Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.     

Chronic inactive gastritis and coccoid Helicobacter pylori in patients treated for gastroesophageal reflux disease or with H pylori eradication therapy

Gastric biopsy specimens from 105 consecutive adults with persistent dyspepsia who did not have changes due to esophageal reflux disease changes or gastric or duodenal ulcers at endoscopy were scored using the updated Sydney gastritis classification system. The medication history of proton pump inhibitors (PPIs) or Helicobacter pylori eradication therapy during the month before endoscopy was retrieved. Of the patients, 72 (68.6%) had chronic inactive gastritis, and 7 (6.7%) had antral-predominant, chronic mild active gastritis. H pylori infection was present in 36 patients (34.3%), of whom 29 had chronic inactive gastritis. Forty-six patients (43.8%) had a positive medication history, including 40 (56%) of 72 with chronic inactive gastritis. The most common morphologic feature associated with H pylori infection was moderate chronic inactive gastritis, which was found most often in patients who had received recent PPIs or H pylori eradication therapy. Pathologists should be aware of the extensive use of these medications, their association with chronic inactive gastritis, and rare H pylori thatfrequently are coccoid shaped. Modified Giemsa stain may not be the optimal method to detect H pylori in this group of patients.     

A urease-negative mutant of Helicobacter pylori constructed by allelic exchange mutagenesis lacks the ability to colonize the nude mouse stomach.

The urease of Helicobacter pylori has been proposed to be one of its pathogenic factors. A kanamycin resistance determinant was inserted in a cloned urease gene, and transformation-mediated allelic exchange mutagenesis was carried out to introduce the disrupted gene into the corresponding wild-type chromosomal region of a clinical isolate of H. pylori, CPY3401. The resulting mutant, HPT73, had the null activity of urease. Nude mouse stomachs were challenged with these two isogenic strains to examine the role of urease in pathogenesis. Gastritis was found in the CPY3401-challenged stomachs, from which bacteria indistinguishable from CPY3401 were recovered. There was no gastritis in the HPT73-challenged stomachs, and we could not recover H. pylori from them. These results indicated that H. pylori urease is essential for colonizing the nude mouse stomach.     

Immunohistochemical detection of Helicobacter pylori with a novel monoclonal antibody: Its clinicopathological significance and validity in the routine pathological diagnosis

The immunological mechanism of Helicobacter pylori-induced chronic gastritis is still unknown. In our previous study using a novel anti-H. pylori monoclonal antibody and surgically resected stomachs from gastric cancer patients, we succeeded to detect H. pylori captured by macrophages in gastric lamina propria and lymph nodes, and proved that the H. pylori-positive macrophages correlated with chronic gastritis. To elucidate this correlation in the cases without gastric cancer, we examined H. pylori in 519 gastric biopsy specimens of 242 cases using immunohistochemistry with the novel antibody. Also, we evaluated the validity of the novel antibody in the routine pathological diagnosis. In 402 specimens from the cases without gastric tumors, the bacteria were detected not only in the mucous layer of 148 specimens but also in the lamina propria of 144 specimens. The specimens only with the intramucosal bacteria showed high-grade chronic and low-grade acute inflammation, whereas the specimens only with the intra-mucous bacteria tended to show the low-grade chronic and high-grade acute inflammation. Statistically, H. pylori in the lamina propria correlated with chronic gastritis. When compared to commercially available anti-H. pylori antibody and Giemsa staining, the novel antibody showed the highest sensitivity to detect the bacteria in the lamina propria. These results suggest that H. pylori in the lamina propria is thought to be deeply related with the development of H. pylori-induced chronic gastritis also in the cases without gastric cancer. And, the novel antibody is proved to be very useful in the routine pathological assessment of H. pylori infection.     

Helicobacter pylori.

Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori has been found in the stomachs of humans in all parts of the world. In developing countries, 70 to 90% of the population carries H. pylori. In developed countries, the prevalence of infection is lower. There appears to be no substantial reservoir of H. pylori aside from the human stomach. Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes. H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen. All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium. A variety of tests to diagnose H. pylori infection are now available. Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy. In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy. In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection.     

Histology of chronic gastritis with and without duodenitis in patients with Helicobacter pylori infection.

AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90.5% H pylori positive), and 11 had other diagnoses. In the H pylori positive patients, the median gastritis score was higher in the duodenitis group (6, range 3-9) than in the chronic gastritis only group (5, range 2-8), because of greater neutrophil activity scores in patients with duodenitis (median score 2 v 1). There were no differences in the density of H pylori infection, inflammation, atrophy, or intestinal metaplasia between patients with chronic gastritis only and those with duodenitis. CONCLUSIONS: These results suggest that H pylori positive patients with duodenitis have a more severe form of gastritis than those without associated duodenal inflammation. This is because of increased neutrophil activity, which seems to be independent of the density of H pylori infection.     

Helicobacter pylori-induced gastritis in the domestic cat.

Helicobacter pylori has been cultured from the inflamed gastric mucosae of naturally infected cats; the lesions in H. pylori-infected cat stomachs mimic many of the features seen in H. pylori-infected human stomachs. To determine whether H. pylori-negative specific-pathogen-free cats with normal gastric mucosae were susceptible to colonization by this bacterium and whether gastritis developed after infections, four H. pylori-negative cats treated with cimetidine were orally dosed three times with 3 ml (1.5 x 10(8) CFU/ml) of H. pylori every 4 days. All four cats became persistently colonized as determined by gastric cultures and PCRs from serial gastric biopsy samples and necropsy samples at 7 months postinfection. H. pylori was not isolated from the two control cats, nor were their gastric tissues positive by PCR; one of the two cats had a few focal lymphocytic aggregates in the body submucosa, whereas the second cat had a normal gastric mucosa. All four H. pylori-infected cats had multifocal gastritis consisting of lymphoid aggregates plus multiple large lymphoid nodules, which were most noticeable in the antral mucosa. In addition, one H. pylori-infected cat had a moderate diffuse infiltration of polymorphonuclear leukocytes in the subglandular region of the antrum. H. pylori-like organisms were focally distributed in glandular crypts of the antrum. Two of the H. pylori-infected cats had significant (eightfold) increases over baseline in levels of immunoglobulin G H. pylori serum antibody. The H. pylori isolates from the four experimentally infected cats had restriction fragment length polymorphism patterns specific for the flaA gene that were identical to those of the inoculating strain. H. pylori readily colonizes the cat stomach and produces persistent gastritis.     

Gastrin (G) cells and somatostatin (D) cells in patients with dyspeptic symptoms: Helicobacter pylori associated and non-associated gastritis

BACKGROUND: Gastrin G cells and somatostatin D cells are important regulators of gastric acid secretion and alterations in their relative numbers may play a key role in gastroduodenal disease. AIM: To investigate the effect of Helicobacter pylori infection on the density of immunoreactive G and D cells in gastric antral and corpus biopsies from patients with dyspeptic complaints. METHODS: One hundred and twenty two patients with dyspeptic complaints had two antrum and two corpus biopsies taken during upper endoscopy. The severity of inflammation and the density of H pylori were evaluated semiquantitatively. In addition, the density and distribution of neuroendocrine cells, especially G and D cells, were examined using immunohistochemistry. Patients were divided into three groups, those with H pylori positive gastritis, H pylori negative gastritis, and histologically normal gastric mucosa. RESULTS: The number of immunoreactive G cells was significantly higher and the number of immunoreactive D cells lower in patients with H pylori positive gastritis compared with H pylori negative gastritis or histological normal gastric mucosa. The percentage of G cells as a percentage of mucosal endocrine cells was also raised and that of D cells was decreased. CONCLUSIONS: Helicobacter pylori infection produces alterations in the number of endocrine cells responsible for regulating acid secretion in relation to intragastric pH and feeding. The alterations correlate best with the severity of inflammation and not with H pylori density.     

Helicobacter pylori in gastroduodenal diseases: Rapid identification by endoscopic brush cytology

Previous reports showed Helicobacter pylori (H. pylori) in type B gastritis-affected stomachs. This study was carried out to compare H. pylori staining effectiveness on biopsy to brush cytology. Tissue and brush parallel samples of gastric mucosa with abnormal or normal appearances were examined: 57.6% H. pylori-positive pieces from the antrum and 19.2% from the body were found, versus 65.3% and 25% H. pylori-positive brush smears, respectively. H. pylori resembling organisms were mainly related to chronic and acute antral inflammations and were often associated with higher amounts of round-shaped cocco-bacteria. In addition, H. pylori direct stain on brushing is proposed as the most rapid and reliable method for the routine diagnosis of Helicobacter pylori infection, in both ulcer or nonulcer gastritis.     

The comparison of histologic gastritis in patients with duodenal ulcer, chronic gastritis, gastric ulcer and gastric cancer

This study was designed to investigate the differences of histologic gastritis according to the endoscopic diagnosis, and between H. pylori positive and negative gastritis, using the Sydney system. A total of 122 patients (42 duodenal ulcer, 31 chronic gastritis, 35 gastric ulcer and 14 gastric cancer) underwent endoscopy with biopsies from the antrum and body. Among the 122 patients, 104 (85%) were H. pylori positive. H. pylori density of the antrum was significantly higher in duodenal ulcer than in chronic gastritis, gastric ulcer, and gastric cancer. The positivity of intestinal metaplasia was lowest in duodenal ulcer and highest in gastric cancer. H. pylori density as well as grade of activity, inflammation and atrophy were significantly higher in the antrum than in the body in duodenal ulcer, while in chronic gastritis, gastric ulcer and gastric cancer there was no difference of H. pylori density, activity, inflammation and atrophy between the antrum and body. The grade of activity and chronic inflammation were significantly higher in H. pylori positive patients than in H. pylori negative patients in both the antrum and body. In conclusion, the gastritis of duodenal ulcer was mainly localized to the antrum, while the gastritis of chronic gastritis, gastric ulcer or gastric cancer was rather uniform in the antrum and body. H. pylori seemed to be related to the development of chronic inflammation and activity.     

Helicobacter pylori infection and erosive gastritis

One hundred and eleven patients were included in the study. Thirty seven had erosive gastritis, thirty four chronic gastritis and forty were controls without any gastrointestinal diseases confirmed by symptoms and upper gastrointestinal endoscopy. Patients with erosive gastritis were divided into non-steroidal anti-inflammatory drug (NSAID) users and non-users. H pylori status was determined by urease test, serology and/or histology. The prevalence of H pylori was compared between the various groups. The prevalence of H pylori infection in erosive gastritis, chronic gastritis and controls was 68%, 76% and 65%, respectively, the difference was not significant (P > 0.05), 8 out of 11 patients with erosive gastritis and NSAID use (73%) were positive for H pylori. Likewise 17/26 patients with erosive gastritis without NSAID use (65%) were positive for H pylori (P > 0.05). Body of the stomach (65%) was the commonest site for erosions compared to antrum (43%) or fundus (27%) (P < 0.02). H pylori infection does not predispose to erosive gastritis. NSAID use does not affect H pylori prevalence. Routine H pylori eradication is, therefore, not indicated in patients with erosive gastritis infection. Body of the stomach is the most predominant site for erosions.     

Duodenal bulb biopsy findings for patients with non-ulcer dyspepsia with or without Campylobacter pylori gastritis

Duodenal bulb biopsy specimens from 85 patients with non-ulcer dyspepsia (30 of whom had normal stomachs and 52 of whom had Campylobacter pylori gastritis) were examined for the presence and amount of gastric surface epithelial metaplasia (using both the hematoxylin and eosin stain and the Alcian blue-periodic acid-Schiff method), acute inflammation, and C. pylori (using the Giemsa stain). Gastric metaplasia occurred in the duodenal bulb in 61% of patients with gastric C. pylori and in an identical percentage for those who lacked C. pylori gastritis. For patients with gastric metaplasia, foci of metaplastic cells were seen in 70% of their bulb biopsy fragments. The Alcian blue-periodic acid-Schiff stain was superior to the hematoxylin and eosin stain for detecting gastric metaplasia. Only one of 33 patients without gastric C. pylori had gastritis and duodenitis. Fourteen of 52 (27%) patients with C. pylori gastritis had duodenitis; C. pylori was seen in the duodenal biopsy specimens from 13 of these patients. The organisms were often few, requiring oil immersion microscopy for detection. Each patient with duodenitis had gastric metaplasia, but some of these metaplastic foci were not inflamed. When present in the duodenum of patients with C. pylori gastritis, gastric metaplasia, acute inflammation, and C. pylori are typically patchy. Hence, several biopsy fragments of the duodenal bulb would be required for studies designed to determine the effectiveness of compounds used to treat C. pylori duodenitis.     

Serum pepsinogen I and II concentrations and IgG antibody to Helicobacter pylori in dyspeptic patients.

AIMS--To investigate the association between histologically confirmed gastritis, carriage of Helicobacter pylori and pepsinogen (PG) I and PG II concentrations. METHODS--Prospective study of 81 dyspeptic patients undergoing upper gastrointestinal endoscopy was made. The extent of gastric mucosal inflammation and the presence of H pylori was determined, and serology to evaluate PG I and II concentrations and IgG titres to H pylori was carried out. RESULTS--The presence of H pylori was strongly correlated with high IgG antibody titres to H pylori and gastritis. Patients who were H pylori positive had significantly higher PG I and PG II concentrations and a significantly lower PG I:PG II ratio than patients who were negative for H pylori. In 13 patients with duodenal ulcer and H pylori positive gastritis serum PG I concentrations were significantly higher than in H pylori positive patients without duodenal ulcer. Significant correlations were found between the age of patients and serum PG II, the PG I:PG II ratio, IgG antibodies to H pylori, the severity of body gastritis and H pylori infection, and between the degree of gastritis in the body of the stomach and the PG II concentration. CONCLUSIONS--Serum PG I and II concentrations, together with a fall in the PG I:PG II ratio, could be used as predictors of H pylori infection as well as serum IgG antibody response to H pylori.     

Acute inflammation of the proliferative zone of gastric mucosa in Helicobacter pylori gastritis.

The neutrophilic infiltration has been regarded to represent the activity of Helicobacter pylori gastritis. It may involve the epithelium and/or lamina propria. The incidence and degree of the two types of infiltration do not correlate with each other frequently. We correlated the two types of neutrophilic infiltration with H. pylori infection and other pathologic parameters respectively in 300 randomly selected gastric biopsies as well as serial biopsies from a separate group of 95 patients who were treated for H. pylori infection. The "random biopsies" had chronic gastritis of various degrees, and the organisms were identified in 239 cases (79.7%); in the "treated group," the organisms disappeared completely in 62 cases (65.3%). Characteristically, the intraepithelial neutrophilic infiltration was predominantly localized to the proliferative zone of the gastric mucosa (zone 2) where the density of H. pylori was considerably lower than the surface epithelium. In the "random biopsies," both acute epithelial and interstitial neutrophilic infiltration correlated significantly (p < 0.01) with the H. pylori infection. In the "treated group," however, only acute epithelial inflammation correlated significantly (p < 0.01) with the eradication of infection while acute interstitial inflammation did not. Acute epithelial inflammation was no less frequently present in advanced chronic gastritis than in early chronic gastritis. Acute epithelial inflammation of the proliferative zone is a characteristic pathologic finding of H. pylori gastritis, and appears to be directly associated with the pathogenesis of H. pylori gastritis and its progression.     

Bile reflux and intestinal metaplasia in gastric mucosa.

AIM: To determine associations between enterogastric bile reflux and gastric mucosal pathology. METHOD: A retrospective study using fasting gastric juice bile acid measurements and antral or prestomal biopsy specimens from 350 patients, 66 of whom had previously undergone surgery that either bypassed or disrupted the pyloric sphincter. RESULTS: Bile reflux was positively associated with reactive gastritis and negatively with Helicobacter pylori density. After stratification for previous surgery, age, and H pylori status, the histological feature most strongly associated with bile reflux was intestinal metaplasia, including all its subtypes. The prevalence of intestinal metaplasia was greatest in patients with both H pylori infection and high bile acid concentrations. Bile reflux was also positively associated with the severity of glandular atrophy, chronic inflammation, lamina propria oedema and foveolar hyperplasia. CONCLUSIONS: Bile reflux is a cause of reactive gastritis. It modifies the features of H pylori associated chronic gastritis. The changes are not confined to patients who have had surgery to their stomachs. The positive associations with atrophy and intestinal metaplasia have implications for models of gastric carcinogenesis.     

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.     

Nodular gastritis and pathologic findings in children and young adults with Helicobacter pylori infection

PURPOSE: The aim of this study was to investigate the pathologic characteristics of nodular gastritis in children and young adults infected with Helicobacter pylori (H. pylori). MATERIALS AND METHODS: A total of 328 patients were enrolled in this study, and the diagnosis of H. pylori infection was done with gastroduodenal endoscopy concomitant with a CLO(TM) test and pathologic analysis of the biopsy specimens. Diagnoses of normal, superficial gastritis, nodular gastritis, and peptic ulcer disease were made from the gastroduodenal endoscopic findings. The density of H. pylori organisms in the gastric mucosa was rated as normal, mild, moderate, or marked. The pathologic findings of nodular gastritis were based on the histopathologic findings of inflammation, immune activity, glandular atrophy and intestinal metaplasia. Each of these findings was scored as either normal (0), mild (1), moderate (2), or marked (3) according to the updated Sydney system and using visual analog scales. The gastritis score was the sum of the four histopathologic scores. RESULTS: In this study, nodular gastritis (50.6%) was most common, and mild density (51.5%) H. pylori infection was also common upon microscopic examination. Intestinal metaplasia occurred in 9 patients (2.7%). CONCLUSION: Logistic regression revealed a significant increase in the incidence of nodular gastritis with gastritis score (p=0.008), but not an association with sex, age, or H. pylori density. Gastritis score was the only significant factor influencing the occurrence of nodular gastritis. Intestinal metaplasia, which was originally thought to be a pre-malignant lesion, occurred in 2.7% of the patients with H. pylori infection.     

Helicobacter pylori in gastroduodenal diseases

OBJECTIVE: To determine the prevalence and disease association of Helicobacter pylori (H. pylori) in dyspeptic patients in southwest Nigeria. Setting: Obafemi Awolowo University Teaching Hospitals Complex, Ile-lfe, Nigeria. METHODS: Consecutive dyspeptic patients for upper gastrointestinal endoscopy from January 1996 to March 1997 were investigated for H. pylori in gastric biopsy by histopathology and culture. Patients without gastroduodenal ulcerations or neoplastic lesions constituted the nonulcer dyspeptic (NUD) group. RESULTS: 138 (92 males, 46 females) patients aged 4.5-85 years [mean (7) = 45+/-SD 17.8 years] who had upper gastrointestinal endoscopy were analyzed for presence of H. pylori. Eighty-three had histopathology alone, while 55 others had both histology and culture. Endoscopic diagnosis included duodenal ulcer (DU) (n=35, 23%); gastric ulcer (n=4, 3%); gastric cancer (n=14, 9%); NUD, including gastritis (n=49, 32%); duodenitis (n=47, 31%); and normal (n=16, 11%). Overall, H. pylori was positive in 107 of 138 (77.5%) patients. There was a significant association of H. pylori with DU and NUD (p<0.000). Three-quarters of cases of normal endoscopy harbored H. pylori. The finding of 80% and 85% H. pylori in gastritis and duodenitis, respectively, was of interest. CONCLUSIONS: These findings suggest that DU and NUD were the main clinical expressions of H. pylori infection in southwest Nigerian dyspeptic patients similar to what is found in developed nations. Of note is the high incidence of H. pylori in endoscopically normal patients.     

Enterococcus gastritis

Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis.