Development Of Peptic Ulcer Disease Research Articles

Helicobacter pylori

Helicobacter pylori represents one of the most common and medically prominent infections worldwide. Infection with this microaerobic, gram-negative bacterium has been established as an etiologic factor in the development of peptic ulcer disease. In addition, H pylori infection has been associated firmly with the development of gastric neoplasia, including gastric adenocarcinomas and gastric mucosa-associated lymphoid tissue lymphomas. Effective antimicrobial treatment depends on sensitive and accurate diagnostic approaches. This review article discusses invasive and noninvasive strategies for diagnosis of H pylori infection. Invasive methods requiring endoscopic evaluation include bacteriologic culture and susceptibility testing, histopathologic studies, molecular diagnostics, and rapid urease testing. Noninvasive approaches include fecal antigen detection, serologic testing, and urea breath testing.

Occurrence of peptic ulcer disease in connective tissue disease patients associated with xerostomia.

Saliva plays a role in mucosal protection and ulcer healing. : To study whether decreased salivary production leads to peptic ulcer disease in connective tissue disease patients associated with xerostomia. Two hundred and two connective tissue disease patients (90 with xerostomia and 112 without xerostomia) were enrolled. Their demographic data and use of medications were recorded. Peptic ulcer disease was confirmed by endoscopy. The stimulated salivary output and secretory epidermal growth factor level were measured. Compared with non-xerostomic counterparts, xerostomic patients manifested a higher occurrence of peptic ulcer disease (31% vs. 12%, P = 0.001), lower stimulated salivary output (9.3 +/- 4.1 vs. 22.9 +/- 5.9 mL/15 min, P < 0.001) and lower stimulated salivary epidermal growth factor output (1.40 +/- 0.77 vs. 3.00 +/- 0.96 ng/min, P < 0.001). Multivariate analysis disclosed that an older age (> or = 60 years) (odds ratio, 4.71; P < 0.001), xerostomia with stimulated salivary output of < or =1 mL/min (odds ratio, 7.54; P = 0.014) and the use of non-steroidal anti-inflammatory drugs (odds ratio, 5.76; P = 0.031) were the risk factors leading to peptic ulcer disease. In addition, xerostomic connective tissue disease patients receiving non-steroidal anti-inflammatory drugs manifested an extremely high risk of development of peptic ulcer disease (odds ratio, 19.78; P < 0.001). Ageing, the use of non-steroidal anti-inflammatory drugs and poor salivary function are potential risk factors for the development of peptic ulcer disease in patients with connective tissue disease. If these xerostomic subjects consume non-steroidal anti-inflammatory drugs, they will encounter an extremely high peptic ulcer disease risk.

Generalized anxiety disorder and peptic ulcer disease among adults in the United States.

Previous research has suggested a link between chronic anxiety and peptic ulcer disease, though recent evidence documenting an infectious cause (Helicobacter pylori) for ulcer has led to doubt about this association. The goal of the current study was to determine the relationship between generalized anxiety disorder (GAD) and self-reported peptic ulcer disease (PUD) among adults in the community. Data were drawn from the National Comorbidity Survey, a representative household survey of the adult population of the United States (N = 8098). Multivariate logistic regression analyses were used to determine the relationship between GAD and self-reported ulcer, controlling for differences in sociodemographic characteristics and psychiatric and medical comorbidity. GAD was associated with a significantly increased risk of self-reported PUD (odds ratio = 2.8, 95% confidence interval = 1.4-5.7; p = .0002) after adjusting for differences in sociodemographic characteristics, comorbid mental disorders, and physical morbidity. Further analyses revealed a dose-response relationship between number of GAD symptoms (odds ratio = 1.2, 95% confidence interval = 1.1-1.4; p = .001) and increased risk of self-reported PUD. These findings are consistent with and extend previous clinical and epidemiologic data, providing evidence of a dose-response relationship between GAD and self-reported PUD among adults in the general population. The mechanism of this association remains unknown. Future work investigating the relationship between onset of GAD and development of PUD in prospective, longitudinal, epidemiologic data with objective measures of physical health status and mental health may be useful in improving our understanding of this link.

Research agenda for pediatric gastroenterology, hepatology and nutrition: acid-peptic diseases. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

Research agenda for pediatric gastroenterology, hepatology and nutrition: acid-peptic diseases. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation.

The potential risk factors leading to peptic ulcer formation in autoimmune disease patients receiving corticosteroid treatment.

To study the potential risk factors leading to peptic ulcer disease among autoimmune disease patients on corticosteroid treatment. One hundred and thirty-eight corticosteroid-treated autoimmune disease patients were enrolled; their demographic data were recorded and laboratory data were measured. Endoscopy was performed to assess the occurrence of peptic ulcer disease. Helicobacter pylori infection was diagnosed on the basis of rapid urease test and histological examination. Twenty-eight (20%) of 138 autoimmune disease patients had peptic ulcer disease, including 17 with gastric ulcer, eight with duodenal ulcer and three with gastric ulcer plus duodenal ulcer. Eighty five (62%) had used non-steroidal anti-inflammatory drugs and 46 (33%) had H. pylori infection. The majority of peptic ulcer disease subjects showed the following characteristics: age >or= 60 years; male; smokers; non-steroidal anti-inflammatory drug users, particularly the non-specific cyclo-oxygenase inhibitors; presence of hyperpepsinogenaemia I; low H. pylori colonization (P < 0.05). Multivariate analysis revealed that an age >or= 60 years [odds ratio (OR), 6.80; P = 0.001], smoking (OR, 7.94; P = 0.004) and the use of non-specific cyclo-oxygenase inhibitors (OR, 4.71; P = 0.030) were the predominant risk factors for the development of peptic ulcer disease among these patients, whereas H. pylori infection showed a protective role (OR, 0.20; P = 0.022). Old age, smoking and the use of non-specific cyclo-oxygenase inhibitors are risk factors for peptic ulcer disease in autoimmune disease patients on corticosteroid treatment. H. pylori infection appears to protect against peptic ulcer disease in these patients.

Helicobacter pylori anti-CagA antibodies: prevalence in symptomatic and asymptomatic subjects in Turkey.

Several reports have shown the prevalence of anti-CagA antibodies to be associated with the development of peptic ulcer diseases, while others have indicated that there is no such association. To examine the prevalence of antibodies to CagA and other Helicobacter pylori antigens in symptomatic and asymptomatic subjects in Turkey. subjects and Sixty-six symptomatic subjects, 16 to 74 years of age, were examined for H pylori by biopsy-based tests and ELISA. One hundred nineteen asymptomatic subjects, 20 to 65 years of age, were also tested serologically for the presence of H pylori. Samples from both groups that were found to be positive for H pylori by ELISA were then tested by immunoblotting. Fifty-four (82%) symptomatic subjects and 76 (64%) asymptomatic subjects were found to be H pylori-positive by ELISA. Samples from 30 symptomatic subjects who were found to be H pylori-positive by ELISA were analyzed by immunoblotting. Antibodies to CagA (116 kDa) antigen were detected in immunoblots of 11 of 14 (79%) with chronic gastritis, 12 of 13 (92%) with duodenal ulcer and three of three (100%) with gastric cancer. Antigens of the following molecular weights were also detected in these 30 subjects: 89 kDa (VacA) in 21 (70%), 37 kDa in 21 (70%), 35 kDa in 19 (63%), 30 kDa in 27 (90%) and 19.5 kDa in 19 (63%). Immunoblots of 40 ELISA-positive asymptomatic subjects showed that 33 (83%) had antibodies to CagA antigen, 26 (65%) to VacA antigen, 30 (75%) to a 37 kDa antigen, 30 (75%) to a 35 kDa antigen, 39 (98%) to a 30 kDa antigen and 36 (90%) to a 19.5 kDa antigen. Antibodies to CagA antigen were prevalent in both groups, regardless of the presence of gastroduodenal disease.

Relevance of vacA genotypes of Helicobacter pylori to cagA status and its clinical outcome.

Background :Determination of vacA mosaicism may be important because specific Helicobacter pylori vacA genotype can be used to predict different clinical outcome. The aim of this study was to assess the relationship of vacA genotypes of Helicobacter pylori to cagA status and its development of peptic ulcer diseases in Korean patients.Methods :Gastric biopsy specimens were obtained from 53 patients with gastric ulcer (GU), 57 with duodenal ulcer (DU) and 26 with chronic gastritis (CG) patients; all patients were infected with Helicobacter pylori. Bacterial mRNAs in the gastric mucosa were amplified by RT-PCR, using synthetic oligonucleotide primers specific for the vacA and the cagA gene. Patients with vacA s1 subtype were further examined to determine whether they had s1a or s1b subtype.Results :There was no correlation in frequency of vacA s1 and/or s1a genotype between CG and either GU or DU, as the vacA s1 and s1a/m1 were present in the majority of strains independent of clinical status (s1 ; 100.0% versus 94.3 % or 93.0 % and s1a/m1 : 76.9% versus 62.3% or 64.9%, respectively). Likewise, there was no difference in the prevalence of the cagA gene between CG and either GU or DU patients (92.3% versus 90.6% or 98.2%, respectively). In addition, the cagA-negative status did not predict the presence of vacA s2 genotype.Conclusion :These results strongly suggest that either cagA or vacA s1 and/or s1a is not proved to be a useful marker to distinguish disease-specific Helicobacter pylori strains for the development of peptic ulcer diseases in Korean patients.

271. INCREASED EXPRESSION OF HUMAN β-DEFENSINS (hBD) 1 AND 2 INH.PYLORI-POSITIVE AND -NEGATIVE GASTRITIS

Introduction: H.pylori is the causative agent of most cases of chronic superficial gastritis in humans and a risk factor for the development of peptic ulcer disease and gastric cancer. Our...

Helicobacter pylori infection in children: update.

Despite its worldwide distribution, the pathogenesis of Helicobacter pylori associated gastroduodenal disease remains poorly understood. What is clear is that H. pylori infection rarely resolves spontaneously and that the chronic gastritis that accompanies infection is typically maintained for the duration of infection. Ultimately, if untreated, this chronic inflammation predisposes a subset of individuals to develop gastric or duodenal ulcers and even gastric cancer. Chronic long-lasting H. pylori infection, particularly when acquired early in childhood, can predispose an individual to a significantly increased risk of developing gastric cancer. These studies were so compelling that the World Health Organization has recently classified H. pylori as a type 1 human carcinogen. Since the discovery of H. pylori less than 20 years ago, this infection has continued to generate considerable interest in the medical and scientific community. As we enter the new millenium, there are now a number of effective treatments for children in whom H. pylori-associated peptic ulcer disease is diagnosed. Although there is now overwhelming evidence to confirm that H. pylori plays an etiologic role in the development of peptic ulcer disease, only a small number of these children develop H. pylori disease. In this review, we highlight some of the recently published pediatric studies addressing the role H. pylori plays in the development of gastroduodenal disease in children.

Allelic variation in Helicobacter pylori: progress but no panacea

See article on page 499 Helicobacter pylori colonisation in the stomach is associated with increased risk for the development of peptic ulcer disease and non-cardia gastric adenocarcinoma.1 However, the incidences...

Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implications for managing infection in children.

Helicobacter pylori in childhood: new insights into the immunopathogenesis of gastric disease and implications for managing infection in children.

The relation between Helicobacter pylori and nonsteroidal anti-inflammatory drugs

Both infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs (NSAIDs) can result in gastritis and ulcers. H. pylori has been identified as a major etiologic factor in the development of peptic ulcer disease; however, its relationship to NSAID-associated toxicity is less well characterized. Several studies have suggested that NSAID use does not increase susceptibility to H. pylori, and the converse has also been suggested, namely, that H. pylori does not exacerbate NSAID-associated injury. H. pylori itself may stimulate production of gastric prostaglandins, which may have a role in ulcer healing. More carefully controlled studies may be better able to elucidate the individual and synergistic mechanisms involved in ulceration induced by H. pylori and NSAIDs. Recent studies have suggested that elimination of H. pylori before NSAID treatment decreases ulcer occurrence. Therefore, at this time, eradication of H. pylori should be considered only in certain high-risk patients, i.e., those with a history of gastroduodenal ulcers.

H. pylori stimulates gastrin release from canine antral cells in primary culture.

Patients chronically infected with Helicobacter pylori are known to have hypergastrinemia. Previous studies have demonstrated the stimulation of gastrin from isolated G cells by monocytes and cytokines. The aim of this study was to determine if H. pylori can directly stimulate gastrin secretion. The secretion of gastrin from canine G cells in 48-h primary cultures was investigated using either live H. pylori bacteria or various bacterial extracts from three well-characterized strains. Whole bacterial sonic extracts and water-extracted surface proteins, but not PBS extracts, from strains 43579 (CagA+/VacA+), 60190 (CagA+/VacA+), and 60190:v1 (CagA+/VacA-) significantly stimulated gastrin release. Controls demonstrated that gastrin stimulation by the sonic extracts was not due to a direct toxic effect on G cells. We conclude that H. pylori produces a soluble factor(s), which can directly stimulate gastrin release in enriched canine G cell cultures. This stimulatory effect may play an important role in the H. pylori-associated hypergastrinemia and subsequent development of peptic ulcer disease.

Relationship between mucosal levels of interleukin 8 and toxinogenicity of Helicobacter pylori

To investigate if an association exists between in-vivo mucosal levels of IL-8 and bacterial expression of cytotoxin and cagA gene of H. pylori. Seventy-two dyspeptic patients referred for endoscopy were studied, including 36 patients with peptic ulcer (PU) and 36 with non-ulcer dyspepsia (NUD). Biopsies were taken for histology, H. pylori culture and measurement of IL-8 by ELISA. To test the ability of H. pylori to produce cytotoxin (VacA), broth culture supernatants were assayed on Vero cells and vacuolation measured. PCR was used to detect the cagA gene of H. pylori. H. pylori was isolated in 52 of 72 patients studied. Among the 52 strains, 25 (49%) were VacA+ve/cagA+ve; 12 (23%) were VacA-ve/cagA-ve; the remaining 15 strains (28%) were either VacA+ve/cagA-ve or VacA-ve/cagA+ve. IL-8 levels (median (interquartile) pg/mg) in patients infected with VacA+ve (1.5 (0.64, 2.84)) or cagA+ve strains (1.25 (0.72, 2.34) were significantly higher than in those with VacA-ve (0.76 (0.4, 1.0)) or cagA-ve strains (0.5 (0.4, 1.5); p<0.05). The neutrophil infiltration score was also higher in patients infected with VacA+ve or cagA+ve strains than in those infected with VacA-ve or cagA-ve strains (p<0.05). VacA+ve/cagA+ve strains were associated with an enhanced production of mucosal IL-8 in vivo and correlated with a stronger infiltration of neutrophils. Enhanced mucosal production of IL-8 and its role in neutrophil chemotaxis and activation could be important in H. pylori-induced gastroduodenal inflammation and in the development of peptic ulcer disease.

Infection with Helicobacter pylori Expressing the cagA Gene Is Not Associated with an Increased Risk of Developing Peptic Ulcer Diseases in Korean Patients

Background: Helicobacter pylori strains possessing the cagA gene have been postulated to have a disease-specific relationship to peptic ulcer. The purpose of this study was to investigate the relationship between the infection with Helicobacter pylori expressing the cagA gene and the development of peptic ulcer diseases in Korean patients. Methods: Genomic DNA and bacterial mRNA in the gastric mucosa were amplified by polymerase chain reaction (PCR) and reverse transcription PCR, using synthetic oligonucleotide primers to cagA genes to compare the prevalence of cagA genes in 35 patients with non-ulcer gastritis and 99 patients with gastric or duodenal ulcer disease (53 and 46, respectively). Two different primer sets for the cagA gene were used. The first primer set amplified a 298-bp region (nucleotides 1751-2048), and the second set amplified a 349-bp region (nucleotides 1228-1249). Results: The expected 298- and 349-bp PCR amplicons were identified as follows: 1) 32 (91.4%) and 30 (85.7%) of 35 non-ulcer gastritis patients; 2) 51 (96.2%) and 50 (94.3%) of 53 benign gastric ulcer patients; and 3) 46 (100.0%) and 40 (87.0%) of 46 duodenal ulcer patients, respectively. Conclusion: These results strongly suggest that the cagA gene will not prove to be a useful marker to distinguish disease-specific H. pylori strains in the development of peptic ulcer diseases in Korean patients.

Comparison of Salivary and Serum Enzyme Immunoassays for the Diagnosis ofHelicobacter pyloriInfection

Infection with Helicobacter pylori has been established as an important risk factor for the development of peptic ulcer disease, gastritis and gastric cancer. The diagnosis of H pylori infection can be established by invasive or noninvasive techniques. Two noninvasive enzyme immunoassays (EIAs) for antibody detection - HeliSal and Pylori Stat - were compared with histology. Both assays detect immunoglobulin (Ig) G directed against purified H pylori antigen. The test populations consisted of 104 consecutive patients scheduled for upper gastrointestinal endoscopy. Of these patients, 97 (93%) had symptoms compatible with peptic ulcer disease. Saliva and serum were collected simultaneously at the time of endoscopy. Salivary EIA had a sensitivity of 66%, specificity of 67%, positive predictive value of 67% and negative predictive value of 66% compared with the serum EIA, where the results were 98%, 48%, 64% and 96%, respectively. Although the salivary EIA is an appealing noninvasive test, it was not a sensitive and specific assay. The serum EIA also lacked specificity, but was highly sensitive with a good negative predictive value. Although a negative serum EIA rules out H pylori infection, a positive result must be interpreted in the clinical context and confirmed with a more specific measure.

Pathophysiology of Helicobacter pylori-induced Gastritis and Peptic Ulcer Disease

Helicobacter pylori causes persistent infection and inflammation in the human stomach, yet only a small fraction of persons harboring this organism develop peptic ulcer disease. An important question is why this variation in infection outcome exists. Recent studies have demonstrated that H pylori isolates possess substantial phenotypic and genotypic diversity that may engender differential host inflammatory responses that influence clinical outcome. Further investigation in this field may help to define which H pylori-infected persons bear the highest risk for subsequent development of peptic ulcer disease, and thus enable physicians to focus eradication therapy.

Colony Variation of Helicobacter pylori: Pathogenic Potential Is Correlated to Cell Wall Lipid Composition

Background: Differences in expression of disease after infection with Helicobacter pylori have so far been connected with host factors and bacterial interstrain variation. In this study, spontaneous and ecology-mediated intrastrain variation was examined. Methods: Four clinical isolates of H. pylori were shown to give rise to two colony forms. Bacterial morphology was examined by electron microscopy. Bacterial fractions were examined for proteins using ion exchange chromatography and SDS-PAGE; for lipids using thin-layer chromatography, lipid anion-exchange chromatography, column chromatography on silica gel, 31P-NMR, gas chromatography and mass spectrometry. Bacterial in vitro invasiveness and adhesiveness were examined in two different systems, and urease and VacA toxin were assayed by Western blot analysis. Results: H. pylori was shown to give rise to two colony forms: at normal pH the population was dominated by L colonies. One strain was chosen for further studies. Bacteria from L colonies retained VacA toxin and urease, did not invade or adhere to epithelial cells, and contained normal quantities of phosphatidylethanolamine. In a small frequency, spontaneous S colonies were formed. Bacteria from these colonies released VacA and urease, adhered to and invaded epithelial cells and contained increased amounts of lysophosphatidyl ethanolamine and phosphatidyl serine. After addition of HC1 to the culture medium (pH 6), almost only S colonies were formed. The results demonstrate that environmental factors, such as HC1, can change the bacterial cell wall, and thereby enhance expression of virulence factors of H. pylori in vitro. A similar in vivo variation would have implications for our understanding of the interaction between HC1 secretion in the gastric mucosa and H. pylori in the development of peptic ulcer disease.

Gastric non-Hodgkin lymphomas of mucosa-associated lymphoid tissue are not associated with more aggressive Helicobacter pylori strains as identified by CagA.

Primary gastric non-Hodgkin lymphoma of mucosa-associated lymphoid tissue (MALT-NHL) is strongly related to Helicobacter pylori (H pylori) infection. CagA positive H pylori strains appear to be more aggressive, as reflected by a greater degree of gastric inflammation and higher levels of Il-8 production. Using a polymerase chain reaction-based assay, cagA status was determined in H pylori strains of 12 patients with gastric MALT-NHL, 38 patients with peptic ulcer disease, and 39 patients with non-ulcer dyspepsia. CagA-positive H pylori strains were significantly more frequent in peptic ulcer disease than in non-ulcer dyspepsia (Fisher's exact test p <0.001). An increased frequency of CagA-positive strains was not identified in gastric MALT-NHL compared to non-ulcer dyspepsia patients (Fisher's exact test P <.3). Therefore, it can be concluded that infection with more aggressive strains is associated with the development of peptic ulcer disease, but plays a minor role, if any, in the development of gastric MALT-NHL.

New Therapeutic Approaches to Peptic Ulcer Disease: The Role of Helicobacter Pylori.

One of the most common bacterial infections of human involves Helicobacter pylori, a spiral, gram-negative bacterium that is now thought to be a dominant factor in the development of peptic ulcer disease and may be significant in causing certain forms of gastric cancer. Almost 100% of patients with duodenal ulcer and 70 to 90% affected with gastric ulcer are infected with H. pylori. In order to achieve cure of H. pylori--induced ulcer disease, it is necesary to eradicate the bacterial infection. Mere suppression or clearance infection without eradication is associated with a >80% recurrence of the ulcer. The epidemiology, microbiology, and pathogenesis of H. pylori infections are reviewed. Diagnostic methods and optimal treatment strategies for H. pylori infections are examined. The most current diagnostic and treatment algorithms for peptic ulcer disease are discussed critically, and future directions for drug development aimed at eradication of H. pylori infection are considered.