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Rejane Mattar,1 Sergio Barbosa Marques,1 Anibal Ferreira dos Santos,1 Maria do Socorro Monteiro,1 Kiyoshi Iriya,2 Flair José Carrilho1 1Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, SP, Brazil; 2Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP, Brazil Objective: To verify whether the variable number of tandem repeat (VNTR) polymorphism in the IL-1RN gene that encodes the interleukin (IL)-1 receptor antagonist (IL-1Ra) plays a role in the outcome of gastrointestinal diseases associated with Helicobacter pylori (H. pylori) infection. Methods: Patients with normal endoscopy (n = 71), inflammation of the upper gastrointestinal tract only (n = 196), gastric ulcer (n = 28), duodenal ulcer (n = 76), and gastric cancer (n = 19) were studied. H. pylori infection was diagnosed by the urease test, histological examination, and polymerase chain reaction. The IL-1 receptor antagonist gene (IL-1RN intron 2 VNTR) was analyzed by polymerase chain reaction. Gastritis was scored according to the updated Sydney system of classification. Results: H. pylori infection was an independent risk factor for mild (odds ratio [OR] = 5.53 [95% confidence interval [CI] = 2.63–11.64; P < 0.05]), moderate (OR = 83.93 [95% CI = 29.7–237.18; P < 0.05]) and marked (OR = 47.47 [95% CI = 5.39–418.05; P < 0.05]) gastritis. The carriage of IL-1RN*2/*2 had a significant protective effect of H. pylori infection (OR = 0.31 [95% CI = 0.17–0.57; P < 0.05]). H. pylori infection was identified as an independent risk of inflammation, duodenal ulcer, and gastric ulcer. The carriage of IL-1RN*2/*2 was an independent risk factor for gastric cancer (OR = 5.81 [95% CI = 1.06–31.98; P < 0.05]); nonetheless, the carriage of allele 2 (IL-1RN*2/*2 plus IL-1RN*L/*2) had an independent protective effect on duodenal ulcer (OR = 0.45 [95% CI = 0.22–0.91; P < 0.05]). Conclusions: Allele 2 of the VNTR IL-1RN polymorphism had a protective effect against duodenal ulcer and H. pylori infection; however, it increased the risk of gastric cancer. Keywords: Helicobacter pylori, IL-1RN polymorphism, gastric cancer, peptic ulcer

Objectives: Endoscopic resection is the preferred approach to treat early Barrett's neoplasia, reducing the need for surgical interventions. However, the best choice between endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) remains unclear. The study aimed to compare the efficacy and safety of EMR vs. ESD for early Barrett's neoplasia., Methods: An electronic search was conducted in MEDLINE, Central Cochrane, EMBASE, and LILACS until November 2023. Studies comparing ESD vs. EMR in the treatment of patients with early Barrett's neoplasia were included. This study was performed according to the Preferred Report Items for Systematic Reviews and Meta-Analyses guidelines. The ROBIN-I tool was used to analyze the risk of bias and GRADE to measure the quality of the evidence., Results: A total of 9352 patients from 15 observational studies were included. Patients undergoing ESD had significantly higher rates of en-bloc (odds ratio [OR] 25.96, 95% confidence interval [CI] 13.82, 48.74; I 2  = 52%; P < 0.00001) and R0 (OR 5.10, 95% CI 3.29, 7.91; I 2  = 73%; P < 0.00001) with a higher risk of adverse events, including bleeding, stricture formation, and perforation. In a subgroup analysis of patients who did not receive radiofrequency ablation, ESD had a lower recurrence rate than EMR (OR 0.22, 95% CI 0.05, 0.94; I 2  = 88%; P = 0.04)., Conclusion: Endoscopic submucosal dissection is more effective than EMR in treating early Barrett's neoplasia at the expense of higher adverse events rates., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background/aims: Radiofrequency ablation (RFA) is the first-line therapy for dysplastic Barrett's esophagus (BE). Therefore, cryotherapy has emerged as an alternative treatment option. This study aimed to compare the efficacies of these two techniques based on the rates of complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Adverse events and recurrence have also been reported., Methods: An electronic search was conducted using the Medline (PubMed), Embase, LILACS, and Google Scholar databases until December 2022. Studies were included comparing cryotherapy and RFA for treating dysplastic BE with or without early esophageal neoplasia. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Three retrospective cohort studies involving 627 patients were included. Of these, 399 patients underwent RFA, and 228 were treated with cryotherapy. There was no difference in CE-IM (risk difference [RD], -0.03; 95% confidence interval [CI], -0.25 to 0.19; p=0.78; I2=86%) as well as in CE-D (RD, -0.03; 95% CI, -0.15 to 0.09; p=0.64; I2=70%) between the groups. The absolute number of adverse events was low, and there was no difference in the recurrence rate., Conclusion: Cryotherapy and RFA were equally effective in treating dysplastic BE, with or without early esophageal neoplasia.

Gastric cancer is an aggressive disease with low long-term survival rates. An early diagnosis is essential to offer a better prognosis and curative treatment. Upper gastrointestinal endoscopy is the main tool for the screening and diagnosis of patients with gastric pre-neoplastic conditions and early lesions. Image-enhanced techniques such as conventional chromoendoscopy, virtual chromoendoscopy, magnifying imaging, and artificial intelligence improve the diagnosis and the characterization of early neoplastic lesions. In this review, we provide a summary of the currently available recommendations for the screening, surveillance, and diagnosis of gastric cancer, focusing on novel endoscopy imaging technologies.

Background: Caustic ingestion and development of esophageal strictures are recognized major public health problems in childhood. Different therapeutic methods have been proposed in the management of such strictures., Objective: To evaluate efficacy and risk of endoscopic topical application of mitomycin C in the treatment of caustic esophageal strictures., Methods: We searched MEDLINE, EMBASE, Central Cochrane, and LILACS databases. The outcomes evaluated were dysphagia resolution rate, number of dilations performed in resolved cases, and the number of dilations performed in all patients., Results: Three randomized clinical trials were included for final analysis with a total of 190 patients. Topical mitomycin C application group showed a significant increase in dysphagia resolution rate, corresponding to a 42% higher dysphagia resolution as compared to endoscopic dilation alone, with statistical significance between the two groups (RD: 0.42 - [CI: 0.29-0.56]; P-value <0.00001). The mean number of dilations performed in resolved cases were significantly less in the topical mitomycin C application group, compared to endoscopic dilations alone, with statistical significance between the two groups (MD: 2.84 [CI: 1.98-3.69]; P-value <0.00001). When comparing the number of dilations in all patients, there was no statistical difference between the two groups (MD: 1.46 [CI: -1.53-4.44]; P-value =0.34)., Conclusion: Application of topical mitomycin C with endoscopic dilations in caustic esophageal strictures was more effective in dysphagia resolution than endoscopic therapy alone in the pediatric population. Moreover, topical mitomycin C application also reduced the number of dilation sessions needed to alleviate dysphagia without rising morbidity.

Background: Rectal bleeding is the most important symptom of intestinal neoplasia; thus, tests of occult blood detection in stools are widely used for pre neoplastic lesions and colorectal cancer (CRC) screening., Objective: Evaluate the accuracy of OC-Sensor quantitative test (Eiken Chemical, Tokyo, Japan) at cut-off 10 µg Hb/g feces (50 ng/mL) in a cohort of subjects that had to undergo diagnostic colonoscopy, and if more than one sample collected in consecutive days would improve the diagnostic accuracy of the test., Methods: Patients (mean age 56.3±9.7 years) that underwent colonoscopy prospectively randomly received one (1-sample FIT, FIT 1) or two (2-sample FIT, FIT 2) collection tubes. They collected the stool sample before starting colonoscopy preparation. Samples were analyzed by the OC-Auto Micro 80 (Eiken Chemical, Tokyo, Japan). The performance of FIT 1 and FIT 2 were compared to the colonoscopy findings., Results: Among 289 patients, CRC was diagnosed in 14 (4.8%), advanced adenoma in 37 (12.8%), early adenoma in 71 (24.6%) and no abnormalities in 141 (48.8%). For FIT 1, the sensitivity for CRC was 83.3% (95%CI 36.5-99.1%), for advanced adenoma was 24% (95%CI 10.1-45.5%), with specificity of 86.9% (95%CI 77.3-92.9%). For FIT 2, the sensitivity for CRC was 75% (95%CI 35.6-95.5%), for advanced adenoma was 50% (95%CI 22.3-77.7%), with specificity of 92.9% (95%CI 82.2-97.7%). The positive likelihood ratios were 1.8 (95%CI 0.7-4.4 for FIT 1) and 7.1 (95%CI 2.4-21.4 for FIT 2) for advanced adenoma, and 6.4 (95%CI 3.3-12.3, for FIT 1) and 10.7 (95%CI 3.8-29.8, for FIT 2) for CRC. The negative likelihood ratio were 0.9 (95%CI 0.7-1, for FIT 1) and 0.5 (95%CI 0.3-0.9, for FIT 2) for advanced adenoma, and 0.2 (0.03-1.1, for FIT 1) and 0.3 (0.08-0.9, for FIT 2) for CRC. The differences between FIT 1 and FIT 2 performances were not significant. However, the comparison of the levels of hemoglobin in feces of patients of FIT 1 and FIT 2 showed that the differences between no polyp group and advanced adenoma and CRC were significant., Conclusion: The accuracy of OCR Sensor with 10 µg Hb/g feces cut-off was comparable to other reports and two-sample collection improved the detection rate of advanced adenoma, a pre neoplastic condition to prevent CRC incidence.

Objective: Characterization of partial remission using the insulin dose-adjusted HbA1c (IDAA1c) ≤ 9 definition in a multiethnic Brazilian population of children and adolescents with type 1 diabetes (T1D), in addition with the determination of both Class II HLA genotype and autoantibodies., Methods: We analyzed the prevalence of partial remission in 51 new-onset T1D patients with a median time follow-up of 13 months from diagnosis. For this study, anti-GAD65, anti-IA2 and HLA class II genotyping were considered., Results: Partial remission occurred in 41.2% of T1D patients until 3 months after diagnosis, mainly in those aged 5-15 years. We have demonstrated a significant increase in the haplotypes of class II HLA DRB1*0301-DQB1*0201 in children and adolescents with a partial remission phase of the disease (42.9% vs 21.7% in non-remitters, P = .0291). This haplotype was also associated with the reduction of anti-IA2 antibodies production. Homozygote DRB1*03-DQB1*0201/DRB1*03-DQB1*0201 children had the lowest prevalence of IA-2A antibodies (P = .0402). However, this association does not correlate with the time of the remission phase., Conclusion: Although the number of patients studied was reduced, our data suggested that the association between genetics and decrease in antibody production to certain islet auto-antigen may contribute, at least in part, to the remission phase of T1D., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It has been proposed that the combination of gastrin-17 (G-17), pepsinogens I and II (PGI and PGII), and anti-Helicobacter pylori (H. pylori) antibodies (GastroPanel®, BIOHIT HealthCare, Helsinki, Finland) could serve as biomarkers of atrophic gastritis., Objective: This study aimed to ensure the diagnostic accuracy of GastroPanel® and evaluate the effect of proton pump inhibitors (PPIs) on these biomarkers., Methods: Dyspeptic patients who underwent gastrointestinal endoscopy were enrolled in the present study. Histological findings, which were the gold standard to stratify groups, were as follows: no atrophy (controls); antrum atrophy; corpus atrophy; multifocal atrophy; and neoplasia. G-17, PGI, PGII, and anti-H. pylori immunoglobulin (Ig)G antibodies were assayed using commercially available kits. The ratio of PGI/PGII was calculated., Results: Among 308 patients, 159 (51.6%) were PPI users. The overall prevalence of atrophy was 43.8% (n=135). Ninety-two (29.9%) patients were H. pylori positive according to anti-H. pylori IgG levels. G-17 levels were not low in those with antrum atrophy but were high in those with corpus and multifocal atrophies. PGI levels were significantly lower in those with corpus and multifocal atrophies. The sensitivity of PGI <30 µg/L to detect corpus atrophy was 50% (95% CI 27.8-72.1%), with a specificity of 93.2% (95% CI 84.3-97.5%), a positive likelihood ratio of 7.4 (95% CI 2.9-19.2), and a negative likelihood ratio of 0.5 (95% CI 0.3-0.8). A small number of subjects (n=6) exhibited moderate to intense atrophy (4%), among whom 66.7% exhibited decreased PGI levels. PPI significantly increased the levels of G-17 and PGI, except in those with corpus and multifocal atrophies, in whom PGI levels were not increased by PPIs., Conclusion: GastroPanel® (Gastrin-17, PGI, and PGI/PGII ratio) did not demonstrate high sensitivity for detecting gastric atrophy.

Background and study aims  Endoscopic imaging of Barrett's esophagus (BE) with advanced technologies, such as optical coherence tomography (OCT) and volumetric laser endomicroscopy (VLE), allows targeted biopsies and may reduce the number of random biopsies to detect esophageal neoplasia in the early stages during endoscopic BE surveillance. The aim of this study was to evaluate the accuracy of OCT and VLE in diagnosis of intestinal metaplasia, dysplasia, and high-grade dysplasia (HGD), and intramucosal carcinoma (IMC) in BE. Patients and methods  In this systematic review and meta-analysis, the primary outcome measure was diagnostic accuracy of OCT and VLE, in comparison with the gold standard. In the meta-analysis, we calculated sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) for both methods. We performed analyses by patient and by lesion. Results  We evaluated 14 studies involving a collective total of 721 patients and 1565 lesions. In the analysis by lesion, VLE showed a pooled sensitivity, specificity, LR+, LR-, DOR, and SROC AUC of 85 %, 73 %, 3.2, 0.21, 15.0, and 0.87, respectively, for detection of HGD/IMC. In the analysis by lesion for detection of HGD/EAC, OCT showed a pooled sensitivity, specificity, LR+, LR-, DOR, and summary receiver operating characteristic area under the curve of 89 %, 91 %, 9.6, 0.12, 81.0, and 0.95, respectively. The accuracy of OCT in identifying intestinal metaplasia showed a pooled sensitivity, specificity, LR+, LR-, and DOR of 92 %, 81 %, 5.06, 0.091, and 55.58, respectively. Conclusion  OCT- and VLE-guided targeted biopsies could improve detection of dysplasia and neoplasia. Further studies could determine whether the use of such biopsies might replace the current protocol.

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.

Background: Polypectomy of colorectal polyps is the mainstay of colorectal cancer prevention. Identification of the best polypectomy technique is imperative., Objective: This review aims at comparing efficacy of nine different resection methods for small colorectal polyps (<10 mm)., Methods: We searched and selected only randomized controlled trials. Primary outcome was complete resection rates of small polyps by histological eradication. Secondary outcomes were: adverse events, retrieval tissue failures rates and duration of procedure., Results: Eighteen trials including 3215 patients and 5223 polyps were analysed. Overall, cold polypectomy had a significantly shorter time of procedure than hot polypectomy (RD -5.92, 95%CI -9.90 to -1.94, P<0.05), with no statistical difference on complete histological eradication (RD 0.08, 95%CI -0.03 to 0.19, P>0.05). Regarding cold polypectomy techniques, cold snare was found superior to cold forceps on complete and en-bloc resection rates and less time consuming. When comparing endoscopic mucosal resection (EMR) with hot-snare and cold-snare, the latter showed no-inferiority on histological eradication, adverse events or retrieval tissue failure rates., Conclusion: Cold polypectomy is the best technique for resection of small colorectal polyps. Among cold methods, dedicated cold snare was found superior on histological eradication. Cold snare endoscopic mucosal resection might be considered an option for polyps from 5 to 9 mm.

Objectives: The stool antigen assay for H. pylori infection diagnosis with monoclonal antibodies is a simple and recommended technique by the Maastricht V/Florence consensus report. Recently, Pylori K-Set K-1219 (Coris Bioconcept Sprl, Belgium) and HP-F23 (Symbiosys, Brazil) have been made commercially available in Brazil. Thus, the aim of this study was to evaluate the diagnostic accuracies of these two rapid stool antigen tests by immunochromatographic assays (index tests) for the clinical practice., Design and Methods: A total of 98 patients who underwent upper gastrointestinal endoscopy and 13 C-urea breath test entered the study. H. pylori infection status was defined by the combination of the rapid urease test and the 13 C-urea breath test (reference standard). Two observers who were aware of H. pylori status performed the reading of index tests. Diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value with 95% confidence intervals, positive likelihood ratio, negative likelihood ratio and kappa index measure of agreement) were determined., Results: The index tests where in perfect agreement with the H. pylori status with kappa values of 0.87 for Pylori K-Set K-1219 and 0.92 for HP-F23. The sensitivity of HP-F23 was 97.9% (IC95%: 87.5-100) and specificity was 93.8% (IC95%; 84-97.2).The positive likelihood ratio was 15.8, and the negative likelihood ratio was 0.02. The Pylori K-Set K-1219 had a sensitivity of 87.7% (IC95%: 74.5-94.9) and a specificity of 100% (IC95%: 91.6-100); the positive likelihood ratio was ∞, and the negative likelihood ratio was 0.1. The test line on the cassette device of HP-F23 was stronger than of the Pylori K-Set K-1219., Conclusion: The HP-F23 test performed better in clinical practice. Nonetheless, the 13 C-urea breath test is more reliable technique. Moreover, caution must be paid to the trace or clear pale test line readings that were observed in false positive and false negative results, leading to incorrect management of the patient., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: In the early stage esophageal cancer, changes in the mucosa are subtle and pass unnoticed in endoscopic examinations using white light. To increase sensitivity, chromoscopy with Lugol's solution has been used. Technological advancements have led to the emergence of virtual methods of endoscopic chromoscopy, including narrow band imaging (NBI). NBI enhances the relief of the mucosa and the underlying vascular pattern, providing greater convenience without the risks inherent to the use of vital dye. The purpose of this systematic review and meta-analysis was to evaluate the ability of NBI to diagnose squamous cell carcinoma of the esophagus and to compare it to chromoscopy with Lugol's solution., Methods: This systematic review included all studies comparing the diagnostic accuracy of NBI and Lugol chromoendoscopy performed to identify high-grade dysplasia and/or squamous cell carcinoma in the esophagus. In the meta-analysis, we calculated and demonstrated sensitivity, specificity, and positive and negative likelihood values in forest plots. We also determined summary receiver operating characteristic (sROC) curves and estimates of the areas under the curves for both per-patient and per-lesion analysis., Results: The initial search identified 7079 articles. Of these, 18 studies were included in the systematic review and 12 were used in the meta-analysis, for a total of 1911 patients. In per-patient and per-lesion analysis, the sensitivity, specificity, and positive and negative likelihood values for Lugol chromoendoscopy were 92% and 98, 82 and 37%, 5.42 and 1.4, and 0.13 and 0.39, respectively, and for NBI were 88 and 94%, 88 and 65%, 8.32 and 2.62, and 0.16 and 0.12, respectively. There was a statistically significant difference in only specificity values, in which case NBI was superior to Lugol chromoendoscopy in both analyses. In the per-patient analysis, the area under the sROC curve for Lugol chromoendoscopy was 0.9559. In the case of NBI, this value was 0.9611; in the per-lesion analysis, this number was 0.9685 and 0.9587, respectively., Conclusions: NBI was adequate in evaluating the esophagus in order to diagnose high-grade dysplasia and squamous cell carcinoma. In the differentiation of those disorders from other esophageal mucosa alterations, the NBI was shown to be superior than Lugol.

Objectives: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis., Methods: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers)., Results: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found., Conclusion: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions.

Human leukocyte antigens (HLA) have a pivotal role in immune response and may be involved in antigen recognition of periodontal pathogens. However, the associations of HLA with chronic periodontitis (CP) have not been previously studied in the Brazilian population. In an attempt to clarify the issue of genetic predisposition to CP, we examined the distribution of HLA alleles, genotypes, and haplotypes in patients from Southern Brazil. One hundred and eight CP patients and 151 healthy and unrelated controls with age-, gender-, and ethnicity-matched were HLA investigated by polymerase chain reaction with sequence specific oligonucleotides. To exclude smoking as a predisposing factor, statistical analyses were performed in the total sample and in nonsmoking individuals. The significant results showed a positive association of the A∗ 02/HLA-B∗ 40 haplotype with CP (total samples: 4.2% versus 0%, Pc = 0.03; nonsmokers: 4.3% versus 0%, Pc = 0.23) and a lower frequency of HLA-B∗ 15/HLA-DRB1∗ 11 haplotype in CP compared to controls (total samples: 0.0% versus 4.3%, Pc = 0.04; nonsmokers: 0 versus 5.1%, P = 1.0). In conclusion, the HLA-A∗ 02/B∗ 40 haplotype may contribute to the development of CP, while HLA-B∗ 15/DRB1∗ 11 haplotype might indicate resistance to disease among Brazilians.

Context and Objective: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings., Design and Setting: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp)., Methods: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence., Results: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097)., Conclusion: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.

Context: In spite of Helicobacter pylori infection being the etiological cause of peptic ulcer and its high prevalence in Brazil, the prevalence of peptic ulcer disease has been poorly studied., Objectives: To verify the peptic ulcer disease prevalence in patients of a tertiary care hospital., Methods: Diagnostic findings from 1,478 consecutive endoscopies were correlated with the urease test results for H. pylori infection diagnosis and demographic data in a total of 3,779 endoscopies performed in 2005. The mean age of the patients was 51.14 ± 16.46, being 613 (41.5%) men., Results: Peptic ulcer was diagnosed in 494 (33.4%) patients with a mean age of 54.86 ± 14.53, 205 (52%) were men, being 391 (26.5%) duodenal ulcer and 103 (7%) gastric ulcer. Normal endoscopy was found in 272 (18.4%) patients with a mean age of 38.4 ± 15.22, being 49 (18%) men. The comparison of peptic ulcer group with the patients that had normal endoscopy revealed that H. pylori infection [P = 0.005; OR = 1.70; 95% CI = 1.17-2.47], male gender [P<0.0001; OR = 5.53; 95%CI = 3.67-8.34] and older age [P<0.0001; OR = 1.08; 95%CI = 1.06-1.09] increased the risk of peptic ulcers. The overall H. pylori prevalence was 53% (786)., Conclusions: Prevalence of duodenal ulcer is high in a Brazilian population that had H. pylori infection associated with older age and male gender as important determinants to gastrointestinal diseases outcome. Future prospective studies should confirm these findings.

Background: H. pylori seroprevalence in Brazilians varies and is dependent on socioeconomic status, sanitation conditions and ethnicity; furthermore, H. pylori is not always associated with the incidence of gastric cancer, suggesting the role of more virulent strains. The purpose of this study was to analyze the association of more virulent H. pylori strains with gastric cancer., Methods: DNA was extracted from gastric biopsies of thirty-four cases of gastric cancer (11 intestinal-type, 23 diffuse-type), and thirty-four of patients with endoscopic gastritis. The presence of cagPAI genes (cagA, cagA promoter, cagE, cagM, tnpB, tnpA, cagT and the left end of the cagII (LEC)) and babA were analyzed by PCR., Results: Comparison of H. pylori isolates from gastric cancer and gastritis patients showed significant associations of tnpA and LEC with gastric cancer (73.5% [OR, 6.66; 95% CI, 2.30-19.25] and 58.8% [OR, 10.71; 95% CI, 3.07-37.28] of cases, respectively). Other cagPAI genes were detected in both groups at similar frequencies., Conclusions: tnpA and LEC of H. pylori cagPAI were associated with gastric cancer; nonetheless, these results were restricted within this group of patients and further studies are needed to confirm these results in a larger sample and determine their role in gastric carcinogenesis.

Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.

This study aimed to analyse the association of gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. We studied 122 donor/recipient pairs who received HLA-identical transplants from siblings at the Universidade Estadual de Campinas, Brazil, between June 1996 and June 2006. Donor/recipient alleles for TNFA-238 and IL2-330/+166 single-nucleotide polymorphisms (SNP) were analysed by PCR-SSP. No association was observed between the risk of acute graft-versus-host disease (GVHD) and these SNP. However, our findings suggest that the polymorphism of promoter gene TNFA-238GA is associated with the occurrence and severity of chronic GVHD. The probability of chronic GVHD in patients with GA genotype at position -238 of TNFA gene is 91.7% in contrast to 59.4% in patients with GG genotype (P = 0.038). In patients with donor GA genotype the probability of chronic GVHD is 90.8%, and 57.9% in patients with donor GG genotype (P = 0.038). The probability of extensive chronic GVHD in patients with TNFA-238GA is 91.7% compared with 46.3% in patients with TNFA-238GG (P = 0.0046). In patients with donor GA genotype at position -238 of the TNFA gene, it is 81.7%, compared with 44.5% in patients with donor GG genotype (P = 0.016). However, further studies with more patients are required to identify cytokine gene polymorphisms and their association with transplant-related complication in Brazil, particularly due to ethnic background, the relatively low power of detection of genetic markers of this study, and the complexity of the MHC region.

Objective: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia)., Methods: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA)., Results: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95%IC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95%IC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95%IC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95%IC = 1.34-4.16) was associated to increased risk of CML developing., Conclusion: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

Aim: The influence of panel-reactive antibody level (%PRA) on crossmatch results was evaluated among 866 patients on the waiting list for cadaveric renal allografting from January 2001 to August 2005. We evaluated the results for 124 potential donors for a kidney, including 2008 crossmatches. Four hundred eighteen patients were tested against only 1 donor., Methods: Serum samples were screened for anti-HLA antibodies using immunoglobulin (Ig)G enzyme-linked immunosorbent assay (ELISA) PRA kit and the %PRA of the most reactive sample (peak) was used for patient stratification, according to sensitization level. Crossmatches were performed on fresh donor T lymphocytes from peripheral lymph nodes, using classical and anti-human-globulin enhanced complement-dependent cytotoxicity (CDC-T) methods. The tests were performed using peak and current patient sera before and after dithiothreitol treatment. The crossmatch was assumed to be negative when no reactivity was observed in all tests., Results: The incidences of positive crossmatch were as follows: 72.3%, 14.6%, and 7.2%, among patients with PRA >50%, PRA

Two novel alleles, human leukocyte antigen (HLA)-B*3569, -B*4450 and a confirmatory sequence of HLA-A*2631 were identified during a routine typing for the Brazilian Bone Marrow Donor Registry. Sequence analysis of coding exons 2 and 3 revealed a single nucleotide substitution in HLA-B*3569 and two single nucleotide substitutions in HLA-B*4450, compared with closely related alleles. At the protein level, these substitutions result in a change of a single amino acid residue in each of HLA-B*3569 and -B*4450 at positions 74 (Arg > Pro) and 80 (Thr > Ile), respectively. These variations are located in the highly polymorphic region at the end of the alpha(1) domain of the HLA molecule. It appears that HLA-B*3569 arose from the analogous HLA-B*3510 through a point mutation. However, HLA-B*4450 may have arisen from HLA-B*440301 and -B*4425 by gene conversion.

Objective: To evaluate how the Judicial Power safeguards the social right to pharmaceutical assistance as well as the relationships between the legal and political systems to safeguard this right., Methods: There were assessed decisions in lawsuits of drug supply in the state of São Paulo, Southern Brazil, between 1997 and 2004. Discourse of the Collective Subject of procedural actors was the methodological approach used., Results: In 96.4% of the cases analyzed, judges' discourse sentenced the State. In these cases, the State was obliged to provide drugs exactly as requested by the plaintiff, even when drugs were not registered in the National Health Surveillance Agency (9.6% of cases). Also, 100% of the lawsuits were proposed by individual plaintiffs; in 77.4% of the cases the plaintiff requested an specific drug of a specific pharmaceutical company; and in 93,5%, the drugs were provided to the plaintiff through an urgent preliminary order., Conclusions: The Judicial Power is not taking into account in its decisions political elements of drug policies, established to enforce the social right to pharmaceutical assistance. The Judicial Power is hindering the collective decision making process by the political system, prioritizing plaintiffs' individual needs over community interests.

Background: Neonatal thrombocytopenia (NT) occurs in 0.5 to 0.9% of unselected Caucasian newborns. However, the prevalence of this complication in other populations is unknown. In this study the prevalence/causes of NT was determined in Brazilian newborns, a population characterized by admixture among Indigenous, Africans, and Caucasians., Study Design: A prospective study was carried out in a 3-year period, to determine the prevalence and causes of thrombocytopenia in cord blood samples. Genotyping for HPA 1-5 systems was performed in pairs of mother/neonates with and without thrombocytopenia. All mothers with genotypic mismatches from each group were tested for HPA-specific antibody using the MAIPA technique to identify alloimmunization., Results: Platelet counts <100 x 10(9)/L were detected in 1.5% of 9,332 unselected newborns. In 0.15%, platelet count was <50 x 10(9)/L. Clinically significant bleeding was rare. Underlying diseases were present in 48% of the thrombocytopenic cases. HPA 1-5 system genotype mismatches occurred in 50% of gestations, but did not predict the risk for thrombocytopenia. Notably, mismatched genotypes for HPA-5 were slightly increased in the thrombocytopenic group. The presence of anti-HPA-5b antibodies was observed in 0.05% of unselected pregnancies, but increased to 12% among mothers of neonates with thrombocytopenia and mismatched genotype (N = 51)., Conclusions: Neonatal thrombocytopenia is common among Brazilian newborns at rates comparable with those described among Caucasians. These data suggest that screening for genotypic HPA mismatch, followed by an HPA-specific immunoassay system, particularly for the HPA-5 system, among mothers of newborns with thrombocytopenia in our population would allow the identification of pregnancies at risk of alloimmune thrombocytopenia.

The purpose of this study was to verify whether the presence of any of the Helicobacter pylori cagPAI genes or segments--cagA, cagA promoter, cagE, cagM, tnpB, tnpA, cagT and the left end of the cag II (LEC) region--would be a useful marker for the risk of peptic ulcer disease development. H. pylori DNA extracted from positive urease tests of 150 peptic ulcer patients and 65 dyspeptic controls was analysed by PCR. Duodenal ulcers were present in 110, gastric ulcers in 23 and both gastric and duodenal ulcers in 17 patients. A significant association (P <0.001) was found between a conserved cagPAI and peptic ulcer disease (34 %). The positivity of the cagA gene varied according to the region of the gene that was amplified. The region near to the promoter was present in almost all of the H. pylori isolates (97.2 %). The segment from nt 1764 to 2083 and the extreme right end were frequently deleted in the isolates from the controls (P <0.01). The positivity of the promoter region of cagA and cagT, cagE, cagM and LEC showed a significant difference between the isolates from peptic ulcer patients and from the controls (P <0.01). Patients usually had moderate gastritis; however, the intensity of the active inflammation was higher in the peptic ulcer group (P <0.001). cagT, cagM, LEC and the right end terminus of the cagA-positive H. pylori isolates were associated with a 27-fold, 8-fold, 4-fold and 4-fold risk of peptic ulcer disease, respectively, and may be useful markers to identify individuals at higher risk of peptic ulcer disease development in Brazil.

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (HSCT), and cytokines are recognized as important mediators of GVHD. Polymorphisms in the regulatory regions of several cytokine genes have been associated with a number of immune diseases as well as organ transplant complications. In this study we have investigated the role of tumor necrosis factor-alpha(-308), interleukin (IL)-6(-174), IL-10(-1082, -819, -592), Interferon-gamma(-874), and transforming growth factor-beta1(+869, +915) polymorphisms on HSCT outcome. Donor/recipient genotypes were analyzed by polymerase chain reaction with sequence specific primers (PCR-SSP). Although we have found a small number of low IL-6, a polymorphism at position -174 of the recipient and donor IL-6 gene was associated with the increased incidence of chronic GVHD. Therefore, this study emphasizes the probable potential role of genetic variability of donor and recipient in determining outcome after transplantation.

The application of DNA-based methods for human leukocyte antigen (HLA) genotyping has revealed an ever-increasing degree of polymorphism within the HLA-DRB loci and has resulted in the discovery of new alleles. We have identified a new DRB1 allele that was subsequently named DRB1*1360 by the WHO Nomenclature Committee. This allele is unusual for a DRB1*13 allele, as it is present on a DRB5 haplotype rather than the normal DRB3 haplotype found in association with DRB1*13 alleles., (Copyright 2004 Blackwell Munksgaard)

The association of HLA class II haplotypes with type I diabetes was analyzed in 56 Southeastern Brazilian families using affected family-based controls (AFBAC) method. DRB1-DQA1-DQB1 alleles were determined by polymerase chain reaction/sequence-specific primer genotyping. This study first revealed the great haplotype diversity of Brazilians (65 different haplotypes even with incomplete DRB1 subtyping), probably due to the admixture of Africans genes with European and Amerindian genes in this population. The results revealed increased frequencies of the DRB1*03-DQA1*0501-DQB1*02 and DRB1*0401-DQA1*03-DQB1*0302 haplotypes in the patient group The highest risk for type I diabetes was associated with the heterozygote DRB1*03/*04 genotype as largely reported, and DRB1*03/X and DRB1*04/Y genotypes conferred a significant, but much lower disease risk. Protection from type I diabetes revealed some peculiarities in Southeastern Brazilians: a lack of significant protecting effect of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, and an apparent protection conferred by the DRB1*13-DQB1*0301, DRB1*11-DQB1*0301, and DRB1*01-DQB1*0501 two-locus haplotypes. The risk to type I diabetes in the highly diversified Southeastern Brazilians evidenced specific information to the prediction of the disease in this region of the country.

HLA class II genes are strongly associated with susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). The present study reports the HLA-DRB1 genotyping of 41 IDDM patients and 99 healthy subjects from the Southeast of Brazil (Campinas region). Both groups consisted of an ethnic mixture of Caucasian, African Negro and Amerindian origin. HLA-DRB1*03 and *04 alleles were found at significantly higher frequencies among IDDM patients compared to the controls (DRB1*03: 48.8% vs 18.2%, P < 0.005, RR = 4.27; DRB1*04: 43.9% vs 15.1%, P < 0.008, RR = 4.37) and were associated with a susceptibility to the disease. DRB1*03/*04 heterozygosity conferred a strong IDDM risk (RR = 5.44). In contrast, the HLA-DRB1*11 allele frequency was lower among IDDM patients (7.3% vs 26.3% in controls), but the difference was not significant. These data agree with those described for other populations and allow genetic characterization of IDDM in Brazil.