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Helicobacter pylori (Hp) infects the stomach of about half of the human population and is strongly associated with the risk of gastric cancer (GC) and its premalignant precursors. The cag pathogenicity island (cagPAI) is a region of the Hp genome encoding for key molecular machinery involved in the infection process. Following a sequencing study, we selected 50 genetic polymorphisms located in seven cagPAI genes and tested their associations with the risk of advanced gastric premalignant lesions and GC in 1220 subjects from various Latin American populations showing the whole spectrum of phenotypes from gastritis to GC. We found that three polymorphisms of cagA are associated with the risk of advanced gastric premalignant lesions (incomplete intestinal metaplasia [ie, Type 2 and 3] or dysplasia), and that six polymorphisms located in cagA, cagL and cagI were associated with risk of GC. When corrected for multiple testing none of the associations were statistically significant. However, scores built by integrating the individual polymorphisms were significantly associated with the risk of advanced gastric premalignant lesions and GC. These results have the potential of establishing markers for risk stratification in the general population, in view of targeting Hp eradication to high-risk population groups.

The processes tapped by the widely-used word association (WA) paradigm remain a matter of debate: while some authors consider them as driven by lexical co-occurrences, others emphasize the role of meaning-based connections. To test these contrastive hypotheses, we analyzed responses in a WA task in terms of their normative defining features (those describing the object denoted by the cue word). Results indicate that 72.5% of the responses had medium-to-high coincidence with such defining semantic features. Moreover, 75.51% of responses had medium-to-high values of Relevance (a measure of the importance of the feature for construing a given concept). Furthermore, most responses (62.7%) referred to elements of the situation in which the concept usually appears, followed by sensory properties (e.g., color) of the denoted object (27.86%). These results suggest that the processes behind WA tasks involve a reactivation of the cue item’s semantic properties, particularly those most relevant to its core meaning.

Semantic feature production norms provide many quantitative measures of different feature and concept variables that are necessary to solve some debates surrounding the nature of the organization, both normal and pathological, of semantic memory. Despite the current existence of norms for different languages, there are still no published norms in Spanish. This article presents a new set of norms collected from 810 participants for 400 living and nonliving concepts among Spanish speakers. These norms consist of empirical collections of features that participants used to describe the concepts. Four files were elaborated: a concept–feature file, a concept–concept matrix, a feature–feature matrix, and a significantly correlated features file. We expect that these norms will be useful for researchers in the fields of experimental psychology, neuropsychology, and psycholinguistics. Fil: Vivas, Jorge. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; Argentina Fil: Vivas, Leticia Yanina. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; Argentina Fil: Comesaña, Ana. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; Argentina Fil: García Coni Bosch, Ana Virginia. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; Argentina Fil: Vorano, Agostina. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; Argentina

Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon y (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR) = 1.37, 95% confidence interval (CD = 1.01 -1.86, and OR = 1.49,95% Cl = 1.01 -2.19, respectively]. Two SNPs of PTGS2 were associated with risk of dysplasia (OR=1.60, 95% Cl=1.01-2.54, and OR= 0.66, 95% Cl =0.43-0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis.

Background Helicobacter pylori infection is associated with the development of gastric cancer. Although infection with an H. pylori strain containing the cytotoxin-associated (cag A) gene (a marker for a pathogenicity island) may increase the risk of atrophic gastritis and gastric cancer, the relationship of variants in pathogenic H. pylori genes to the severity and progression of precancerous lesions is not well defined. Methods Gastric biopsy specimens were obtained at enrollment from 2145 participants in a chemoprevention trial in Tachira State, Venezuela, and examined histologically to determine the severity of precancerous lesions. The presence of H. pylori DNA in gastric biopsies and the strain type according to presence or absence of the cagA gene were detected by polymerase chain reaction and specific probes. The relationship between H. pylori DNA and histologic diagnosis was analyzed by polytomous logistic regression. Rates of progression and regression of precancerous lesions were determined from biopsies from additional annual gastroscopies (mean follow-up = 3.5 years). All statistical tests were two-sided. Results At enrollment, there was a strong association between cagA-positive H. pylori infection and the severity of gastric precancerous lesions, but cagA-negative H. pylori was associated only with chronic gastritis. Using individuals with normal mucosa or superficial gastritis as control subjects, the odds ratio for dysplasia was 15.5 (95% confidence interval [CI] = 6.42 to 37.2) in cagA-positive individuals compared with uninfected individuals and 0.90 (95% CI = 0.37 to 2.17) for individuals infected with cagA-negative H. pylori compared with uninfected individuals. Individuals infected with cagA-positive H. pylori appeared more likely to experience progression (and less likely to experience regression) of precancerous lesions than those infected with cagA-negative H. pylori , but the differences did not attain statistical significance. Conclusions This large epidemiologic study shows a strong relationship between the presence of H. pylori DNA in gastric biopsies and the severity of precancerous lesions that is specific to cagA-positive strains. The association between H. pylori and gastric carcinoma may have been previously underestimated due to the poor accuracy of serologic H. pylori markers and lack of discrimination by cagA genotype. J Natl Cancer Inst 2007;99: 1328 – 34

Background. Within the framework of a chemoprevention trial on stomach cancer, two substudies based on repeat measurement were undertaken to evaluate reliability of histological diagnoses of gastric precancerous lesions. Methods. A subgroup of 45 subjects received two endoscopies separated by a period of one month. The two biopsies were reviewed by a single pathologist. A second subsample of 50 subjects had a single endoscopy and the biopsy results were reviewed by two pathologists. Agreement between the two diagnoses was assessed by Cohen's Kappa and by repeat frequency. Results. When the same samples were reviewed by the pathologists involved in the trial, agreement was very high for advanced lesions (repeat frequency = 0.96 for intestinal metaplasia and 1.00 for dysplasia) but lower for less advanced lesions (repeat frequency = 0.73 for superficial gastritis and chronic gastritis, 0.65 for atrophic gastritis). When the same pathologist reviewed two sets of biopsies taken less than 2 months apart, the combination of random observer error and biopsy sampling error gave rise to quite low agreement, especially for early lesions, mainly attributable to biopsy sampling error. Comparison of diagnoses made at routine reading and at review by the same pathologist and by different pathologists showed substantial overall agreement with the exception of one pathologist for whom agreement was moderate. Conclusions. These results confirm that misclassification of histological diagnosis may be a relevant problem in chemoprevention trials of stomach cancer, more so when baseline diagnosis is taken into account in the analysis to estimate progression and regression rates of precancerous lesions. Further, the results suggest that misclassification is limited to early lesions, while diagnostic reliability of severe lesions is quite high.

Determinants of plasma pepsinogens (PG) levels were studied in 1365 participants in a chemoprevention trial for gastric pre-cancerous lesions being conducted in Venezuela. Gastric biopsies, plasma samples and information on smoking and dietary habits were obtained at baseline examination. Both PG-I and PG-II levels increased progressively with the level of Helicobacter pylori infection in gastric biopsies, resulting in no clear trend in the I/II ratio. Instead, there was a progressive decrease in the I/II ratio with increasing degrees of infiltration of polynuclear cells and monocytes, atrophy, intestinal metaplasia and the stage of pre-cancerous lesions. The mean I/II ratios for atrophic gastritis or more advanced lesions were less than 4.0. When subjects with the I/II ratio 4 or higher were used as controls, severe reduction in the I/II ratio (< 2.0) was inversely associated with tobacco consumption. This may be due to a pharmacological effect of nicotine. The severe reduction of I/II ratio was also inversely associated with fresh fruit consumption. In addition, a decreased I/II ratio was positively associated with rice/pasta and arepas (tortilla made from corn) consumption and inversely associated with plantain consumption. Possible effects of vitamins and starchy food on the development of atrophic gastritis need to be studied further.

The bacterium Helicobacter pylori (HP) has been implicated in the etiology of precancerous lesions of the stomach and there is evidence suggesting that it may influence the efficacy of chemoprevention of gastric cancer with vitamin C. Eradication seldom has been attempted in populations from developing countries, with a high prevalence of HP frequently resistant to metronidazole. A randomized, double-blind, controlled trial to evaluate the efficacy of colloidal bismuth subcitrate (120 mg q.i.d.) and amoxycillin (500 mg q.i.d.) in eradicating HP was conducted in 220 subjects drawn from a population with a high prevalence of metronidazole-resistant HP in Tachira state, Venezuela. One month after completion of two weeks' treatment, eradication rates of 6.5 percent in the treatment group and two percent in the placebo group were estimated on the basis of HP diagnosis in biopsies, and of 13.9 percent compared with 3.9 percent on the basis of a 14C-urea breath test, although the negative predictive value of the breath test was very low compared with HP diagnosis in biopsies. In the treatment group, particularly among males, a significant decrease in bacterial load was detected. Reasons for failure of treatment in high HP-prevalence areas are discussed, and it is suggested that primary prevention of HP infection may be the optimal approach to reducing levels of stomach cancer in these high-risk groups.

Infection by Helicobacter pylori is recognized as a risk factor for gastric cancer and peptic ulcer disease. Venezuela has regions with different gastric cancer risks; the Andean region has the highest gastric cancer mortality in the country. We performed a cross-sectional study on 357 patients who underwent endoscopy attending 2 private (n = 76) and one public hospital in Caracas, Venezuela (n = 215), and one public hospital in the Andes (n = 66) to determine H. pylori infection (by a rapid biopsy urease test and histology). The proportion of infected patients in Caracas was significantly higher in public hospitals (72%) than in private hospitals (46%; P = 0.00001), and there was no significant variation the Andes and Caracas (P = 0.7001). When analyzing the data from the public hospital in Caracas, we found that the frequency of infected patients was significantly higher during the rain (96%) than during the dry months (70%, P = 0.00000001). Differences in prevalence of infection in symptomatic patients was not related to the risk of gastric cancer but to socioeconomic differences. Rain-dependent factors that may be exacerbating the clinical activity of nonulcer dyspepsia in people infected with H. pylori deserve further study.

Using data from a Venezuelan cohort of 1,948 adults, the gastric detection of Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR) of the vacA gene in 1 antral biopsy was compared to the detection of H. pylori by histopathology (hematoxylin-eosin and Giemsa staining) in 5 biopsies (antrum and corpus). Overall, H. pylori was detected in 85% and 95% of the subjects by PCR and histopathology, respectively. When results were analyzed by severity of precancerous lesions, PCR on 1 biopsy detected the bacteria less often than histopathology on 5 biopsies in subjects with normal gastric mucosa and non-atrophic gastritis. However, in subjects with the most severe lesions (intestinal metaplasia type III and dysplasia), PCR on 1 biopsy detected H. pylori as often as histopathology on 5 biopsies, and significantly more often than histopathology on a single biopsy. In conclusion, these findings confirm that histopathology on 5 biopsies is an accurate tool for H. pylori detection in most subjects, compared to the PCR method on 1 biopsy. Nevertheless, the elevated sensitivity of PCR for detecting the bacteria in advanced precancerous lesions, and the possibility to use PCR to distinguish between cagA-positive and cagA-negative strains, makes the PCR technique especially useful in studies of stomach cancer.

To evaluate disease characteristics of childhood onset SLE in Latin America and to compare this information with an adult population in the same cohort of GLADEL. A protocol was designed as a multicenter, multinational, inception cohort of lupus patients to evaluate demographic, clinical, laboratory and serological variables, as well as classification criteria, disease activity, organ damage and mortality. Descriptive statistics, chi square, Fisher's exact test, Student's t test and multiple logistic regression were used to compare childhood and adult onset SLE. 230 patients were < 18 years and 884 were adult SLE patients. Malar rash, fever, oral ulcers, thrombocytopenia and hemolytic anemia and some neurologic manifestations were more prevalent in children (p < 0.05). On the other hand, myalgias, Sjögren’s syndrome and cranial nerve involvement were more frequently seen in adults (p < 0.05). Afro-Latin-American children had a higher prevalence of fever, thrombocytopenia and hemolytic anemia. White and mestizo children had a higher prevalence of malar rash. Mestizo children had a higher prevalence of cerebrovascular disease and cranial nerve involvement. Children met SLE ACR criteria earlier with higher mean values than adults (p: 0.001). They also had higher disease activity scores (p: 0.01), whereas adults had greater disease damage (p: 0.02). In Latin America, childhood onset SLE seems to be a more severe disease than adults. Some differences can be detected among ethnic groups.

As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.

A case-control study to evaluate risk factors for gastric cancer was carried out among 292 cases of gastric cancer and 485 controls in a high-risk area of Venezuela. Subjects were interviewed using a structured questionnaire, which elicited information on residential history, socio-economic status, family history of gastric diseases, smoking, drinking and dietary habits. Habitual diet was estimated from a meal-structured food frequency questionnaire on 75 food items. There was a strong inverse association with social class, as measured by education and by indicators of poverty. The results of the dietary analysis suggest that a diet high in starch and low in meat, fish and fresh vegetables increases risk of gastric cancer. A protective effect was observed for frequent consumption of allium vegetables. Inverse associations were found with height, which may reflect nutritional status in childhood, and with refrigerator use in the first two decades of life. Alcohol and tobacco consumption was investigated among males only, since the prevalence of alcohol and tobacco use was very low in females. Alcohol drinkers were at higher risk than non-drinkers and there was a small excess risk for current smokers compared with never smokers. There was some evidence of familial aggregation of gastric cancer. These findings will have important implications in planning preventive strategies for gastric cancer in Venezuela.

Our objective was to identify the determinants of plasma levels of anti-oxidant vitamins which have been linked with decreased risk of cancer and other chronic diseases. Correlation analyses were performed between baseline plasma levels of ascorbic acid, alpha- and beta-carotenes, cryptoxanthin, lycopene and alpha- and gamma-tocopherols and baseline information on dietary and other demographic and life-style factors among 1,364 subjects 35-69 years of age, who are participants in a chemoprevention trial on pre-cancerous lesions of the stomach in Venezuela. Males had lower levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin and higher levels of alpha-tocopherol than females. This finding was confirmed in non-smokers and non-drinkers. In females, but not in males, age was positively associated with levels of ascorbic acid, cryptoxanthin, alpha- and beta-carotene and gamma-tocopherol. Male tobacco users had lower plasma levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin than nonusers, and regular alcohol drinkers had a decreased plasma levels of beta-carotene compared with non-drinkers. Female tobacco users had lower levels of ascorbic acid and cryptoxanthin than non-users, and regular alcohol drinkers had lower levels of ascorbic acid and lycopene than non-drinkers. Frequencies of consumption of fresh fruits, fruit juice, raw vegetables and plantains showed weak positive associations with plasma levels of several vitamins studied in both sexes. Sex, age in females, tobacco and alcohol use and dietary consumption affected plasma anti-oxidant vitamin levels in this population significantly. These factors may influence the effect of anti-oxidant treatment in intervention trials.