Vera Lucia Sdepanian

CARD15 and IL23R Influences Crohn's Disease Susceptibility But Not Disease Phenotype in a Brazilian Population

Background: Although many genetic variants are identified in association with Crohns disease (CD), CARD15, IL23R, and ATG16L1 association with CD have been firmly confirmed in Caucasians of European ancestry. The prevalence of CD is rapidly rising in Brazil, where European ancestry is firmly admixed with natives and Africans, resulting in a heterogeneous population. We investigated the contribution of CARD15, IL23R, and ATG16L1 with CD risk in a heterogeneous Brazilian population. Methods: Genotyping for CARD15 (R702W, G908R, 3020insC), IL23R (rs1004819, rs7517847, rs11209026, rs10889677, rs1495965), and ATG16L1 (rs2241880) was performed in 187 children and adults with CD and 255 healthy ethnically matched controls. Clinical records were systematically reviewed and detailed phenotypic information was obtained. Results: At least 1 CARD15 risk allele was present in 30% of the CD patients compared with 10% of controls. Variants of CARD15 (3020insC and R702W) and IL23R (rs1004819, rs11209026, and rs1088967) were associated with CD. However, no genotype–phenotype correlations were found among the Brazilian CD population with CARD15 or IL23R variants. No significant association was achieved with ATG16L1. Conclusions: CARD15 and IL23R confer susceptibility to CD in the Brazilian population. However, the presence of these variants did not influence disease phenotype. Further research should be focused on larger sample sizes with population admixture analysis to better understand the risks and genotype–phenotype correlation in populations like Brazil where the prevalence of CD is rapidly rising.

Ingestão de nutrientes e estado nutricional de crianças em dieta isenta de leite de vaca e derivados

OBJETIVO: Avaliar a ingestao alimentar e o estado nutricional de criancas em dieta isenta de leite de vaca e derivados. METODOS: Foram avaliadas 26 criancas, na primeira consulta realizada em ambulatorio de gastroenterologia pediatrica, que vinham recebendo dieta isenta de leite de vaca e derivados (media de idade = 19,1 meses) e 30 criancas com dieta normal, isto e, sem nenhum tipo de restricao alimentar (media de idade = 16,8 meses). Empregou-se o metodo do dia alimentar habitual para a obtencao dos dados sobre consumo alimentar. A ingestao alimentar foi comparada entre os grupos e em relacao as Dietary Reference Intakes (DRIs). O estado nutricional foi avaliado com base nos escores z de peso/idade, estatura/idade e peso/estatura. RESULTADOS: O grupo em dieta isenta de leite de vaca apresentou menor ingestao de energia (p = 0,005), proteinas (p < 0,001), lipidios (p < 0,001), calcio (p < 0,001) e fosforo (p < 0,001) quando comparado ao grupo controle. Houve maior numero de criancas no grupo em dieta isenta de leite de vaca com ingestao de energia, calcio e fosforo inferior as DRIs em comparacao ao grupo controle. As medias dos escores z dos grupos com dieta isenta de leite de vaca e controle, foram, respectivamente: estatura/idade -0,81±1,06 versus +0,42 ±1,25 (p < 0,001), peso/idade -1,03±1,21 versus +0,02 ±0,91 (p < 0,001) e peso/estatura -0,63 ±1,08 versus +0,30 ±1,11 (p = 0,004). CONCLUSOES: Durante a terapeutica de exclusao do leite de vaca e seus derivados, deve ser realizado, periodicamente, monitoramento da ingestao alimentar qualitativa e quantitativamente, a fim de se prevenir provaveis inadequacoes no atendimento as necessidades nutricionais, bem como prejuizo ao crescimento e desenvolvimento dessas criancas.

Doença celíaca: a evolução dos conhecimentos desde sua centenária descrição original até os dias atuais

In the recent past, some celiac disease features have been discussed in literature specially related to genetic susceptibility, pathogenesis, clinical presentation and diagnostic criteria. Immunological abnormalities characteristic of celiac disease, such as circulating antibodies and increased numbers of intra-epithelial lymphocytes containing a high percentage of gamma-delta T cells have been demonstrated. Other pictures of clinical presentation besides the classical one deserve attention namely short stature, iron-resistant anaemia, enamel hypoplasia, constipation, neurological manifestation and osteoporosis, among others. Asymptomatic presentation has been recognized since development of serological markers such as anti-gliadin, anti-reticulin and anti-endomysium antibodies. Up to now, small intestinal biopsy is the only decisive diagnostic approach. A Federal law has recently imposed food manufactures to place labels informing the presence of gluten in industrialized foods in Brazil. Lately there has been an increase in celiac disease patients registered in the Brazilian Celiac Association.

Artificial intelligence techniques applied to the development of a decision-support system for diagnosing celiac disease.

BACKGROUND Celiac disease (CD) is a difficult-to-diagnose condition because of its multiple clinical presentations and symptoms shared with other diseases. Gold-standard diagnostic confirmation of suspected CD is achieved by biopsying the small intestine. OBJECTIVE To develop a clinical decision-support system (CDSS) integrated with an automated classifier to recognize CD cases, by selecting from experimental models developed using intelligence artificial techniques. METHODS A web-based system was designed for constructing a retrospective database that included 178 clinical cases for training. Tests were run on 270 automated classifiers available in Weka 3.6.1 using five artificial intelligence techniques, namely decision trees, Bayesian inference, k-nearest neighbor algorithm, support vector machines and artificial neural networks. The parameters evaluated were accuracy, sensitivity, specificity and area under the ROC curve (AUC). AUC was used as a criterion for selecting the CDSS algorithm. A testing database was constructed including 38 clinical CD cases for CDSS evaluation. The diagnoses suggested by CDSS were compared with those made by physicians during patient consultations. RESULTS The most accurate method during the training phase was the averaged one-dependence estimator (AODE) algorithm (a Bayesian classifier), which showed accuracy 80.0%, sensitivity 0.78, specificity 0.80 and AUC 0.84. This classifier was integrated into the web-based decision-support system. The gold-standard validation of CDSS achieved accuracy of 84.2% and k=0.68 (p<0.0001) with good agreement. The same accuracy was achieved in the comparison between the physicians diagnostic impression and the gold standard k=0. 64 (p<0.0001). There was moderate agreement between the physicians diagnostic impression and CDSS k=0.46 (p=0.0008). CONCLUSIONS The study results suggest that CDSS could be used to help in diagnosing CD, since the algorithm tested achieved excellent accuracy in differentiating possible positive from negative CD diagnoses. This study may contribute towards developing of a computer-assisted environment to support CD diagnosis.

Celiac disease: clinical characteristics and methods used in the diagnosis of patients registered at the Brazilian Celiac Association

OBJETIVO: avaliar as caracteristicas clinicas e os metodos utilizados no diagnostico dos pacientes cadastrados na Associacao dos Celiacos do Brasil - Secao Sao Paulo. METODOS: foi enviado por correio um questionario a respeito das caracteristicas clinicas e dos metodos diagnosticos da doenca celiaca para 584 membros cadastrados. RESULTADOS: foram analisados 289 questionarios respondidos (49,5%) dos 584 enviados. Quanto as caracteristicas clinicas da doenca celiaca no momento do diagnostico, observou-se que na amostra estudada a forma classica foi mais frequente (88,9%) do que a forma nao classica (11,1%). Nos ultimos cinco anos houve aumento da proporcao da forma classica tardia de 44,5% para 64,2% (p=0,004) e da forma nao classica de 5,2% para 16,8% (p=0,005). O tempo de duracao dos sintomas ate o estabelecimento do diagnostico foi superior a 1 ano em 75% dos pacientes com manifestacao clinica nao classica. Biopsia de intestino delgado nao foi realizada no momento do diagnostico em 19% dos pacientes. Observou-se que, nos ultimos 5 anos, maior numero de pacientes (24,4%) nao realizaram biopsia de intestino delgado no momento do diagnostico em relacao aos realizados ha 5 ou mais anos (11,1%) (p=0,007). CONCLUSOES: na amostra estudada, a forma classica continua sendo a manifestacao clinica mais frequente da doenca celiaca. Apesar do predominio da forma classica tardia, observamos aumento da proporcao da forma nao classica. 19% dos pacientes diagnosticados como portadores de doenca celiaca nao realizaram biopsia de intestino delgado no momento do diagnostico, especialmente nos ultimos 5 anos, apesar de a caracterizacao da atrofia vilositaria subtotal ou total da mucosa do intestino delgado ser um criterio imprescindivel para o diagnostico de doenca celiaca.

Gastroesophageal reflux disease: exaggerations, evidence and clinical practice

OBJECTIVE there are many questions and little evidence regarding the diagnosis and treatment of gastroesophageal reflux disease (GERD) in children. The association between GERD and cows milk protein allergy (CMPA), overuse of abdominal ultrasonography for the diagnosis of GERD, and excessive pharmacological treatment, especially proton-pump inhibitors (PPIs) are some aspects that need clarification. This review aimed to establish the current scientific evidence for the diagnosis and treatment of GERD in children. DATA SOURCE a search was conducted in the MEDLINE, PubMed, LILACS, SciELO, and Cochrane Library electronic databases, using the following keywords: gastroesophageal reflux; gastroesophageal reflux disease; proton-pump inhibitors; and prokinetics; in different age groups of the pediatric age range; up to May of 2013. DATA SYNTHESIS abdominal ultrasonography should not be recommended to investigate gastroesophageal reflux (GER). Simultaneous treatment of GERD and CMPA often results in unnecessary use of medication or elimination diet. There is insufficient evidence for the prescription of prokinetics to all patients with GER/GERD. There is little evidence to support acid suppression in the first year of life, to treat nonspecific symptoms suggestive of GERD. Conservative treatment has many benefits and with low cost and no side-effects. CONCLUSIONS there have been few randomized controlled trials that assessed the management of GERD in children and no examination can be considered the gold standard for GERD diagnosis. For these reasons, there are exaggerations in the diagnosis and treatment of this disease, which need to be corrected.Objective there are many questions and little evidence regarding the diagnosis and treatment of gastroesophageal reflux disease (GERD) in children. The association between GERD and cows milk protein allergy (CMPA), overuse of abdominal ultrasonography for the diagnosis of GERD, and excessive pharmacological treatment, especially proton-pump inhibitors (PPIs) are some aspects that need clarification. This review aimed to establish the current scientific evidence for the diagnosis and treatment of GERD in children.

Review articleGastroesophageal reflux disease: exaggerations, evidence and clinical practiceDoença do refluxo gastroesofágico: exageros, evidências e a prática clínica?

OBJECTIVE there are many questions and little evidence regarding the diagnosis and treatment of gastroesophageal reflux disease (GERD) in children. The association between GERD and cows milk protein allergy (CMPA), overuse of abdominal ultrasonography for the diagnosis of GERD, and excessive pharmacological treatment, especially proton-pump inhibitors (PPIs) are some aspects that need clarification. This review aimed to establish the current scientific evidence for the diagnosis and treatment of GERD in children. DATA SOURCE a search was conducted in the MEDLINE, PubMed, LILACS, SciELO, and Cochrane Library electronic databases, using the following keywords: gastroesophageal reflux; gastroesophageal reflux disease; proton-pump inhibitors; and prokinetics; in different age groups of the pediatric age range; up to May of 2013. DATA SYNTHESIS abdominal ultrasonography should not be recommended to investigate gastroesophageal reflux (GER). Simultaneous treatment of GERD and CMPA often results in unnecessary use of medication or elimination diet. There is insufficient evidence for the prescription of prokinetics to all patients with GER/GERD. There is little evidence to support acid suppression in the first year of life, to treat nonspecific symptoms suggestive of GERD. Conservative treatment has many benefits and with low cost and no side-effects. CONCLUSIONS there have been few randomized controlled trials that assessed the management of GERD in children and no examination can be considered the gold standard for GERD diagnosis. For these reasons, there are exaggerations in the diagnosis and treatment of this disease, which need to be corrected.Objective there are many questions and little evidence regarding the diagnosis and treatment of gastroesophageal reflux disease (GERD) in children. The association between GERD and cows milk protein allergy (CMPA), overuse of abdominal ultrasonography for the diagnosis of GERD, and excessive pharmacological treatment, especially proton-pump inhibitors (PPIs) are some aspects that need clarification. This review aimed to establish the current scientific evidence for the diagnosis and treatment of GERD in children.

Effectiveness of infliximab in Brazilian children and adolescents with Crohn disease and ulcerative colitis according to clinical manifestations, activity indices of inflammatory bowel disease, and corticosteroid use.

Objective: The objective of the study was to evaluate the response to infliximab in children and adolescents with Crohn disease and ulcerative colitis up to week 22. Patients and Methods: A total of 21 patients with inflammatory bowel disease (IBD) received 5 mg/kg of infliximab at weeks 0, 2, 6, and 14. The following parameters were evaluated: clinical manifestations; activity indices of IBD, including the Pediatric Crohn Disease Activity Index for Crohn disease, the Lightiger Colitis Activity Index and the Pediatric Ulcerative Colitis Activity Index for ulcerative colitis, and the modified Harvey-Bradshaw Index for Crohn disease and ulcerative colitis; and the reduction or suspension of corticosteroid use. Results: All of the patients had improvements in clinical manifestations after the first infusion of infliximab. At week 22, 18 of 21 (85.7%) patients were categorized as being in remission, 3 of 21 (14.3%) patients were categorized as having clinical improvement, and none of the patients were categorized as having no response. There was a statistically significant difference in all of the IBD activity indices at weeks 2, 6, 14, and 22 compared with time 0. The corticosteroid use was completely discontinued in 6 of 15 patients by week 22. Conclusions: Infliximab is effective in the treatment of Crohn disease and ulcerative colitis in children and adolescents up to week 22.

Twenty-four-hour esophageal pH monitoring in children and adolescents with chronic and/or recurrent rhinosinusitis

Gastroesophageal reflux (GER) disorder was studied in children and adolescents with chronic and/or recurrent rhinosinusitis not associated with bronchial asthma. Ten children with a clinical and radiological diagnosis of chronic and/or recurrent rhinosinusitis, consecutively attended at the Pediatric Otolaryngology Outpatient Clinic, Federal University of São Paulo, were evaluated. Prolonged esophageal pH monitoring was used to investigate GER disorder. The mean age of the ten patients evaluated (eight males) was 7.4 +/- 2.4 years. Two patients presented vomiting as a clinical manifestation and one patient presented retrosternal pain with a burning sensation. Twenty-four-hour esophageal pH monitoring was performed using the Sandhill apparatus. An antimony probe electrode was placed in the lower third of the esophagus, confirmed by fluoroscopy and later by a chest X-ray. The parameters analyzed by esophageal pH monitoring included: total percent time of the presence of acid esophageal pH, i.e., pH below 4 (<4.2%); total number of acid episodes (<50 episodes); number of reflux episodes longer than 5 min (3 or less), and duration of the longest reflux episode (<9.2 min). One patient (1/10, 10%) presented a 24-h esophageal pH profile compatible with GER disorder. This data suggest that an association between chronic rhinosinusitis not associated with bronchial asthma and GER disorder may exist in children and adolescents, especially in those with compatible GER disorder symptoms. In these cases, 24-h esophageal pH monitoring should be performed before indicating surgery, since the present data suggest that 10% of chronic rhinosinusitis surgeries can be eliminated.

Assessment of gliadin in supposedly gluten-free foods prepared and purchased by celiac patients

Background The present study was designed to evaluate the presence of gliadin in homemade foods prepared by patients with celiac disease and/or their relatives, as well as in processed products consumed by such patients in São Paulo, Brazil, by enzyme immunoassay (EIA) and Western blot (WB) analysis. Methods One hundred ninety samples were analyzed: 108 homemade foods prepared in homes of patients with celiac disease, 81 processed products, and 1 positive control of homemade food. All samples were analyzed by EIA based on monoclonal antibodies to heat stable ω-gliadins and related prolamins from wheat, rye, and barley. Samples were also analyzed using the WB technique. Results Only one (0.9%) of 108 homemade foods contained detectable amounts of gliadin, as determined by EIA. Twelve of 81 processed products contained gliadin by EIA, as follows: 5 of 61 without gluten listed in the ingredients, 2 of 11 malt extracts, 1 of 2 wheat starches, 1 of 2 types of beer, and all 3 positive control products. Gliadin content of these products was between 4 and 10 mg of gliadin/100 g of product, except for the wheat starch sample (28 mg of gliadin/100 g) and all 3 samples with gluten (>4000 mg of gliadin/100 g). The positive control of homemade food contained 152 mg of gliadin/100 g. One hundred three of 190 samples were analyzed by WB, and 21 of these were gliadin positive. A comparison of results obtained by EIA and WB showed no statistical differences between the methods. Conclusions The greater part of the foods prepared in homes of patients with celiac disease and most processed products supposed to be gluten-free did not contain gliadin. Therefore, celiac patients adequately prepare gluten-free homemade food and have the expertise to purchase processed gluten-free food in São Paulo, Brazil.