In Japanese patients with type A gastritis with pernicious anemia the condition is very poorly associated with Helicobacter pylori infection.

There are conflicting views about the association between type A gastritis with pernicious anemia (PA) and infection with Helicobacter pylori, and currently, no definite conclusion has been reached. In this study, we evaluated H. pylori infection in patients with type A gastritis who developed PA. The study included a total of 25 Japanese patients (13 males and 12 females) who had been diagnosed with PA at our department, with a mean age of 71.2 years. We diagnosed infection with H. pylori by measuring serum H. pylori-IgG antibodies in all 25 patients, and we performed gastric biopsy in 17 patients. They were all negative for H. pylori-IgG antibody (0/25) and H. pylori on gastric biopsy (0/17). Although the prevalence of H. pylori infection (70-80 %) in our age-matched controls in Japan is higher than the prevalence in similar populations in western countries, we believe that type A gastritis with PA is very poorly associated with H. pylori infection.

Microbial and metabolic profile of achlorhydric stomach: comparison of pernicious anaemia and hypogammaglobulinaemia.

The microbial flora and some of its metabolites and enzymes in the stomach were compared in patients with achlorhydria, pernicious anaemia, and primary hypogammaglobulinaemia and in patients with dyspepsia with normal gastric acidity. Detailed analysis of the flora of the gastric juice and of the mucosa from the antrum, body, and fundus in six patients with hypogammaglobulinaemia (mean pH 8.2), seven patients with pernicious anaemia (mean pH 7.3), and five patients with dyspepsia (mean pH 1.9) yielded 22 different genera of bacteria, mainly from the patients with achlorhydria, the most common being streptococci, micrococci, staphylococci, veillonella, and lactobacilli. A similar flora was found associated with the mucosa at all three sites. Various metabolites were also looked for. beta Glucoronidase and C14 lipase were found in patients with hypogammaglobulinaemia but not in those with pernicious anaemia or dyspepsia. Volatile fatty acids were not found. Relatively high concentrations of ethanol were found in the patients with hypogammaglobulinaemia compared with those with pernicious anaemia (p = 0.02). Similar concentrations of dimethylamine were found in all three groups, but the concentrations of trimethylamine were much higher in patients with pernicious anaemia and hypogammaglobulinaemia. The high concentrations of some microbial enzymes and ethanol differentiated the group with hypogammaglobulinaemia from the rest, and these may bear some relation to the high incidence of gastric cancer in patients with hypogammaglobulinaemia.

The relationship between gastric-oral Helicobacter pylori and oral hygiene in patients with vitamin B12-deficiency anemia.

OBJECTIVE: The aim of this study was to determine whether a relationship exists between gastric and oral Helicobacter pylori and oral hygiene in patients with vitamin B12 deficiency. STUDY DESIGN: One hundred eight patients with vitamin B12 deficiency who were H pylori -positive in their gastric mucosa were enrolled in the study. These patients were divided into 3 groups determined by Oral Hygiene Index (OHI) scores of good, fair, or poor. H pylori was detected in the dental plaque with camphylobacter-like organism test gels. All patients were treated with a combination regimen to eradicate H pylori. RESULTS: H pylori positivity in dental plaque was correlated with OHI scores; the positivity was 28.5%, 90.2%, or 100% in patients with good, fair, or poor OHI scores, respectively. The eradication of H pylori was associated with recovery from anemia and increased serum vitamin B12 level (P <.0001 and P <.0001). The patients with poor OHI scores had the most frequent gastric recurrence of H pylori (58.3%) compared with those with fair OHI scores (41.2%) and good OHI scores (4.8%). CONCLUSIONS: H pylori seems to be an etiologic factor in vitamin B12 deficiency, since anemia was cured and the level of vitamin B12 in the serum increased as a result of its eradication. However, eradication of H pylori from gastric mucosa alone is not enough to prevent gastric recurrence of the bacteria. Proper oral hygiene must be established to eliminate H pylori in dental plaque. Therefore, we suggest that control of H pylori in dental plaque is necessary to control recurrence of H pylori.

Bacterial overgrowth as a consequence of reduced gastric acidity.

Reduction in acid secretion in atrophic gastritis allows bacterial colonization of the stomach, most extremely in achlorhydric patients with pernicious anaemia, in whom overgrowth may cause nitrate reduction and formation of potentially carcinogenic N-nitroso compounds. Subsequent bacterial contamination of the upper small intestine can induce mucosal damage and malabsorption. The situation is similar after gastrectomy. In achlorhydria and after gastrectomy, the risk of gastric cancer is increased. There is controversy as to the risks of long-term treatment with H2-receptor antagonists. Increase in nitrate-reducing bacteria, nitrite and N-nitrosamine have been observed in patients by some investigators but not in volunteers and patients by others. Bacterial concentrations after cimetidine are inversely related to pretreatment acid secretory capacity. Demonstration of increased mutagenicity of gastric juice after H2-receptor antagonists gives grounds for caution. Drastic acid reduction may in future be reserved for short-term and intermittent treatment and mild or moderate reduction for long-term treatment of peptic ulcer and ulcer prevention.

Role of Helicobacter pylori infection in the development of pernicious anemia.

It is now accepted that most patients with atrophic gastritis of the stomach have been infected with Helicobacter pylori. Several investigators have also suggested the possibility that H. pylori is involved in the early stages of pernicious anemia, which leads to severe atrophic gastritis of the fundus. In this article, studies investigating the association of this specific form of atrophic gastritis and H. pylori infection are reviewed. Most of the published studies indicate that patients with pernicious anemia are infected with H. pylori less often than are age-matched controls. However, because H. pylori infection may be present before the development of pernicious anemia, prospective studies during the pre-pernicious anemia stage of gastritis are needed.

The pathological examinations of gastric mucosa in patients with Helicobacter pylori-positive and -negative pernicious anemia.

BACKGROUND: The basic histopathological finding in gastric mucosa is chronic atrophic gastritis in patients with pernicious anemia. MATERIALS AND METHODS: We evaluated the frequency of Helicobacter pylori and pathological examinations of gastric mucosa in pernicious anemia (n = 30) by endoscopical findings and biopsy. The results were compared with gastric mucosa specimens of patients with H. pylori-positive nonulcer dyspepsia (n = 36) and H. pylori-negative nonulcer dyspepsia (n = 21). RESULTS: H. pylori was diagnosed in 12 patients (40%) with pernicious anemia. Fundal biopsy examinations showed atrophic gastritis in 30 patients (100%), intestinal metaplasia in 13 patients (43.3%), lymphoid follicle in 15 patients (50%), and dysplasia in 6 patients (20%). Antral biopsy examinations showed atrophic gastritis in 8 patients (26.6%), intestinal metaplasia in 8 patients (26.6%), lymphoid follicle in 8 patients (26.6%), and dysplasia in 3 patients (10%). The frequency of fundal inflammation, atrophy, intestinal metaplasia, lymphoid follicle, and dysplasia and antral intestinal metaplasia and mild antral dysplasia were found to be higher in those in the pernicious anemia group than in the nonulcer dyspeptic patients. Antral inflammation, atrophy, and moderate and severe antral dysplasia were found to be higher in those in the nonulcer dyspeptic group. CONCLUSIONS: Particularly, fundal precancerous lesions were found to be more frequent in patients with pernicious anemia independent of H. pylori.

Pernicious anaemia and Campylobacter like organisms; is the gastric antrum resistant to colonisation?

Gastric biopsies from 86 patients with pernicious anaemia were examined for Campylobacter like organisms with particular attention to those showing an antral gastritis in addition to the usual pattern of body gastritis. All the patients had chronic atrophic gastritis in the body but Campylobacter like organisms were found at this site in only three patients. Thus the Type A pattern of gastritis (autoimmune) seen in patients with pernicious anaemia is only rarely associated with Campylobacter like organisms. Forty four of these patients had biopsies from body and antrum, 16 showed an antral gastritis of whom only one had Campylobacter like organism present. Twenty five of this latter group of patients were rebiopsied after five years. There was no change in the pattern of gastritis, and the same single patient remained colonised. The frequency of an antral gastritis in patients with pernicious anaemia was 36% yet the frequency of antral colonisation by Campylobacter like organisms was very low (6%). These results show that, as in the body, Campylobacter like organisms are not associated with gastritis when it occurs at this site in pernicious anaemia. The antral gastritis that may accompany body gastritis in pernicious anaemia seems more likely therefore to be an extension of primary type A body gastritis (autoimmune) rather than a secondary type B (chronic) gastritis and, it is argued, the antrum may exhibit resistance to colonisation.

Pernicious anaemia, intragastric bacterial overgrowth, and possible consequences.

Intragastric bacterial colonization is well known in pernicious anaemia (PA), but its consequences have rarely been investigated. We have studied the clinical history, blood samples, and endoscopic biopsies from the stomach and duodenum of 80 patients with PA. In a random subgroup of 22 patients gastric juice was collected for aerobic culture and for estimation of nitrate, nitrate-reducing bacteria, nitrite, and N-nitrosamines; duodenal juice was studied in parallel in eight of these subjects. Gastric and duodenal juice had high bacterial counts; faecal organisms were found in 14 patients. The mean count of nitrate-reducing bacteria was significantly higher than in a control group of patients with peptic ulcer disease (p less than 0.001), as was the nitrite concentration (p less than 0.001). Thirty-three of the 80 patients had gastric dysplasias; 1 early gastric carcinoma was also found. Duodenitis was present in 39 out of 80 cases, in 6 associated with partial villous atrophy. A history of malabsorption and/or chronic intermittent diarrhoea was obtained significantly more often from patients with duodenitis. Four patients developed acute gastroenteritis shortly before or during the time of the study, two having a salmonella infection. Bacterial overgrowth in PA may be facilitated by altered immunological conditions, since low serum levels of IgA and IgG were found in this patient group.

Bacterial colonization and nitrite concentration in the achlorhydric stomachs of patients with primary hypogammaglobulinaemia or classical pernicious anaemia.

The degree and type of bacterial colonization was similar in achlorhydric patients with either severe primary hypogammaglobulinaemia or classical pernicious anaemia. This suggests that antibodies do not play a significant part in controlling the gastric flora in achlorhydric patients. The nitrite concentration in gastric juice was higher in the hypogammaglobulinaemia patients, raising the possibility that these patients may have very high levels of nitrite-derived mutagenic compounds in their gastric juice. This may account for the high incidence of gastric cancer in these patients.

Helicobacter pylori infection in pernicious anemia: a prospective controlled study.

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Positive correlation between H,K-adenosine triphosphatase autoantibodies and Helicobacter pylori antibodies in patients with pernicious anemia.

BACKGROUND: Helicobacter pylori is a major cause of gastritis, and the parietal cell H,K-adenosine triphosphatase (ATPase) is a major autoantigen in autoimmune atrophic corpus gastritis, which may eventually lead to pernicious anemia and/or neuropathy. Whether the bacterium induces the autoimmune response is unknown. METHODS: By means of enzyme-linked immunosorbent assay the occurrence of antibodies against porcine H,K-ATPase and H. pylori was determined in sera from 30 patients with pernicious anemia. RESULTS: All sera scored positive against H,K-ATPase, and 25 (83%) scored positive against H. pylori. The titers of antibodies against both antigen preparations inversely correlated with the duration of disease. A possible common epitope in the antigen preparations was tested with a competition assay. There was no indication of a common epitope in either human or porcine H,K-ATPase and H. pylori. CONCLUSIONS: There was a positive correlation and a high incidence of antibodies against H,K-ATPase and H. pylori in sera from patients with pernicious anemia. These antibodies recognized different epitopes.

Helicobacter pylori infection, vitamin B12 and homocysteine. A review.

It has been suggested that there is an association between Helicobacter pylori infection, reduced cobalamin absorption and cobalamin status and, consequently, elevated homocysteine levels. This would offer an explanation why H. pylori infection is associated with coronary heart disease. To date, more than 25 studies have been published that either deal with H. pylori infection and homocysteine, H. pylori infection and cobalamin status, or both. The design of these studies differs widely in terms of definition of H. pylori status, measuring cobalamin status, selection of study cohorts and geographical study areas. Therefore, results are fairly inconclusive at present and do not suggest a major role of H. pylori infection in the development of cobalamin deficiency and elevated homocysteine levels.

The microflora of the postoperative stomach.

The microflora and pH have been assessed in gastric aspirates from 163 patients after gastric surgery and have been compared with 51 patients with gastro-oesophageal carcinoma, 152 unoperated patients with peptic ulceration, 72 of whom were receiving cimetidine, 3 patients with pernicious anaemia and 27 normal subjects. The total viable bacterial count was closely related to the pH of the aspirate and was independent of the cause of the hypochlorhydria; 90 per cent of aspirates of pH 1--2 were sterile, while 94 per cent of those of pH 4--8 contained bacteria. Escherichia coli was found significantly more frequently in the postoperative and cancer groups, and Clostridium spp. were significantly more common in patients with carcinoma. Elevated gastric juice nitrite concentrations were significantly more common in aspirates of pH 4--8 and this correlated well with the presence of nitrate-reducing bacteria. The pH of an aspirate is a good indicator of the presence of bacteria and may be useful in selecting patients requiring postoperative prophylactic antibiotic cover. Hypochlorhydric patients are exposed to increased concentrations of nitrite and there may be an increased risk of gastric cancer induced by N-nitrosocompounds.

Intestinal bacterial flora and bile salt studies in hypogammaglobulinaemia.

Five patients with adult acquired hypogammaglobulinaemia, four of whom were achlorhydric, were studied. Jejunal bacterial counts were much higher than those in a control group of acid secretors, but were similar to those in a control group of patients with pernicious anaemia; Giardia lamblia were isolated from the jejunal content of all patients with hypogammaglobulinaemia. The concentration of conjugated bile acids in the fasting state was lower in hypogammaglobulinaemia than in pernicious anaemia, but in the two hypogammaglobulinaemic patients with steatorrhoea there was a normal bile salt response to a fatty meal.

Is Helicobacter pylori involved in the pathogenesis of the gastritis characteristic of pernicious anaemia? Comparison between pernicious anaemia relatives and duodenal ulcer relatives.

The aim of the study was to evaluate whether Helicobacter pylori could be involved in the early stages of the severe corpus atrophy that is characteristic of overt pernicious anaemia and is usually H. pylori-negative. The behaviour of H. pylori infection and chronic gastritis was studied in 159 first-degree relatives of pernicious anaemia (PA) probands and was compared with that in 137 first-degree relatives of duodenal ulcer (DU) probands. DU is as a rule associated with H. pylori infection. PA relatives showed a markedly higher prevalence of severe corpus atrophy and of parietal cell antibodies than DU relatives. However, the prevalences of H. pylori did not show significant differences between the two groups of relatives. The age-specific prevalences of H. pylori infection increased similarly in both series of relatives up to geriatric age, together with an increase in the mean scores of corpus gastritis. However, in older age the prevalence of H. pylori in PA relatives showed a marked decrease, in spite of the increase in the mean gastritis score. The present result suggests the possibility that H. pylori is involved in the early PA stages that lead to severe corpus atrophy. The later progress of gastritis seems to be dependent on factors other than H. pylori, most likely 'autoimmune' mechanisms.

Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro.

Reassessment of the ;gastric bactericidal barrier' to enteric bacteria in man included studies of the bactericidal activity of (1) the normal and achlorhydric stomach in vivo and (2) normal and achlorhydric gastric juice and other media in vitro. Within 30 minutes virtually all bacteria (Serratia marcescens) were eliminated in the normal stomach whereas no reduction occurred in the achlorhydric stomach in one hour. In vitro, identical bactericidal activity was observed at the same pH (from 2.0 to 7.0) in normal gastric juice, achlorhydric gastric juice, aqueous HCl, and nutrient broth. At pH less than 4.0, 99.9% of the bacteria were killed within 30 minutes. The presence of profuse bacterial flora, including coliforms, found in markedly acid-deficient but not in normal stomachs, correlates well with the absence of bactericidal activity. Thus, the ;gastric bactericidal barrier' is primarily pH-hydrochloric acid dependent, with other constituents of gastric juice contributing little, if any, detectable effect on the destruction of microorganisms.