Serological diagnosis of Helicobacter pylori--evaluation of four tests in the presence or absence of non-steroidal anti-inflammatory drugs.

The host's humoral immune response to Helicobacter pylori has been used in the diagnosis of active infection with these organisms. Several commercial tests are available but there are few and unconfirmed reports of their efficacy. This study aimed to assess and compare the efficacy of the following H pylori serological tests in patients treated or not treated with non-steroidal anti-inflammatory drugs (NSAID): Pyloriset Latex, Helico-G, Biolab Malakit, and Bio-Rad GAP Test IgG. Venous blood was tested at random in 124 patients, 64 of whom had received NSAID and 60 who had not. H pylori IgG antibodies were detected by latex agglutination (Pyloriset), or by ELISA (the remaining tests). Endoscopic gastric antral biopsy specimens were also obtained for urease activity, culture, and histology. Detection of H pylori by at least two of these was considered as a true positive, and its absence in all biopsy specimens as a true negative. The sensitivity values in the presence (or absence) of NSAID were: Pyloriset Latex, 59 (60)%; Helico-G, 79 (74)%; Biolab Malakit, 85 (81)%; and Bio-Rad GAP Test IgG, 100 (95)%. The respective specificity values were: 50 (71)%, 47 (59)%, 50 (65)%, and 30 (29)%. The Bio-Rad GAP Test IgG has the highest sensitivity and the lowest specificity values regardless of NSAID intake. The sensitivity of the other tests, however, is less than that of the standard biopsy related tests and their specificity is even lower in chronic NSAID users.     

非幽门螺杆菌非NSAID药物相关性溃疡

幽门螺旋杆菌(H pylori)和非甾体类抗炎药(NSAIDs)已被公认为消化性溃疡的两个最主要的病因.近年来,越来越多的临床证据表明,非H pylori和非NSAID溃疡的发生比例正在逐渐增加.这可能与H pylori感染率的降低以及临床规范的根除H pylori治疗有关,同时也与使用NSAIDs时注意防范其对胃肠道的损害有关.非H pylori和非NSAIDs溃疡病与胃酸分泌变化、胃排空异常、胃黏膜防御机制下降、应激、吸烟、遗传以及其他慢性疾病有关.在治疗上抑制胃酸,保护胃黏膜仍然是主要的手段.对这类溃疡病治疗上应更积极.     

Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs (NSAID) independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID-induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 (COX-2) expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.     

Helicobacter pylori, non-steroidal anti-inflammatory drugs and smoking in risk pattern of gastroduodenal ulcers

BACKGROUND: Helicobacter pylori, NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age. METHODS: 5967 dyspeptic patients underwent 13C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported. RESULTS: Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study. CONCLUSIONS: Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).     

Interaction between Helicobacter pylori and non-steroidal anti-inflammatory drugs in peptic ulcer bleeding

BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs (NSAIDs) are the two primary causes of peptic ulcer disease. How H. pylori and NSAIDs interact and influence the development of ulcer bleeding is still not clear. METHODS: A hospital-based, age- and sex-matched case-control study was conducted. Multivariate and stratified analyses were performed for further evaluation of the interaction between H. pylori and NSAIDs. RESULTS: Ninety-seven patients (52 gastric ulcers, 45 duodenal ulcers) and 97 non-ulcer controls were enrolled in the study. H. pylori and NSAIDs were both found to be independent risk factors for ulcer bleeding (H. pylori odds ratio, 2.22; 95% confidence interval (CI), 1.23-4.01; NSAIDs odds ratio, 4.57; 95% CI, 2.50-8.35). There was no synergistic effect. In contrast, a negative interaction was observed in the logistic regression and stratified analysis, although the difference was not significant (H. pylori adjusted odds ratio, 3.47; 95% CI, 1.73-6.95; NSAID adjusted odds ratio, 6.16; 95% CI, 3.14-12.09). CONCLUSION: H. pylori increases the risk of peptic ulcer bleeding but may play a protective role in NSAID users.     

How does Helicobacter pylori infection interact with non-steroidal anti-inflammatory drugs?

There have been conflicting clinical data on whether Helicobacter pylori (H. pylori) contributes to the pathogenesis of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). The discrepant findings reflect the complex interaction between H. pylori and NSAIDs, which has generated divergent results under different clinical conditions. This chapter reviews the pathogenetic mechanisms in ulcer formation that are common to H. pylori and NSAIDs, and explains how a better understanding of these factors might resolve some of the controversies. Existing evidence indicates that the interaction between H. pylori and NSAIDs is not an 'all-or-none' relationship. Factors such as previous exposure to NSAIDs, a past history of ulcer complication, gastric acid output, neutrophil infiltration, concurrent acid suppressive therapy and the type of NSAID used (aspirin versus non-aspirin NSAIDs) would influence the role of H. pylori as a risk factor in NSAID users. Recommendations on H. pylori eradication for different subgroups of NSAID users are proposed.     

非甾体抗炎药应用及幽门螺杆菌感染对消化性溃疡出血的影响

消化性溃疡(peptic ulcer)是消化系统常见的疾病之一,其病因多种多样.消化性溃疡的主要并发症是合并出血.近年来,幽门螺杆菌(Helicobacter pylori, H.pylori)感染和非甾体抗炎药(non-steroidal anti-inflammatory drugs, NSAIDs)应用对溃疡出血的影响日益受到重视.本文总结了这两方面因素与溃疡出血的关系,提出了相应的治疗策略.     

Helicobacter pylori and nonsteroidal anti-inflammatory drugs.

The complex interaction between H. pylori and NSAIDs implies that it is over simplistic to conclude that their relationship is independent, synergistic, or antagonistic without considering the influence of other factors. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs and low-dose aspirin all affect the outcome. Several recommendations can be made with regard to the indications of H. pylori eradication for patients requiring NSAIDs. First, patients taking NSAIDs who have ulcers or previous ulcer disease should be tested for the bacterium, and it should be eradicated if present because it is impossible to determine whether the ulcers are caused by H. pylori or NSAIDs or both. Antiulcer drugs should be prescribed to prevent ulcer recurrence for patients who continue to require NSAIDs. Although the efficacy of omeprazole is enhanced by H. pylori infection, it is not justified to leave a pathogen in the stomach in exchange for a modest therapeutic gain. Second, for patients who take low-dose aspirin, eradication of H. pylori substantially reduces the risk of ulcer bleeding. It is advisable that patients taking low-dose aspirin who are at risk of ulcer bleeding should be tested for H. pylori and treated for it if the infection is found. Third, for patients who are about to start NSAIDs, screen-and-treat H. pylori has the potential of reducing the ulcer risk at an affordable incremental cost. It might be argued that any interaction between H. pylori and NSAIDs would become irrelevant in the era of COX-2-selective NSAIDs. Even among patients who are receiving a COX-2-selective NSAID, however, a large-scale study showed that the ulcer risk is significantly higher in H. pylori-positive patients than in uninfected patients. This finding suggests that the relative importance of H. pylori in ulcer development might increase with a reduced toxicity of COX-2-selective NSAIDs. With an increasing use of low-dose aspirin for cardiovascular prophylaxis, the problem of aspirin-related ulcer disease is expected to rise. Given the significant role of H. pylori in the latter condition, screen-and-treat H. pylori might be a useful strategy for the prevention of ulcer complications in high-risk patients receiving low-dose aspirin in the future.     

幽门螺杆菌感染、服用非甾体抗炎药与消化性溃疡的关系

目的 研究消化性溃疡患者由于幽门螺杆菌（H.pylori）感染或服用非甾体抗炎药（NSAIDs）的发生率.方法 选取湖北省武汉市武昌医院2010年3月-2012年7月诊治的152例消化性溃疡患者,将其作为治疗组,同时选取同一时间段到消化科就诊的234例非消化性溃疡患者,将其作为对照组.结果 胃溃疡组感染H.pylori的几率是对照组的2.308倍,十二指肠溃疡组是对照组的8.186倍;胃溃疡组服用NSAIDs的几率是对照组的6.072倍,十二指肠溃疡组是对照组的2.823倍;胃溃疡组同时感染H.pylori和服用NSAIDs的几率是对照组的14.972倍,十二指肠溃疡组是对照组的28.873倍.结论 H.pylori感染同时服用了NSAIDs患者增加消化性溃疡的发生危险性,两种因素同时存在可以起协同作用,增加消化性溃疡的发生几率.     

Role of Helicobacter pylori eradication in aspirin or non-steroidal anti-inflammatory drug users

Helicobacter pylori(H pylori) infection and the use of non steroidal anti-inflammatory drugs (NSAIDs) including aspirin at any dosage and formulation represent well-established risk factors for the development of uncomplicated and complicated peptic ulcer disease accounting for the majority of such cases. Although the interaction between H pylori and NSAID/aspirin use in the same individuals was questioned in some epidemiological studies, it has now become widely accepted that they are at least independent risk factors for peptic ulcer disease. According to data from randomized intervention trials, naive NSAID users certainly benefit from testing for H pylori infection and, if positive, H pylori eradication therapy prior to the initiation of NSAID. A similar strategy is also suggested for naive aspirin users, although the efficacy of such an approach has not been evaluated yet. Strong data also support that chronic aspirin users with a recent ulcer complication should be tested for H pylori infection and, if positive, receive H pylori eradication therapy after ulcer healing, while they appear to benefit from additional long-term therapy with a proton pump inhibitor (PPI). A similar approach is often recommended to chronic aspirin users at a high risk of ulcer complication. H pylori eradication alone does not efficiently protect chronic NSAID users with a recent ulcer complication or those at a high-risk, who certainly should be treated with long-term PPI therapy, but H pylori eradication may be additionally offered even in this setting. In contrast, testing for H pylori or PPI therapy is not recommended for chronic NSAID/aspirin users with no ulcer complications or those at a low risk of complications.     

Mucosal erosions in longterm non-steroidal anti-inflammatory drug users: predisposition to ulceration and relation to Helicobacter pylori.

The importance of erosions in longterm non-steroidal anti-inflammatory drug (NSAID) users, their relevance to ulceration and their relation to Helicobacter pylori are unclear. This study assessed the incidence of peptic ulcers in the presence or absence of erosions or H pylori in a group of longterm NSAID users (n = 50), undergoing endoscopy at 0, 4, 12, and 24 weeks while continuing with NSAIDs. Ulcers diagnosed at baseline endoscopy were excluded. Ulcers developed in nine of 23 patients (39%) with pre-existing erosions compared with six of 27 (22%) without erosions (p < 0.05). The group infected with H pylori (n = 30) had a total of 18 patients (60%) with erosions, a total of 12 ulcers (40%), and eight ulcers (27%) complicating previous erosions, compared with five (25%, p < 0.01), three (15%, p < 0.05), and one (5%, p < 0.01) respectively in patients not infected with H pylori (n = 20). Ulcer development was not influenced by the initial number of erosions but strongly associated with H pylori positive duodenal erosions. It is concluded that ulcers are more likely to develop in longterm NSAID users who have mucosal erosions or H pylori, or both.     

幽门螺杆菌和非甾体抗炎药对胃上皮细胞增殖的影响

目的　从体外研究的角度探讨幽门螺杆菌 (Hp)和非甾体抗炎药 (NSAID)对胃上皮细胞增殖的影响及其相互作用。方法　胃癌细胞株AGS与Hp和 (或 )吲哚美辛、阿司匹林体外共培养 ,通过MTT比色法和WesternBlot法检测增殖细胞核抗原 (PCNA) ,观察Hp和NSAID对胃上皮细胞增殖的影响。结果　MTT比色法显示CagA阳性的标准Hp菌株NCTC116 37能明显促进胃上皮细胞增殖 ,吸光度 (A)值明显升高 (P <0 .0 5 ) ,而CagA阴性的标准Hp菌株NCTC12 90 8则未发现有促增殖作用 ,且Hp对上皮细胞生长的效应取决于Hp作用的密度 ,在低密度 (3.2× 10 4～ 4 .0× 10 6CFU/ml)时NCTC116 37促进胃上皮细胞生长 ,在高密度 (>2× 10 7CFU/ml)时则抑制其生长 (P <0 .0 5 )。吲哚美辛和阿司匹林均能抑制胃上皮细胞生长 (P <0 .0 5 ) ,并呈浓度依赖性。当Hp和NSAID共同作用于AGS细胞时 ,Hp的促生长作用被逆转 ,呈现出抑制细胞生长的效应 ,A值明显降低 (P <0 .0 5 )。PCNA的WesternBlot检测结果发现 ,Hp菌株NCTC116 37可明显促进细胞PCNA的表达 ,而吲哚美辛和阿司匹林则抑制其表达 ,当两者共同作用于AGS细胞时 ,PCNA的表达明显减弱。结论　Hp对胃上皮细胞的增殖效应与Hp的密度及菌株差异有关 ,CagA阳性的Hp易促进胃上皮细胞生长 ,NSAID可抑制其     

Changes in Helicobacter pylori status in patients with rheumatoid arthritis under non-steroidal anti-inflammatory drugs

BACKGROUND: The role of Helicobacter pylori infection in rheumatoid arthritis (RA) patients during treatment with non-steroidal anti-inflammatory drugs (NSAID) is still unclear. METHODS: By means of endoscopy and biopsy, gastroduodenal lesions and H. pylori status were repeatedly examined in 88 RA patients at intervals ranging from 26 to 49 months. Histology and culture were applied to determine H. pylori status. Serial changes in gastroduodenal lesions and histologic score for mucosal atrophy were compared among groups classified by initial and second H. pylori status. RESULTS: There were 28 patients with continuously positive H. pylori infection (CP group), 33 patients with continuously negative H. pylori infection (CN group), 7 patients in whom H. pylori status became negative (PN group), and 20 patients in whom H. pylori status could not be determined (UD group). Age, duration and species of NSAID, disease activity of RA, gastroprotective drugs applied and the prevalence of gastroduodenal mucosal lesions were not different among the groups at either the initial or the second examination. In the PN group, the score for mucosal atrophy at the second examination was significantly lower than at the initial examination, whereas no difference was found for the CP, CN and UD groups. Overall, histologic score for mucosal atrophy was higher in H. pylori-positive patients than in H. pylori-negative patients at both initial and second examination. CONCLUSIONS: In RA patients using NSAIDs, H. pylori infection may not affect the course of gastroduodenal lesions and activity of RA, but the infection contributes to mucosal atrophy.     

Risk of ulcer bleeding in patients infected with Helicobacter pylori taking non-steroidal anti-inflammatory drugs

OBJECTIVE: To determine whether Helicobacter pylori is an independent risk factor for bleeding peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. DESIGN: A prospective matched case-control study. SETTING: Odense University Hospital, Denmark. SUBJECTS: 132 patients with a bleeding peptic ulcer (n=124) or haemorrhagic gastritis (n=8) at endoscopy who had taken an NSAID in the previous week and 136 controls who had taken NSAIDs without gastrointestinal complications. The controls were recruited from rheumatology and geriatric outpatient clinics. MEASUREMENTS: H pylori status assessed by serology and 13C-urea breath test and regarded as positive if either test was positive. Data on potential confounding factors including smoking and alcohol were collected by interview. MAIN RESULT: H pylori was present in 57% of cases and 43% of controls. The adjusted odds ratio of bleeding from a peptic ulcer owing to H pylori infection in NSAID users was 1.81 (95% CI 1.02 to 3.21) and was similar in aspirin and non-aspirin NSAID users. Peptic ulcer bleeding was also statistically significantly associated with a history of previous ulcer bleeding, dyspepsia within the previous 3 months, drinking alcohol but not with smoking. About 16% of bleeding peptic ulcers in NSAID users could be attributed to H pylori infection. CONCLUSION: NSAID users infected with H pylori have an almost doubled risk of bleeding peptic ulcer compared with uninfected NSAID users.     

Helicobacter pylori and bleeding duodenal ulcer: prevalence of the infection and role of non-steroidal anti-inflammatory drugs.

BACKGROUND: Several authors have reported low prevalence of Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both invasive and non-invasive methods, and to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Ninety-two patients with bleeding DU were prospectively studied. The use of NSAIDs was evaluated by specific questionnaire. As a control group, 428 patients undergoing outpatient evaluation for the investigation of dyspepsia and found to have a DU at endoscopy were included. At endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test was carried out in all patients. Breath test was repeated in patients treated with omeprazole during the hospitalization if H. pylori was not detected with the first test. RESULTS: Gastric biopsies could be obtained in 39 patients with UGIB. Three patients with UGIB treated with omeprazole and being H. pylori-negative with the first breath test were finally considered infected with the second test. Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7% with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value for both diagnostic tests was 0.64. NSAID intake was more frequent in patients with UGIB (34%) than in those without UGIB (5.6%) (P < 0.001), while H. pylori infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those without UGIB (99.1% (98%-100%); P < 0.001). Even in patients with UGIB, NSAID intake was the only risk factor in 5% of cases. The proportion of cases without H. pylori infection and without NSAID intake was very low in both bleeding and non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7% (89%-99%) when patients taking NSAIDs were excluded. In the multivariate analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB; however, neither H. pylori status nor the interaction between H. pylori infection and NSAID intake correlated with UGIB. In the multivariate analysis in the subgroup of patients with UGIB, NSAID use was the only variable which correlated with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). CONCLUSIONS: The most important factor associated with H. pylori-negative bleeding DU is NSAID use, and if this factor is excluded prevalence of infection is almost 100% (97%), similar to that found in patients with non-bleeding DU (and without NSAID intake). Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to that of non-complicated DU disease.     

Effect of Helicobacter pylori colonisation on gastric mucosal eicosanoid synthesis in patients taking non-steroidal anti-inflammatory drugs.

Colonisation with Helicobacter pylori may influence susceptibility to gastroduodenal injury and ulceration in patients taking non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to determine if Helicobacter pylori colonisation altered eicosanoid synthesis by gastric mucosa in these patients. Sixty five patients with long-standing NSAID intake and 23 control subjects underwent endoscopy. In vitro gastric antral biopsies were stimulated by vortex mixing and eicosanoid measurements determined by radioimmunoassay. Helicobacter pylori colonisation was determined by a CLO test (a gel based rapid urease test) and histological assessment. Median prostaglandin E2 synthesis by gastric mucosa was 61.0 (interquartile range: 19.2-73.1) pg/mg in control subjects colonised with Helicobacter pylori compared with 46.5 (23.3-65.5) pg/mg in Helicobacter pylori negative subjects. This was not significantly different. Treatment with NSAIDs was associated with a significant difference (p < 0.001) in prostaglandin E2 (PGE2) synthesis between those colonised with Helicobacter pylori (37.5(22.0-77.3) pg/mg) compared with patients not infected (12.6(7.0-19.3) pg/mg). Values in patients taking NSAIDs who were colonised were not different from control subjects. Synthesis of PGE2 was strongly associated with type B (chronic active), but not type C (chemical) gastritis. Dyspeptic symptoms were more common in subject colonised with Helicobacter pylori (p < 0.002) and were associated with higher PGE2 synthesis. In patients taking NSAIDs Helicobacter pylori colonisation removes rather then enhances depression of PGE2 synthesis associated with NSAIDs and may promote dyspepsia associated with ulcers and prevent superficial mucosal injury.     

Effect of non-steroidal anti-inflammatory drugs on gastric and duodenal prostaglandin concentrations in patients with Helicobacter pylori infection.

BACKGROUND/AIMS: Both Helicobacter pylori and non-steroidal anti-inflammatory drugs are reported to affect gastroduodenal prostaglandin synthesis. However, their influence on gastric mucosal prostaglandins remains unclear. The aim of this study was to investigate the influence of nonsteroidal anti-inflammatory drugs on mucosal prostaglandin synthesis in patients with Helicobacter pylori infection. METHODOLOGY: We enrolled 87 Helicobacter pylori-infected patients in this study (gastric ulcer: 33, duodenal ulcer: 41, and non-ulcer dyspepsia: 13). Of them, 27 patients received non-steroidal anti-inflammatory drugs. Endoscopy was performed and biospy specimens from gastric body, antrum and duodenal bulb were assessed for Helicobacter pylori and prostaglandin concentration. RESULTS: A significantly lower mucosal prostaglandin E2 level at gastric body (142.2 +/- 28.1 ng/mg vs. 222.0 +/- 12.4 ng/mg, mean +/- SEM) and antrum (131.3 +/- 26.4 ng/mg vs. 226.0 +/- 19.0 ng/mg) was noted in Helicobacter pylori-infected gastric ulcer patients with non-steroidal anti-inflammatory drugs ingestion than in that of patients without non-steroidal anti-inflammatory drugs ingestion (p < 0.05). Using a multivariate analysis, we found that non-steroidal anti-inflammatory drug was an independent variable affecting gastric and duodenal mucosal prostaglandin E2 synthesis in patients with Helicobacter pylori-infected gastric ulcer. CONCLUSIONS: Non-steroidal anti-inflammatory drugs decrease gastroduodenal mucosal prostaglandin E2 synthesis in gastric ulcer patients with Helicobacter pylori infection.