Showing papers on "Chronic gastritis published in 2004"

Helicobacter pylori in peptic ulcer disease.

Abstract: Infection with Helicobacter pylori is very common throughout the world; causes chronic gastritis; predisposes to gastric and duodenal ulcers and is recognised as a class 1 gastric carcinogen. The disease has a relatively low mortality, but it results in substantial suffering and high economic costs.

Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and host specific colonisation during Helicobacter pylori infection

Abstract: Background and aims: Recent studies linked cytokine gene polymorphisms to H pylori related gastric cancer development. The current study evaluated the role of cytokine gene polymorphisms for mucosal cytokine expression, the gastric inflammatory response, and bacterial colonisation during H pylori infection. Patients and methods: In 207 H pylori infected patients with chronic gastritis, polymorphisms at different loci of the interleukin (IL)-10, IL-1B, IL-1 receptor antagonist (IL-1RN), tumour necrosis factor (TNF)-A, and interferon (IFN)-G genes were genotyped by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, and allelic discriminating TaqMan PCR. Mucosal cytokine mRNA copy numbers were determined by real time quantitative PCR. Presence of bacterial virulence factors was investigated by cagA, vacAs1/2, and babA2 PCR. Biopsies were assessed with regard to the degrees of granulocytic/lymphocytic infiltration and the presence of intestinal metaplasia (IM) and atrophic gastritis (AG). Results: Proinflammatory IL-1 polymorphisms (IL-1RN*2+/IL-1B−511T/−31C+) were associated with increased IL-1β expression, more severe degrees of inflammation, and an increased prevalence of IM and AG. Carriers of the IL-10−1082G/−819C/−592C alleles (GCC haplotype) had higher mucosal IL-10 mRNA levels than ATA haplotype carriers and were associated with colonisation by more virulent cagA+, vacAs1+, and babA2+ H pylori strains. The TNF-A−307(G/A) and IFN-G+874(A/T) polymorphisms did not influence mucosal cytokine expression or the inflammatory response to H pylori. Conclusions: Cytokine gene polymorphisms influence mucosal cytokine expression, gastric inflammation, and the long term development of precancerous lesions in H pylori infection. Host polymorphisms are associated with certain bacterial strain types, suggesting host specific colonisation or adaptation. These findings contribute to the understanding of the complex interplay between host and bacterial factors involved in the development of gastric pathology.

Prevalence of gastric precancerous lesions in Ardabil, a high incidence province for gastric adenocarcinoma in the northwest of Iran.

Abstract: Background/Aims: Ardabil Province, in northwestern Iran, has the highest rate of gastric (predominantly cardia) adenocarcinoma in Iran. This study aimed to investigate the feasibility of endoscopic screening and to look for associated Helicobacter pylori infection and gastric precancerous lesions. Methods: One thousand one hundred and five adult volunteers, residents of Ardabil and Meshkinshahr, districts, 40 years old and above were selected and invited by a simple random household canvass in rural and urban locations. Informed consents were obtained and upper gastrointestinal video endoscopy was performed to biopsy all visible lesions and standard sites in the antrum, corpus, and cardia Results: One thousand and eleven of the invited individuals agreed to participate, including 494 men and 517 women, with a mean (SD) age of 53.32 (10.39) years. Endoscopy was well tolerated by all subjects; 96.7% of antral and 80.7% of cardia mucosal biopsies were satisfactory. The urease test or histology for H pylori was positive in at least 89.2% of subjects. Histological evidence of mucosal atrophy was seen in 39.3% of antral and 21.9% of cardia samples. Chronic gastritis with or without activity, reactive atypia of glandular epithelium, intestinal metaplasia, dysplasia, and cancer were found in 95.1%, 38.0%, 8.7%, 0.2%, and 0.3% of antral and 85.3%, 22.9%, 3.8%, 0.3%, and 0.1% of cardiac biopsies, respectively. Conclusion: Endoscopic screening for upper gastrointestinal diseases was feasible and well tolerated in Ardabil, Iran. Most subjects showed H pylori infection. Atrophic gastritis, reactive atypia, and intestinal metaplasia were common in antrum, corpus, and cardia subsites.

Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice.

Abstract: In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying ApcMin mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.

Primary gastric lymphoma.

Abstract: AIM: The purpose of this review is to describe the various aspects of primary gastric lymphoma and the treatment options currently available. METHODS: After a systematic search of Pubmed, Medscape and MDconsult, we reviewed and retrieved literature regarding gastric lymphoma. RESULTS: Primary gastric lymphoma is rare however, the incidence of this malignancy is increasing. Chronic gastritis secondary to Helicobacter pylori (H pylori) infection has been considered a major predisposing factor for MALT lymphoma. Immune histochemical marker studies and molecular biology utilizing polymerase chain reaction have facilitated appropriate diagnosis and abolished the need for diagnostic surgical resection. Advances in imaging techniques including Magnetic Resonance Imaging (MRI) and Endoscopic Ultrasonography (EUS) have helped evaluation of tumor extension and invasion. The clinical course and prognosis of this disease is dependent on histopathological sub-type and stage at the time of diagnosis. Controversy remains regarding the best treatment for early stages of this disease. Chemotherapy, surgery and combination have been studied and shared almost comparable results with survival rate of 70%-90%. However, chemotherapy possesses the advantage of preserving gastric anatomy. Radiotherapy alone has been tried and showed good results. Stage IIIE, IVE disease treatment is solely by chemotherapy and surgical resection has been a remote consideration. CONCLUSION: We conclude that methods of diagnosis and staging of the primary gastric lymphoma have dramatically improved. The modalities of treatment are many and probably chemotherapy is superior because of high success rate, preservation of stomach and tolerable complications.

Therapeutic Vaccination against Helicobacter pylori in the Beagle Dog Experimental Model: Safety, Immunogenicity, and Efficacy

Abstract: Helicobacter pylori is a spiral-shaped, gram-negative bacterium that infects the stomach of >50% of the population worldwide, with higher prevalence in the developing countries. H. pylori induces chronic inflammation of the stomach mucosa, causing chronic gastritis and peptic ulcer (9, 33); moreover, H. pylori infection is related to gastric mucosa-associated lymphoid tissue lymphoma (4) and to an increased risk of gastric cancer (36), as also proved in animal models (13, 38). Current therapies, based on one antisecretory agent plus antibiotics, although effective in 80 to 90% of cases, face problems of patient compliance, increasing antibiotic resistance, and possible recurrence or reinfection; in spite of continuous effort to improve these treatments, no major breakthroughs have been achieved in the most recent years (30). To overcome the limits of antibiotic-based therapies, the vaccine approach has been undertaken since the last decade, leading us to identify some relevant bacterial antigens as candidates for vaccines (2). On the other hand, animal models of H. pylori infection have been developed to study the interaction between the bacterium and the host, the mechanisms of immune response to either infection or vaccination, and to determine the efficacy of both prophylactic and therapeutic vaccination (2, 17, 26, 34). Among these animal models, that of the beagle dog reproduces several aspects of the human infection with H. pylori. In fact, in the beagle dog model, intragastric administration of H. pylori results in a long-term chronic infection, characterized by gastritis, epithelial alterations, superficial erosions, and the appearance of macroscopic follicles in the gastric mucosa, mainly in the antral region of the stomach (28, 29). Most of the examples of vaccination against H. pylori in animal models reported in the literature concern the use of either whole-cell preparation or single purified antigens, administered mucosally. Previous work in our laboratories has shown the feasibility of both prophylactic and therapeutic vaccination in mice with a mixture of three H. pylori toxins—CagA, VacA, and NAP—relevant in the pathogenesis of infection (8, 22, 32). Moreover, parenteral vaccination of beagle dogs with these H. pylori antigens gave good rate of protection against subsequent H. pylori experimental challenge (unpublished data). We report here data from experiments aimed at evaluating the therapeutic approach of vaccination in beagle dogs experimentally infected with H. pylori, using recombinant CagA, VacA, and NAP, administered intramuscularly at different doses and vaccination schedules.

Gastric mucosal cytokine and epithelial cell responses to Helicobacter pylori infection in Mongolian gerbils.

Abstract: Experimental infection with Helicobacter pylori in Mongolian gerbils results in chronic gastritis and gastric cancer. To investigate epithelial cell proliferation, apoptosis, and mucosal cytokine responses in gastritis, Mongolian gerbils were infected with the H pylori SS1 strain. At 4 weeks post-infection, gastritis was predominantly within the antrum, but extended to the corpus in approximately 50% of gerbils by 36 weeks. Epithelial cell proliferation and apoptosis in glandular epithelial cells were increased with infection. Antral cell proliferation, but not apoptosis, correlated significantly with gastric inflammation. In female gerbils, H pylori significantly increased expression of transcripts for IFN-gamma and IL-12p40, but not TGF-beta or IL-10, in the gastric mucosa. Significantly reduced IFN-gamma and IL-12p40 responses were observed in male gerbils infected with H pylori, but epithelial proliferative and apoptotic responses were comparable to those of females. These studies demonstrate that the female gerbil cytokine response to H pylori has a Th1 profile and that there are gender differences in the magnitude of the gastric cytokine responses to H pylori. The absence of a down-regulatory cytokine response may account for the more severe gastritis observed with H pylori infection in gerbils than in mice.

Granulomatous gastritis: a clinicopathologic analysis of 18 biopsy cases.

Abstract: Granulomas in gastric biopsy specimens are extremely rare, and in Western countries, more than half are associated with Crohn's disease. To evaluate the incidence and their etiology in a gastric carcinoma (and Helicobater pylori infection)-prevalent area, gastric mucosal biopsies were reviewed and their clinicopathologic findings were analyzed. The clinicopathologic diagnoses of the 18 patients with granulomatous gastritis were as follows: chronic gastritis with (n = 14) and without (n = 1) H. pylori infection; gastric adenocarcinomas (n = 2); and Crohn's disease (n = 1). Almost all cases of granulomatous gastritis in this study showed small erosions or ulcers on the endoscopic examinations. H. pylori were found to be one of the most common causes of granulomatous gastritis after excluding all other causes for the granulomas in this study. The granulomas were more frequently found in the antrum, superficially located, and were related to damage within a pit in which the H. pylori were commonly observed. These findings suggest that H. pylori can be causal in the pathogenesis of granulomatous gastritis.

Plasma ghrelin concentration correlates with the levels of serum pepsinogen I and pepsinogen I/II ratio--a possible novel and non-invasive marker for gastric atrophy

Abstract: Background/Aims; Ghrelin, a novel growth-hormone-releasing peptide, has been reported to be localized mainly in the A-like cells in the gastric fundic mucosa. With the extension of gastric inflammation caused by H. pylori infection, gastric roucosal atrophy extends from the antrum to the corpus, which is the predominant site of localization of the ghrelin-producing A-like cells. The present study was designed to investigate the correlation between the plasma ghrelin levels and the extent of gastric mucosal atrophy in patients with chronic gastritis caused by H. pylori infection. Methodology: Sixty-nine patients with dyspeptic symptoms were enrolled for the study. Of these, 41 patients were confirmed to become negative for H. pylori after therapy to eradicate the infection. The other 28 patients were diagnosed as positive for H. pylori, infection. Blood samples were collected from all the patients after 12 hours of fasting, before upper gastrointestinal endoscopy was performed. The plasma levels of total and active ghrelin, as well as the serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured by radioimmunoassay. Based on endoscupic assassment, the atrophic changes in the gastric mucosa were classified as open-type atrophy or closed-type atrophy. Results: There were no significant differences in the plasma total and active ghrelin levels between H. pylori-positive and H. pylori-eradicated (negative) patients. The serum levels of PGI correlated well with the plasma levels of total ghrelin (p 70 ng/mL or PGI/II >3.0). The plasma levels of total as well as active ghrelin were also significantly decreased in patients with endoscopically diagnosed open-type atrophy as compared with those in patients with endoscopically diagnosed closed-type atrophy (p<0.01), especially in the H. pylori-eradicated cohorts. Conclusions: The plasma levels of ghrelin, which correlated well with the serum levels of PGI as well as the PGI/II ratio, decreased with increasing extent of gastric mucosal atrophy, suggesting that it could be a potentially useful non-invasive marker for chronic atrophic gastritis.

The Helicobacter pylori vacuolating cytotoxin: from cellular vacuolation to immunosuppressive activities.

Abstract: Helicobacter pylori is a highly successful bacterial pathogen of humans, infecting the stomach of more than half of the world's population. The H. pylori infection results in chronic gastritis, eventually followed by peptic ulceration and, more rarely, gastric cancer. H. pylori has developed a unique set of virulence factors, actively supporting its survival in the special ecological niche of the human stomach. Vacuolating cytotoxin (VacA) and cytotoxin-associated antigen A (CagA) are two major bacterial virulence factors involved in host cell modulation. VacA, so far mainly regarded as a cytotoxin of the gastric epithelial cell layer, now turns out to be a potent immunomodulatory toxin, targeting the adapted immune system. Thus, in addition to the well-known vacuolating activity, VacA has been reported to induce apoptosis in epithelial cells, to affect B lymphocyte antigen presentation, to inhibit the activation and proliferation of T lymphocytes, and to modulate the T cell-mediated cytokine response.

The Helicobacter pylori plasticity region locus jhp0947-jhp0949 is associated with duodenal ulcer disease and interleukin-12 production in monocyte cells.

Abstract: Colonization with Helicobacter pylori always results in chronic gastritis, which is controlled by infiltration of mononuclear cells and the subsequent release of cytokines like interleukin (IL)-12. To identify H. pylori factors involved in inducing cytokine production in mononuclear cells, a random H. pylori mutant library was screened for the inability to induce IL-12 production in monocyte THP-1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent twofold decrease in the amount of IL-12 induction compared to the parental strain 1061 (P<0.01). Further characterization of mutant M1 revealed that the kanamycin resistance cassette had integrated in the jhp0945 gene, which is situated in an H. pylori strain-specific plasticity region. Three reference strains possessing this plasticity region induced significantly higher amounts of IL-12 when compared to the H. pylori 26695 reference strain, which does not possess this plasticity region. The role in disease outcome of jhp0945 as well as the neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch population cohort. Firstly, the presence of jhp0947 was completely linked with that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and jhp0949 genes, but not of jhp0945, was significantly associated with duodenal ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947–jhp0949 locus may be a novel putative H. pylori marker for disease outcome independent of the cag PAI.

Prevalence of Helicobacter pylori infection among adult dyspeptic patients in Ethiopia

Abstract: In developing countries such as Ethiopia, where chronic gastritis and peptic-ulcer disease are the most common endoscopic findings, it is important to study the association between Helicobacter pylori infection and gastroduodenal diseases. Both invasive and non-invasive diagnostic methods were therefore used to investigate 300, consecutive, adult patients with dyspepsia, from the gastrointestinal clinic of Tikur Anbassa University Hospital, Addis Ababa. The apparent overall prevalence of H. pylori infection varied according to the detection method employed. Culture revealed H. pylori in only 69% of the patients but this pathogen appeared more common when rapid urease tests (71%), PCR-denaturating gradient gel electrophoresis (91%), histopathology (81%), silver staining (75%) or stool-antigen tests (81%) were employed. Antibodies to H. pylori were detected, both by enzyme immuno-assay (EIA) and immunoblotting, in approximately 80% of the patients, whether the antigens used were of a reference strai...

GSTT1, GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

Abstract: AIM: To test the hypothesis that, in the Southeastern Brazilian population, the GSTT1, GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer METHODS: We conducted a study on 100 cases of gastric cancer (GC), 100 cases of chronic gastritis (CG), and 150 controls (C) Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR CYP2E1/PstI genotyping was performed using a PCR-RFLP assay RESULTS: No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups However, a significant difference between CG and C was observed, due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group The GSTT1 null genotype occurred more frequently in Negroid subjects, and the GSTM1 null genotype in Caucasians, while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori CONCLUSION: Our findings indicate that there is no obvious relationship between the GSTT1, GSTM1 and CYP2E1 polymorphisms and gastric cancer

Progression of Chronic Hepatitis and Preneoplasia in Helicobacter hepaticus-Infected A/JCr Mice

Abstract: Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylori chronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepati...

Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor κB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma

Abstract: AIM: Several epidemiological studies have demonstrated a close association between Helicobacter pylori (H Pylori) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences, leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pylori infection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8 -hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due to oxidative DNA damage. METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling [including nuclear factor-κB(NFκB), MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2), inhibitor of apoptosis protein (IAP ) and myeloid cell leukemia-1 (Mcl-1)] by Western-blot assay. RESULTS: The concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFκB, Mcl-1 and IAP were detected in patients infected with H pylori compared with patients who were not infected with H pylori. Furthermore, 8-OHdG, iNOS, NFκB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients. CONCLUSION: Chronic H pylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the hypothesis that oxygen-free radical-mediated damage due to H pylori plays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.

Heightened susceptibility to chronic gastritis, hyperplasia and metaplasia in Kcnq1 mutant mice.

Abstract: Increased susceptibility to gastric cancer has been associated with a wide range of host genetic and environmental factors, including Helicobacter pylori infection. Helicobacter pylori infection is postulated to initiate a progression through atrophic gastritis, metaplasia and dysplasia to cancer, and has been associated with reduction of acid output and dysregulation of stomach mucins. Here, we present the characterization of two mouse lines carrying mutant alleles of the gene encoding the Kcnq1 potassium channel, which very rapidly establish chronic gastritis in a pathogen-exposed environment. These mice develop gastric hyperplasia, hypochlorhydria and mucin dysregulation independent of infection. Metaplasia, dysplasia and pre-malignant adenomatous hyperplasia of the stomach have been observed in these Kcnq1 mutant mice, also independent of infection. The data presented here suggest that Kcnq1 mutant mice can be used both as an efficient model for the development of atrophic gastritis after infection and to determine the processes during the later stages of progression to gastric cancer independent of infection. Thus, Kcnq1 mutant mice are a powerful new tool for investigating the connection between acid balance, Helicobacter infection and mucin disruption in the progression to gastric cancer.

Histological aspects and role of mast cells in Helicobacter pylori-infected gastritis.

Abstract: SUMMARY Background: Mast cells are one of the main proinflammatory cells, while their knowledge in Helicobacter pylori infection has not been summarized. Methods: We reviewed studies on mast cells in H. pylori infection, and summarized the histological aspects and roles. Results: The density of mast cells is greater in H. pyloriinfected than in non-infected subjects. Increased mast cell density in infected gastritis significantly decreases after eradication. On electron microscopy, mast cells in infected gastric mucosa show degranulation. Some experimental studies demonstrate that mast cells are degranulated with H. pylori-derived products. Conclusions: Mast cells are actively involved in the pathogenesis of H. pylori-infected gastritis. The possible roles are to initiate and promote the formation of oedema through degranulated and secreted mediators, and to release multiple chemotactic factors, which induce inflammatory cells to infiltrate to the site of oedema, showing acute inflammatory changes. Mast cells also stimulate the degradation of pericellular matrices and the growth of cells in their vicinity, and thereby promote tissue turnover. In chronic H. pylori infection, these reactions continue until the bacteria are eradicated. Mast cells may act both to maintain gastritis and to repair tissue damage in H. pylori-infected chronic gastritis.

Gastroduodenal lesions and Helicobacter pylori infection in hemodialysis patients.

Abstract: OBJECTIVES The purpose of this prospective study is to determine the prevalence of upper gastrointestinal (GI) abnormalities and Helicobacter pylori (H. pylori) infection among stable chronic hemodialysis (HD) patients. METHODS The study was carried out at King Fahd Hospital of the University, Al-Khobar, Kingdom of Saudi Arabia during the period January 1996 to June 1997. Fifty-four chronic HD patients underwent upper GI endoscopy. Endoscopic changes were described and multiple antral gastric biopsies were taken for histological examination and detection of H. pylori infection. Gastric biopsy findings were compared to findings in 60 consecutive patients with normal renal function undergoing endoscopy for assessment of dyspepsia. RESULTS Fifty-four stable chronic HD patients (32 men, mean age 42.4 +/- 18 years) underwent upper GI endoscopy and multiple antral gastric biopsies for histological examination and H. pylori detection. The endoscopic findings were abnormal in 49 (90.7%) patients. Chronic gastritis was seen in 20 (37%) patients, acute gastritis was seen in 13 (20.1%) patients, duodenal ulcer was seen in 6 (11.1%) patients, duodenitis with or without erosions was seen in 5 (9.3%) patients, gastroduodenitis was seen in 3 (5.56%) patients, and gastroesophageal reflux disease was seen in 2 (3.7%) patients. Histological examination of multiple antral gastric biopsies documented chronic active gastritis in 28 (51.9%) patients. Helicobacter pylori were present in 34(63%) patients. Helicobacter pylori were detected in the majority (85.7%) of patients with the histological diagnosis of chronic active gastritis. Patients harboring H. pylori were significantly older than negative patients (52 +/- 16.1 versus 33.9 +/- 17.3 years, p<0.018). In a group of 60 patients with normal renal function undergoing endoscopy for assessment of dyspeptic symptoms during the same period, chronic active gastritis was found in 40 (66.7%) patients and H. pylori was detected in 38 (63.3%) patients. CONCLUSIONS Upper GI abnormalities are common among HD patients even in the absence of symptoms. Biopsy proven chronic active gastritis is the most common histological diagnosis among these patients and is highly associated with H. pylori infection. Prevalence of H.pylori infection in HD patients is similar to those with normal renal function undergoing endoscopy for dyspepsia. Helicobacter pylori infected HD patients tend to be older than patients without H.pylori infection.

Prevalence of Helicobacter pylori infection among patients with dyspepsia in South-Western Saudi Arabia.

Abstract: OBJECTIVES Helicobacter pylori (H. pylori) infection is a major cause of various upper gastrointestinal (UGI) disorders. The aim of this study was to determine the prevalence of H. pylori among patients with dyspepsia. METHODS A prospective study was carried out in the Gastroenterology Division, King Fahd Central Hospital, Gizan, Kingdom of Saudi Arabia from January 1995 to December 1998. Four hundred and eighty-eight patients with dyspepsia were consecutively examined using the UGI endoscopy during a 4-year period. Data analyzed included demographic details, clinical indications for the examination, endoscopic findings and results of the histopathologic assessment for H. pylori. RESULTS Overall, H. pylori were detected in 268 (54.9%) of the gastric biopsies from 488 patients (322 males and 166 females, aged 13-90 years). Helicobacter pylori infection was present in 140 (60.1%) of 253 patients with chronic gastritis diagnosed by endoscopy and in 49 (62.8%) of 78 patients with duodenal ulcers (DU). The rate in DU patients was significantly higher than the rate (43.6%) in patients with normal endoscopic findings (odds ratio [OR]=2.18, 95% confidence interval [CI] 1.02-4.70; p=0.04]. Of 455 biopsies with histologic gastritis, 268 (OR=58.9%, 95% CI 54.2-63.4) were positive for H. pylori and all specimens (n=33) with no histological evidence of gastritis were negative. CONCLUSIONS The well-described association of H. pylori with DU and non-ulcer dyspepsia was confirmed by our study. However, the rate of H. pylori in our patients was at the lower end of the range (50-80%), which was previously reported among largely urban populations in Saudi Arabia suggests differences in the prevalence of H. pylori-infections between urbanized and rural populations. Helicobacter pylori negative peptic ulcer disease remains an important entity that may be associated with the use of non-steroidal anti inflammatory drugs and in our environment, the habitual chewing of qat leaves (catha edulis).

Detection of micrometastasis of gastric carcinoma in peripheral blood circulation.

Abstract: AIM: To detect the micrometastasis of gastric carcinoma in peripheral blood circulation using immunomagnetic beads sorting technique and RT-PCR technique, and to discuss its significance and the difference between the two methods. METHODS: Density gradient centrifugation was used to isolate mononuclear cells from peripheral blood, immunomagnetic beads sorting technique and RT-PCR technique were used to detect the disseminated carcinoma cells. HE, immunocytochemical and immunofluorescence staining were also used to identify the characteristics of the cells separated with immunomagnetic beads sorting technique. RESULTS: Cells expressing cytokeratin were separated and enriched from the peripheral blood specimens of patients suffering from gastric carcinoma or chronic gastritis. After HE staining, two kinds of cells with little cytoplasm were found. Majority of these cells had small and round nuclei, even chromatins and the thickness of nuclear membrane was normal. Immunohistochemical staining indicated that there were CD34 and CD45 expression on the cell membrane of this kind of cells and these cells also showed expressed human telomerase reverse transcriptase by immunofluorescence staining, but the expression of carcinoembryonic antigen was absent. So, these cells might hematopoiesis precursors. Another kind of cells had larger and abnormal nuclei with thicker nuclear membranes. Massed chromatins and poly-nucleoli were found in the nuclei. These cells expressed human telomerase reverse transcriptase and carcinoembryonic antigen, but CD34 and CD45 were not found on the cell membrane. So, these cells were considered as gastric carcinoma cells escaping from the original focuses and existing in the peripheral blood circulation. Carcinoma cells were found in 25 of 60(41.7%) specimens of peripheral blood from patients with gastric carcinoma, while there were no such cells separated from the blood specimens of chronic gastritis patients. The difference of positive rates of disseminated carcinoma cells between two groups was markedly significant (P < 0.005). The expressions of CK20 mRNA in peripheral blood specimens were examinated with RT-PCR. CK20 mRNA was detected from 32 of 60(53.3%) peripheral blood specimens in the group of gastric carcinoma patients, while none of the specimens from patients suffering from chronic gastritis had CK20 mRNA. Significant difference was also found between two groups (P < 0.005). Statistic analyses also showed that there was a significant difference between the positive rates of two methods in detecting the disseminated carcinoma cells from the peripheral blood circulation of gastric carcinoma patients (P < 0.05). CONCLUSION: The results demonstrated that there were disseminated carcinoma cells in the peripheral blood circulation of some patients with gastric carcinoma. Disseminated carcinoma cells can be detected from the peripheral blood samples with immunomagnetic beads sorting technique and RT-PCR technique. The positive rate of RT-PCR technique is higher than that of immunomagnetic beads sorting technique in detecting micrometastasis.

Monoallelic Methylation of the APC Promoter Is Altered in Normal Gastric Mucosa Associated with Neoplastic Lesions

Abstract: Adenomatous polyposis coli (APC) promoter hypermethylation has been reported frequently in normal gastric mucosa, but it remained to be clarified whether this occurs in every individual. In this study, methylation of the APC promoter was analyzed in histologically normal-appearing gastric mucosa samples by methylation-sensitive single-strand conformation analysis and by a methylation-sensitive dot blot assay. Epithelial cell samples were collected by microdissection from tissue sections. Equal amounts of methylated and unmethylated APC alleles were found in all gastric mucosa samples from patients without any gastric lesions (20 samples). Allele-specific methylation analysis showed that the methylation of the APC promoter was monoallelic; however, which allele was methylated depended on the cell type. Increased or decreased methylation was found in 10 of 36 (28%) normal gastric mucosa samples adjacent to a gastric or esophageal adenocarcinoma. No allelic loss was found at the APC locus. Modification of the methylation status was also found in 3 of 21 (14%) normal-appearing gastric mucosa samples adjacent to intestinal metaplasia. In contrast, all normal mucosa samples in cases with chronic gastritis but without metaplasia or dysplasia showed a monoallelic methylation pattern. Our results indicate the following: (a) In normal gastric mucosa, the APC promoter shows monoallelic methylation, which is not due to imprinting but most likely due to allelic exclusion; (b) the excluded allele differs between foveolar and glandular epithelial cells; (c) the APC methylation pattern is frequently altered in normal-appearing gastric mucosa of gastric or esophageal adenocarcinoma patients; and (d) such alterations also occur in normal gastric mucosa adjacent to intestinal metaplasia.

Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer

Abstract: Background and aims. Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1–B, IL-6, IL-8 and TNF-α. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-α and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. Methods. Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-α -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. Results: No significant correlation could be revealed between the TNF-α and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). Conclusion. Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype.

Helicobacter pylori infection in Finland.

Abstract: Helicobacter pylori causes chronic gastritis worldwide and it is the most important single factor in peptic ulcer disease. Up to half of H. pylori infected individuals develop atrophic gastritis over years and decades. H. pylori infection has also been classified as a class I carcinogen in human gastric cancer. Most infections are obtained in childhood, in Finland mainly before the age of 7 years but the exact transmission routes are not known. The infection shows an age‐dependent pattern, the infection being rare among children but gradually becoming more prevalent among older age groups. As new infections are few in adults and the infection only rarely disappears without effective antimicrobial therapy, the occurrence of the infection in the old actually reflects the prevalence of the infection in their childhood. In developed countries, such as Finland, a rapid decline of H. pylori prevalence rate has been demonstrated. In order to speed up this natural decline of the infection, a unique population bas...

Evidence of Helicobacter pylori infection in dental plaque and gastric mucosa.

Abstract: Objective To determine the presence of Helicobacter pylori (H. pylori ) in dental plaque of individuals suffering from H. pylori associated gastric disease. Design descriptive. Place and duration of study The study was conducted at the Department of Medicine in collaboration with Departments of Dentistry and Pathology at PNS Shifa, Karachi during a period extending from July 1998 to June 1999. Patients and methods Patients presenting with symptoms/signs of chronic gastritis were included in the study. Specimens of dental plaque and gastric biopsy were collected from all the patients. The dental plaque specimen was processed for helicourease test and the gastric biopsy specimens were processed both for the helicourease test and histopathology. Results Out of all patients studied (n=52), 32 (61.53%) were positive for helicourease test with gastric biopsy while 48 (92.30%) were positive with dental plaque. The histopathology of gastric biopsy showed H. pylori associated chronic active gastritis in 42 (80.76%) patients. Eight (15.38%) patients showed chronic active gastritis which was not associated with H. pylori while in 2 (3.84%) patients the gastric biopsy specimen was unremarkable. Conclusion Majority of the patients have possible H. pylori colonization in dental plaque while about two-thirds have H. pylori associated chronic active gastritis. Oral cavity may be the first place for colonization and then the infection involves the gastric mucosa.

Possibility of non-invasive diagnosis of gastric mucosal precancerous changes.

Abstract: AIM: To assess the possibility of non-invasive screening of atrophic chronic gastritis for preventing further development of gastric cancer. METHODS: One hundred and seventy-eight consecutive Helicobacter pylori (H pylori)-positive dyspeptic patients after detection of serum levels of pepsinogen-1 (PG-1) and gastrin-17 (G-17) by enzyme immunoassay were proposed for endoscopy and histology. The serologic and morphologic results were compared with estimating the sensitivity, specificity and prognostic values of the tests. RESULTS: There was statistically significant reverse dependence between the grade of stomach mucosal antral or corpus atrophy and the proper decreasing of serum G17 or PG1 levels. The serologic method was quite sensitive in the diagnosis of non-atrophic and severe antral and corpus gastritis. Also, it was characterized by the high positive and negative prognostic values. CONCLUSION: Detection of serum G-17 and PG1 levels can be offered as the screening tool for atrophic gastritis. The positive serologic results require further chromoendoscopy with mucosal biopsy, for revealing probable progressing of atrophic process with development of intestinal metaplasia, dysplasia or gastric cancer.

Autoantibody production in chronic idiopathic urticaria is not associated with Helicobacter pylori infection

Abstract: Chronic idiopathic urticaria (CIU) is a dermatological syndrome, characterized by raised erythematous skin lesions, that affects 20% of the general population and has been associated with autoimmunity. However, some reports have also suggested a close relationship between CIU and Helicobacter pylori infection, which is endemic in developing countries and associated with chronic gastritis, peptic ulcer disease, and gastric carcinoma. In the present study, we investigated the occurrence of autoantibodies in sera from 23 CIU subjects infected with H. pylori and from 23 CIU subjects without this infection. The presence of anti-thyroid antibodies was determined by indirect hemagglutination assay and the presence of autoantibodies to IgE and C1INH was determined by ELISA. Antibodies to thyroid antigens were detected at low titers from 100 to 400 in three of 23 (13%) CIU-infected subjects and in four of 23 (17%) CIU-noninfected subjects. The titers of anti-IgE autoantibodies were similar in these CIU groups, presenting absorbances of 1.16 +/- 0.09 and 1.07 +/- 0.16, respectively, while a titer of 1.14 +/- 0.15 was detected in the healthy control group. The concentration of anti-C1INH autoantibodies was the same in the CIU-infected and -noninfected subjects (7.28 +/- 1.31 and 7.91 +/- 2.45 ng/ml, respectively), and was 7.20 +/- 2.25 ng/ml in the healthy control group. However, the serum levels of complexed anti-C1INH antibodies were increased in CIU-infected subjects compared to CIU-noninfected subjects and healthy controls with an absorbance of 1.51 +/- 0.21 vs 1.36 +/- 0.16 and 1.26 +/- 0.23, respectively (P<0.05), indicating an impaired clearance of immune complexes in CIU-infected patients. In conclusion, no correlation was observed between H. pylori infection and autoantibody production in CIU patients consistent with reports of clinical studies.

Inflammation, immunity and vaccines for Helicobacter pylori.

Abstract: Helicobacter pylori causes chronic gastritis in the human stomach, yet only a minority of infected individuals develop peptic ulcer disease, atrophic gastritis, or gastric malignancies. The severity, progression, and consequences of H. pylori infection have been shown to depend on the host genetic background, and in particular on gene polymorphisms affecting the host immune response. Numerous studies published last year brought new information on the mechanisms by which the host genetic make-up modifies the inflammatory and immune responses to H. pylori and the induction of tissue damage secondary to the infection. Novel insights on the regulatory role of H. pylori on the adaptive T-cell response and on its consequences for the persistence of the infection and for the development of vaccines are discussed.