MICA and KIR: Immunogenetic Factors Influencing Left Ventricular Systolic Dysfunction and Digestive Clinical Form of Chronic Chagas Disease.

Tissue damage observed in the clinical forms of chronic symptomatic Chagas disease seems to have a close relationship with the intensity of the inflammatory process. The objective of this study was to investigate whether the MICA (MHC class I-related chain A) and KIR (killer cell immunoglobulin-like receptors) polymorphisms are associated with the cardiac and digestive clinical forms of chronic Chagas disease. Possible influence of these genes polymorphisms on the left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease was also evaluated. This study enrolled 185 patients with positive serology for Trypanosoma cruzi classified according to the clinical form of the disease: cardiac (n=107) and digestive (n=78). Subsequently, patients with the cardiac form of the disease were sub-classified as with LVSD (n=52) and without LVSD (n=55). A control group was formed of 110 healthy individuals. Genotyping was performed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP). Statistical analyzes were carried out using the Chi-square test and odds ratio with 95% confidence interval was also calculated to evaluate the risk association. MICA-129 allele with high affinity for the NKG2D receptor was associated to the LVSD in patients with CCHD. The haplotype MICA*008~HLA-C*06 and the KIR2DS2-/KIR2DL2-/KIR2DL3+/C1+ combination were associated to the digestive clinical form of the disease. Our data showed that the MICA and KIR polymorphisms may exert a role in the LVSD of cardiac patients, and in digestive form of Chagas disease.

Hypovitaminosis D in patients with Crohn's disease / Hipovitaminose D em pacientes portadores da doença de Crohn

Objective: Vitamin D has been widely studied as a mediator of the immune response, becoming evident the prevalence of hypovitaminosis D in patients with Crohn's disease. This work aims at evaluating the serum levels of vitamin D in patients suffering from Crohn's disease in a southeast region of Brazil. Methods: It is a prospective study, with statistical analysis of the values of serum vitamin D measured between April 2014 and April 2015 in patients with Crohn's disease. Individuals with mild anal complaints, without any colorectal involvement, comprised the control group. Results: One hundred and four patients whose average age was 40.6 years were evaluated, being 56 (53.8%) female and 48 (46.2%) male. The average serum vitamin D level was 21.6 ng/mL, with standard deviation 13.85. The control group was comprised by 66 individuals, whose average age was 48.9 years. With 38 (57.6%) female and 28 (42.4%) male. In this group the average serum vitamin D level was 40.9 ng/mL. Statistical significance was demonstrated with p<0.0001. Conclusion: There was high prevalence of hypovitaminosis D in patients with Chron's disease, when compared to the control group. Hypovitaminosis D was not evidenced in patients in the latter group.

Objetivo: A vitamina D tem sido amplamente estudada como mediadora da resposta imune, tornando-se evidente a prevalência de hipovitaminose D em pacientes com doença de Crohn. Este trabalho objetiva avaliar os níveis séricos de vitamina D nos pacientes com portadores de doença de Crohn em uma região do sudeste do Brasil. Métodos: Trata-se de estudo prospectivo, com análise estatística dos valores da vitamina D sérica dosados entre Abril de 2014 e Abril de 2015 em pacientes com doença de Crohn. Indivíduos com queixas anais leves, sem qualquer acometimento colorretal, compuseram o grupo controle. Resultados: Foram avaliados 104 pacientes, cuja média de idade foi de 40,6 anos, sendo 56 (53,8%) mulheres e 48 (46,2%) homens. O nível sérico de vitamina D médio foi 21,6 ng/mL, com desvio-padrão de 13,85. O grupo controle foi composto por 66 indivíduos, cuja média de idade foi 48,9 anos, com 38 (57,6%) mulheres e 28 (42,4%) homens. Neste grupo o nível sérico médio de vitamina D foi 40,9 ng/mL. Foi demonstrada significância estatística com p<0,0001. Conclusão: Houve elevada prevalência de hipovitaminose D em pacientes com doença de Crohn, quando comparados ao grupo controle. Não foi evidenciada hipovitaminose D entre os pacientes deste último grupo.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Terminal ileum of patients who underwent colonoscopy: endoscopic, histologic and clinical aspects.

CONTEXT: For the diagnosis of the diseases which affect the terminal ileum, the colonoscopy allows macroscopic evaluation and the performing of biopsies. Studies with criteria for the endoscopic and histological characterization of this segment are scarce and there are still some doubts about the need of biopsies in patients with normal ileoscopy. OBJECTIVE: Study the terminal ileum of patients who underwent colonoscopy considering: endoscopic and histological correlation; agreement between results of the initial histological evaluation and slides review, and the chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea to show histological alterations. METHODS: In a prospective study, 111 patients who presented smooth mucosa without enanthema in the endoscopic exam of the terminal ileum were selected. Biopsies of the ileal mucosa of such patients were performed, being the slides routinely examined and reviewed afterwards. RESULTS: The correlation between patients with normal ileoscopy and ileum with preserved histological architecture was of 99.1%. The agreement between initial histological evaluation and slides review calculated by the Kappa test was 0.21. In patients with abdominal pain and/or chronic diarrhea, the chance of showing histological alterations was 2.5 times higher than the others. CONCLUSIONS: The correlation between endoscopic and histological findings was high. The agreement between the initial histologic evaluation and slides review was not satisfactory. The chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea, showing histological alterations was higher in relation to the asymptomatic ones or with other symptoms, although the clinical importance of this datum was not evaluated.

Terminal ileum of patients who underwent colonoscopy: endoscopic, histologic and clinical aspects / Íleo terminal de pacientes submetidos a colonoscopia: aspectos endoscópicos, histológicos e clínicos

CONTEXT: For the diagnosis of the diseases which affect the terminal ileum, the colonoscopy allows macroscopic evaluation and the performing of biopsies. Studies with criteria for the endoscopic and histological characterization of this segment are scarce and there are still some doubts about the need of biopsies in patients with normal ileoscopy. OBJECTIVE: Study the terminal ileum of patients who underwent colonoscopy considering: endoscopic and histological correlation; agreement between results of the initial histological evaluation and slides review, and the chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea to show histological alterations. METHODS: In a prospective study, 111 patients who presented smooth mucosa without enanthema in the endoscopic exam of the terminal ileum were selected. Biopsies of the ileal mucosa of such patients were performed, being the slides routinely examined and reviewed afterwards. RESULTS: The correlation between patients with normal ileoscopy and ileum with preserved histological architecture was of 99.1 percent. The agreement between initial histological evaluation and slides review calculated by the Kappa test was 0.21. In patients with abdominal pain and/or chronic diarrhea, the chance of showing histological alterations was 2.5 times higher than the others. CONCLUSIONS: The correlation between endoscopic and histological findings was high. The agreement between the initial histologic evaluation and slides review was not satisfactory. The chance of subjects with normal ileoscopy with abdominal pain and/or chronic diarrhea, showing histological alterations was higher in relation to the asymptomatic ones or with other symptoms, although the clinical importance of this datum was not evaluated.

CONTEXTO: Para o diagnóstico de doenças que afetam o íleo terminal, a colonoscopia permite avaliação macroscópica e realização de biopsias. Estudos com critérios para caracterização endoscópica e histológica desse segmento são escassos e ainda persistem dúvidas quanto à necessidade de biopsias em pacientes com ileoscopia normal. OBJETIVO: Estudar o íleo terminal de pacientes submetidos a colonoscopia, considerando correlação endoscópica e histológica; concordância entre resultados da avaliação histológica inicial e revisão de lâminas e chance de indivíduos com ileoscopia normal, com dor abdominal e ou diarreia crônica apresentarem alterações histológicas. MÉTODOS: Estudo prospectivo, no qual foram selecionados 111 pacientes, que apresentaram ao exame endoscópico do íleo terminal mucosa lisa e sem enantema. Foram realizadas biopsias da mucosa ileal nesses indivíduos, sendo as lâminas examinadas rotineiramente e revisadas posteriormente. RESULTADOS: A correlação entre pacientes com ileoscopia normal e íleo com arquitetura histológica preservada foi de 99,1 por cento. A concordância entre avaliação histológica inicial e revisão de lâminas calculada pelo teste de Kappa, foi 0,21. Nos pacientes com ileoscopia normal, com dor abdominal e ou diarreia crônica, a chance de apresentarem alterações histológicas foi 2,5 vezes maior em relação aos demais. CONCLUSÃO: A correlação entre achados endoscópicos e histológicos foi elevada. A concordância entre avaliação histológica inicial e revisão de lâminas não foi satisfatória. A chance de indivíduos com ileoscopia normal, com dor abdominal e ou diarreia crônica, apresentarem alterações histológicas foi maior, porém a importância clínica desse dado não foi avaliada.

Infliximabe na doença de crohn: experiência clínica de um centro terciário paulista / Infliximab in crohn's disease: clinical experience from a single tertiary center of Sao Paulo State

Introdução: Na Doença de Crohn (DC) ocorre uma reatividade anormal dos linfócitos T da mucosa intestinal e produção excessiva de citocinas pró-inflamatórias, entre as quais o fator de necrose tumoral alfa (TNF-á). O infliximabe é um anticorpo monoclonal anti-TNF-á indicado no tratamento de pacientes com DC fistulizante ou não responsiva ao tratamento convencional. Objetivos: Caracterizar as indicações clínicas do infliximabe na DC em um serviço referencial paulista, avaliandopadrões de resposta e a efetividade do tratamento através do Índice de Atividade da DC (CDAI). Pacientes e Métodos: O estudo foi observacional retrospectivo e analisou dados de 21 pacientes com DC em uso de infliximabe atendidos no Hospital de Base de RioPreto entre janeiro de 2004 e julho de 2008. Resultados: Houve predomínio de pacientes do sexo feminino (67%), com média de idade de 33 anos. As indicações mais freqüentes foram fístulas perianais (48%). Resposta clínica total à droga ocorreu em 43% dospacientes, e resposta parcial em 47%; a diferença da média do CDAI entre os grupos antes e após o tratamento foi de 244,61 pontos (p< 0,0005). Conclusões: O infliximabe induziu melhora clínica em 90% dos pacientes, acompanhada de redução da atividade dadoença na avaliação através de um índice padronizado.

Introduction: In Crohn's Disease (CD) occurs an abnormal reactivity of T lymphocytes of intestinal mucosa and anexceeding production of proinflammatory cytokines, such as the tumor necrosis factor- alpha (TNF-á). Infliximab is a monoclonal antibody against TNF-á, indicated for treatment of patients with fistulizing or refractory CD. Objectives: To characterize theclinical indications of infliximab in CD at a referral center of Sao Paulo State, assessing patterns of response and treatment effectiveness by Crohn's Disease Activity Index (CDAI). Patients and Methods: This was an observational, retrospective study; data of 21 patients with CD receiving infliximab therapy at Hospital de Base de Rio Preto between January 2004 and July 2008 were analyzed. Results: Female patients were predominant (67%) and mean age was 33 years. Perianal fistulas represented the most common indication for infliximab use (48%). Complete clinical response to drug occurred in 43% of patients, and partial response in 47%; the mean difference of CDAI between the groups, before and after infliximab treatment, was 244.61 points (p<0.0005). Conclusions: Infliximab induced clinical improvement in 90% of patients, with concomitant reduction of disease activity as measured by a standardized index.