología , Niño , Estudios de Cohortes , Colitis Ulcerosa/terapia , Enfermedad de Crohn/terapia , Etnicidad , Humanos , Estudios Prospectivos , Inhibidores del Factor de Necrosis Tumoral
2.
J Crohns Colitis ; 14(4): 445-454, 2020 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-31136648

RESUMEN

BACKGROUND AND AIMS: Incidence of paediatric inflammatory bowel disease [IBD] in Canada is among the highest worldwide, and age of onset may be decreasing. In a multicentre nationwide inception cohort study, we examined variation in phenotype of IBD throughout the paediatric age spectrum. METHODS: Children aged ≥2 years [y] and <17y [A1 age at diagnosis], with new onset IBD, were systematically evaluated at sites of the Canadian Children IBD Network. Prospectively recorded phenotypic data were compared between age groups. RESULTS: Among 1092 children (70% Caucasian; 64% Crohn's disease [CD], 36% ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U]; median age 13 y, interquartile range [IQR] 11-15 y), 210 [19%] were diagnosed before the age of age 10 y [Paris A1a] and 43 [4%] before age 6 y (very-early-onset [VEO-IBD]). CD was less common in younger children [42%, 56%, 66%, respectively, of VEO-IBD, A1a; A1b]. Colon-only IBD [UC/IBDU or CD-colon] was present in 81% of VEO-IBD and 65% of A1a; ileal disease increased progressively, reaching plateau at age 10 y. CD location was ileocolonic [L3] in 53% overall. Ileitis [L1] increased with age [6% of VEO-IBD; 13% of A1a; 21% of A1b], as did stricturing/penetrating CD [4% of A1a; 11% of A1b]. At all ages UC was extensive [E3/E4] in >85%, and disease activity moderate to severe according to Physician's Global Assessment [PGA] and weighted Paediatric Crohn's Disease Activity Index/Paediatric Ulcerative Colitis Activity Index [wPCDAI/PUCAI] in >70%. Heights were modestly reduced in CD [mean height z score -0.30 ± 1.23], but normal in UC/IBD-U. CONCLUSIONS: Paris classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Edad de Inicio , Variación Biológica Poblacional , Canadá/epidemiología , Niño , Estudios de Cohortes , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad
3.
Osteoporos Int ; 28(11): 3169-3177, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28791436

RESUMEN

We evaluated the impact of Crohn's disease on muscle and bone strength, mass, density, and geometry in children with newly diagnosed CD and found profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low. INTRODUCTION: Crohn's disease (CD) is an inflammatory condition of the gastrointestinal tract that can affect the musculoskeletal system. The objective of this study was to determine the prevalence of vertebral fractures and the impact of CD on muscle and bone mass, strength, density, and geometry in children with newly diagnosed CD. METHODS: Seventy-three children (26 girls) aged 7.0 to 17.7 years were examined within 35 days following CD diagnosis by lateral spine radiograph for vertebral fractures and by jumping mechanography for muscle strength. Bone and muscle mass, density, and geometry were assessed by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography (pQCT). RESULTS: Disease activity was moderate to severe in 66 (90%) patients. Mean height (Z-score -0.3, standard deviation (SD) 1.1, p = 0.02), weight (Z-score -0.8, SD 1.3, p < 0.01), body mass index (Z-score -1.0, SD 1.3, p < 0.01), lumbar spine areal bone mineral density (BMD; Z-score -1.1, SD 1.0, p < 0.01), total body bone mineral content (Z-score -1.5, SD 1.0, p < 0.01), and total body lean mass (Z-score -2.5, SD 1.1, p < 0.01) were all low for age and gender. pQCT showed reduced trabecular volumetric BMD at the tibial metaphysis, expansion of the bone marrow cavity and thin cortices at the diaphysis, and low calf muscle cross-sectional area. Jumping mechanography demonstrated low muscle power. Only one patient had a vertebral fracture. CONCLUSIONS: Children with newly diagnosed CD have profound muscle and bone deficits; nevertheless, the prevalence of vertebral fractures at this time point was low.


Asunto(s)
Enfermedad de Crohn/complicaciones , Osteoporosis/etiología , Absorciometría de Fotón/métodos , Adolescente , Densidad Ósea/fisiología , Niño , Enfermedad de Crohn/fisiopatología , Estudios Transversales , Femenino , Humanos , Masculino , Fuerza Muscular/fisiología , Osteoporosis/fisiopatología , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/fisiopatología , Radiografía , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/fisiopatología , Tibia/fisiopatología , Tomografía Computarizada por Rayos X/métodos
4.
Aliment Pharmacol Ther ; 31(11): 1186-91, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20222910

RESUMEN

BACKGROUND: Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD). AIMS: To investigate whether reported genes/loci were also associated with CD in Canadian children. DESIGN AND METHODS: A case-control design was implemented at three paediatric gastroenterology clinics in Canada. Children < or =18 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in five genome-wide association studies reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. RESULTS: A total of 406 cases and 415 controls were studied. The mean (+/-s.d.) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.6%), had ileo-colonic disease (L3 +/- L4, 52.0%) and inflammatory behaviour (B1 +/- p, 86.9%) at diagnosis. Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01). Associations with SNP rs4613763 in the PTGER4 locus were marginally nonsignificant (P = 0.07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement. CONCLUSION: The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.


Asunto(s)
Enfermedad de Crohn/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad , Adolescente , Edad de Inicio , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad de Crohn/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Genoma , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo
5.
Osteoporos Int ; 21(2): 331-7, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19504034

RESUMEN

UNLABELLED: Children with inflammatory bowel disease (IBD) manifest low bone mass; the cause remains unclear. We performed transilial bone biopsies in 20 IBD children at diagnosis and found a mild cortical bone deficit and slow bone turnover. It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit. INTRODUCTION: Children with newly diagnosed IBD can have low bone mineral density and disturbed bone metabolism, but the tissue level characteristics of the bone involvement in pediatric IBD have not been elucidated. METHODS: In the present study, we evaluated the skeletal status, including static histomorphometry on transiliac bone samples, in 20 patients (age range 8.4 to 17.7 years, 12 boys) with newly diagnosed IBD and compared results to published normative data. RESULTS: Despite normal height (mean Z-score 0.04, SD 1.2), areal bone mineral density at the lumbar spine was moderately low (mean age- and sex-specific Z-score -0.8, SD 1.1). Total body bone mineral content and lean mass were low for age and sex as well (mean Z-scores -1.2, SD 0.9 and -2.0, SD 0.9, respectively). Biochemical bone markers indicated low bone formation and resorption activity. Bone histomorphometry revealed a slightly low cortical width (mean 23%, SD 25%, below the result expected for age) but a normal amount of trabecular bone. The percentage of trabecular bone surface covered by osteoid or osteoclasts was low, suggesting that both bone formation and bone resorption were suppressed. CONCLUSIONS: Our results indicate that young patients manifest a mild cortical bone deficit at the iliac crest and slow trabecular bone turnover even at diagnosis, in the setting of IBD.


Asunto(s)
Ilion/patología , Enfermedades Inflamatorias del Intestino/complicaciones , Osteoporosis/etiología , Adolescente , Biopsia , Densidad Ósea/fisiología , Remodelación Ósea/fisiología , Niño , Estudios Transversales , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/fisiopatología , Vértebras Lumbares/fisiopatología , Masculino , Osteoporosis/patología , Osteoporosis/fisiopatología , Estudios Prospectivos
6.
Gut ; 58(11): 1490-7, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19651626

RESUMEN

OBJECTIVE: Health administrative databases can be used to track chronic diseases. The aim of this study was to validate a case ascertainment definition of paediatric-onset inflammatory bowel disease (IBD) using administrative data and describe its epidemiology in Ontario, Canada. METHODS: A population-based clinical database of patients with IBD aged <15 years was used to define cases, and patient information was linked to health administrative data to compare the accuracy of various patterns of healthcare use. The most accurate algorithm was validated with chart data of children aged <18 years from 12 medical practices. Administrative data from the period 1991-2008 were used to describe the incidence and prevalence of IBD in Ontario children. Changes in incidence were tested using Poisson regression. RESULTS: Accurate identification of children with IBD required four physician contacts or two hospitalisations (with International Classification of Disease (ICD) codes for IBD) within 3 years if they underwent colonoscopy and seven contacts or three hospitalisations within 3 years in those without colonoscopy (children <12 years old, sensitivity 90.5%, specificity >99.9%; children <15 years old, sensitivity 89.6%, specificity >99.9%; children <18 years old, sensitivity 91.1%, specificity 99.5%). Age- and sex-standardised prevalence per 100 000 population of paediatric IBD has increased from 42.1 (in 1994) to 56.3 (in 2005). Incidence per 100 000 has increased from 9.5 (in 1994) to 11.4 (in 2005). Statistically significant increases in incidence were noted in 0-4 year olds (5.0%/year, p = 0.03) and 5-9 year olds (7.6%/year, p<0.0001), but not in 10-14 or 15-17 year olds. CONCLUSION: Ontario has one of the highest rates of childhood-onset IBD in the world, and there is an accelerated increase in incidence in younger children.


Asunto(s)
Algoritmos , Bases de Datos Factuales/estadística & datos numéricos , Enfermedades Inflamatorias del Intestino/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Ontario/epidemiología , Distribución de Poisson , Prevalencia
7.
Aliment Pharmacol Ther ; 29(9): 1025-31, 2009 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-19210299

RESUMEN

BACKGROUND: A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD). AIMS: To examine whether IL-10-CD associations extended to paediatric-onset CD. METHODS: We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (

Asunto(s)
Enfermedad de Crohn/genética , Haplotipos/genética , Interleucina-10/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Edad de Inicio , Canadá/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad de Crohn/epidemiología , Femenino , Frecuencia de los Genes , Humanos , Masculino , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto Joven
8.
Gut ; 52(6): 827-33, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12740338

RESUMEN

BACKGROUND: Mucins are large complex glycoproteins that protect intestinal mucosal surfaces by limiting access of environmental matter to their epithelial cells. Several mucin genes have been described, including MUC3 that is a membrane associated mucin of the small intestine. Increased MUC3 mRNA transcription is induced by incubation of intestinal epithelial cells with a Lactobacillus strain known to be adherent to them. AIMS: To determine whether increased epithelial cell MUC3 mucin expression in response to Lactobacillus strains results in increased extracellular secretion of MUC3 mucins and the importance of epithelial cell adherence in modulation of MUC3 mucin expression. METHODS: HT29 cells grown to enhance expression of MUC3 mucins were incubated with selected Lactobacillus strains. Spent cell culture medium was collected for detection of secreted MUC3 mucins using dot blot immunoassay with a generated MUC3 antibody. Post-incubation HT29 cell RNA was collected for analysis of MUC3 expression by northern blot analysis using a MUC3 cDNA probe. In vitro binding studies using Lactobacillus strains incubated alone or coincubated with enteropathogenic Escherichia coli strain E2348/69 were used for adherence and inhibition of adherence studies, respectively. RESULTS: Lactobacillus strains with minimal ability to adhere to HT29 cells failed to induce upregulation of mucin gene expression. There was a direct correlation between upregulation of MUC3 mucin mRNA expression and extracellular secretion of MUC3 mucin. The same Lactobacillus strains that increased extracellular secretion of MUC3 mucin led to reduced adherence of enteropathogen E coli E2348/69 during coincubation experiments. CONCLUSION: Probiotic microbes induce MUC3 mucin transcription and translation with extracellular secretion of the MUC3 mucins. Epithelial cell adherence enhances the effects of probiotics on eukaryotic mucin expression.


Asunto(s)
Adhesión Bacteriana/fisiología , Mucosa Intestinal/metabolismo , Lactobacillus/fisiología , Mucinas/biosíntesis , Northern Blotting , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Escherichia coli/patogenicidad , Escherichia coli/fisiología , Técnica del Anticuerpo Fluorescente Indirecta , Células HT29 , Humanos , Sueros Inmunes/inmunología , Mucosa Intestinal/microbiología , Mucina 3 , Mucinas/genética , Mucinas/inmunología , ARN Mensajero/genética , Regulación hacia Arriba
9.
Curr Opin Pediatr ; 10(5): 499-506, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9818248

RESUMEN

Inflammatory bowel diseases remain a significant chronic disease affecting children and adolescents. Although corticosteroids remain the standard form of therapy for many patients, an era of biological agents for therapy in inflammatory bowel diseases is upcoming with human trials using these agents now forthcoming. In addition, studies on maintenance of remission are beginning to address the selection of those patients most likely to benefit from aminosalicylate therapies, the risks of relapse from using cyclooxygenase inhibitors, the lack of benefit from lipoxygenase inhibitors, and possible future methodologies to examine the effectiveness of the immuno-suppressive agent 6-mercaptopurine. Further development of the hypothesis that new-onset disease may be different than longstanding disease can be appreciated with reports of cytokine analysis in new-onset inflammation and the high risk of progression of disease in new-onset ulcerative proctitis in children. With more reports on the role of intestinal epithelial cells in intestinal diseases, it is now clear that this cell layer is not a passive bystander with regard to the interactions between the luminal contents and immune system components found within the lamina propria; new studies suggest that novel therapeutic strategies may be possible. This review summarizes recently reported aspects of Crohn's disease and ulcerative colitis, with an emphasis on issues-pertinent for younger patients.


Asunto(s)
Quimiocinas CXC , Colitis Ulcerosa/terapia , Enfermedad de Crohn/terapia , Antiinflamatorios/uso terapéutico , Budesonida/uso terapéutico , Quimiocina CXCL5 , Quimiotaxis de Leucocito , Niño , Colitis Ulcerosa/fisiopatología , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/fisiopatología , Humanos , Interleucina-10/uso terapéutico , Interleucina-8/análogos & derivados , Estado Nutricional
10.
J Pediatr ; 132(5): 830-5, 1998 May.
Artículo en Inglés | MEDLINE | ID: mdl-9602195

RESUMEN

OBJECTIVE: The objective of this study was to describe the clinical outcome of children with Crohn's disease treated with subcutaneous methotrexate. SUBJECTS/METHODS: Fourteen patients (10 boys) with extensive Crohn's disease diagnosed at a mean age of 10.6 +/- 3.6 years had previously received various medical therapies for 4.3 +/- 4.0 years. Because of the severity of their disease, 6-mercaptopurine had been introduced but discontinued because of the patients' failure to respond (n = 11) or the development of pancreatitis (n = 3). Subsequently, low-dose, weekly, subcutaneous methotrexate was initiated. Pediatric Crohn's Disease Activity Index scores and prednisone requirement were followed as outcome measures. RESULTS: Overall, 9 (64%) of the 14 patients showed improvement, including 6 (55%) of 11 patients who had previously received an adequate trial of 6-mercaptopurine and all three patients who were intolerant of 6-mercaptopurine. Improvement in clinical and laboratory measures occurred by 4 weeks and were similar whether (n = 8) or not (n = 6) the dose of corticosteroids was increased before the start of subcutaneous methotrexate. Three patients were tapered from their initial methotrexate dose after the minimization of corticosteroids and remain well. One patient receiving daily corticosteroids died suddenly after acute onset of illness. Among patients responding, methotrexate was discontinued because of side effects (n = 2) or electively (n = 2). Of the latter two patients, one has resumed methotrexate after disease relapse, whereas the other patient has had a sustained remission. CONCLUSIONS: Low-dose, weekly, subcutaneous methotrexate can induce remission in some pediatric patients with Crohn's disease who fail to adequately respond to other immunomodulator medications.


Asunto(s)
Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Mercaptopurina/uso terapéutico , Metotrexato/uso terapéutico , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Subcutáneas , Masculino , Metotrexato/administración & dosificación , Estudios Prospectivos , Recurrencia , Inducción de Remisión , Factores de Riesgo , Resultado del Tratamiento
11.
J Eukaryot Microbiol ; 45(2): 17S-23S, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9561779

RESUMEN

Mucins secreted from the gastrointestinal epithelium from the basis of the adherent mucus layer which is the host's first line of defense against invasion by Entamoeba histolytica. Galactose and N-acetyl-D-galactosamine residues of mucins specifically inhibit binding of the amebic 170 kDa heavy subunit Gal-lectin to target cells, an absolute prerequisite for pathogenesis. Herein we characterized the secretory mucins isolated from the human colon and from three human colonic adenocarcinoma cell lines: two with goblet cell-like (LS174T and T84) and one with absorptive cell-like morphology (Caco-2). By Northern blot analysis the intestinal mucin genes MUC2 and MUC3 were constitutively expressed by confluent LS174T and Caco-2 cells, whereas T84 cells only transcribed MUC2 and not MUC3 mRNA. 3H-glucosamine and 3H-threonine metabolically labeled proteins separated as high M, mucins in the void (Vo > 10(6) Da) of Sepharose-4B column chromatography and remained in the stacking gel of SDS-PAGE as depicted by fluorography. All mucin preparations contained high amounts of N-acetyl-glucosamine, galactose, N-acetyl-galactosamine, fucose and sialic acid, saccharides typical of the O-linked carbohydrate side chains. Mucin samples from the human colon and from LS174T and Caco-2 cells inhibited E. histolytica adherence to chinese hamster ovary cells, whereas mucins from T84 cells did not. These results suggest that genetic heterogeneity and/or posttranslational modification in glycosylation of colonic mucins can affect specific epithelial barrier function against intestinal pathogens.


Asunto(s)
Adenocarcinoma Mucinoso/química , Moléculas de Adhesión Celular/química , Colon/química , Neoplasias del Colon/química , Entamoeba histolytica/química , Mucinas/química , Adenocarcinoma Mucinoso/fisiopatología , Aminoácidos/análisis , Animales , Northern Blotting , Células CHO , Células CACO-2 , Cromatografía en Agarosa , Cromatografía de Gases , Cricetinae , Electroforesis en Gel de Poliacrilamida , Entamebiasis/parasitología , Fluorometría , Regulación Neoplásica de la Expresión Génica , Interacciones Huésped-Parásitos/fisiología , Humanos , Mucinas/genética , Mucinas/fisiología , ARN Mensajero/biosíntesis , Células Tumorales Cultivadas
12.
Liver Transpl Surg ; 4(2): 166-9, 1998 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9516570

RESUMEN

Children who have undergone liver transplantation may develop chronic diarrhea for a number of reasons. Three children who underwent liver transplantation for liver failure, all of whom had had previous biliary and intestinal surgeries and whose postoperative course was marked by signs and symptoms of intestinal malabsorption including chronic diarrhea, are described. Duodenal aspirates showed a panoply of bacterial species, and duodenal histology featured villus atrophy in two: one associated with luminal gram-positive cocci and another with acute and chronic duodenitis. Oral antibiotics cleared the symptoms. Small bowel bacterial overgrowth may need to be considered in children with chronic diarrhea after liver transplantation, especially when previous intestinal surgery has taken place. Long-term antibiotic therapy may be required to effectively eradicate the offending organisms to suppress symptoms.


Asunto(s)
Diarrea/microbiología , Intestino Delgado/microbiología , Trasplante de Hígado , Administración Oral , Antibacterianos/administración & dosificación , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Preescolar , Duodeno/microbiología , Femenino , Humanos , Lactante , Masculino
13.
Glycoconj J ; 15(12): 1155-63, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10372971

RESUMEN

To determine whether cell growth conditions impacted carbohydrate expression, HT29 cells were gradually transferred from a conventional glucose-containing media to a glucose-free galactose containing media. Indirect immunofluorescence on acetone fixed cells showed increased expression of sialyl Lewis A antigen (CA19-9), sialyl Lewis C (DUPAN2) and Tn/sialyl-Tn on the surface of HT29 cells grown in the glucose-free galactose containing media compared to those grown in the glucose containing media. Sialyltransferases responsible for the synthesis for these sialylated epitopes were Increased in the galactose-fed HT29 cells. Media overlying the cells was subjected to isopycnic ultracentrifugation in cesium chloride and the fractions derived from both glucose and galactose media with equivalent buoyant densities of 1.56 g/L, which are predicted to contain mucin glycoforms, were further separated by HPLC using a Mono-Q anion exchange column. The chromatograph of eluent from the sample derived from the cells growing in the galactose containing media showed an increased peak that reacted with the anti-sialyl Lewis A antibody, CA19-9. These results show that alteration of in vitro culture conditions may cause HT29 colonic carcinoma cells to alter the expression of sialylated carbohydrates.


Asunto(s)
Adenocarcinoma/inmunología , Antígenos de Neoplasias/inmunología , Antígeno CA-19-9/inmunología , Neoplasias del Colon/inmunología , Adenocarcinoma/patología , Antígenos de Neoplasias/aislamiento & purificación , Western Blotting , Antígeno CA-19-9/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Neoplasias del Colon/patología , Técnica del Anticuerpo Fluorescente Indirecta , Galactosa , Glucosa , Células HT29 , Humanos , Sialiltransferasas/metabolismo
14.
Liver Transpl Surg ; 3(6): 591-3, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9404958

RESUMEN

The cause of eosinophilic gastroenteropathy in older children and adults is unknown. In this report, two post-liver transplantation children treated with low-dose cyclosporine A and alternate-day low-dose prednisone are described who were administered a single bolus administration of a lympholytic dose of corticosteroids without taper and who developed intestinal symptomatology several weeks later. Histologic examination of mucosal biopsy specimens from various regions of the gastrointestinal tract showed an intense eosinophilic infiltration of the mucosa and lamina propria. The patients recovered after corticosteroid administration was tapered. Post-transplant gastroenteric eosinophilic inflammation may need to be considered in patients on immunomodulatory medications who have chronic intestinal symptomatology.


Asunto(s)
Eosinofilia/etiología , Gastroenteritis/etiología , Trasplante de Hígado , Complicaciones Posoperatorias , Antiinflamatorios/uso terapéutico , Niño , Colon/patología , Eosinofilia/patología , Femenino , Gastroenteritis/patología , Humanos , Masculino , Metilprednisolona/uso terapéutico
15.
J Pediatr ; 131(5): 741-4, 1997 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9403656

RESUMEN

The purpose of this study was to determine the effectiveness of an amino acid-based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were receiving casein hydrolysate formula (CHF). Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms. Sigmoidoscopy with rectal biopsy was performed in all infants. The infants then received an amino acid-based infant formula, Neocate, for 2 weeks. After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. The histologic features in these infants varied from eosinophilic infiltration to normal. We conclude that not all infants with apparent formula protein-induced colitis respond to CHF and that these infants may have resolution of their symptoms when fed an amino acid-based infant formula.


Asunto(s)
Proteínas en la Dieta/efectos adversos , Alimentos Formulados , Proctocolitis/inducido químicamente , Hidrolisados de Proteína/efectos adversos , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Masculino , Proctocolitis/diagnóstico , Proctocolitis/terapia , Estudios Retrospectivos , Sigmoidoscopía
16.
Am J Sports Med ; 25(4): 527-32, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9240987

RESUMEN

The purpose of this study was to evaluate the results and complications of anterior cruciate ligament surgery in middle-aged patients. Forty-five consecutive patients over 40 years old (average age, 44.6 years) who had arthroscopically assisted anterior cruciate ligament reconstructions with midthird patellar tendon autografts were evaluated. The patients returned for interviews, physical examinations, radiographs, Biodex dynamometer strength testing, and KT-1000 arthrometer testing at an average of 37 months after their surgeries (range, 24 to 96 months). The mean Lysholm and Gillquist score was 91, which corresponds to symptoms only with vigorous activity. The overall scores from the International Knee Documentation Committee form were 29 (64%) normal or nearly normal and 2 (4%) severely abnormal. Side-to-side differences as determined by the KT-1000 arthrometer were < or = 3 mm in 31 of 40 patients (78%), between 3 and 5 mm in 4 patients (10%), and > 5 mm in 5 patients at 30 pounds of anterior displacement. Seventy-six percent of the patients (N = 34) returned to their preoperative activity levels. Three patients required repeat arthroscopic surgery for persistent knee pain and two patients had graft ruptures. This study shows that when middle-aged patients undergo surgery, their results can be successful and satisfying to a degree similar to those of younger patients.


Asunto(s)
Ligamento Cruzado Anterior/cirugía , Adulto , Factores de Edad , Ligamento Cruzado Anterior/diagnóstico por imagen , Ligamento Cruzado Anterior/fisiopatología , Lesiones del Ligamento Cruzado Anterior , Artralgia/etiología , Artralgia/cirugía , Artroscopía/efectos adversos , Traumatismos en Atletas/cirugía , Endoscopía/efectos adversos , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Inestabilidad de la Articulación/cirugía , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Contracción Muscular , Ligamento Rotuliano/trasplante , Examen Físico , Complicaciones Posoperatorias , Radiografía , Rango del Movimiento Articular , Reoperación , Estudios Retrospectivos , Rotura , Trasplante Autólogo , Resultado del Tratamiento
17.
J Pediatr Gastroenterol Nutr ; 25(1): 93-7, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9226535

RESUMEN

BACKGROUND: Recurrence of Crohn's disease after surgery is a common occurrence, pointing to the need for a strategy to prevent recurrent disease. We report the postoperative course of 10 patients who required intestinal resections for complications related to Crohn's disease. METHODS: All patients had a Pediatric Crohn's Disease Activity Index score of 10 or greater. Among these patients, 5 began treatment with 6-mercaptopurine in the perioperative period. All 10 had received various combinations of prednisone and salicylate compounds. Patients who were given 6-mercaptopurine did not discontinue the medication until 2 years after the surgery. RESULTS: To date, none of the five patients who were placed on 6-mercaptopurine have had recurrence of their Crohn's disease (mean disease-free period 32.6 +/- 18.4 months). Among those five patients not receiving 6-mercaptopurine there have been three relapses (mean time to relapse 3.7 +/- 1.2 months). Log-rank sum analyses of Kaplan-Meier survival curves show benefit to patients receiving 6-mercaptopurine in preventing relapses after intestinal resection (p < 0.05). CONCLUSIONS: Although the underlying pathophysiologic reasons leading to the high relapse rate after intestinal surgery in Crohn's disease are unknown, we conclude that treatment with 6-mercaptopurine in the perioperative period may be warranted to help prevent the recurrence of Crohn's disease after surgery.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Enfermedad de Crohn/prevención & control , Mercaptopurina/uso terapéutico , Adolescente , Adulto , Niño , Enfermedad de Crohn/fisiopatología , Enfermedad de Crohn/cirugía , Estudios de Seguimiento , Humanos , Intestinos/cirugía , Periodo Posoperatorio , Recurrencia , Análisis de Supervivencia , Factores de Tiempo
18.
Am J Gastroenterol ; 92(7): 1209-12, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9219802

RESUMEN

This is a retrospective review of five pediatric cases of inflammatory bowel disease with gastroduodenal as well as pancolonic inflammation. The presumptive diagnosis was Crohn's disease in all. Three of five also had microscopic ileitis. Chronic active gastritis was present at diagnosis in all five and duodenitis in four of five. None ever had noncaseating granulomas in any location. Prolonged (mean, 22 months) and ineffective trials of multiple medical therapies were carried out before subtotal proctocolectomy, which allowed the diagnosis of ulcerative colitis to be made in all children. Surgery remained curative after follow-up of over 1 yr (mean, 16 months). This experience confirms that gastroduodenal inflammation occurs in children with ulcerative colitis. Presence of gastroduodenal inflammation does not ensure the diagnosis of Crohn's unless other characteristic features of Crohn's are present. Accurate discrimination between Crohn's and ulcerative colitis remains important in management of pediatric inflammatory bowel disease to facilitate timely surgical referral. Upper gastrointestinal tract inflammation in ulcerative colitis warrants further study.


Asunto(s)
Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/patología , Enfermedades Intestinales/patología , Gastropatías/patología , Adolescente , Niño , Colectomía , Colitis Ulcerosa/cirugía , Enfermedad de Crohn/patología , Diagnóstico Diferencial , Femenino , Humanos , Inflamación , Enfermedades Intestinales/etiología , Masculino , Gastropatías/etiología
19.
Gastroenterology ; 111(6): 1593-602, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8942739

RESUMEN

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis.


Asunto(s)
Anomalías Múltiples/fisiopatología , Enfermedades Pancreáticas/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Fenotipo , Pronóstico , Síndrome
20.
Liver Transpl Surg ; 2(6): 431-7, 1996 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9346689

RESUMEN

Our objective was to determine the immunologic response to two influenza vaccine doses in 39 children who had undergone liver transplantation. Patients received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Sera were collected 4 weeks after each dose and analyzed by a hemagglutination inhibition assay (HAI) for evidence of antibody response to the antigens A/Taiwan/1/86 (H1N1), A/Beijing/32/92 (H3N2), and B/Panama/45/95. Patients with HAI titers of 1:40 or greater were considered to have protective titers. Twenty-six (67%) patients showed a 1:40 or greater titer response to A/Beijing/32/92 1 month after the first vaccination. Only two additional patients were found to have similar titers after the second dose. A higher proportion of patients with protective titers were on smaller amounts of prednisone for body weight or alternate day low dose (< 10 mg/day) prednisone compared to patients on daily low dose or daily high dose prednisone. Patients with protective titers were significantly older (9.0 +/- 2.8 years) than those without protective titers (4.2 +/- 3.4 years, p = .002) following the first inoculation of the A/Beijing/32/92 vaccine component. Similar results were found for the second vaccination and with the H1N1 antigen. Cyclosporine level, gender, and body mass index were not associated with any outcome measures. We conclude that most liver transplant recipients had a protective antibody titer after a single influenza inoculation, but little further advantage was gained after an additional dose. Vaccination of household contacts of younger patients and those patients on daily prednisone or patient chemoprophylaxis may offer greater benefit in prevention of influenza in liver transplant recipients than multiple vaccine doses with current vaccine preparations.


Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Trasplante de Hígado/inmunología , Adolescente , Factores de Edad , Formación de Anticuerpos/inmunología , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Rechazo de Injerto/tratamiento farmacológico , Pruebas de Hemaglutinación , Humanos , Esquemas de Inmunización , Inmunosupresores/uso terapéutico , Lactante , Masculino , Estadísticas no Paramétricas , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/inmunología
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