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RESUMO O sofrimento psíquico do estudante universitário, particularmente do estudante de Medicina, é conhecido e tem sido motivo de preocupação. O Núcleo de Apoio Psicopedagógico ao Estudante da Faculdade de Medicina (Napem) da Universidade Federal de Minas Gerais tem como função acolher o estudante que demanda ajuda espontaneamente. O objetivo deste trabalho foi analisar os motivos da busca por atendimento descritos pelos próprios estudantes ao preencherem a ficha de inscrição no Napem. Foram catalogadas 273 fichas, que representam o total de inscrições de novos estudantes em dois anos da última década. Para preservar a identidade dos estudantes, os anos analisados não foram identificados. Desse grupo, 235 eram estudantes de Medicina, 28 de Fonoaudiologia, 4 do curso superior de Tecnologia em Radiologia e 6 eram estudantes de outros cursos. A metodologia utilizada para análise dos dados foi qualitativa, com análise de conteúdo, e o teste do qui-quadrado foi empregado para a comparação de frequências. Os motivos descritos pelos estudantes foram alocados em cinco categorias estabelecidas pelos pesquisadores – distúrbios do humor, problemas pessoais, características de personalidade, questões acadêmicas e outros. Os resultados mostraram que os distúrbios do humor foram os mais frequentemente relatados (44,3%), seguidos por características de personalidade (26,4%) e por problemas pessoais (13,9%). As questões acadêmicas foram as que apresentaram menor frequência (5,5%). O desejo de morrer foi descrito por 17 (6,2%) estudantes. Quando os estudantes de Medicina foram comparados aos dos demais cursos, não foi observada diferença estatisticamente significativa entre as categorias (p = 0,21), sendo também observado o predomínio de motivos alocados na categoria distúrbios do humor (41,7%). Entretanto, quando considerados separadamente os dois períodos analisados, a frequência de distúrbios do humor nos alunos do curso de Medicina foi significativamente maior (p = 0,0005) entre os inscritos no segundo ano, comparados aos inscritos no primeiro ano do estudo. Deve ser ressaltado, ainda, que quase 50% do total de estudantes que se inscreveu no segundo ano analisado neste estudo cursavam os períodos iniciais, resultado significativamente maior (p = 0,002) quando comparado ao dos inscritos no primeiro ano do estudo. Embora reconhecendo as limitações referentes à análise da demanda preliminar de atendimento formulada pelo aluno ao procurar ajuda, particularmente quando expressa de forma escrita, acredita-se que os resultados deste estudo possam contribuir para a organização dos serviços de apoio psíquico e servir de alerta para essa questão. Pela magnitude do problema, fica evidente a necessidade da existência de espaços de acolhimento para os estudantes e de atuação precoce no início do curso, com atividades que possam recebê-los e escutá-los quando do ingresso na faculdade, como, por exemplo, os programas de tutoria. ABSTRACT The psychological distress experienced by university students, particularly medical students, is well-known and has long been a cause for concern. In the School of Medicine of the Universidade Federal de Minas Gerais, the School of Medicine Psychopedagogical Student Support Center (Núcleo de Apoio Psicopedagógico ao Estudante da Faculdade de Medicina - NAPEM) provides care to students who spontaneously seek help. The purpose of this study was to analyze the reasons described when completing the Napem application form by students for their seeking the assistance. A total of 273 students enrolled in the two years studied, which were both in the last decade. To preserve the identity of the students, the years analyzed were not identified. Of this group, 235 were medical students, 28 students of Speech Therapy, four undergraduate students of Technology in Radiology and six were students of other courses. The methodology used for data analysis was qualitative, with content analysis and the frequency comparison was performed using the chi-square test. The reasons to seek care written by the students in the application form were placed in five categories established by the researchers – “mood disorders,” “personal problems,” “personality traits,” “academic issues” and others. The results showed that “mood disorders” were the most frequently reported (44.3%), followed by “personality traits” (26.4%) and “personal problems” (13.9%). The “academic questions” presented the lowest frequency (5.5%). The desire to die was described by 17 (6.2%) students. When the medical students were compared to the students of the other courses, there was no statistically significant difference among the frequencies of the five categories (p = 0.21) with motives allocated in the category “mood disorders” (41.7%) being predominantly observed. However, when considering two studied periods separately, the frequency of the category “mood disorders” for medical students was significantly higher (p = 0.0005) in the second year than in the first year of study. It should be emphasized that almost 50% of the students enrolled in the second year analyzed attended the centre for first two years, a significantly higher result (p = 0.002) when compared to those enrolled in the first year of the study. Even recognizing the limitations regarding the analysis of the student’s preliminary demand for care when seeking help, particularly when expressed in written form, it is believed that the results of this study can contribute to the organization of psychological support services. Due to the magnitude of the problem, there is a clear need to have welcome spaces for the students with activities that can receive them and listen to them when they enter college, such as mentoring programs.

RESUMO Vários estudos têm demonstrado que as atitudes centradas no paciente entre os estudantes de Medicina decaem ao longo do curso de graduação. A relação médico-paciente sofre influência profunda da contemporaneidade, e, cada vez mais, comunicar-se na prática clínica torna-se um desafio. O processo de educar em medicina deve encorajar os estudantes a compartilhar o processo de tomada de decisão com seus pacientes. Os estudantes devem compreender não somente o que preocupa seus pacientes, mas também o que os motiva no cuidado em saúde. No processo ensino-aprendizagem, a adoção de medidas eficazes direcionadas ao aprimoramento da escuta e das habilidades de comunicação torna-se a pedra angular na construção da relação médico-paciente de alta qualidade. O objetivo deste estudo foi avaliar o impacto da disciplina “relação médico-paciente” nas atitudes centradas no paciente entre os estudantes de Medicina. Também foi avaliada a influência de variáveis demográficas e do período do curso de Medicina nessas atitudes. Metodologia Foram incluídos 279 estudantes de Medicina que responderam ao questionário Patient-Practitioner Orientation Scale (PPOS): 128 (45,9%) estudantes matriculados na disciplina “Relação médico-paciente” e 151 (54,1%) estudantes voluntários, que não cursaram a disciplina, pareados por sexo e idade aos que frequentaram a disciplina. Os dados foram analisados no software SPSS 17.0 (SPSS Inc., Chicago IL, EUA). Regressão linear múltipla foi realizada para determinar se variáveis demográficas e o período do curso de Medicina estavam independentemente associados aos escores do PPOS (escore total; dimensões sharing e caring). Modelos logísticos foram criados para avaliar associação entre a disciplina “Relação médico-paciente” e os escores das subescalas do PPOS. Resultados Na análise de regressão linear, sexo feminino (p ≤ 0,01), idade mais avançada (p ≤ 0,02) e estar cursando os primeiros anos da faculdade de Medicina (p ≤ 0,02) estavam significativamente associados às atitudes mais centradas no paciente. Maior pontuação na subescala sharing estava independentemente associada à participação na disciplina “Relação médico-paciente” (4,50 ± 0,65 para aqueles que frequentaram vs. 4,33 ± 0,65 para aqueles não matriculados na disciplina, p = 0,03) em modelo logístico ajustado por sexo, idade e período do curso de Medicina. Educadores da área da saúde devem buscar estratégias inovadoras que estimulem atitudes humanísticas, melhorem as habilidades de comunicação e influenciem de forma decisiva as atitudes adotadas pelos estudantes de Medicina, que devem estar focadas no cuidado centrado no paciente/pessoa. ABSTRACT Several studies have demonstrated that medical students’ attitudes toward patient-centred care tend to decline throughout undergraduate education. At present, the adequate translation of the communication skills among medical students into clinical practice remains a challenge. Regardless of the increased efforts of educators to improve the provision of patient care, learning to communicate as a professional physician remains a complex process. Objectives To evaluate the impact of the “doctor-patient relationship” discipline on medical students’ attitudes towards patient-centred care, and to examine whether variables related to demographic characteristics and different stages of education are associated to medical student’s patient-centred attitudes. Methods Two-hundred and seventy nine medical students who responded a Patient-Practitioner Orientation Scale (PPOS), a validated instrument exploring attitudes towards the doctor-patient relationship were enrolled: 128 (45.9%) who attended the “Doctor-Patient Relationship” discipline and 151 (54.1%) volunteer students, matched by sex and age, who have not taken the discipline. Multiple linear regression analyses were used to quantify the independent association between PPOS scores (overall PPOS, ‘sharing’ and ‘caring’ dimensions), demographic variables and year of medical school. Logistic models were created to quantify the independent association between the “doctor-patient relationship” discipline and PPOS and the sub-scales scores. Results In the linear regression analysis, female gender (p ≤ 0.01), older age (p ≤ 0.02) and earliest years of medical school (p ≤ 0.02) were significantly associated with more patient-centred attitudes. Higher score on the ‘sharing’ sub-scale was independently associated with attending the “doctor-patient relationship” discipline (4.50 ± 0.65 for those who have studied the discipline vs. 4.33 ± 0.65 for those who have not studied the discipline, p = 0.03) after adjustment, in logistic models, for student’s age, gender and years on the medical course. Medical educators should be focused on innovative strategies that stimulate humanistic attitudes, improve communication skills and truly change medical students’ behaviour towards patient-centred care.

Summary Helicobacter pylori eradication induces platelet recovery in a subgroup of patients with chronic immune thrombocytopenia (cITP), but the mechanisms involved are still not understood. We aimed to evaluate the effect of H. pylori eradication on platelet response and to identify the associated serum cytokine profile in 95 patients with cITP. Serum cytokine concentrations were determined by enzyme-linked immunosorbent assay prior to and 6 months after H. pylori eradication. Remission of cITP was observed in 17 (288%) of 59 patients in whom the bacterium was eradicated. Six months after treatment, a significant reduction in the concentrations of T-helper (Th) 1 and Th17 cells and an increase in T regulatory (Treg) and Th2-cell commitment cytokines were observed in patients who recovered, but not in those whose platelet count did not recover. Patients who had a platelet response to eradication of the bacteria had higher pre-treatment serum levels of c-interferon (IFNG, IFN-c), transforming growth factor-b (TGFB1, TGF-b) and interleukin 17 (IL17A, IL-17) than patients who did not respond, but only higher pre-treatment TGFB1 levels was independently associated with platelet response. In conclusion, amelioration of cITP after eradication of H. pylori was linked to a more efficient suppression of Th1 and Th17 response and a more pronounced Treg cell response.

To compare children and adults in respect to the effect of H. pylori infection on the gastric concentrations of cytokines linked to innate and Th1 immune response, as well as to investigate the changes in the gastric concentrations of the studied cytokines according to the age. We studied 245 children (142 H. pylori-negative and 103 H. pylori-positive) and 140 adults (40 H. pylori-negative and 100 H. pylori-positive). The gastric concentrations of cytokines representative of the innate and Th1 response were higher in the H. pylori-positive than in the -negative children and adults. The gastric concentrations of IL-1α and TNF-α were significantly higher, while those of IL-2, IL-12p70 and IFN-γ were lower in the infected children than in the infected adults. In the infected children, the gastric concentration of IL-1α, IL-2, IL-12p70 and IFN-γ increased, whereas in adults, the gastric concentrations of IFN-γ and IL-12p70 decreased with the aging. Increased gastric concentration of Th1 associated cytokines correlated with increased degree of gastritis that is the background lesion for the development of the H. pylori associated severe diseases. Concluding, Th1 response to H. pylori infection varies according to the age and seems to have determinant implication in the H. pylori infection outcomes.

Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [ 13 C]urea breath test ([ 13 C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian ( n = 415) and Peruvian ( n = 908) infants. [ 13 C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori -positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated ( r = 0.62; P < 0.001). The positivity of the tests was higher ( P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil ( P = 0.02), whereas in Peru it decreased with increasing age ( P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [ 13 C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.

Th17 cells seem to have an important role in the efficacy of vaccines against Helicobacter pylori. Because children are a target group for human vaccination and Th17/T(reg) cells have intrinsically linked and antagonic commitments, we compared the gastric levels of Th17- and T(reg)-associated cytokines of children and adults. IL-6, IL-10 and TGF-β1 levels and Foxp3(+) cell numbers were higher, but IL-1β, IL-17A and IL-23 were lower in infected children than in infected adults. In conclusion T(reg) instead of Th17 cell response to H. pylori-infection predominates in children.

Background: The detection of the putative disease-specific Helicobacter pylori marker duodenal ulcer promoting gene A (dupA) is currently based on PCR detection of jhp0917 and jhp0918 that form the gene. However, mutations that lead to premature stop codons that split off the dupA leading to truncated products cannot be evaluated by PCR. Methods: We directly sequence the complete dup Ao f 75dupA-positive strains of H. pylori isolated from patients with gastritis (n = 26), duodenal ulcer (n = 29), and gastric carcinoma (n = 20), to search for frame-shifting mutations that lead to stop codon. Results: Thirty-four strains had single nucleotide mutations in dupA that lead to premature stop codon creating smaller products than the predicted 1839 bp product and, for this reason, were considered as dupA-negative. Intact dupA was more frequently observed in strains isolated from duodenal ulcer patients (65.5%) than in patients with gastritis only (46.2%) or with gastric carcinoma (50%). In logistic analysis, the presence of the intact dupA independently associated with duodenal ulcer (OR = 5.06; 95% CI = 1.22– 20.96, p = .02). Conclusion: We propose the primer walking methodology as a simple technique to sequence the gene. When we considered as dupA-positive only those strains that carry dupA gene without premature stop codons, the gene was associated with duodenal ulcer and, therefore, can be used as a marker for this disease in our population.

Background: Helicobacter pylori infection is acquired predominantly in childhood. There is also evidence that children loss the infection. Therefore, factors that account for children remain infected need to be investigated because once established the infection persists throughout the life unless treated. Methods: This study aimed to evaluate the H. pylori infection in children of a low-income community at baseline and 8 years later to determine the predictor factors linked to the maintenance, acquisition, and loss of the infection using regression models of generalized estimating equations. H. pylori status was determined by 13 C-urea breath test. Results: Data from 37.7% (133 ⁄ 353) of the children were available. No difference between the characteristics of the included and nonincluded children was observed. The prevalence of infection increased from 53.4 to 64.7%. Thirty-nine children (29.3%) remained noninfected, 47.4% remained infected, 17.3% became infected, and 6.0% lost the infection. Factors associated with to remain infected compared with to remain noninfected included the age, increased number of children in the household, and the use of well water instead of municipal water. The acquisition of the infection was associated with the male gender. Conclusion: Factors linked to remain and to gain H. pylori infection in a poor region were increased number of children in the household and the male gender. Also, the acquisition rates were higher than the loss rates, which lead to an increase in the infection prevalence with age.

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.

The dupA of Helicobacter pylori has been suggested as a virulence marker associated with the development of duodenal ulcer disease. However, the studies performed in different geographical areas have shown that there are variations in the prevalence of dupA and its association with H. pylori clinical outcomes. Our group did not observe associations between the presence of dupA and H. pylori clinical outcomes in Brazil. On the other hand, we observed 2 mutations in the sequence of dupA that lead to stop codons: a deletion of an adenine at position 1311 and an insertion of an adenine at position 1426 of the gene. Our aim was to evaluate associations of the presence of dupA with duodenal ulcer and gastric cancer, considering dupA-positive only those H. pylori strains that do not have the mutations in the gene sequence. We also evaluated the effect of infection with a strain carrying an intact dupA on the gastric mucosa histology and IL-8 gastric levels. Colonization with strains that had the intact dupA was negatively associated with gastric carcinoma (p=0.001, OR=0.32, 95% CI=0.16-0.66). The presence of dupA was also associated with an increased degree of antral mucosa inflammation (p=0.01) and with decreased corpus atrophy (p0.01) as well as with increased gastric mucosa IL-8 levels (p=0.04). In conclusion, the infection with a H. pylori strain containing the dupA without the stop codon polymorphisms is associated with a lower risk of development of gastric carcinoma in Brazilian subjects.

Background and Aims: To further evaluate intrafamilial transmission of H. pylori infection during childhood, we investigated the prevalence of H. pylori in family members from a poor H. pylori high-prevalence urban community in the Northeast of Brazil. Methods: H. pylori infection was investigated in 570 members of 128 households, by 13C-urea breath test in children and by ELISA in mothers and other adult relatives. Results: The overall prevalence of H. pylori infection (376/570) increased with age (p

Summary Chronic Immune Thrombocytopenia (cITP)isan acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B )31T/C, IL1RN variable number tandem repeats (VNTR), IL2 )330T/G, and TNF )307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg 392stop ) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P =0 AE001) and of the IL2 )330 polymorphic allele G (P =0 AE004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1a and IL-1b were observed in cITP (P

Background: Polymorphisms in genes linked to the innate and adaptive immune response may be involved in inflammatory bowel disease pathogenesis. Our aim was to investigate associations among IL1B-511, IL1B-31, IL1RN, TNFA-307, TLR-2, TLR-4, IL2-330, NOD2 G908R, NOD2 L1007fsinsC polymorphisms and both Crohn's disease (CD) and ulcerative colitis (UC) in a Brazilian population. Methods: We studied 43 patients with CD, 42 with UC, and 541 blood donors. Polymorphisms were evaluated by PCR, PCR-CTPP, or PCR-RFLP. Data were analyzed in multivariate models adjusting for confounding factors. Results:IL1RN VNTR (P = 0.00, odds ratio [OR] = 2.43, 95% confidence interval [CI] = 1.50–3.90), as well as TNFA-307 polymorphic allele (P = 0.05, OR = 1.70, 95% CI = 1.00–2.94) were associated with UC. Both NOD2 mutations (G908R, P = 0.02, OR = 6.83, 95% CI = 1.62–25.45, and L1007fsinsC, P = 0.00, OR = 20.00, 95% CI = 3.21–124.69) were associated with CD. Conclusions: Our analyses showed positive associations between proinflammatory polymorphisms at IL1RN and TNFA-307 loci and UC, as well as polymorphisms in the NOD2 gene and CD. These results highlight the importance of different genetic profiles associated with CD and UC. (Inflamm Bowel Dis 2008)

Duodenal ulcer-promoting gene (dupA) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori-associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA-positive (p=1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p=0.30) and gastric carcinoma (87.65%, p=0.31). Conversely, cagA-positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67-18.50; adults: OR=3.33, 95% CI=2.14-5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51-12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults (p=0.01). In conclusion, dupA is highly frequent and not associated with H. pylori-associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.

The aim was to determine the prevalence and risk factors associated with Helicobacter pylori infection among children up to 6 years. Cross-sectional study carried out in a poor urban community in Fortaleza Northeast Brazil. A standardized questionnaire was applied. Helicobacter pylori status was evaluated by 13/C-urea breath test (13/C-UBT) in children up to 48 months and by ELISA in the mothers. Sera were assayed by the Cobas Core anti-H. pylori IgG EIA. The overall prevalence of H. pylori infection was 40% (88/217) 41% (46/112) boys and 40% (42/105) girls were infected. The prevalence rate of infection by H. pylori increased significantly with age from 29% (27/93) in the youngest group (3 months to 2 years) to 59% (35/59) in the oldest group (6 years) (p

Background: Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. Aim: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. Patients: Sixty-two H pylori -positive elderly patients with cobalamin deficiency were prospectively studied. Methods: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. Results: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) μmol/l at the 6 month follow-up (p H pylori eradication (p Conclusions: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Background Because to date there is no available study on STAT3 polymorphism and gastric cancer in Western populations and taking into account that Helicobacter pylori CagA EPIYA-C segment deregulates SHP-2/ERK-JAK/STAT3 pathways, we evaluated whether the two variables are independently associated with gastric cancer. Methods We included 1048 subjects: H. pylori-positive patients with gastric carcinoma (n = 232) and with gastritis (n = 275) and 541 blood donors. Data were analyzed using logistic regression model. Results The rs744166 polymorphic G allele (p = 0.01; OR = 1.76; 95 % CI = 1.44-2.70), and CagA-positive (OR = 12.80; 95 % CI = 5.58-19.86) status were independently associated with gastric cancer in comparison with blood donors. The rs744166 polymorphism (p = 0.001; OR = 1.64; 95 % CI = 1.16-2.31) and infection with H. pylori CagA-positive strains possessing higher number of EPIYA-C segments (p = 0.001; OR = 2.28; 95 % CI = 1.41-3.68) were independently associated with gastric cancer in comparison with gastritis. The association was stronger when host and bacterium genotypes were combined (p

The aim of this study was to evaluate the role of breastfeeding and the infection status of the mother in the acquisition of Helicobacter pylori infection in a poor urban community in northeastern Brazil. Helicobacter pylori status was evaluated by 13C-urea breath test in individuals under the age of 14 years and by ELISA in the mothers. The prevalence of H. pylori infection was 55.8% (197/353) in the children and it increased with age (P0.0001). Of the children in whom breastfeeding status was known, 93.2% (316/339) were breastfed. The H. pylori prevalence did not differ between breastfed and never breastfed children (55% vs. 52%) even when children were breastfed for6 months. The prevalence of infection was much higher in children whose mothers were H. pylori infected than in children whose mothers were not infected, resulting in a crude odds ratio (OR) of 3.11 (95% CI 1.57-6.19) and 2.40 after adjustment for potential confounders (95% CI 1.12-5.15). This study suggests that breastfeeding does not protect against acquisition of H. pylori in northeastern Brazil; conversely, an infected mother may have an important role in transmission of the disease to the child.

Background: Helicobacter species are associated with inflammatory bowel disease in rodents and in nonhuman primates. Therefore, we prospectively investigated the presence of Helicobacter species in the intestinal mucosa of patients with and without Crohn's disease by culture and polymerase chain reaction (PCR) assays. Materials and Methods: Mucosal fragments were obtained from the ileum, different colon regions, and rectum of 43 patients with Crohn's disease and of 74 patients without inflammatory bowel disease. Results: Helicobacter pylori strains, identified by 16S rRNA gene sequencing, were more frequently isolated and PCR-detected in the intestinal mucosa of patients with ulcerative colitis-like Crohn's disease than in intestinal mucosa of the control group. Otherwise, anti-H. pylori immunoglobulin G levels were significantly lower in fibrostenosing and fistulating Crohn's disease subgroups. No other Helicobacter species were found in the intestinal mucosa of the patients. Conclusions: Although our results suggest an association between the presence of H. pylori in the intestine and ulcerative colitis-like phenotype of Crohn's disease, H. pylori infection in the actual causality of Crohn's disease is still to be determined.

Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-gamma and IL-4, in H. heilmannii gastric infection in genetically IFN-gamma- or IL-4-deficient mice. The serum IFN-gamma and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmannii-negative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-gamma(-/-) C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4(-/-) than in WT BALB/c mice. Serum IFN-gamma levels were significantly higher in IL-4(-/-) than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-gamma levels was seen between H. heilmannii-positive (11.3 +/- 3.07 pg/mL, mean +/- SD) and -negative (11.07 +/- 3.5 pg/mL) WT BALB/c mice, in the group of IL-4(-/-) animals, the serum concentration of IFN-gamma was significantly higher in the infected ones (38.16 +/- 10.5 pg/mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-gamma playing a central role in gastric inflammation.

Introduction Most studies that have evaluated the stomachs of patients with Chagas disease were performed before the discovery of Helicobacter pylori and used no control groups. This study compared the gastric features of chagasic and non-chagasic patients and assessed whether gastritis could be associated with Chagas disease. Methods Gastric biopsy samples were taken from patients who underwent endoscopy for histological analysis according to the Updated Sydney System. H. pylori infection was assessed by histology, 16S ribosomal ribonucleic acid (rRNA) polymerase chain reaction (PCR), serology and the 13C-urea breath test. Patients were considered H. pylori-negative when all of these diagnostic tests were negative. Clinical and socio-demographic data were obtained by reviewing medical records and using a questionnaire. Results The prevalence of H. pylori infection (70.3% versus 71.7%) and chronic gastritis (92.2% versus 85%) was similar in the chagasic and non-chagasic groups, respectively; such as peptic ulcer, atrophy and intestinal metaplasia. Gastritis was associated with H. pylori infection independent of Chagas disease in a log-binomial regression model. However, the chagasic H. pylori-negative patients showed a significantly higher grade of mononuclear (in the corpus) and polymorphonuclear (PMN) (in the antrum) cell infiltration. Additionally, the patients with the digestive form of Chagas disease showed a significantly lower prevalence of corpus atrophy than those with other clinical forms. Conclusions The prevalence of H. pylori infection and of gastric histological and endoscopic features was similar among the chagasic and non-chagasic patients. Additionally, this is the first controlled study to demonstrate that H. pylori is the major cause of gastritis in patients with Chagas disease.

Duodenal ulcers in children are associated with Helicobacter pylori gastric infection with cagA-positive strains, but factors linked to the host are poorly known. The authors evaluated the role of proinflammatory interleukin-1 gene cluster polymorphisms in the pathogenesis of duodenal ulcer. They studied prospectively 437 children 1 to years old, 209 of whom were H. pylori positive and 228 of whom were H. pylori negative. IL1B-511-C/T, -31T/C, and IL1RN Variable number of tandem repeats were genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism, PCR with confronting two-pair primers, and PCR, respectively. cagA status was evaluated by PCR. The role of the proinflammatory cytokine genotypes in the genesis of duodenal ulcer was evaluated before and after stratification of H. pylori status on logistic regression models. In the group of children without duodenal ulcer, no association was observed between H. pylori status and proinflammatory polymorphisms. Furthermore, no association between IL1 cluster genotypes and cagA status was seen in the H. pylori-positive children. However, increasing age, male sex, and IL1RN*2 were independently associated with duodenal ulcer. After stratification, in the H. pylori-positive children, increasing age, male sex, the presence of ILRN*2 allele, and cagA-positive status were independently associated with duodenal ulcer. The risk for the development of duodenal ulcer increased when a combined association of the presence of IL1RN*2 allele and infection by a cagA-positive H. pylori strain was the variable. This study provides evidence supporting independent roles of IL1RN*2 allele and cagA-positive status in the genesis of duodenal ulcer in children.

Helicobacter pylori cagA-positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL-1 gene cluster and tumor necrosis factor-α (TNFA)-307 polymorphisms, as well as cagA-positive status, are associated with gastric carcinoma in a non-Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori-positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme-linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B-511/-31, IL1RN (interleukin-1 receptor antagonist) and TNFA-307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2-pair primers. We found that the IL1RN2 polymorphic allele (OR = 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA-positive status was the strongest independent factor associated with gastric carcinoma (OR = 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA-positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma. © 2005 Wiley-Liss, Inc.

Background & Aims: Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1β activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD). TNFA -308 polymorphisms were also studied. Methods: We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The cag A status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B -511/-31, IL1RN , and TNFA -308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controlling for confounding factors. Results: IL1B -31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and IL1RN ∗2 allele polymorphisms were associated with GERD. After stratification, in the group of H. pylori -positive patients, cag A-positive status, IL1B -31 polymorphic alleles, IL1RN ∗2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the H. pylori -negative group, IL1B -31C/C genotype was inversely associated with GERD even after adjustment for age and sex. Conclusions: This study provides evidence supporting the independent protective role of cag A-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD.

We evaluated the role of the family in the transmission of Helicobacter pylori infection in preschool-aged children from a rural district in the State of Minas Gerais, Brazil. Sixty-six families (66 index children, 63 mothers, 60 fathers and 134 siblings), defined as at least one parent living in the same household with at least one offspring up to 8 years old, were studied. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression controlling for age, gender, number of children in household and H. pylori status of the father, mother and siblings. The prevalence of the infection was 69.7% (469 of 673) and it increased with age (P < 0.001). Positive mothers were a strong and independent risk factor for infection (OR 22.70; 95% CI 2.31-223.21). Positive siblings were also positively associated with infection (OR 1.81; 95% CI 1.01-3.30).

Data concerning the geographic distribution of iceA alleles are scarce, and information on the association of the gene with the disease is rare and still controversial. Furthermore, no such study has been developed in Brazil, where duodenal ulcer and gastric adenocarcinoma are very common. We investigated, by PCR, the frequency of iceA alleles and cagA status in Helicobacter pylori strains isolated from 142 patients (62 children and 80 adults; 66 female; mean age, 30.0 years; age range, 3 to 78 years) with gastritis, duodenal ulcer, or gastric adenocarcinoma. iceA was identified in bacterium samples obtained from all patients. Eleven (7.7%) of them were infected with multiple strains. Among the patients with nonmixed infection, iceA2 allele was detected in 118 (90.1%). iceA2 allele was associated with ulcer ( P = 0.02) and with carcinoma ( P = 0.001). iceA2 amplicons of 229, 334, or 549 bp were detected, but none of them was associated with the patient's disorder. iceA2 strains were more frequent in patients older than 7 years ( P = 0.001). The gene was also more frequent in strains obtained from males ( P = 0.02). cagA was more common in strains obtained from carcinoma ( P = 0.0008) and ulcer patients ( P < 0.006). cagA -positive strains were more frequent in children older than 7 years ( P < 0.003). No association between cagA status and sex was found ( P = 0.28). In conclusion, we think iceA should not be used as a reliable marker for predicting the clinical outcome of H. pylori infection.

The prevalence of Helicobacter pylori infection was assessed in a randomly selected sample of individuals from low-income community in Fortaleza, Northeastern Brazil. Overall, 384 out of 610 participants (62.9%) were H. pylori positive. A 47.5% infection rate was found in subjects aged six months to 10 years old, increased to 73.3% in subjects aged 11-20 years and then continued to increase with age reaching up to 87% in those over 60 years old. After this age group, the prevalence decreased slightly. The prevalence of infection increased significantly with age (p

Helicobacter pylori infection is predominantly acquired early in life. The prevalence of the infection in childhood is low in developed countries, whereas in developing countries most children are infected by 10 y of age. In poor resource settings, where malnutrition, parasitic/enteropathogen and H. pylori infection co-exist in young children, H. pylori might have potentially more diverse clinical outcomes. This paper reviews the impact of childhood H. pylori infection in developing countries that should now be the urgent focus of future research. The extra-gastric manifestations in early H. pylori infection in infants in poor resource settings might be a consequence of the infection associated initial hypochlorhydria. The potential role of H. pylori infection on iron deficiency, growth impairment, diarrheal disease, malabsorption and cognitive function is discussed in this review.

Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1β and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori-positive (n = 47) than in -negative (n = 78) children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1β expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1β can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.

The hypothesis that Helicobactermight be a risk factor for human liver diseases has arisen after the detection of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases. Nevertheless, no explanation that justifies the presence of the bacterium in the human liver has been proposed. We evaluated the presence of Helicobacterin the liver of patients with hepatic diseases of different aetiologies. We prospectively evaluated 147 patients (106 with primary hepatic diseases and 41 with hepatic metastatic tumours) and 20 liver donors as controls. Helicobacter species were investigated in the liver by culture and specific 16S rDNA nested-polymerase chain reaction followed by sequencing. Serum and hepatic levels of representative cytokines of T regulatory cell, T helper (Th)1 and Th17 cell lineages were determined using enzyme linked immunosorbent assay. The data were evaluated using logistic models. Detection of Helicobacter pylori DNA in the liver was independently associated with hepatitis B virus/hepatitis C virus, pancreatic carcinoma and a cytokine pattern characterised by high interleukin (IL)-10, low/absent interferon-γ and decreased IL-17A concentrations (p < 10-3). The bacterial DNA was never detected in the liver of patients with alcoholic cirrhosis and autoimmune hepatitis that are associated with Th1/Th17 polarisation. H. pylori may be observed in the liver of patients with certain hepatic and pancreatic diseases, but this might depend on the patient cytokine profile.

INTRODUCTION: In this study, we evaluated the seroprevalence of Helicobacter pylori infection among chagasic and non-chagasic subjects as well as among the subgroups of chagasic patients with the indeterminate, cardiac, digestive, and cardiodigestive clinical forms. METHODS: The evaluated subjects were from the Triângulo Mineiro region, Minas Gerais, Brazil. Chagasic patients showed positive reactions to the conventional serological tests used and were classified according to the clinical form of their disease. Immunoglobulin G antibodies specific to H. pylori were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The overall H. pylori prevalence was 77.1% (239/310) in chagasic and 69.1% (168/243) in non-chagasic patients. This difference was statistically significant even after adjustment for age and sex (odds ratio = 1.57; 95% confidence interval, 1.02-2.42; p = 0.04) in multivariate analysis. The prevalence of infection increased with age in the non-chagasic group (p = 0.007, χ2 for trend), but not in the chagasic group (p = 0.15, χ2 for trend). H. pylori infection was not associated with digestive or other clinical forms of Chagas disease (p = 0.27). CONCLUSIONS: Our findings demonstrate that chagasic patients have a higher prevalence of H. pylori compared to non-chagasic subjects; a similar prevalence was found among the diverse clinical forms of the disease. The factors contributing to the frequent co-infection with H. pylori and Trypanosoma cruzi as well as its effects on the clinical outcome deserve further study.

Background Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. Results The number of EPIYA C segments was significantly associated with the increased risk of gastric carcinoma (OR = 3.08, 95% CI = 1.74 to 5.45, p < 10-3) even after adjustment for age and gender. Higher number of EPIYA C segments was also associated with gastric atrophy (p = 0.04) and intestinal metaplasia (p = 0.007). Furthermore, patients infected by cag A strains possessing more than one EPIYA C segment showed decreased serum levels of pepsinogen I in comparison with those infected by strains containing one or less EPIYA C repeat. Otherwise, the number of EPIYA C segments did not associate with duodenal ulcer. Conclusions Our results demonstrate that infection with H. pylori strains harbouring more than one CagA EPIYA C motif was clearly associated with gastric cancer, but not with duodenal ulcer. Higher number of EPIYA C segments was also associated with gastric precancerous lesions as demonstrated by histological gastric atrophic and metaplastic changes and decreased serum levels of pepsinogen I.

Helicobacter pylori infection is associated with peptic ulcer and gastric carcinoma. The oral cavity may be a reservoir for H. pylori; however, the results of studies on this subject are controversial. We employed single-step and nested polymerase chain reactions (PCR) to detect the presence of the vacA, ureA and 16S rDNA genes of H. pylori in the stomach, saliva and dental plaque of 30 subjects. The results were confirmed by sequencing. Nested 16S rDNA and ureA amplification was achieved in 80% of gastric, 30% of saliva and 20% of dental plaque specimens. Sequencing of 10, seven and four 16S rDNA products from stomach, saliva and dental plaque, respectively, showed > 99% identity with H. pylori. Sequencing of the other four oral cavity PCR products showed similarity with Campylobacter and Wolinella species. Additionally, the vacA genotype identified in the samples of different sites was the same within a given subject.H. pylori may be found in the oral cavity of patients with gastric infection, thus it could be a source of transmission. However, results obtained with detection methods based only on PCR should be interpreted with caution because other microorganisms that are phylogenetically very close to H. pylori are also present in the mouth.

Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1β were observed in cITP (P10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P10(-3) and P = 0·04 respectively) and blood donors (P10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.

We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B -511C → T, IL1B -31 T → C, IL1RN allele 2, IL2 -330 T → G, TNFA -307 G → A, TLR2 Arg677Trp, TLR2 Arg753Gln, TLR4 Asp299Gly, and TLR5 392STOP polymorphisms were determined in 541 blood donors. IL2 -330 T → G allele carriers had a decreased H. pylori infection risk (OR = 0.63, 95% CI = 0.43–0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-γ and IL-10/TGF-β levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori -positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-γ = 18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10 = 6.99 vs. 14.17 pg/mL, TGF-β = 45.88 vs. 93.44 pg/mL) ( p −3 for all). In conclusion, in the context of H. pylori infection, IL2 -330 T → G polymorphism is functional and is associated with decreased risk of infection in adults.

Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2, and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486 children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160 without duodenal ulcer). cagA status of H. pylori infection was investigated by PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms. Otherwise, the presence of TLR4 polymorphic allele was associated with infection by cagA-positive strains and with increased gastric levels of interleukin-8 and interleukin-10. TLR4 polymorphism might ultimately contribute to more severe consequences of the infection in adulthood since it was associated with susceptibility to cagA-positive H. pylori infection early in life.