Risk factors for ulcer development in patients with non-ulcer dyspepsia: a prospective two year follow up study of 209 patients.

BACKGROUND AND AIMS: A subset of non-ulcer dyspepsia (NUD) disorders can evolve into peptic ulcer disease. This prospective study attempted to determine the independent risk factors for ulcer formation in NUD patients, and compared the natural history of Helicobacter pylori positive and negative NUD subjects. METHODS: From May 1997 to April 1999, consecutive NUD patients were enrolled into the study. Endoscopy was performed routinely on enrolment, at the end of the second and 12th months, and whenever there was a dyspepsia attack. Patients were prospectively followed up for two years. RESULTS: Peptic ulcers occurred in 16 of 209 NUD patients during the two year follow up period. Multivariate analysis of 13 host and bacterial factors demonstrated that advanced age (odds ratio 2.90), H pylori infection (odds ratio 3.59), and use of non-steroidal anti-inflammatory drugs (NSAID; odds ratio 4.46) were independently significant in predicting subsequent peptic ulcer development. NUD patients with all three risk factors had a 75% (3/4) risk of developing peptic ulcer but the ulcer incidence in patients without any of the risk parameters was only 1.2% (1/84). The resolution rate of symptoms in the H pylori positive NUD patients was similar to the H pylori negative patients (57.9% v 49.1%; 95% confidence interval (CI) -5 to 22). However, rates for subsequent peptic ulcer and erosion development were significantly higher in H pylori positive patients than in H pylori negative patients (ulcer 12.6% v 3.5%, 95% CI 1-16; erosion 23.2% v 12.3%, 95% CI 1-21). CONCLUSION: A small but significant proportion of NUD patients develop peptic ulcer after long term follow up. H pylori infection, NSAID use, and advanced age are independent risk factors for subsequent ulcer formation. Follow up endoscopy is strongly indicated for an NUD patient with multiple risk factors for ulcer formation when symptoms recur.

Risk factors for presentation with bleeding in patients with Helicobacter pylori-related peptic ulcer diseases.

At present, there is no study that simultaneously addresses the apparent differences between bacterial and host factors in patients with bleeding and nonbleeding Helicobacter pylori-related ulcer diseases. Therefore, we designed this prospective study to evaluate whether there are identifiable differences between the two groups of patients whose H. pylori-related peptic ulcer diseases present with bleeding or dyspepsia. From July 1996 to November 1996, consecutive patients presenting with upper gastrointestinal bleeding or dyspepsia were enrolled if H. pylori-related ulcer diseases were confirmed. Fifteen clinical, endoscopic, histologic, and serologic factors were tested for association with ulcer bleeding by a logistic regression analysis. In the study period, bleeding occurred in 39 out of 119 patients with H. pylori-related peptic ulcer diseases. Multivariate analysis showed that ingestion of nonsteroidal antiinflammatory drugs (NSAIDs; p = 0.0156; odds ratio = 5:4), ulcer size > or = 1 cm (p = 0.0033; odds ratio = 4:2), and low bacterial density (p = 0.0030; odds ratio = 4:1) were independent factors associated with the risk of bleeding. There were no associations between ulcer bleeding and age, sex, smoking, alcohol consumption, the histologic grade of gastritis, location and number of ulcers, and the cytotoxin-associated gene (CagA) status of H. pylori strain. Therefore, we concluded that H. pylori-related ulcer patients who use NSAIDs or have large ulcers are more likely to present with upper gastrointestinal bleeding; that the CagA-bearing strains are not associated with the development of bleeding complication in patients with peptic ulcer diseases; and that the exact reason concerning the association between low bacterial density and ulcer bleeding merits further investigation.

Impact of Helicobacter pylori eradication on the development of MALT, gland atrophy and intestinal metaplasia of the antrum.

BACKGROUND: Chronic Helicobacter pylori infection leads to the development of mucosa-associated lymphoid tissue (MALT), gland atrophy, intestinal metaplasia, and in certain individuals, gastric lymphoma and adenocarcinoma. We conducted a prospective study to determine the effect of H pylori eradication on the development of MALT, gland atrophy and intestinal metaplasia. METHODS: From July 1995 to October 1996, 63 consecutive patients with H pylori-associated peptic ulcer disease were enrolled in a bacterial eradication trial. The grade of MALT and the degree of gastritis of the antrum were assessed using Wotherspoon's scale and the Sydney system before treatment, and at eight weeks and one year after H pylori eradication therapy. RESULTS: During the study period, 43 patients received complete follow-up. In the patient group with eradication failure (n = 22), MALT score was significantly decreased at the end of the eighth week (p < 0.05) but returned to the initial level by one year of follow-up. There were no changes in the scores for inflammation, neutrophil activity, gland atrophy or intestinal metaplasia at the end of the eighth week and at one year following H pylori eradication therapy. In contrast, there was a marked reduction in the MALT, inflammation, and activity scores at eight weeks (p < 0.01, < 0.05 and < 0.05, respectively) and one year after treatment (p < 0.05, < 0.001 and < 0.001, respectively) in the patient group with successful eradication (n = 21). However, no significant changes in gland atrophy and intestinal metaplasia were observed during the follow-up period. CONCLUSIONS: Eradication of H pylori leads to regression of MALT in the stomach, but the degrees of gland atrophy and intestinal metaplasia remain unchanged, even after one-year of follow-up.

Impact of bacterial eradication on the cell proliferation and p53 protein accumulation in Helicobacter pylori-associated gastritis.

BACKGROUND: This study investigates the cell proliferation and the expression of p53 protein in Helicobacter pylori (H. pylori)-associated gastritis and assesses the effect of bacterial eradication on these epithelial factors. MATERIAL AND METHODS: Seventy-nine patients with H. pylori-associated gastritis were randomized into the control group (n = 38) and anti-H. pylori group (n = 41). Each patient received endoscopic examinations with gastric biopsy before and 8 weeks after the treatment. The specimens from gastric antrum were immunostained for monoclonal antibodies against the proliferating cell nuclear antigen (PCNA) and p53 protein. RESULTS: In the control group, the total labeling index (L.I.) of PCNA and the positive index (P.I.) of p53 in the whole foveolar epithelium were unchanged after treatment. In the anti-H. pylori group, 35 of 41 cases (85.3%) achieved eradication of H. pylori. Amongst the H. pylori-eradicated cases, the total L.I. of PCNA in the whole foveolar epithelium did not meaningfully alter after H. pylori elimination (p > 0.05). However, a significant reduction of L.I. was observed in the middle compartments of the gastric pits (before vs. after treatment: 14.0 vs. 7.3, p < 0.05). With regard to the p53 expression, the P.I.s were significantly decreased in the whole foveolar epithelium (before vs. after treatment: 0.57 vs. 0.17, p < 0.05) and in each compartment of the gastric pits (before vs. after treatment: [upper compartment]: 0.34 vs. 0.15, p < 0.05; [middle compartment]: 0.67 vs. 0.23, p < 0.05; [lower compartment]: 0.71 vs. 0.20, p < 0.05) after eradication of H. pylori. CONCLUSIONS: Bacterial eradication reverses the hyperproliferating status of the foveolar epithelium in patients with H. pylori gastritis and leads to a decrease in p53 accumulation in the epithelial cells.

Expression of inducible nitric oxide synthase and apoptosis in human lupus nephritis.

To understand the expression of inducible nitric oxide synthase (iNOS) and its possible association with apoptosis in human lupus nephritis, 48 renal tissue samples from patients with lupus nephritis were investigated immunohistochemically and by the terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling method for the detection of iNOS and apoptosis, respectively. Modulation of apoptosis by p53 and Bcl-2 was also evaluated. This study showed immunohistochemical evidence of iNOS expression, predominantly in the glomerular and tubulointerstitial cells of class-IV lupus nephritis. The frequency of iNOS+ glomeruli was significantly correlated with that of apoptosis+ glomeruli, and the frequency of the latter was also significantly correlated with that of the glomeruli showing p53 overexpression. Bcl-2 was predominantly expressed in the cellular and fibrocellular crescents. This study suggests that induction of iNOS, and thus nitric oxide production, plays a role in the occurrence of apoptosis in the glomeruli of lupus nephritis; and the occurrence of apoptosis might in part be modulated by p53 and Bcl-2-related pathways. The expression of Bcl-2 in predominantly cellular and fibrocellular crescents suggests that Bcl-2 may participate in persistent proliferation of the crescentic cells.