Luis Eduardo Bravo

Long term follow up of patients treated for Helicobacter pylori infection

Background:Helicobacter pylori infection induces progressive inflammatory changes in the gastric mucosa that may lead to gastric cancer. Understanding long term effects resulting from the cure of this infection is needed to design cancer prevention strategies. Methods: A cohort of 795 adults with preneoplastic gastric lesions was randomised to receive anti-H pylori treatment and/or antioxidants. At the end of six years of intervention, those who did not receive anti-H pylori treatment were offered it. Gastric biopsies were obtained at baseline, and at 3, 6, and 12 years. A histopathology score was utilised to document changes in gastric lesions. Non-linear mixed models were used to estimate the cumulative effect of H pylori clearance on histopathology scores adjusted for follow up time, interventions, and confounders. Results: Ninety seven per cent of subjects were H pylori positive at baseline, and 53% were positive at 12 years. Subjects accumulated 1703 person years free of infection. A multivariate model showed a significant regression in histopathology score as a function of the square of H pylori negative time. Subjects who were H pylori negative had 14.8% more regression and 13.7% less progression than patients who were positive at 12 years (pu200a=u200a0.001). The rate of healing of gastric lesions occurred more rapidly as years free of infection accumulated, and was more pronounced in less advanced lesions. Conclusions: Preneoplastic gastric lesions regress at a rate equal to the square of time in patients rendered free of H pylori infection. Our findings suggest that patients with preneoplastic gastric lesions should be treated and cured of their H pylori infection.

Helicobacter pylori genotypes may determine gastric histopathology.

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

Effects of acid suppression and bismuth medications on the performance of diagnostic tests for Helicobacter pylori infection.

OBJECTIVE:This study was designed to investigate whether acid suppression and bismuth medications interfere with the performance of diagnostic tests for Helicobacter pylori (H. pylori) infection.METHODS:Sixty patients with previous diagnoses of atrophic gastritis and H. pylori infection made in gastric biopsies taken at Hospital Departmental, Pasto, Colombia, were enrolled in the study. 13C breath urea test (UBT) and stool antigen test (HpSA) were performed simultaneously. Two baseline tests were performed: one 7 days before and another the day before starting medications. A total of 20 patients received for 2 wk one of the following treatments: a) ranitidine; b) lansoprazole; or c) bismuth subsalicylate. The tests were repeated while the patients were on the prescribed medication on days 7 and 14 and then 2 wk after finishing the medication.RESULTS AND CONCLUSIONS: :Utilizing standard cut-off values for the tests, our results indicate that in the case of the 13C UBT test, ranitidine does not interfere with the results, whereas lansoprazole and bismuth may be expected to yield a significant proportion of false negative results (30–40% for lansoprazole and 45–55% for bismuth). In the case of the HpSA test, ranitidine does not interfere, whereas lansoprazole and bismuth may be expected to yield a nonsignificant proportion of false negative results (15–25% for lansoprazole and 10–15% for bismuth). Absolute values for both tests may be used to study the effects of the pharmacological agents on the characteristics of the infection.

Impact of Helicobacter pylori infection on growth of children: A prospective cohort study

Objective The aim of this study was to prospectively follow a cohort of children without Helicobacter pylori infection and to compare growth velocity in the children who become infected during follow-up with that of children who remained infection-free. Methods Three hundred forty-seven children in general good health, aged 12 to 60 months, who tested negative for H. pylori by the 13C-urea breath test, from three daycare centers in a lower-middle class borough of Cali, Colombia, were monitored for 2.5 years. Anthropometric measurements were performed every 2 months and breath tests every 4 months. Linear mixed models were used to analyze growth velocity in relation to onset of H. pylori infection. Results One hundred five (30.3%) children who were uninfected at the start of the study became infected during follow-up. Growth velocity in infected children was reduced by 0.042 ± 0.014 cm/mo (P = 0.003) (approximately 0.5 cm/yr) after adjusting for age. The rate of deceleration in growth velocity was relatively constant over time. Conclusions Among these lower-middle class children aged 12 to 60 months from a population with high prevalence of H. pylori infection, a new and sustained infection was followed by significant growth retardation.

Virulence-associated genotypes of helicobacter pylori: do they explain the african enigma?

OBJECTIVES: n nThe aim of this study was to compare the distribution of virulence-associated genotypes of Helicobacter pylori in two Colombian populations with contrasting gastric cancer risk but with similar H. pylori infection prevalence. n nMETHODS: n nGastric biopsies were taken from 241 subjects from the high gastric cancer risk area of Pasto and from 93 subjects from the low risk area of Tumaco. Four gastric biopsies from each patient were fixed in 10% buffered formalin for histopathologic analysis, and one was frozen immediately in liquid nitrogen and used for genotyping. CagA and vacA genotypes were determined by multiplex polymerase chain reaction and reverse hybridization on a line probe assay. n nRESULTS: n nIn patients from the population with high risk for gastric cancer, statistically significant higher relative frequencies of cagA positive and vacA s1 and m1 genotypes were found as compared to the population from the low risk area. n nCONCLUSIONS: n nAlthough H. pylori infection has been recognized as a cause of gastric cancer in humans, some large populations with high prevalence of infection have low gastric cancer rates. This so-called “African enigma” so far remains unexplained. Our findings suggest that virulence-associated genes of H. pylori may partially explain the African enigma. Other factors, including human genetic polymorphisms and diet, are also suspected to play a major role. Further investigations are needed to test this hypothesis.

Morphometric evaluation of gastric antral atrophy: improvement after cure of Helicobacter pylori infection

OBJECTIVE:Our purpose was to find out if morphometric techniques can document long term changes in gastric antral atrophy after curing Helicobacter pylori infection with or without dietary supplementation with antioxidant micronutrients.METHODS:Study subjects were 132 adult volunteers from a Colombian region with high gastric cancer rates. Participants were randomly assigned to ascorbic acid, β-carotene, and anti-H. pylori treatment, following a factorial design. Gastric biopsies were obtained at baseline and after 72 months of intervention. Atrophy was evaluated by a standard visual analog scale and by morphometry.RESULTS:Statistically significant changes in antral atrophy were detected with morphometric techniques after intervention in subjects who received anti-H. pylori treatment. A nonsignificant trend was also observed with visual scores. This effect was greater among those who were free of infection at the end of the trial. After accounting for the effect of anti-H. pylori treatment, no significant effect was noted for dietary supplementation with ascorbic acid and/or β-carotene.CONCLUSIONS:We conclude that gastric atrophy improves significantly after long term control of H. pylori infection. This effect can be demonstrated both by conventional histological grading and by morphometry.

Age at acquisition of Helicobacter pylori infection: Comparison of two areas with contrasting risk of gastric cancer

Background.u2002 Helicobacter pylori infection is usually acquired during childhood and is a known risk factor for the development of gastric malignancies in adulthood. It has been reported that early age at first infection may determine a neoplastic outcome in adults. The purpose of this study was to determine the prevalence of Helicobacter pylori infection in children residing in areas with high (Pasto) and low risk (Tumaco) of gastric cancer in Colombia to evaluate whether differences in the age of acquisition of H. pylori infection were present in the two populations.

Detection and typing of Helicobacter pylori cagA/vacA genes by radioactive, one-step polymerase chain reaction in stool samples from children

The detection and molecular typing of Helicobacter pylori virulence genes in human stool specimens by polymerase chain reaction (PCR) require an adequate amount of bacterial DNA and an appropriately adjusted PCR protocol. DNA was isolated from stool samples of 39 H. pylori-infected and nine uninfected Colombian children using the QIAamp Kit following the manufacturers instructions but with modifications. DNA templates were amplified for the vacA s and m regions and for the cagA gene by PCR using radioactively labeled (32P) primers. The modifications in the standard Qiagen protocol of stool DNA extraction increased the final concentration of eluted total stool DNA 4.7 times (117 +/- 17 versus 22 +/- 3 ng/microl; P < 0.0001). Nevertheless, its amplification by regular PCR programs (30-40 cycles) did not generate visible signals because of the very low ratio of H. pylori DNA to other DNA. PCR for 80 cycles successfully amplified vacA in 36/39 samples (sensitivity, 92.3%) and cagA fragments in 21/39 (53.8%) fecal DNA samples. Both s and m vacA regions were amplified in 33/36 (91.7%) DNA samples. The s1m1 genotype was the most commonly isolated variant, accounting for 17/36 or 47.2% of positive samples. The s2m2 genotype was ascertained to be frequent also (14/36 or 38.9%). Almost all (94.1%) s1m1 genotypes were cagA positive. The majority of s2m2 genotypes (78.6%) were not associated with the cagA gene. Neither cagA nor vacA fragments were amplified from DNA isolates of H. pylori-uninfected children nor from DNA isolated from six gastrointestinal bacterial strains (specificity, 100%). The data suggest that the proposed modified technique of DNA extraction and PCR assay of stool samples may be an effective and reliable noninvasive tool for the detection and typing of H. pylori cagA/vacA virulence genes in infected individuals.

MUC1 polymorphism confers increased risk for intestinal metaplasia in a Colombian population with chronic gastritis

Gastric cancer (GC) stands as the second most common cause of cancer death for males worldwide, and intestinal metaplasia (IM) is a lesion that precedes GC development. In previous works it was shown that polymorphisms of MUC1 gene are associated with increased risk for GC and IM. The aim of the present study was to evaluate MUC1 gene polymorphism in patients with chronic gastritis from Colombia. A Portuguese population of patients with chronic gastritis was used for comparative purposes. A total of 67 Colombian cases and 52 Portuguese cases were analysed by restriction analysis and Southern blotting. MUC1 allele frequencies were significantly different between the two populations, with an overall prevalence of smaller alleles in Colombian samples. Colombian cases showed a lower prevalence of individuals homozygous for small MUC1 mucins in cases without IM (62.5%) when compared with cases with IM (86.0%). The same trend, although not statistically significant, is observed in the Portuguese population. In conclusion, our study shows that Colombian patients with chronic gastritis have a significantly higher prevalence of small MUC1 alleles than the Portuguese population. Our study also shows that small MUC1 genotypes are associated with increased risk for IM development in Colombian patients.

Unsuccessful treatment results in survival of less virulent genotypes of Helicobacter pylori in Colombian patients

ysis. Before treatment, active chronic gastritis (grade 3) was present in all patients. After treatment, all of the patients were still found asH. pylori-positive. The grade of gastritis andH. pylori density were unchanged in all cases. The mean symptom score was not also significantly changed in both groups before and after treatment (Table 1). There were not any side effects in either group. Although it has shown that garlic extracts have a broad action upon almost all kinds of bacteria (3), this clinical study showed no effect of garlic oil on H. pylori infection. Together with the study by Graham et al., it was concluded that neither fresh garlic nor garlic oil capsules have any therapeutic effect onH. pylori infection.