Serum pepsinogen concentrations as a measure of gastric acid secretion in Helicobacter pylori-negative and -positive Japanese subjects

Background Although previous studies have indicated that serum pepsinogen I levels, as well as the pepsinogen I/II ratio, were positively correlated with maximal gastric output, the relationship may be different between Helicobacter pylori-negative and -positive subjects. The aim of this study was to investigate the relation between serum pepsinogen concentrations and gastric acid secretion in H. pylori-positive and -negative subjects separately. Methods The presence of H. pylori infection, the serum pepsinogen concentrations, and gastric acid secretion were investigated in 182 subjects without localized lesions in the upper gastrointestinal tract. Serum pepsinogen concentration was measured by radioimmunoassay, and maximal gastric acid output was estimated by an endoscopic gastrin test, as we have previously shown. Results In H. pylori-positive subjects, serum pepsinogen I levels and the pepsinogen I/II ratio were significantly correlated with gastric acid secretion, although the latter showed a better correlation (r = 0.40 and 0.53, respectively). On the other hand, in H. pylori-negative subjects, serum pepsinogen concentrations were well correlated with acid secretion (r = 0.57), but there was no relation between the pepsinogen I/II ratio and acid secretion. Conclusions The correlations between serum pepsinogens and gastric acid secretion differ, depending on the presence or absence of H. pylori infection. With the use of serum pepsinogens as a simple measure of gastric acid secretion, therefore, consideration of H. pylori infection status is needed. Because the determination of the acid secretory level has some clinical implications in both H. pylori-positive and -negative subjects, its estimation by serum pepsinogen concentrations can be of practical use.     

Interrelationships betweenHelicobacter pylori infection,nonsteroidal antiinflammatory drugs and gastroduodenal disease

Helicobacter pylori and nonsteroidal antiinflammatory drugs independently cause gastroduodenal mucosal injury but the relationship between them remains unclear. We have performed a double-blind, parallel-group, placebo-controlled prospective study in 77 healthy volunteers aged 19–35 years who were randomly allocated to indomethacin (N=15), one of three oxicams (piroxicam, chlortenoxicam, or CHF 1194;N=36), or placebo (N=26). Esophagogastroduodenoscopy was performed before and after four weeks of treatment and the mucosal appearances graded. Colonization withH. pylori was established at each endoscopy and gastrointestinal symptoms were assessed by daily diary card. Seven subjects (9%) were positive forH. pylori before treatment (one placebo, one indomethacin, and five an oxicam); theirH. pylori status remained unchanged. Two of 70H. pylori-negative subjects becameH. pylori-positive (2.9%), both of whom had received placebo. The endoscopic score deteriorated in 1/6 drug-treatedH. pylori-positive subjects and in 0/1 taking placebo. Of theH. pylori-negative subjects whose endoscopic score deteriorated, three (13%) were taking placebo, four (28.6%) indomethacin, and eight (25.8%) an oxicam. Upper gastrointestinal symptoms were reported in eight (30.8%) of the subjects taking placebo (one subject negative forH. pylori became positive), eight (53.3%) indomethacin (oneH. pylori-positive), and 10 (27.8%) an oxicam (oneH. pylori-positive). There were no statistically significant differences between theH. pylori-negative andH. pylori-positive groups whether on drug or placebo. These findings suggest thatH. pylori infection, at least in the short term, neither influences the propensity of nonsteroidal antiinflammatory drugs to produce macroscopic gastroduodenal mucosal injury nor does it effect the occurrence of upper gastrointestinal symptoms.     

NSAID Gastric Ulceration: Predictive Value of Gastric pH, Mucosal Density of Polymorphonuclear Leukocytes, or Levels of IL-8 or Nitrite

NSAID use and Helicobacter pylori both cause damage to the gastric mucosa and can cause peptic ulcers. Our aim was to test the relationship between gastric mucosal polymorphonuclear leukocyte (PMN) infiltration and the severity of NSAID-induced gastric injury. H. pylori density, mucosal interleukin-8 (IL-8), and nitrite levels were assessed after receiving placebo and again after receiving 1000 mg of naproxen daily for three days. Histology was graded using a visual analog scale (0–5). IL-8 levels were assayed by ELISA and nitrite levels by Griess reaction. Eleven healthy volunteers with H. pylori infection entered. All had normal-appearing gastric mucosa after placebo. Postnaproxen gastric damage included three with none, one with mild, three with moderate, two with severe, and three were very severe mucosal injury (including one with an ulcer >5 mm). There was an inverse correlation between endoscopic score and the pH of the gastric juice post-therapy (R = –0.77, P = 0.004). There was no significant change in histologic or biochemical parameters from pretreatment levels. And none of the parameters (eg, PMN density) predicted endoscopic outcome. In conclusion, there was no relation between mucosal PMN density and endoscopic mucosa injury. PMN infiltration, while not predictive, may be a surrogate for an H. pylori infection-related increased risk of NSAID ulcers.     

Influence ofHelicobacter pylori on gastric mucosal adaptation to naproxen in man

Our objective was to determine whetherH. pylori influences gastric mucosal injury and adaptation caused by naproxen. Twenty-four healthy volunteers, 12H. pylori-positive and 12H. pylori-negative, were given a 28-day course of naproxen 500 mg twice a day. They were each gastroscoped to assess gastric mucosal damage and mucosal blood flow before and at 1, 7, and 28 days during treatment. Maximal gastric mucosal damage (median grade+IQR) occurred during the first 24 hr in both groups and was of similar magnitude (H. pylori-positive: 2.5, 2.0–3.0P<0.01;H. pylori-negative: 2.0, 1.0–3.0P<0.01). This damage was associated with a fall in antral but not corpus mucosal blood flow. With continued NSAID administration, gastric damage resolved confirming adaptation (H. pylori-positive 1.0, 0–2.0,H. pylori-negative: 1.0, 0–1.0) and antral mucosal blood flow returned to baseline in both groups by day 28. These observations suggest that initial gastric mucosal injury is not influenced byH. pylori colonization and adaptation occurs regardless of its presence.     

Effect of eradication ofHelicobacter pylori infection on gastric epithelial cell proliferation

Helicobacter pylori infection has been linked with gastric carcinoma. Epithelial cell proliferation is an indicator of cancer risk. The aim of this study was to assess gastric epithelial cell proliferation before and after eradication therapy and to assess the efficacy of treatment ofH. pylori infection using lanzoprazole and clarithromycin. Twenty-three patients withH. pylori-associated gastritis were treated with lanzoprazole 30 mg daily for four weeks and clarithromycin 500 mg three times a day for two weeks. Antral mucosal biopsies were taken for gastric epithelial cell proliferation analysis using thein vitro bromodeoxyuridine (BrdU) immunohistochemical technique before and four weeks after eradication therapy. Labeling index percent (LI%) was calculated as the percent ratio of proliferating cells to the total number of cells in the gastric pit. Efficacy of treatment was assessed in 16 subjects. Eight were negative forH. pylori infection 28 days after therapy and in eight patientsH. pylori infection was not eradicated. The eradication rate for the regimen was 50%. Cell kinetics were assessed in 19 subjects who completed treatment. Patients withH. pylori infection had a significantly higher LI% compared to normal (N=19, LI%: 5.01±0.3 vs 3.2±0.2,N=29). Eradication ofH. pylori infection significantly reduced epithelial cell proliferation (N=9, LI%:5.2±0.4 to 3.2 ±0.8,P<0.001), whereas it was unaltered in those whose infection was not eradicated (N=10, LI%: 4.8±0.4 to 5.5±0.5,P=0.18). Eradication ofH. pylori reduces gastric epithelial cell proliferation to normal levels and may reduce the long-term the risk of gastric carcinoma.We wish to thankLederle for their support with this trial.     

Association betweenH. pylori,duodenal mechanosensory thresholds,and small intestinal motility in chronic unexplained dyspepsia

Alterations of small intestinal sensory thresholds and small intestinal dysmotility are associated with functional dyspepsia. Because gastric and duodenal afferents partly project to the same areas, we postulated that patients with functional dyspepsia andH. pylori infection would be characterized by lower duodenal sensory thresholds. We evaluated 16 patients with functional dyspepsia and 16 age- and sex-matched controls. All patients had undergone an extensive diagnostic work-up to exclude organic lesions. Mechanosensitive function was tested in the third portion of duodenum utilizing a barostat device, and small intestinal motility was assessed before and during duodenal nutrient infusion with a five-channel low-compliance perfusion system.H. pylori status was assessed by a validated serological test. Small intestinal sensory thresholds (first perception and maximal tolerated pressure) were significantly lower in patients (21.1±2.1 and 30.9±1.8 mm Hg) compared to controls (33.0±2.2 and 38.8±0.9 mm Hg, allP<0.003). Nine of 16 patients compared with five of 16 controls wereH. pylori positive (P=0.15). Thresholds forH. pylori-negative (28.7±2.8 and 36.5±1.1 mm Hg) or -positive subjects (25.0±3.0 and 32.7±2.4 mm Hg) were overall not significantly different (P>0.3). However, in patients with defined highH. pylori titers (>50 units/ml) defineda priori, thresholds for first perception were significantly lower (14.7±2.9 mm Hg,N=5) compared to patients withH. pylori titers below this threshold (24.3±2.9 mm Hg,N=4) or withoutH. pylori infection (23.8±3.4 mm Hg,P<0.05). During duodenal nutrient infusion, the duodenal motility index increased (P<0.03). This increase was not significantly different in patients and controls or inH. pylori-negative and -positive subjects. Sensory abnormalities are present in patients with functional dyspepsia. In a small subgroup of patients with highH. pylori titers, sensory abnormalities may be linked toH. pylori infection.Supported by a grant from Deutsche Forschungsgemeinschaft, grant number Ho 1193/3-1,2 and by the Gastrointestinal Motility Research Award from the German Association of Digestive Diseases (donated by the Janssen Research Foundation).     

Blood leukocyte differential inHelicobacter pylori infection

Helicobacter pylori causes a chronic infection in gastric mucosa, but its systemic effects are largely unknown. Our aim was to characterize the effect ofH. pylori infection and gastric mucosal inflammation on the peripheral blood leukocyte count. An endoscopic series of 96 patients (40 men and 56 women), with a mean age of 62 years (range 49–80) was studied. Endoscopy with eight stepwise biopsies was performed and the occurrence ofH. pylori was studied from sections stained with Warthin-Starry. The severity of inflammation in antral and body mucosa was estimated. The peripheral blood leukocyte count and differential count were determined by the automatic flow cytometric method. The total number of blood leukocytes and the numbers of lymphocytes and basophils were significantly increased inH. pylori-positive patients (N=58), as compared withH. pylori-negative ones (N=38). The total number of blood leukocytes correlated with the numbers of neutrophils, eosinophils, and mononuclear cells in the gastric mucosa. The number of basophils correlated with the number of mucosal neutrophils and mononuclear inflammatory cells. The results show that mucosal inflammation due toH. pylori infection is reflected in the amount of peripheral blood leukocytes. Basophilia suggests involvement of allergic mechanisms inH. pylori gastritis.     

Diagnosis of Helicobacter pylori Infection from Antral Biopsies in Pediatric Patients: Is Urease Test that Reliable?

Our objectives were to determine if the urease (CLO) test alone is a reliable diagnostic test for H. pylori gastritis in children and if the density of H. pylori influences the CLO test result. We performed a combined retrospective and prospective study reviewing the results of CLO-test and histology of gastric mucosal biopsy from 67 patients (35 females) with H. pylori gastritis. Two antral biopsies were inoculated on the CLO-test and two processed for histology to grade the severity of gastritis and H. pylori density. The mean age of patients was 11 years (sd ± 4.53). Only 50 patients tested positive for H. pylori on CLO-test, whereas all patients were positive on histology. %The sensitivity of the CLO-test was 75%. There was a significant association between CLO-test positivity and the density of H. pylori organisms on histology (P < 0.01), and with the severity of gastritis (P < 0.001) by the Pearson chi-square test. However, there was no association between the density of H. pylori and severity of gastritis. In conclusion, the CLO-test is not reliable as a sole diagnostic test for H. pylori gastritis in children because of a significant number of false negatives. Histologic examination of gastric mucosal biopsy is superior to the CLO-test in diagnosing H. pylori infection.     

Helicobacter pylori Infection Is Not Associated with Delayed Gastric Emptying or Upper Gastrointestinal Symptoms in Diabetes Mellitus

This study evaluated the relationship between gastric emptying and upper gastrointestinal symptoms with H. pylori status in patients with diabetes mellitus. Sixty-three outpatients (44 type 1, 19 type 2, age 45 ± 1.5 years) underwent measurements of gastric emptying of a mixed solid and liquid meal, gastrointestinal symptoms (gastric and esophageal), glycemic control (HbA_lc), and autonomic nerve function. Anti-H. pylori IgG antibodies were quantified using a validated kit. Gastric emptying of solid and/or liquid was delayed in 47 (75%) patients, and 31 (49%) had autonomic neuropathy. Fifteen (24%) of the patients were H. pylori positive. There were no differences in gastric emptying (solid retention at 100 min: 67.5 ± 5.7% vs 63.2 ± 3.6%; P = 0.63, liquid T50: 35.5 ± 2.9 min vs 42.5 ± 3.4 min; P = 0.42), upper gastrointestinal symptoms (gastric 3.9 ± 0.7 vs 4.0 ± 0.4; P = 0.94 or esophageal 1.7 ± 0.5 vs 1.3 ± 0.2; P = 0.42) or HbA_lc (8.8 ± 0.4% vs 8.6 ± 0.2%; P = 0.89) between H. pylori-positive and -negative patients. We conclude that H. pylori infection is not associated with delayed gastric emptying or upper gastrointestinal symptoms in diabetes.     

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patie     

Alteration of correlation between serum pepsinogen concentrations and gastric acid secretion after H. pylori eradication

Purpose  The measurement of serum pepsinogens is clinically useful to represent gastric acid secretion. Since both serum pepsinogens and gastric acid secretion are considerably altered by H. pylori eradication, the correlation between these two parameters could be different prior to and after eradication. In this study, we investigated the correlation between the two parameters prior to and after eradication. Methods  One hundred eighteen H. pylori-positive patients with peptic ulcers or chronic gastritis were enrolled in this retrospective analysis. In all participants both the measurement of serum pepsinogens and the determination of gastric acid secretion were performed prior to and at 1 month after successful eradication. In 85 subjects, the same assessments were repeated at 7 months. Correlations between serum pepsinogens and gastric acid secretion were assessed using linear regression analysis. Results  The pepsinogen I/II ratio (r = 0.56) was a better indicator of gastric acid secretion in H. pylori-infected subjects than pepsinogen I itself (r = 0.31). Eradication of H. pylori altered the association, causing pepsinogen I (r = 0.55) to become a better indicator of gastric acid secretion compared with the pepsinogen I/II ratio (r = 0.40) at 1 month after eradication, followed by similar tendencies at 7 months. Conclusion  Using different serum biomarkers (pepsinogen I/II ratio prior to eradication or pepsinogen I after eradication), the measurement of serum pepsinogens is useful for predicting the individual gastric acid secretion level not only in H. pylori-infected subjects, but also in subjects with histories of eradication of the infection.     

Breath ammonia measurement in Helicobacter pylori infection

Our aim was to define the utility of breath ammonia measurement in assessing Helicobacter pylori infection. Volunteers breathed into a device containing three fiberoptic NH₃ sensors at baseline and after ingesting 300 mg of urea. Breath ammonia levels were compared to the [¹⁴C]urea breath test. Thirteen subjects were tested. Before urea ingestion, H. pylori-positive subjects had significantly lower breath ammonia levels than negative subjects (mean ± sd, 0.04 ppm ± 0.09 vs 0.49 ppm ± 0.24, P = 0.002) and had a significantly greater increases in breath ammonia after urea ingestion (range 198–1494% vs 6–98%). One H. pylori-positive subject underwent treatment and breath ammonia levels shifted from the pattern seen in positive subjects to that seen in negative subjects. In conclusion, breath ammonia measurement for H. Pylori-positive and negative subjects showed distinct patterns. Breath ammonia measurement may be feasible as a diagnostic test for H. pylori.     

Gastric adaptation to aspirin and Helicobacter pylori infection in man

Abstract The relationship between Helicobacter pylori infection and aspirin (ASA)-induced gastropathy and gastric adaptation to ASA remains unclear. We compared gastric damage and adaptation after repeated exposures to ASA in the same subjects without H. pylori infection and those infected by H. pylori before and after eradication of this H. pylori. Twenty-four volunteers in two groups (A and B), without H. pylori infection (group A) and with H. pylori infection (group B) before and after H. pylori eradication, were given ASA 2 g/day or placebo for 14 days. Mucosal damage was evaluated by endoscopy and gastric microbleeding; mucosal prostaglandin (PG) E₂ generation and luminal transforming growth factor (TGF)α were determined on days 0,3,7 and 14 of the ASA course. In all subjects, ASA-induced gastric damage reached a maximum on day 3. In H. pylori-positive subjects this damage was maintained at a similar level up to the 14th day of observation. Following H. pylori eradication, the damage was significantly lessened at day 14, as revealed by both endoscopy and microbleeding, and was accompanied by increased mucosal release of TGFα. Prostaglandin E₂ generation was significantly higher in H. pylori-positive subjects than after H. pylori eradication, but ASA treatment resulted in greater than 90% reduction of this generation independent of H. pylori status. Gastric adaptation to ASA is impaired in H. pylori-positive subjects but eradication of this bacterium restores this process.     

Characterization of virulence factors of mouse-adapted Helicobacter pylori strain SS1 and effects on gastric hydrophobicity

Gastric infection with Helicobacter pylori results in chronic active gastritis and in some individuals is associated with complications such as peptic ulceration and gastric cancers. A balance between bacterial factors and host responses may determine disease outcome. The mouse-adapted H. pylori strain SS1 has been utilized as a model to study disease pathogenesis. Although chronic gastritis is observed in this murine model of H. pylori infection, other complications of disease seen in the human host (such as peptic ulceration) are not identified. The objectives of this study were to characterize virulence factors of the mouse-adapted H. pylori strain SS1 and determine host responses to infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase chain reaction was performed to detect the presence of the cagA and cagE genes. Chemokine responses from human gastric epithelial cells infected with H. pylori SS1 were assessed by measurement of the concentration of interleukin-8 in cell-free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham-infected. Eight weeks following infection, gastric tissues were obtained for histological analysis and surface hydrophobicity was measured by axisymmetric drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive, and cagE positive, but induced only a modest interleukin-8 response (684 ± 140 pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate (4170 ± 410 pg/ml, P < 0.0005). Increased inflammation was observed in the stomachs of H. pylori strain SS1-infected animals compared to uninfected controls. Gastritis was not associated with any disease complications. Despite mucosal inflammation, infected mice did not demonstrate alterations in gastric surface hydrophobicity (42.2° ± 2.2° and 41.4° ± 3.2° for C57BL/6 and gld, respectively) compared to uninfected mice (43.2° ± 2.3° and 39.5° ± 1.6°, respectively). In conclusion, murine infection with H. pylori SS1, which contains putative bacterial virulence factors, results in gastric inflammation. However, the mucosal changes are not associated with alterations in surface hydrophobicity. Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve as an entirely appropriate model to study host factors associated with disease complications.     

Circulating Ghrelin Levels in Patients with Various Upper Gastrointestinal Diseases

The stomach is the main source of circulating ghrelin. Plasma concentrations of this hormone in patients with various upper gastrointestinal diseases remain undetermined. Thus we measured plasma ghrelin levels by radioimmunoassay in 225 subjects, including 134 Helicobacter pylori-infected and 91 uninfected subjects. They included 67 patients with chronic gastritis (CG), 26 with benign gastric polyp (BGP), 24 with gastric ulcer (GU), 24 with reflux esophagitis (RE), 18 with duodenal ulcer (DU), 28 with acute gastritis (AG), 23 with gastric cancer (GC), and 39 who had normal mucosa on upper endoscopy (N). Plasma pepsinogen I and II levels were also measured. The extent of gastritis was assessed endoscopically. Ghrelin levels differed significantly among the different disease groups. Plasma ghrelin concentrations were lowest in the CG group, followed by the GU group, and highest in the AG patients. There was a significant difference in the levels between differentiated and undifferentiated GC. Ghrelin concentrations in BGP, RE, and DU patients were comparable to those in the N group. Ghrelin circulating levels were lower in H. pylori-positive than –negative individuals, but the significant differences among disease groups were still observed in H. pylori-infected and uninfected populations. Ghrelin concentrations correlated positively with plasma pepsinogen I levels and I/II ratios and inversely with the extent of H. pylori-related gastritis. Plasma ghrelin levels varied widely in diverse conditions of the upper digestive tract, reflecting the inflammatory and atrophic events of the background gastric mucosa. Further investigation is warranted to unravel the mechanisms of the high circulating ghrelin levels in certain upper gastrointestinal diseases.     

Topographic study ofHelicobacter pylori and HLA-DR antigen expression on gastric epithelium

Helicobacter pylori and HLA-DR antigen expression on gastric epithelium, identified by an indirect immunoperoxidase staining method using monoclonal antibodies againstH. pylori and HLA-DR antigens, were studied topographically. Fitty-nine biopsy specimens from 41 patients who had neither gastric cancer nor peptic ulcers were examined.H. pylori was observed predominantly over or on the surface epithelium, while HLA-DR antigens were frequently expressed on the epithelium of the isthmus region. These observations led to the conclusion that there was no direct topographic association betweenH. pylori and epithelial HLA-DR expression. However, the frequency of HLA-DR expression inH. pylori-positive (28/29) specimens was significantly higher than that inH. pylori-negative (18/30) specimens (P<0.01). Furthermore, a greater number ofH. pylori was associated with a stronger expression of HLA-DR antigens (P<0.001). We conclude thatH. pylori is indirectly related to HLA-DR expression on gastric epithelium.H. pylori is the first microbial agent that has been suggested to be associated with epithelial HLA-DR expression in the human gastrointestinal tract.     

Helicobacter pylori infection accelerates human gastric mucosal cell proliferation

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation inH. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whomH. pylori) recurred.H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation inH. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whomH. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P<0.01,P<0.001), and 6 months later, it had markedly decreased (P<0.05,P<0.05) and returned to normal. In patients in whomH. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but whenH. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest thatH. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.     

Helicobacter pylori infection in combination with the serum pepsinogen I/II ratio and interleukin-1β-511 polymorphisms are independent risk factors for gastric cancer in Thais

Background Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1β-511 polymorphisms are suspected to be risk factors for gastric cancer. Methods A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1β-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups. Results The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10–4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4–6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50–0.81; P = 0.014). Conclusions A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1β-511 C/C genotype may be independent risk factors for gastric cancer in Thais. Presented at the 19th World Congress of the International Society of Digestive Surgery, Pacifico Yokohama, Japan, December 8–11, 2004 (Helicobacter pylori Symposium)     

Antral Glutathione Concentration and Glutathione S-Transferase Activityin Patients with and WithoutHelicobacter pylori

Previously we demonstrated an inverse relation between cancer of the gastrointestinal tract and glutathione S-transferase activity of the gastrointestinal mucosa. Chronic infection with H. pylori has been associated with an increased risk of gastric cancer. The aim of this study was to investigate the levels of glutathione and glutathione S-transferase activity in H. pylori-infected and noninfected antral mucosa. Glutathione and glutathione S-transferases were measured in antral biopsies of patients with nonulcer dyspepsia without H. pylori infection (A), with prior H. pylori infection who became H. pylori negative after eradication therapy (B) and with proven H. pylori infection (C). Glutathione concentration and glutathione S-transferase activity in group A were 31.0 (range 6.0–59.6) nmol/mg protein and 810 (range 165–1312) nmol/min/mg protein, in group B 27.0 (range 5.0–53.8) nmol/mg protein and 745 (range 403–1199) nmol/min/mg protein, and in group C 18.5 (range 1.6–55.8) nmol/mg protein and 572 (range 144–1047) nmol/min/mg protein, respectively. The glutathione and glutathione S-transferase values were significantly lower in patients infected with H. pylori than in patients who were H. pylori negative.     

Relationship between progression of gastric mucosal atrophy andHelicobacter pylori infection: Retrospective long-term endoscopic follow-up study

A retrospective long-term endoscopic followup study was designed to examine atrophic changes in the gastric mucosa over time inHelicobacter pylori-positive patients. Over a period of 8–17 years (mean, 13.4 years) 22 subjects (5 men, 17 women, mean age, 55 years) without localized gastroduodenal lesions underwent serial endoscopic examinations and serological and microbiological assessments ofH. pylori infection. The extent of atrophic mucosa in the gastric body was expressed using the Kimura-Takemoto classification of atrophic pattern. Atrophic patterns were unchanged over time in 7H. pylori-seronegative and culture-negative subjects with normal stomach, and in 1 seropositive and culture-negative subject with severe atrophy. Seven of 10H. pylori culture-positive subjects not including three with the O-3 pattern, i.e., open type atrophic pattern, exhibited a cephalad shift of atrophic pattern. The cumulative progression rates of atrophy in the culture-positive subjects excluding O-3 subjects, were 10% after 2 years, 20% after 4 years, 50% after 6 years, and 70% after 8 years. The increases in the extent of the atrophic area were discontinuous, in terms of age, in theH. pylori-positive individuals and occasionally advanced rapidly within periods of several years with no relation to age.