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Biomedical subjects

P Correa

Publications and source records attributed to P Correa.

At least 19 recordsLinked to original sources
PubMed2005

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 (p = 0.001). 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.

Acute Disease↗
PubMed2004

Gene expression in gastric biopsies from patients infected with Helicobacter pylori.

BACKGROUND: Helicobacter pylori infection has protean effects on gene expression in the host gastric mucosa, which have been investigated by gene chip analysis in vitro. In this study the effects of H. pylori infection on host gene expression in the gastric antral mucosa in patients were examined. METHODS: One gastric antral biopsy was obtained from a total of 18 untreated patients undergoing routine endoscopic evaluation of chronic abdominal complaints. Nine patients had histologic evidence of H. pylori infection and 9 age- and sex-matched patients had no histologic evidence of H. pylori infection. A microarray analysis was performed using a gene chip containing 35,000 human expressed sequence tags on RNA extracted from endoscopic, gastric antral biopsies, and average gene expression among infected and uninfected patients was compared. RESULTS: Underexpressed genes in infected patients' mucosa included gastric intrinsic factor and several metallothionein isoforms. Overexpressed genes in infected patients' mucosa comprised MHC Class II molecules, immunoglobulin and B-cell activation genes, as well as genes known to induce apoptosis. Changes in expression were confirmed for a subset of genes by SYBR green real-time PCR. CONCLUSIONS: Microarray analysis of antral biopsies from patients with and without H. pylori infection revealed differential expression of metal regulatory, immunity and inflammation-related genes.

Adult↗
PubMed2004

Is gastric cancer preventable?

Gastric cancer is a major health burden worldwide and prevention is the most promising strategy to control the disease. The available scientific evidence indicates that curing Helicobacter pylori infection results in a modest retardation of the precancerous process but does not prevent all cancers. Individuals at the highest risk should be cured of their infection and monitored endoscopically to detect dysplasia and "early" cancer, amenable to successful treatment.

Helicobacter Infections↗
PubMed2003

Therapeutic strategies in gastric cancer.

Gastric cancer continues to be a major public health problem and is the second most common cause of cancer-related deaths in the world. These statistics led the American Society of Clinical Oncology (ASCO) International Affairs Committee to choose gastric cancer as the topic for the International Symposium held at the 2003 ASCO Annual Meeting. Dr Yoshiaki Ito will discuss the role of RUNX3 in the genesis and progression of human gastric cancer. Dr Pelayo Correa will present a compelling argument on the use of Helicobacter pylori therapy and antioxidants in selected high-risk population as chemoprevention strategies for gastric cancer. The controversy regarding the role of extended lymph node dissection for gastric cancer will be discussed by Dr Cornelis J.H. Van De Velde and Dr Mitsuru Sasako. Dr Van De Velde will present the European surgical approach to gastric cancer, and Dr Sasako will review the Japanese experience. The issues of whether certain patients benefit from more aggressive surgical dissection and the potential risks compared with benefits will also be discussed. Dr John Macdonald will discuss the role of adjuvant chemotherapy and adjuvant chemoradiotherapy in resected gastric cancer, as well as the role of chemotherapy in metastatic gastric cancer.

Animals↗
PubMed2003

Food groups and risk of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.

In the time period January 1998-December 2000, a case-control study on squamous cell cancer of the oesophagus was conducted in Montevideo, Uruguay. The main objective of the study was to estimate the odds ratios (ORs) associated with main food groups. For this purpose, 166 patients afflicted with squamous cell oesophageal cancer and 664 hospitalised controls were frequency matched on age and sex. Both series of patients were administered with a structured questionnaire. Aside from queries related with tobacco smoking, alcohol drinking and maté drinking, patients were interviewed with a food-frequency questionnaire (FFQ) on 64 items, representative of the usual Uruguayan diet. Red meat, salted meat and boiled meat displayed strong direct associations (OR for red meat 2.4, 95% CI 1.4-4.2). On the other hand, fish and total white meat showed moderate protective effect (OR for total white meat 0.5, 95% CI 0.3-0.9). Total fruit intake displayed a strong inverse association (OR 0.2, 95% CI 0.1-0.4), whereas total vegetable consumption presented a weak inverse association (OR for total vegetable intake 0.7, 95% CI 0.4-1.2). These results suggest that vegetables, mainly cooked vegetables, are rich in thermolabile protective substances. On the other hand, boiled (stewed) meat, which is ingested at high temperature could be, like maté, a risk factor for squamous cell cancer of the oesophagus.

Adult↗
PubMed2002

Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading.

BACKGROUND AND AIMS: Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers. METHODS: After redefining atrophy as the 'loss of appropriate glands' and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three-level scale. Interobserver reproducibility of the classification was tested by kappa statistics (general and weighted) in a series of 48 cases. RESULTS: The medians of the general agreement and weighted kappa values were 0.78 and 0.73, respectively. The weighted kappa coefficients, obtained by cross-tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement). CONCLUSIONS: By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non-metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.

Atrophy↗
PubMed2001

Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age.

The bacterium Helicobacter pylori colonizes the gastric mucosa of half of the human population, resulting in chronic gastritis, ulcers, and cancer. We sequenced ten gene fragments from pairs of strains isolated sequentially at a mean interval of 1.8 years from 26 individuals. Several isolates had acquired small mosaic segments from other H. pylori or point mutations. The maximal mutation rate, the import size, and the frequency of recombination were calculated by using a Bayesian model. The calculations indicate that the last common ancestor of H. pylori existed at least 2,500-11,000 years ago. Imported mosaics have a median size of 417 bp, much smaller than for other bacteria, and recombination occurs frequently (60 imports spanning 25,000 bp per genome per year). Thus, the panmictic population structure of H. pylori results from very frequent recombination during mixed colonization by unrelated strains.

Bayes Theorem↗
PubMed2001

[Primary hyperparathyroidism is common among postmenopausal women. Identification of genetic risk factors can contribute to individualized treatment].

Primary hyperparathyroidism (pHPT) is commonly seen in postmenopausal women. Along with the clinical characterisation of the disease, studies of molecular genetics have contributed to increased understanding of the etiology of pHPT. Genetic association studies have revealed that certain vitamin D receptor polymorphisms relate to the development of sporadic pHPT. A new type of familial pHPT was recently discovered. Studies of parathyroid adenomas have demonstrated that the tumor suppressor gene MEN1 and the oncogene cyclinD1 are of importance for the tumorigenesis.

Aged↗
PubMed2001

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.

Adult↗
PubMed2001

Anti-inflammatory and tissue-protectant drug effects: results from a randomized placebo-controlled trial of gastritis patients at high risk for gastric cancer.

BACKGROUND: The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt. METHODS: We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo. RESULTS: Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation. CONCLUSION: The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.

Adult↗
PubMed2001

Morphometric assessment of gastric antral atrophy: comparison with visual evaluation.

AIMS: As part of a multinational effort to reach a consensus in the definition and evaluation of atrophic gastritis, we applied morphometric techniques to 22 antral biopsy specimens examined visually by 12 experienced gastrointestinal pathologists. METHODS AND RESULTS: Atrophy was defined as loss of glands. Each pathologist graded atrophy with both non-standardized and standardized approaches. Discriminant function analyses of morphometric measurements were conducted to validate and grade atrophy. Kappa statistics were used to compare the performance of each pathologist against the group mode and against the discriminant functions' grading of atrophy. Three morphometric indexes showed significant differences among categories of atrophy utilizing non-standardized as well as standardized visual atrophy grades: (i) the ratio of glandular length to total mucosal thickness; (ii) the proportion of the secretory compartment area occupied by glands; and (iii) the number of glandular cross sections per 40x microscopic field. The discriminant function analyses verified all cases classified visually as either non-atrophic, or moderately/severely atrophic; it verified as mildly atrophic 40% of the cases classified visually as mildly atrophic; and classified the remaining 60% as moderately or severely atrophic. The kappa statistics were good or excellent for the majority of pathologists. CONCLUSIONS: The evaluation of antral atrophy, simply defined as loss of glands, can be reliable and reproducible. The visual grading of atrophy as absent, moderate and severe is entirely consistent with objective morphometric observations.

Atrophy↗
PubMed2001

The NeiI polymorphism in the cyclin D1 gene and sporadic primary hyperparathyroidism.

OBJECTIVES: The cell cycle regulator cyclin D1 plays an important role in parathyroid tumourigenesis. The NciI polymorphism in exon 4 has recently been associated with early onset of hereditary nonpolyposis colorectal cancer and is a prognostic indicator of nonsmall cell lung cancer and squamous cell carcinomas. Furthermore, a limited study of 28 primary hyperparathyroidism (pHPT) patients displayed a tendency of NciI influence on HPT development. We hypothesized that the NciI polymorphism may relate to a risk of developing pHPT. DESIGN, SETTING AND SUBJECTS: We genotyped 182 patients with sporadic pHPT and matched controls for the cyclin D1 polymorphism. A total of 88 pHPT patients and controls were recruited via a health-screening. RESULTS: The frequency distribution of the NciI genotypes NN, Ni, and ii were in pHPT patients and controls 22, 44 and 34%, and 26, 49 and 25%, respectively. The calculated allele frequencies were A = 0.56; G = 0.44 in cases and A = 0.49; G = 0.51 in controls. The frequency distributions did not differ comparing cases and controls when subgrouped after age and menopausal status. The NciI genotypes were not significantly associated with age of the individuals, serum (s)-calcium, s-parathyroid hormone (PTH), bone mineral density (BMD) or parathyroid tumour weight in any of the groups of pHPT patients or controls. CONCLUSIONS: No significant differences in distribution of the genotypes could be detected between the groups, suggesting that the polymorphism has minor or no pathogenic importance in the development of pHPT. Our results suggest that determination of the NciI polymorphism in the cyclin D1 gene is not a clinically useful tool for prediction of pHPT.

Aged↗
PubMed2001

Plant foods and risk of gastric cancer: a case-control study in Uruguay.

The association between plant foods intake and gastric cancer risk was investigated in a Uruguayan study on environmental factors and cancer. The study included 160 newly diagnosed and histologically verified cases of gastric carcinoma and 320 hospitalized controls. These controls were frequency-matched to the cases on age, sex, residence and urban/rural status. Total vegetable intake was associated with a reduction in risk (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.38-1.08), which was markedly attenuated after adjustment for total fruit intake. The only group of vegetables that persisted as significantly protective after controlling for total energy and total fruit consumption were allium vegetables (OR 0.56, 95% CI 0.34-0.92). On the other hand, total fruit consumption displayed a strong inverse association after controlling for total vegetable intake (OR 0.35, 95% CI 0.21-0.59). Neither tubers nor pulses were associated with gastric cancer risk. Finally, total plant foods were strongly associated with a reduced risk of stomach cancer (OR 0.31, 95% CI 0.18-0.54). It is suggested that vitamins (vitamin C and carotenoids) and bioactive substances (diallyl sulfide) could be involved in the mechanisms of action of plant foods.

Adult↗
PubMed2001

Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin production by inhibiting cyclooxygenase (COX); they are believed to cause gastroduodenal damage by inhibiting the COX-1 isoform and to have analgesic and anti-inflammatory effects by inhibiting the COX-2 isoform. As compared to conventional NSAIDs, celecoxib, a COX-2 specific inhibitor, has been shown in previous single posttreatment endoscopy studies to be associated with lower gastroduodenal ulcer rates. In response to concerns that such studies may under-represent ulceration rates, the present serial endoscopy study was designed to compare cumulative gastroduodenal ulcer rates associated with the use of celecoxib to those of naproxen, a conventional NSAID. METHODS: In this double-blind, parallel-group, multicenter study, 537 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) were randomized to treatment with celecoxib 200 mg b.i.d. (n = 270) or naproxen 500 mg b.i.d. (n = 267) for 12 wk. Gastroduodenal damage was determined from esophagogastroduodenoscopy after 4, 8, and 12 wk of therapy. Arthritis efficacy was evaluated with Patient's and Physician's Global Assessments. RESULTS: Gastroduodenal ulcer rates after celecoxib and naproxen treatment were 4% versus 19% in the 0-4 wk interval (p < 0.001), 2% versus 14% in the 4-8 wk interval (p < 0.001), and 2% versus 10% in the 8-12 wk interval (p < 0.001), respectively. After 12 wk of treatment, the cumulative incidence of gastroduodenal ulcers was 9% with celecoxib and 41% with naproxen. In the celecoxib group, gastroduodenal ulcers were significantly associated with Helicobacter pylori status (p < 0.05), concurrent aspirin usage (p = 0.001), and a history of ulcer (p = 0.010), but not with disease type (OA/RA), age, gender, other relevant medical histories, or concurrent corticosteroid or disease-modifying antirheumatic drugs usage (p > 0.05). Celecoxib produced a significantly lower incidence rate of both gastric (p < 0.001) and duodenal (p < 0.030) ulcers. The two agents produced similar improvements in Patient's and Physician's Global Assessments of arthritis efficacy. The incidence of adverse events and withdrawal rates did not differ significantly between treatments. CONCLUSIONS: As compared to naproxen (500 mg b.i.d.), use of celecoxib (200 mg b.i.d.), a COX-2 specific agent, at the recommended RA dose and twice the most frequently prescribed OA dose, was associated with lower rates of gastric, duodenal, and gastroduodenal ulcers but had comparable efficacy, in patients with OA and RA.

Adult↗
PubMed2001

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, beta-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 beta-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.

Adult↗
PubMed2001

The effect of vaccination with the PAV-250 strain classical swine fever (CSF) virus on the airborne transmission of CSF virus.

The airborne transmission of Classical Swine Fever (CSF) virus to susceptible pigs, as well as the effect of vaccination with the CSF virus PAV-250 strain was investigated on this mode of transmission. Experiment I: four pigs were inoculated with the ALD CSFV strain (10(4.3) 50% TCID) by the intramuscular route, and at the onset of fever, they were introduced into an enclosed chamber. At the end of the experiment surviving pigs were sedated, anesthetized and euthanatized. Experiment II: four pigs were previously vaccinated with the CSF virus PAV-250 strain, and at 14 days post-vaccination they were challenged with the CSF virus ALD strain. In both experiments, four susceptible pigs were exposed to infectious aerosols by placing them in a chamber connected by a duct to the adjacent pen containing the infected animals and were kept there for 86 hs. In Experiment I, pigs exposed to contaminated air died as a result of infection with CSF virus on days 14, 21 and 28 post-inhalation. These four pigs seroconverted from day 12 post-inhalation. CSF virus was isolated from these animals, and the fluorescent antibody test on tonsils was positive. In Experiment II, a vaccinated pig exposed to contaminated air did not seroconvert, nor was CSF virus isolated from lymphoid tissues. However, mild fluorescence in tonsil sections from these pigs was observed. In conclusion, CSF virus was shown to be transmitted by air at a distance of 1 m to susceptible pigs. Vaccination with the PAV-250 CSF virus strain protected the pigs from clinical disease under the same conditions.

Air Microbiology↗