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P Correa

Publications and source records attributed to P Correa.

At least 37 records · Page 2Linked to original sources
PubMed2001

KRAS mutations are not predictive for progression of preneoplastic gastric lesions.

Individuals with atrophic gastritis (n = 863) were recruited to participate in a chemoprevention trial in Nariño, Columbia. The volunteers were randomly assigned to intervention therapies, which included antibiotic treatment for Helicobacter pylori infection, and then daily dietary supplementation with antioxidant micronutrients in a 2(3) factorial design. Biopsies were obtained according to a specified protocol from designated areas in the stomach for each individual at baseline (before intervention therapy), at year 3, and at year 6. A systematic sample of 160 participants was selected from each of the eight treatment combinations, and the first exon of KRAS was examined for mutations. At year 3, the data indicated that individuals with KRAS mutations in their baseline premalignant stomach biopsies were 3.74 times as likely to progress to a higher premalignant stage than those who lacked baseline mutations (P = 0.04; C. Gong et al., Cancer Epidemiol. Biomark. Prevy. 8:167-171, 1999). However, after 6 years, baseline KRAS mutations failed to predict histological progression. Also, KRAS mutation in 72-month biopsies did not predict histological progression.

Antioxidants↗
PubMed2000

Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy.

BACKGROUND: Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño, Colombia, in the Andes Mountains. METHODS: A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided. RESULTS: All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval [CI] = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0-9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia). CONCLUSIONS: In the very high-risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma.

Adult↗
PubMed2000

Cellular dissociation of NF-kappaB and inducible nitric oxide synthase in Helicobacter pylori infection.

The transcription factor nuclear factor kappaB (NF-kappaB) regulates the expression of inducible nitric oxide synthase (iNOS). We hypothesized that induction of iNOS in Helicobacter pylori gastritis may be due to NF-kappaB activation. Antral biopsy specimens from Helicobacter pylori-infected gastritis patients were collected before (n = 30) and after antimicrobial therapy to clear the infection (n = 22). Biopsies were assessed for NF-kappaB by immunohistochemistry (p65). The mRNA and protein of iNOS were localized by in situ RT-PCR and immunohistochemistry. Both of iNOS protein and mRNA were evident in stromal inflammatory cells, but absent in epithelia. Antimicrobial therapy resulted in a 73% reduction in iNOS levels (protein, p <.002). Nuclear staining for NF-kappaB p65 was evident in epithelial cells, especially in the neck region of gastric glands, and inflammatory cells. Treatment to clear H. pylori infection resulted in a 74% reduction in the epithelial staining for NF-kappaB p65 (p =.0001), whereas the lamina propria staining was unaltered. In conclusion, H. pylori infection activates NF-kappaB and iNOS expression. However, as the changes in NF-kappaB and iNOS with H. pylori clearance occurred in different cell types (epithelial vs. inflammatory), it appears that a NF-kappaB-dependent epithelial-derived mediator may be responsible for the induction of iNOS expression.

Base Sequence↗
PubMed2000

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. CONCLUSIONS: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Adult↗
PubMed2000

Association of dietary antioxidants on the severity of gastritis in a high risk population.

PURPOSE: This study is to examine the role of dietary antioxidant intake on the severity of gastritis at the baseline in an intervention study, Chemoprevention of Gastric Dysplasia.METHODS: The Chemoprevention of Gastric Dysplasia is an intervention study conducted in the towns of Pasto and Tuquerres, Colombia. A 79-item food frequency questionnaire was administered to 1,219 subjects at baseline. Endoscopic screening for precancerous gastric lesions was performed in all subjects by biopsy and histologic diagnosis. Subjects without adequate diagnostic material (n = 18) and subjects identified as histologically normal (n = 12) or with gastric cancer (n = 4) were excluded from these analyses. Analysis of Variance on logarithm-transformed data was conducted on dietary antioxidants and the stages of gastritis (atrophic gastritis, intestinal metaplasia, and gastric dysplasia).RESULTS: After adjusting for age, body mass index, smoking status, year of education, total calorie intake, and H-pylori infection status, dietary vitamin C and vitamin E were found to be inversely associated with the severity of gastritis (p < 0.05). Decreased dietary alpha-carotene was found to be marginally associated with gastric dysplasia. Data were then stratified by town where subjects were recruited. The trends for the observed associations were apparent for dietary alpha-carotene, vitamin C and E. However, the association was significant only for vitamin C in Pasto. Compared to subjects with atrophic gastritis, subjects diagnosed with gastric dysplasia have an approximately 15% lower intake of vitamin C.CONCLUSIONS: This study confirmed the protective effect of specific dietary antioxidants on the severity of gastritis. Dietary vitamin C, and to a lesser extent, dietary vitamin E are potentially important for the prevention of gastric cancer.

Journal Article↗
PubMed2000

Transmission of Helicobacter pylori among siblings.

BACKGROUND: Helicobacter pylori infection causes chronic digestive diseases with a major public-health impact, yet the design of prevention measures is hampered by limited knowledge of transmission pathways. We studied the effect of family composition on H. pylori prevalence among rural Colombian children aged 2-9 years. METHODS: 684 children were screened for H. pylori with the 13C-urea breath test. For each child, birth order, birth spacing, number of 2-9-year-old siblings, and number of H-pylori-positive 2-9-year-old siblings was recorded. Odds ratios were estimated by logistic regression, controlling for hygiene-related exposures, socioeconomic indicators, and the number of children in the household. FINDINGS: The odds of infection increased with the number of 2-9-year-old siblings in the household (odds ratios 1.4, 2.3, 2.6, and 4.3 for one, two, three, and four to five siblings, respectively). Compared with first-born children, odds ratios for children born second and third to ninth were 1.8 (95% CI 1.0-3.3) and 2.2 (1.0-4.3), respectively. Compared with children born 10 or more years after the next older household member, those born within 4 years were 4.1 times (CI 2.0-8.6) more likely to be infected; the age gap to the next younger household member displayed a weaker effect. The number of H-pylori-positive 2-9-year-old siblings had a particularly strong effect gradient (1.5, 3.2, 5.6, and 7.1, for one, two, three, and four positive siblings, respectively). INTERPRETATION: Among rural Andean children younger than 10 years, H. pylori infection seems to be transmitted most readily among siblings who are close in age, and most frequently from older siblings to younger ones.

Child↗
PubMed2000

Gastric dysplasia: the Padova international classification.

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.

Adenocarcinoma↗
PubMed1999

Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer.

The pathogenesis of gastric cancer (GC), particularly of the intestinal type, is thought to involve a multistep and multifactorial process. Our objective was to determine the rates of transition from early to advanced gastric lesions in a population in Linqu County, China, where the GC rates are among the highest in the world. An endoscopic screening survey was launched in 1989-1990 among 3,399 residents aged 34-64 years with precancerous lesions diagnosed from biopsies taken from 7 standard locations in the stomach and from any suspicious sites. The cohort was subsequently followed, with endoscopic and histopathologic examinations conducted in 1994. Logistic regression analysis was used to estimate odds ratios (ORs) of progression to advanced lesions of various levels of severity as a function of age, sex and baseline pathology. The rates of progression were higher among older subjects, among men and among subjects with more extensive gastric lesions. 34 incident GCs were identified during the follow-up period. The ORs of GC, adjusted for age and sex, varied from 17.1, for those with baseline diagnoses of superficial intestinal metaplasia (IM), to 29.3, for those with deep IM or mild dysplasia (DYS) or IM with glandular atrophy and neck hyperplasia, to 104.2, for those with moderate or severe DYS, as compared with subjects with superficial gastritis (SG) or chronic atrophic gastritis (CAG) at baseline. Our prospective study of a high-risk population revealed sharp increases in the risk of GC and advanced precursor lesions according to the severity of lesions diagnosed at the start of follow-up. Int. J. Cancer, 83:615-619, 1999. Published 1999 Wiley-Liss, Inc.

Adult↗
PubMed1999

Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression.

Intestinal metaplasia is a well-established premalignant condition of the stomach that is characterized by mucin carbohydrate modifications defined by histochemical methods. The purpose of the present study was to see whether the expression of mucin core proteins was modified in the different types of intestinal metaplasia and to evaluate the putative usefulness of mucins as "molecular markers" in this setting. We used a panel of monoclonal antibodies with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize the expression pattern of mucins. In contrast to normal gastric mucosa, the complete form or type I intestinal metaplasia (n = 20) displayed little or no expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong expression of the intestinal mucin MUC2 in the goblet cells of all cases. The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells. MUC6 was also expressed in 16 cases of type II intestinal metaplasia and in 11 cases of type III intestinal metaplasia. The intestinal mucin MUC2 was expressed in every case of incomplete intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the different types of intestinal metaplasia allows the identification of two patterns: one defined by decreased levels of expression of "gastric" mucins (MUC1, MUC5AC, and MUC6) and expression of MUC2 intestinal mucin, which corresponds to type I intestinal metaplasia, and the other defined by coexpression of "gastric mucins" (MUC1, MUC5AC, and MUC6) together with the MUC2 mucin, encompassing types II and III intestinal metaplasia. Our results challenge the classical sequential pathway of intestinal metaplasia (from type I to type III via a type II intermediate step).

Antibodies, Monoclonal↗
PubMed1999

Geographic distribution of vacA allelic types of Helicobacter pylori.

BACKGROUND & AIMS: Distinct allelic types of Helicobacter pylori vacA have been defined. The geographic distribution of vacA alleles and cagA was assessed in this study. METHODS: A total of 735 cultures from patients in 24 countries were analyzed by polymerase chain reaction and reverse hybridization on a line probe assay (LiPA). RESULTS: In 124 (16.9%) of the 735 cultures, multiple vacA genotypes were detected, permitting analysis of 611 strains. In Europe, a distribution gradient of s1 subtypes was observed. In northern and eastern Europe, 89% were subtype s1a. s1a and s1b were equally present in France and Italy, whereas in Spain and Portugal 89% of strains were subtype s1b. s1a and s1b were approximately equally prevalent in North America. In Central and South America, virtually all s1 strains were subtype s1b. Subtype s1c was observed in 77% of the s1 isolates from East Asia. m1 and m2a have equal presence, except on the Iberian peninsula and in Central and South America, where m1 (86.2%) is more prevalent than m2 (13.8%). Subtype m2b was found exclusively among East Asian s1c strains. In all parts of the world, vacA s1/cagA-positive genotypes were associated with peptic ulcer disease (P < 0.001). CONCLUSIONS: These data indicate a geographic distribution of H. pylori genotypes and aid in understanding the relationship of H. pylori with disease.

Alleles↗
PubMed1999

Evaluation of gastric biopsies for neoplasia: differences between Japanese and Western pathologists.

Cited variations in the evaluation of gastric endoscopic biopsies for neoplasms between pathologists in Japan and those in the United States and Europe (the West) may have stemmed from several causes. The five-tiered group classification of the Japanese Research Society for Gastric Cancer (JRSGC) for interpretation of biopsies is not used in the West. Some differences may also exist in the morphologic criteria to reach a diagnosis of dysplasia or carcinoma. The goals of this study were to test the Western and Japanese classifications of gastric dysplasia and adenocarcinoma and to assess the differences between four Japanese and seven Western pathologists. One hundred biopsies, 20 from each of the five categories of the JRSGC scheme as determined by one observer, were collected. The Japanese observers used the JRSGC system, expressed in Roman numerals, whereas Western pathologists used a five- or six-tiered scheme expressed in diagnostic terms. Pairwise agreement was evaluated using k statistics within both groups. Consensus diagnosis on each biopsy was accepted as the opinion of the majority. The sensitivity and specificity of each reviewer for a certain diagnosis were also assessed. The intragroup agreements were moderate for both the Japanese (mean k = 0.663) and the Westerners (mean k = 0.652). The pairwise agreements between Japanese and Western observers were low (mean k = 0.542). Overall, the sensitivity was low for all Japanese observers for the diagnosis of dysplasia (38.7% vs 92.5%), and the sensitivity for the diagnosis of adenocarcinoma was high in both groups but higher among the Japanese observers (93.9% and 85.2%, respectively). Overall, the Japanese-Western interobserver agreement was moderate. The JRSCG scheme did not translate into higher interobserver agreement among Japanese observers. The sensitivity for the diagnosis of gastric adenocarcinoma was high for both groups, but the specificity was low among the Japanese. The cause seemed to be centered around the diagnosis of dysplasia in the Western system, which was a lesion frequently interpreted as carcinoma in Japan because of the different definitions of carcinoma in each system. Such a discrepancy might be important because it may explain some of the differences in the prevalence and prognosis of early gastric cancer between Japan and the West. An international effort is needed to harmonize morphologic criteria and analyze whether therapeutic consequences may stem from such discrepancies.

Biopsy↗
PubMed1999

Eradication of Helicobacter pylori infection with proton pump-based triple therapy in patients in whom bismuth-based triple therapy failed.

To study the effects of treatment of Helicobacter pylori infection in a hyperendemic population, 143 infected patients from the region of Nariño, Colombia, were treated for 2 weeks with clarithromycin (500 mg twice a day), amoxicillin (1 g twice a day), and either lansoprazole (30 mg twice a day) or omeprazole (30 mg twice a day). All patients belong to a low socioeconomic strata, had multifocal atrophic gastritis documented by gastric biopsies, and had been treated previously and unsuccessfully for 2 weeks with bismuth subsalicylate (262 mg four times a day), amoxicillin (500 mg three times a day), and metronidazole (400 mg three times a day). 13C-urea breath tests were performed 6, 12, 24, and 60 weeks after completing therapy. The 13C-urea breath test was negative in 79.7% of patients 1 month after finishing therapy, and in 69.2% of patients 1 year after finishing treatment. There were no differences in eradication rates between patients treated with omeprazole versus lansoprazole. Dyspepsia symptoms decreased from 74% in patients at baseline to 19% at the time of finishing treatment. In low-socioeconomic status populations with hyperendemic infection, triple therapy using omeprazole or lansoprazole plus clarithromycin and amoxicillin is an effective alternative when previous standard bismuth-based triple therapy has failed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Crohn's disease presenting as septic thrombophlebitis of the portal vein (pylephlebitis): case report and review of the literature.

Septic thrombophlebitis of the portal vein, or pylephlebitis, is an extremely rare complication of intraabdominal infection, most commonly caused by diverticulitis (1). The following case report describes a patient without previous significant medical history presenting with painless jaundice and presumed malignancy. Workup revealed pylephlebitis due to an ileal abscess secondary to Crohn's disease. The patient was successfully treated with broad spectrum antibiotics and terminal small bowel and right colon resection. To our knowledge, this is the first reported case of Crohn's disease diagnosed after presentation with pylephlebitis.

Abdominal Abscess↗
PubMed1999

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.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Sulphomucins favour adhesion of Helicobacter pylori to metaplastic gastric mucosa.

AIMS: To assess the influence of sulphomucin secretion on Helicobacter pylori colonisation and adhesion to metaplastic gastric cells. METHODS: Gastric biopsies from 230 H pylori positive patients with intestinal metaplasia were analysed. Sulphated mucins and H pylori were visualised using a new technique combining high iron diamine-alcian blue mucin stains with the Steiner silver stain for the bacteria. RESULTS: Sulphomucin secretion anywhere in the mucosa and a histological diagnosis of dysplasia increase the risk of H pylori adhesion to metaplastic cells (odds ratios 19.9 and 4.3, respectively). However, only 9.4% of cases showing sulphomucin secretion and 10.8% of cases with dysplasia had evidence of adhesion of H pylori bacteria to metaplastic cells. CONCLUSIONS: The findings suggest that H pylori may play a role in the advanced stages of carcinogenesis. It will be of interest to investigate if the relative small proportion of type III metaplasias that actually progress to carcinoma show persistence of H pylori.

Bacterial Adhesion↗
PubMed1999

The vitamin D receptor (VDR) start codon polymorphism in primary hyperparathyroidism and parathyroid VDR messenger ribonucleic acid levels.

Vitamin D regulates parathyroid cell proliferation and secretion of PTH. Increased prevalence of the polymorphic vitamin D receptor (VDR) alleles b, a, and T has been reported in sporadic primary hyperparathyroidism (PHPT), suggesting that these genetic variants may predispose to the disease. Recently, another polymorphism in the VDR gene was related to bone mineral density, and this VDR-FokI polymorphism causes different lengths of the VDR, implying possible functional consequences. The VDR-FokI polymorphism was studied in 182 postmenopausal women with sporadic PHPT and in matched controls. No significant differences in distribution of the VDR-FokI genotypes could be detected between the groups, although there was a tendency toward overrepresentation of the F allele in the PHPT patients (P = 0.05). There were no significant associations with age, serum calcium, serum PTH, bone mineral density, or parathyroid tumor weight. The VDR genotypes were unrelated to VDR and PTH messenger ribonucleic acid levels in the parathyroid adenomas of 42 PHPT patients. In 23 PHPT patients, the Ca2+-PTH set-points were determined in vivo and were unrelated to the VDR alleles. We suggest that the VDR-FokI polymorphism has at most a minor pathogenic importance in the development of PHPT.

Adult↗