Effects of clarithromycin,omeprazole and leminoprazole on gastric ulcer healing in Helicobacter pylori-infected rats

Abstract We examined whether a single inoculation of Helicobacter pylori can colonize the stomachs of ulcerated rats and delay their healing and whether an antibiotic drug and acid pump inhibitors can enhance the ulcer healing in infected rats. Ulcers were produced by a submucosal injection of acetic acid solution into the gastric wall. Helicobacter pylori (ATCC-43504) was inoculated into rats with and without gastric ulcers. The animals were killed 2, 4, 6, 8 or 10 weeks after the inoculation and the ulcerated area and H. pylori viability were determined. Each test drug and their combination was administered for 1 or 2 weeks after H. pylori inoculation. Helicobacter pylori could not colonize the stomachs of normal rats, but could colonize stomachs with ulcers for 10 weeks at an incidence of >80%. Spontaneous healing of gastric ulcers was delayed by H. pylori infection during these 10 weeks. Daily treatment with clarithromycin significantly and dose-dependently delayed ulcer healing in infected rats. Both omeprazole and leminoprazole significantly enhanced ulcer healing and inhibited the clarithromycin-delayed ulcer healing. We conclude that: (i) H. pylori can colonize rat stomachs with ulcers and delay ulcer healing; (ii) clarithromycin delays ulcer healing in H. pylori-infected rats; and (iii) acid pump inhibitors inhibited the clarithromycin-delayed ulcer healing.     

Influence of gastric colonization with Candida albicans on ulcer healing in rats: Effect of ranitidine,aspirin and probiotic therapy

Objective. Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. Material and methods. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg^?1 day^?1 s.c.) and 2) aspirin (ASA) (60 mg kg^?1 day^?1 i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1β and TNF-α and growth factors EGF and TGFα were assessed in the gastric mucosa. Results. Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1β, TNF-α, EGF and TGFα and a significant increment in plasma IL-1β and TNF-α levels. Conclusions. 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1β and TNFα and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.     

Helicobacter pylori infection delays the healing of acetic acid-induced gastric ulcer in Japanese monkeys

To clarify the relationship between Helicobacter pylori and the healing of gastric ulcers, we investigated the healing of acetic acid-induced gastric ulcers in the antral mucosa of Japanese monkeys (n=5) infected with H. pylori and in control monkeys without H. pylori infection (n=6). Using H. pylori-infected Japanese monkeys as an experimental model, gastric ulcers were induced endoscopically with acetic acid. Healing of ulcers and factors that influenced healing were studied. Continuous colonization with H. pylori was confirmed in the infected group throughout the observation period; no H. pylori were isolated from the gastric mucosa of the control group. White scarring was not observed in any infected monkeys 4 weeks after ulcer formation, but was observed in one (20%) of five monkeys at 6 weeks and in all five monkeys eight weeks after ulcer formation. In the control group, white scarring was observed in one (16.7%) of six monkeys at 4 weeks and in six monkeys at 6 (P< 0.01 vs infected group) and 8 weeks. The ammonia concentration of the gastric secretions and the grade of inflammation were significantly increased in the H. pylori-infected group compared with the control group (P< 0.01 and P< 0.001, respectively). The volume of intracellular PAS-positive substance was decreased (P< 0.025–0.01) at the ulcer margin in the infected group compared with the ulcer margin in the control group. The proliferation of gastric epithelial cells was markedly accelerated at the ulcer margin in the infected group compared with the ulcer margin in control group (P< 0.025–0.01). Our results strongly suggest that H. pylori infection delays the healing of gastric ulcers.     

Endoscopic characteristics and Helicobacter pylori infection in NSAID-associated gastric ulcer

Background and Aim: Helicobacter pylori infection and non‐steroidal anti‐inflammatory drugs (NSAIDs) are deeply involved in the etiology of gastric ulcers. The aim of our study was to clarify the endoscopic characteristics and H. pylori infection status of NSAID‐associated gastric ulcers. Methods: The study group comprised 50 patients (23 men, 27 women; mean age 66.5 years) with NSAID‐associated gastric ulcers and 100 sex‐ and age‐matched patients with gastric ulcer associated with other factors (control group). Ulcer morphology, size and number of lesions, onset site and incidence of hemorrhagic ulcers were investigated endoscopically in both groups. H. pylori infection was diagnosed by serology, histology and ¹³C‐urea breath test. Results: Multiple lesions (68% vs 20%, P < 0.001), occurrence in the antrum (56% vs 6%, P < 0.001), and hemorrhagic ulcer (34% vs 4%, P < 0.001) were significantly more prevalent in patients with NSAID‐associated gastric ulcers than in patients with non‐NSAID‐associated gastric ulcer. The H. pylori infection rate was significantly lower in NSAID‐associated gastric ulcer patients than in non‐NSAID‐associated gastric ulcer patients (48% vs 96%, P < 0.001). In the NSAID‐associated gastric ulcer group, the prevalence of H. pylori infection was significantly lower in patients with ulcers in the antrum than in those with ulcers in the angulus or corpus (25% vs 77.3%, P < 0.001). Conclusions: In contrast to non‐NSAID‐associated gastric ulcers, NSAID‐associated gastric ulcers frequently occur in the antrum with bleeding. The rate of H. pylori infection in NSAID‐associated gastric ulcers is significantly lower than that in non‐NSAID‐associated gastric ulcers.     

A pilot study to evaluate a new combination therapy for gastric ulcer: Helicobacter pylori eradication therapy followed by gastroprotective treatment with rebamipide

Background and Aim: Controversies remain over the need for antiulcer treatment following 1‐week eradication triple therapy for Helicobacter pylori‐positive peptic ulcers. The usefulness of combination therapy for gastric ulcers in Japanese patients, which consists of H. pylori eradication followed by gastroprotective therapy with rebamipide, was therefore evaluated. Methods: The study was conducted in 52 H. pylori‐positive patients with an endoscopically‐proven open gastric ulcer. All patients received 1‐week triple therapy (lansoprazole, amoxicillin and clarithromycin) followed by 7‐week rebamipide therapy. After completion of the combination therapy, all patients underwent evaluation of ulcer healing by endoscopy, gastric ulcer symptoms and H. pylori eradication by rapid urease test and ¹³C‐urea breath test. Results: The ulcer healing rates were 85.7% (36/42) at 8 weeks, 83.3% (30/36) in eradicated patients and 100% (6/6) in non‐eradicated patients. The overall gastrointestinal symptom‐free rate improved from 19.0% at baseline to 88.1% at 8 weeks. H. pylori was effectively eradicated in 85.7% (36/42) of patients. Conclusions: The results suggested that the combination therapy for open gastric ulcer was safe, well‐tolerated and effective. However, data from a double‐blind placebo‐controlled study is necessary to confirm these findings.     

Helicobacter pylori-negative gastric and duodenal ulcers

It is unclear whether Helicobacter pylori infection is essential to the development of peptic ulcers. In this study, we examined the rates of H. pylori-negativity among patients with peptic ulcers. We also attempted to clarify the characteristics of H. pylori-negative peptic ulcers to throw light on the pathogenesis of peptic ulcers. The study included 215 consecutive patients with gastric ulcers (GUs) and 120 consecutive patients with duodenal ulcers (DUs). After routine endoscopic examination and phenol red dye endoscopy, forceps biopsies were performed for culture, histology, and the rapid urease test. A patient was considered H. pylori-negative when the serum anti-H. pylori IgG and the three tests on biopsied specimens were all negative. H. pylori-negative rates were 3.2% in the patients with GUs and 1.7% in the patients with DUs. Lack of atrophy of the gastric mucosa was significantly more common in the H. pylori-negative patients with GUs. A history of ulcer disease was less common and antral ulcers were more common in H. pylori-negative GU patients, but not significantly so. As the urea breath test had not been performed, the possibility of a false-negative result cannot be completely ruled out, but we believe that the H. pylori-negative rate in our study is more reliable than these rates in previous reports, because we visualized H. pylori distribution by phenol red dye endoscopy to avoid false-negative results in biopsies, and we used both biopsy and serum anti-H. pylori IgG findings to establish an H. pylori-negative diagnosis. Since H. pylori-negative peptic ulcers certainly exist, H. pylori infection is thought not to be essential to the development of peptic ulcers. There were few differences between the characteristics of H. pylori-negative and H. pylori-positive peptic ulcers in our study. A large-scale study is required to clarify the characteristics of H. pylori-negative peptic ulcers. Received: September 25, 1998 / Accepted: February 26, 1999     

Influence of Helicobacter pylori Infection on Healing and Relapse of Acetic Acid Ulcers in Mongolian Gerbils

Both Helicobacter pylori and NSAIDs play important roles in the healing and relapse of peptic ulcers in man. We examined how H. pylori infection, indomethacin, and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed gastric ulcers in Mongolian gerbils. Gastric ulcers were induced by serosal application of an acetic acid solution. H. pylori (ATCC43504) was orally administered once into animals with active and healed ulcers. Ulcers healed within eight weeks and remained healed for the following six months. H. pylori infection significantly delayed ulcer healing four weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected Mongolian gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from one to six months after infection, with a gradual increase in size. By the fourth month following a relapse, the serum gastrin level had significantly increased. H. pylori-induced ulcers in the posterior wall coexisted with relapsed ulcers in the anterior wall five and six months later. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. It is concluded that, in Mongolian gerbils, H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse.     

Follow-up survey of a large-scale multicenter,double-blind study of triple therapy with lansoprazole,amoxicillin, and clarithromycin for eradication of Helicobacter pylori in Japanese peptic ulcer patients

Background: To evaluate histopathological changes and effects on inhibition of ulcer recurrence, a follow-up survey was performed in Japanese patients with Helicobacter pylori-positive active peptic ulcers. These patients had previously participated in a large-scale multicenter trial of triple therapy with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of H. pylori. Methods: Patients who had been treated with LPZ only or a combination of LPZ, AMPC, and CAM for a period of 7 days and in whom ulcer healing had been confirmed after treatment were grouped according to successful or failed eradication of H. pylori. They were examined endoscopically to determine whether ulcers had recurred. The updated Sydney system was applied to study histological changes after H. pylori eradication therapy, compared with baseline. Results: Twelve months after treatment for H. pylori eradication, gastric ulcers had recurred in 11.4% of those with successful H. pylori eradication and in 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. These findings proved that H. pylori eradication significantly reduced ulcer recurrence (P < 0.0001 for both types of ulcers). Histopathological findings of inflammation and activity grade in both gastric and duodenal ulcers were more favorable in patients with successful eradication than in those with unsuccessful eradication. Conclusions: H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. Histopathological findings were also improved with regard to inflammation and activity (neutrophils) in patients in whom H. pylori eradication was successful. Received: May 13, 2002 / Accepted: September 6, 2002 Reprint requests to: M. Asaka Editorial on page 410     

Effect of smoking on gastric histology in Helicobacter pylori-positive gastritis

Objective. Smoking and Helicobacter pylori are both deleterious to the gastric and duodenal mucosa. Smoking also seems to modify inflammation in H. pylori infection. The aim of this study was to investigate the relationship between smoking and H. pylori in the Finnish population. Material and methods. We analysed the effect of smoking on gastric inflammation, humoral response to H. pylori and peptic ulcer disease among 318 Finnish H. pylori-positive patients (age 18–75 years; 73 smokers). Gastric histology was evaluated according to the updated Sydney system. Results. Smoking affected neither antral inflammation nor atrophy. In the gastric body, smokers showed milder chronic and neutrophilic inflammation and less atrophy (4% versus 17%, p=0.004). In smokers, H. pylori infiltration was denser in the atrium (mean 2.14 versus 1.87, p=0.02) but less dense in the body (mean 1.55 versus 1.84, p=0.003). Smoking thus seems to decrease inflammation in the gastric body and to delay atrophic changes in the gastric body. Subsequently, the prevalence of duodenal ulcers increased (32% versus 11%, p<0.001), but not the prevalence of gastric ulcers. Smoking also reduced serum IgG antibody titres against H. pylori (mean 8535 versus 5587, p=0.002) and their percentage decrease after successful eradication, possibly affecting serological diagnostic efficacy. Smokers were younger than non-smokers, but when age was taken into account, the differences remained the same. Conclusions. In H. pylori-positive gastritis, smoking reduced inflammation and atrophy in the gastric body as well as humoral response to H. pylori.     

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury

Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1β, IL-4, IL-6, and IL-10; interferon [IFN]-γ; and tumor necrosis factor [TNF]-α) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1β and IFN-γ production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-α production was increased in the infected group, and IL-1β and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process. Received: March 29, 1999 / Accepted: November 26, 1999     

Omentum and basic fibroblast growth factor in healing of chronic gastric ulcerations in rats

Omentum was shown to exhibit angiogenic activity, but its role in healing of chronic gastric ulcers is unknown. This study was designed to compare the effects of omentum and basic fibroblast growth factor (bFGF), a potent angiogenic factor, on healing of chronic gastric ulcers in rats. Several series of rats with gastric ulcers were used: series A with intact omentum (control), series B with omentum resected, and series C with omentum placed on the serosal side of the ulcer. Series A–C were divided into four groups treated with vehicle (I); indomethacin (II), an inhibitor of prostaglandin formation, difluoromethylornithine (DFMO) (III); an inhibitor of polyamine biosynthesis or bFGF (IV). Seven days after ulcer induction, the animals were anesthetized, the gastric blood flow (GBF) was determined by laser Doppler flowmetry (LDF), and the ulcer area was measured by planimetry. Biopsy samples of the ulcer margin were taken for determination of the number of capillaries and myofibroblasts in the granulation tissue. Attachment of omentum significantly accelerated ulcer healing, whereas omentectomy delayed this process. LDF revealed the decrease in the GBF at the ulcer margin to 45% and at the ulcer bed to 18% of the value recorded in the intact adjacent mucosa. Attachment of the omentum significantly increased the blood flow at the ulcer margin and increased the number of capillaries and myofibroblasts in the granulation tissue. Indomethacin (1 mg/kg/day) that inhibited mucosal PGE₂ by about 85% delayed significantly ulcer healing without affecting the blood flow in the ulcer area. DFMO (200 mg/kg intraperitoneally) suppressed ODC activity in the mucosa but did not influence the ulcer healing. bFGF given subcutaneously accelerated dose-dependently ulcer healing and stimulated angiogenesis to a similar extent as the attached omentum. We conclude that omentum enhances the ulcer healing in similar way as bFGF and that this effect is accompanied by the increased angiogenesis and blood flow in the ulcer area.     

Influence of gastric colonization with Candida albicans on ulcer healing in rats: effect of ranitidine, aspirin and probiotic therapy

OBJECTIVE: Candida albicans frequently inhabits the gastrointestinal tract of humans leading to gastrointestinal candidiasis, especially following suppression of gastric acidity, but studies on the relation between this fungal infection and gastric pathology are limited due to lack of convenient animal models resembling Candida infection in humans. MATERIAL AND METHODS. We compared the effects of C. albicans and vehicle inoculation on gastric secretion and healing of gastric ulcers induced by acetic acid in rats treated with 1) ranitidine (30 mg kg(-1) day(-1) s.c.) and 2) aspirin (ASA) (60 mg kg(-1) day(-1) i.g.) with or without probiotic bacteria Lactobacillus acidophillus. At day 0 and at 4, 15 and 25 days after ulcer induction, the ulcer area, the gastric blood flow (GBF), the quantitative gastric cultures of Candida and the expression of mRNAs for pro-inflammatory cytokines IL-1beta and TNF-alpha and growth factors EGF and TGFalpha were assessed in the gastric mucosa. RESULTS: Gastric acid output was reduced by over 40% soon after Candida inoculation and this effect persisted during all time intervals tested. The area of ulcers in control rats significantly decreased at day 15 and the ulcers disappeared almost completely after 25 days of their induction. In contrast, the ulcers were present until day 25 in Candida-inoculated rats followed by a fall in GBF and a rise in plasma gastrin levels, these effects being significantly attenuated by the co-treatment with Lactobacillus. Candidiasis was accompanied by up-regulation of mRNA for IL-1beta, TNF-alpha, EGF and TGFalpha and a significant increment in plasma IL-1beta and TNF-alpha levels. CONCLUSIONS: 1) Persistent colonization with Candida could be achieved in rats treated with antisecretory agents or non-steroidal anti-inflammatory drugs (NSAIDs) such as ASA; 2) candidiasis reduces gastric acid secretion, while delaying ulcer healing possibly due to the impairment in GBF in the ulcer area and enhanced expression and release of IL-1beta and TNFalpha and 3) probiotic therapy could be useful in the treatment against the deleterious action of fungal infection on the healing of pre-existing gastric ulcers.     

Helicobacter pylori‐eradication therapy decreases the level of neutrophil‐derived oxidants in the ulcerous mucosa of the human stomach: Relationship between ulcer stage and mucosal oxidant level

Background: The purpose of the present study was to determine the effect of Helicobacter pylori eradication on the intensity of inflammation in the ulcerous mucosa by measuring the level of neutrophil‐associated oxidants and to understand the role of mucosal inflammation in ulcer relapse from the viewpoints of the scarring stage and the H. pylori‐infection status. The level of inflammation in the gastric mucosa after the eradication of H. pylori was examined using biopsy samples obtained from patients with gastric ulcers. Methods: Gastric mucosal specimens were endoscopically obtained before and after H. pylori‐eradication therapy from 39 patients with gastric ulcers and a positive H. pylori‐infection status. The level of neutrophil‐derived oxidants was then measured in each sample using a luminol‐dependent chemiluminescence (ChL) assay. Results: Chemiluminescence activity in the ulcer portion and the background gastric mucosa (antrum and corpus) was significantly reduced 3 months after successful therapy (n = 32). The ChL activity was further decreased 9 months after successful therapy, but the activity in the ulcer portion remained unchanged. In patients who did not respond to the H. pylori‐eradication therapy (n = 7), the ChL activities were not altered in any mucosal portion after the therapy. Before the H. pylori‐eradication therapy, a higher ChL activity was observed in open ulcer tissue than in scarred tissue. The ChL activity in the scarred tissue was reduced 3 months after the successful eradication of H. pylori; however, the ChL activity in the red scars was significantly higher than that in the white scars. The ChL level in the white scars was almost equivalent to that in the background mucosa 9 months after the completion of the H. pylori‐eradication therapy. Conclusion: The eradication of H. pylori may reduce the level of oxidant production in gastric ulcers, promoting the prevention of ulcer recurrence. Furthermore, the presence of a red scar may indicate unstable healing, even after the successful eradication of H. pylori.     

Gastric Ulcer Relapse

Abstract: In this review we found that the rate of gastric ulcer relapse reached near! 70% over a 13 year period and was nearly 10% after one year from when they reache the white scar stage. A H2-RA or proton pump inhibiter had a high relapse rate the reason being the fragile re-epithelization of the scar³⁾⁴⁾. Factors involved in gastric ulcer relapse are considered to be the fragile re-epithelization of the ulcer, disturbance c blood flow due to fibrosis underneath the ulcer scar, and etiological factors such a smoking and so on. Endoscopic findings of the ulcer scar can statistically suggest th gastric ulcer relapse rate. The main cause of peptic ulcers, especially duodenal ulce relapse, is strongly related to Helicobacter pylori infection. The causes of gastric ulcer relapse are very complicated and variegated. H. pylori infection contributes to les gastric ulcer relapse than duodenal ulcer relapse. To prevent gastric ulcer relapse, therefore, one should consider the eradication c H. pylori, the endoscopic features of the ulcer scar and etiological factors.     

Influence of cure of Helicobacter pylori infection on gastric acidity and gastroesophageal reflux: study by 24-h pH monitoring in patients with gastric or duodenal ulcer

Background Whether or not the eradication of Helicobacter pylori is a risk factor for reflux esophagitis (RE) is a question at issue. To find an answer, it is necessary to clarify the influence of H. pylori eradication on the mechanism of RE.Methods The authors investigated the influence of H. pylori eradication on gastric acidity and gastroesophageal reflux in ten gastric ulcer (GU) patients and ten duodenal ulcer (DU) patients by 24-h simultaneous determination of pH in the stomach and esophagus.Results Though the results indicated enhanced gastric acidity in GU patients at night after H. pylori eradication, no such influence was observed in DU patients. No significant changes in gastroesophageal reflux occurred in GU or DU patients before and after H. pylori eradication. RE after H. pylori eradication occurred in only one patient, with GU. This patient had several risk factors for RE, such as obesity, male sex, and dietary habits to add to the increase in gastric acidity at night that occurred after H. pylori eradication. No increase in gastroesophageal reflux occurred in any DU patients or in the other GU patients that demonstrated enhanced gastric acidity at night after H. pylori eradication.Conclusions The cure of H. pylori infection does not, by itself, cause RE in patients who have few other risk factors for RE.     

The prevalence of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in Japanese children with gastritis or peptic ulcer disease

Background Although Helicobacter pylori infection is typically acquired in childhood, the role of H. pylori infection in gastroduodenal diseases in childhood remains to be defined. The purpose of this study was to evaluate the prevalence of H. pylori infection in children with gastritis, duodenal ulcer, and gastric ulcer.Methods This was a retrospective analysis of 283 Japanese children (mean age, 11.5 years) with non-nodular gastritis (n = 73), nodular gastritis (n = 67), duodenal ulcer (n = 100), and gastric ulcer (n = 43). H. pylori status was based on biopsy tests. Clinical symptoms at the time of endoscopy were analyzed with regard to a possible association with the infection.Results The prevalence of H. pylori in non-nodular gastritis, nodular gastritis, duodenal ulcer, and gastric ulcer was 28.8%, 98.5%, 83.0%, and 44.2%, respectively. H. pylori was significantly linked to duodenal ulcer and gastric ulcers in the age group of 10–16 years, but not in the age group of 9 years and under. In children with H. pylori infection, nodular gastritis was observed in 26.3% of gastric ulcer patients and in 74.7% of duodenal ulcer patients (P < 0.001). H. pylori infection was significantly associated with the prevalence of anemia (P < 0.05).Conclusions H. pylori is the most important causal factor for the development of duodenal ulcer in childhood. While H. pylori infection appears to be a risk factor in gastric ulcer, other causes are responsible for most cases. Nodular gastritis is the most common type of H. pylori gastritis in childhood. Chronic infection with H. pylori is associated with anemia.     

Rebamipide prevents delay of acetic acid-induced gastric ulcer healing caused by Helicobacter pylori infection in Mongolian gerbils

In this study, we examined the effect of rebamipide, a mucoprotective drug, on gastric ulcer healing in Mongolian gerbils infected with H. pylori. Male Mongolian gerbils were inoculated with H. pylori or vehicle alone 12 hr after the production of an acetic acid-induced gastric ulcer. On day 5, the gerbils inoculated with H. pylori were divided into three groups and fed rebamipide-containing diet (0.038%, 60 mg/kg, or 0.0038%, 6 mg/kg), or standard laboratory chow. The gerbils inoculated with the vehicle were fed standard laboratory chow throughout the experiment. The gerbils were killed on day 5, 15, or 30 after ulcer production, and removed stomachs were subjected to calculation of ulcer size, culture for H. pylori, and measurement of myeloperoxidase activity, a marker for neutrophil infiltration, in ulcerated tissue. Apoptotic and proliferating cells of gastric epithelium in ulcer margins were detected by the in situ DNA nick end-labeling method and immunohistochemical staining for 5-bromo-2'-deoxyuridine (BrdU), respectively. Rebamipide did not affect colonization levels of H. pylori. Infection with H. pylori did not affect ulcer size by day 5 but significantly delayed ulcer healing by days 15 and 30, accompanied by an increase in the number of apoptotic cells, a decrease in the number of BrdU-positive cells, and an increase in myeloperoxydase activity. Rebamipide prevented delay of ulcer healing and abolished these effects of H. pylori on cell kinetics and neutrophil infiltration. In conclusion, rebamipide may prevent the delay of acetic acid-induced gastric ulcer healing caused by H. pylori through modulating cell kinetics and inhibiting neutrophil infiltration.     

Does Helicobacter pylori eradication depend on the period of amoxicillin treatment? A retrospective study

In this study, the effect of different periods of amoxicillin (AMPC) treatment on the eradication rate of Helicobacter pylori in 173 patients with peptic ulcers (gastric ulcer, 109; duodenal ulcer, 64) was investigated. AMPC (1.5 g/day) was administered for 2, 4, or 6 weeks with omeprazole (20 mg/day) and plaunotol (240 mg/day), a mucoprotective drug, for 8 weeks. The H. pylori eradication rate was 46.7% for 2 weeks' treatment, 83.4% for 4 weeks' treatment, and 100% for 6 weeks' treatment. The eradication rate had a good correlation with the period of AMPC treatment. The healing rates of peptic ulcer at 4 and 8 weeks were 93.3% and 100%, respectively, in the 2-week group, 98.0% and 99.3% in the 4-week group, and 85.7% and 100% in the 6-week group. The recurrence rate of gastric and duodenal ulcers was 3.5% and 0% respectively, in the patients in whom H. pylori was eradicated and 30.0% and 40%, respectively, in the patients in whom H. pylori was not eradicated for 12 months after the H. pylori eradication treatment. Adverse effects of this regimen were observed in 5 (2.9%) of the 173 patients. Diarrhea was observed in 3 patients and eruption in 2. These adverse effects disappeared within a few days after only AMPC was withdrawn. Therefore, these may be caused by AMPC. The eradication rate of H. pylori depends on the period of AMPC treatment. This regiment, AMPC (1.5 g/day) + omeprazole (20 mg/day) + plaunotol (240 mg/day), is safe and well tolerated for eradication of H. pylori. Received Oct. 17, 1996; accepted June 27, 1997     

History of Helicobacter pylori,duodenal ulcer,gastric ulcer and gastric cancer

Helicobacter pylori(H.pylori)infection underlies gastric ulcer disease,gastric cancer and duodenal ulcer disease.The disease expression reflects the pattern and extent of gastritis/gastric atrophy(i.e.,duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis).Gastric and duodenal ulcers and gastric cancer have been known for thousands of years.Ulcers are generally non-fatal and until the 20th century were difficult to diagnose.However,the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present.It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century.Here,we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern,as it proved to be when it could be examined directly in the late 19th century.The environment before the 20th century favored acquisition of H.pylori infection and atrophic gastritis(e.g.,poor sanitation and standards of living,seasonal diets poor in fresh fruits and vegetables,especially in winter,vitamin deficiencies,and frequent febrile infections in childhood).The latter part of the 19th century saw improvements in standards of living,sanitation,and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent.In the early 20th century physician’s believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for"surgical disease"or for"Sippy"diets.We show that while H.pylori remained common and virulent in Europe and the United States,environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H.pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H.pylori-related diseases.