Interobserver agreement in endoscopic evaluation of reflux esophagitis using a modified Los Angeles classification incorporating grades N and M: a validation study in a cohort of Japanese endoscopists.

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30-40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (kappa) statistics for multiple raters. The kappa-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The kappa-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275-0.315, with a standard error of 0.083-0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis.

Effect of teprenone on gastric mucosal injury induced by Helicobacter pylori in rats.

The aim of this study was to investigate the protective effect of gastric mucus against Helicobacter pylori-induced gastric mucosal injury, measuring intramucosal mucus and the surface hydrophobicity. Male Sprague-Dawley rats' stomachs were exposed to H. pylori suspension (1 x 10(5) ml) plus 1 ml of urea solution (400 mg/dl) with gastric ischemia (withdrawal of 3 ml of blood) for 60 min, 60 min after pretreatment with teprenone (CAS 6809-52-5) (50 mg/rat, intragastric). The control rats were treated in the same manner without pretreatment with teprenone. A high concentration of intragastric ammonia was generated 60 min after administration of H. pylori plus urea in both the control and the teprenone-pretreated rats. A reduction in transmucosal potential difference, formation of hemorrhagic gastric lesions, and impairment in both intramucosal mucus and surface hydrophobicity were observed in the corpus of the control rats. However, the pretreatment with teprenone prevented such a reduction in potential difference and the development of gastric lesions against ammonia through the preservation of gastric mucus. The preservation of gastric mucus might protect gastric mucosa against attacks by H. pylori, suggesting that the mechanism of H. pylori-associated gastric injury is associated with the decrease in gastric mucus.

Relapse of duodenal ulcers after successful eradication of Helicobacter pylori in gastric ulcer patients.

Relapse of duodenal ulcers was observed endoscopically after Helicobacter pylori eradication therapy for gastric ulcer patients in 2 of 32 successful cases. One patient, a 40-year-old woman, received dual therapy with lansoprazole 60mg and amoxicillin 1000mg for 2 weeks because of an intractable, easily-relapsing gastric ulcer accompanied by duodenal ulcer scars that had not relapsed for 5 years. The H. pylori status was assessed by a rapid urease test, light microscopy, culture, and anti-H. pylori antibody. At 24 months after the cure of H. pylori she had upper abdominal pain and showed relapse not of the gastric ulcer but of the duodenal ulcer. The H. pylori status remained negative. The other patient, a 44-year-old man, showed an active gastric ulcer and duodenal ulcer scars at the first endoscopy. He received the same regimen as described above. Ten weeks after completion of the eradication therapy, endoscopy showed healing of the gastric ulcer and relapse of the duodenal ulcer despite successful eradication. These two cases suggest that H. pylori eradication modifies the pathophysiological condition of gastric acid secretion and facilitates relapse of duodenal ulcers.

Factors influencing Helicobacter pylori eradication with 2 week combination therapy of lansoprazole and amoxycillin: intragastric distribution of colonization and gastric mucosal atrophy.

In Japan, gastric ulcers are often accompanied by marked gastric mucosal atrophy. We evaluated the dual therapy of double-dose lansoprazole and amoxycillin for Helicobacter pylori eradication in Japanese ulcer patients and investigated the effects of intragastric distribution of H. pylori colonization and gastric mucosal atrophy on eradication with this combination therapy. Seventy-six H. pylori-positive ulcer patients received lansoprazole (30 mg) plus amoxycillin (500 mg) twice daily for 2 weeks (LA-60 group), lansoprazole (30 mg once daily) plus amoxycillin (500 mg twice daily) for 2 weeks (LA-30 group) or lansoprazole (30 mg once daily) for 6 or 8 weeks (LPZ group). Infection was evaluated by light microscopy, culture and biopsy urease tests. Helicobacter pylori colonization was classified as localized to the corpus (localized type) or involving the antrum and corpus (whole type). Fundic mucosal atrophy was graded according to endoscopic and histological features. Eradication was achieved in 67.6% in the LA-60 group, 31.6% in the LA-30 group, and 0% in the LPZ group, and moderate or severe histological gastritis was improved in the LA-60 group. Eradication was better in localized-type colonization (92%) than whole-type (56%), and better with fundic mucosal atrophy (84%) than without, but poor in both whole-type colonization and scanty mucosal atrophy (47%). The LA-60 therapy achieves better eradication in Japanese ulcer patients with localized H. pylori colonization and/or gastric mucosal atrophy, which are likely to be important predictors for the successful eradication with dual therapy.

Effect of lansoprazole in mono-, dual-, or triple therapy on Helicobacter pylori eradication.

The effect of lansoprazole, in mono, dual, or triple therapy, on the eradication of Helicobacter pylori was reviewed. Lansoprazole has a cytotoxic action against this organism, the MIC being 2.56-5.25 micrograms/ml. In in vitro experiments, lansoprazole exerts direct action, i.e., antibacterial activity of lansoprazole against H. pylori and also inhibits urease activity. With antibiotics, this drug has a synergistic effect against H. pylori. In clinical studies, the eradication rate of H. pylori with lansoprazole is 0%-25% with monotherapy, 22%-33% with dual therapy (of AMPC), and 75%-82.4% with triple therapy with metronidazole and antibiotics. We inves-tigated the effect of lansoprazole on the eradication of H. pylori with dual therapy, the other agent being amoxicillin (AMPC). The eradication rate was 0% when 30 mg lansoprazole was employed as monotherapy, 33% for dual therapy with 30 mg lansoprazole and 1 g AMPC, and 71% for dual therapy with 60 mg lansoprazole and 1 g AMPC, the eradication rate with 60 mg lansoprazole and 1 g AMPC being significantly higher than that with the lower dose of lansoprazole. This result suggested that the greater acid suppression brought about by lansoprazole 60 mg enhances the action of AMPC, indicating that lansoprazole, when used with AMPC, is effective for eradication of H. pylori.

Role of mucosal microcirculation in gastric lesions induced by lateral hypothalamic lesions in rats.

To evaluate the pathophysiology underlying gastric mucosal lesions induced by lateral hypothalamic (LH) lesions, we investigated the changes in acid secretion, gastric mucosal blood flow, gastric mucus and mucosal integrity in the corpus during the 4 h period and 48 h after the production of bilateral electrolytic LH lesions in male Sprague-Dawley rats. Gastric mucosal lesions were macroscopically produced 24 h (63%) and 48 h (83%) after LH lesions, although there were no visible lesions at 7 h. Gastric acid secretion was significantly increased 48 h after LH lesions, compared with that in the control group. Gastric mucosal blood flow and transmucosal potential difference (PD) in the LH lesion group immediately decreased after LH lesions and did not recover during 4 h and at 48 h. On the contrary, in the control group, gastric mucosal blood flow decreased after the brain surgery but soon recovered, and there was no significant change in PD. LH lesions resulted in the reduction of intramucosal mucus to 50% 3 h after LH lesions. Moreover, we exposed the stomach to 10 mmol/L taurocholic acid (TCA) 3 h after LH lesions to examine the disruption in gastric mucosal defensive function in rats with LH lesions. The recovery of the reduced PD by TCA was slow and gastric mucosal lesions were easily formed in the LH lesion group. These results suggest that gastric mucosal ischaemia after lesioning of LH immediately results in the disruption of mucosal defensive function before the formation of visible gastric lesions, and predisposes to the formation of gastric mucosal lesions by a delayed increase in acid secretion.

Products of neutrophil metabolism increase ammonia-induced gastric mucosal damage.

Recent studies have indicated that ammonia is involved in the pathophysiology of Helicobacter pylori-associated gastric mucosal damage. Helicobacter pylori-associated chronic active gastritis is characterized by an invasion of neutrophils. We investigated the interrelationship among hypochlorous acid (oxidant produced by neutrophil), ammonia (product of Helicobacter pylori urease), and monochloramine (product of ammonia and hypochlorous acid) in the development of gastric mucosal damage in rats. Gastric mucosal lesions were produced by exposure of the gastric mucosa to ammonia, urea with urease, or urea with Helicobacter pylori in rats subjected to ischemia. Pretreatment with taurine (scavenger of hypochlorous acid) or antineutrophil serum significantly attenuated gastric mucosal lesions induced by the above test agents. Ammonia-induced gastric mucosal lesions were exacerbated in the presence of hypochlorous acid with concomitant generation of monochloramine. These results suggest that the ammonia, hypochlorous acid, and monochloramine triad may be important in Helicobacter pylori-mediated gastric mucosal damage.

Therapeutic effects of lansoprazole on peptic ulcers in elderly patients.

We studied the effects of lansoprazole on ulcer healing and Helicobacter pylori infection in elderly patients with peptic ulcers. In a group of 24 patients with gastric ulcers, the H. pylori infection rate was 100%. In the course of gastric ulcer healing with famotidine or lansoprazole alone, the H. pylori infection showed no signs of decline. The ulcer healing rates after 8 weeks were similar between the H2-receptor antagonist famotidine (73%), and the proton pump inhibitor lansoprazole (82%). When eradication of H. pylori infection was attempted by concomitant administration of lansoprazole and amoxicillin 500 mg b.i.d. for 2 weeks, the eradication rate was 33% in the group given lansoprazole 30 mg q.d. plus ampicillin 500 mg b.i.d., whereas it was 77% in the group given lansoprazole 30 mg b.i.d. plus ampicillin 500 mg b.i.d. Lansoprazole is considered to be a useful agent for the treatment of patients with peptic ulcers and H. pylori infection and its effectiveness in H. pylori eradication is improved by b.i.d. administration along with ampicillin.

[Role of Helicobacter pylori infection in gastric metaplasia in the duodenum in the production of duodenal ulcer].

Helicobacter pylori (H. pylori) is frequently detected in not only the antrum but also the gastric juice and the duodenum with gastric metaplasia, which is believed to be a response of duodenal mucosa to injury by hyperacidity, in most of duodenal ulcer patients. Conversely, the normal duodenum is not infected with H. pylori in non-duodenal ulcer patients, even if H. pylori is present in the antrum and/or the gastric juice. All patients with H. pylori in the duodenum has the H. pylori infection in the gastric antrum. Patients with H. pylori in the gastric juice also has H. pylori infection in the antrum. These findings may support the following hypothesis in the formation of duodenal ulcer. A high duodenal acid load leads to the formation of gastric metaplasia in the duodenal bulb, where can be easily infected by gastric H. pylori through the gastric juice. As a result of the duodenal colonization of H. pylori, the duodenal mucosa impaired by ammonia of H. pylori could has the formation of duodenal ulcer.

Gastric ammonia has a potent ulcerogenic action on the rat stomach.

BACKGROUND: The pathophysiological mechanism by which Helicobacter pylori induces mucosal injury has not been clarified. The aim of this study was to investigate the role of urea, urease, and ammonia in rat gastric mucosal lesions using an ex vivo chamber model. METHODS: Two groups of rats, normotensive rats and those subjected to ischemia, were studied. The gastric mucosa was examined histologically and macroscopically, and the transmucosal potential difference was measured. RESULTS: Instillation of urea into the stomach generated ammonia in the presence of urease. The amount of ammonia was increased depending on the concentration of urea and was closely associated with the severity of the histological lesions. The exposure of the stomach to 15-60 mmol/L ammonium hydroxide induced both a reduction in transmucosal potential difference and microscopic damage to the gastric mucosa in normotensive rats. Moreover, 15-60 mmol/L ammonium hydroxide produced severe macroscopic gastric lesions in the rats subjected to ischemia. CONCLUSIONS: These results show that ammonia is deleterious to the gastric mucosa and suggest the importance of urea, urease, and ammonia in the pathophysiology of gastric diseases in H. pylori-infected patients.

Sonography in fracture of the penis.

Sonography was performed in 7 patients with fracture of the penis and in 6 cases it demonstrated the exact site of a tear in the tunica albuginea. It was useful in the diagnosis and management of these patients.

Link between Helicobacter pylori-associated gastritis and duodenal ulcer.

We examined the interrelationships among the degree of fundic mucosal atrophy, the prevalence of Helicobacter pylori in the gastric antrum, the gastric juice, and the duodenum with and without gastric metaplasia, in 20 duodenal ulcer patients and 20 non-duodenal ulcer patients. The detection rates of H. pylori in the antrum, the gastric juice, and the duodenum were significantly higher in duodenal ulcer patients (80%, 65%, and 60%) than in non-duodenal ulcer subjects (50%, 20%, and 5%). The frequency of H. pylori was significantly lower in the gastric juice (30%) and the duodenum (10%) in non-duodenal ulcer patients with antral H. pylori, compared with those in duodenal ulcer patients with antral H. pylori. All of seven patients with both gastric metaplasia and H. pylori infection in the duodenum had duodenal ulcer, whereas only 1 of 14 patients without either gastric metaplasia or H. pylori infection in the duodenum had duodenal ulcer. There was normal or mild atrophic mucosa in the fundus of duodenal ulcer patients with H. pylori in the antrum, whereas moderate or severe atrophic mucosa in non-duodenal ulcer patients with H. pylori gastritis. These results suggest that the preserved fundic mucosa, gastric metaplasia in the duodenum, and a greater load of H. pylori to the duodenum through the gastric juice may be prerequisites for the formation of duodenal ulcers.

Helicobacter pylori has an ulcerogenic action in the ischemic stomach of rats.

Helicobacter pylori (H. pylori) is now accepted as an important cause of chronic active gastritis. There also seems to be an association between the colonization of H. pylori in the gastric mucosa and peptic ulceration. However, it has not demonstrated that the instillation of H. pylori into the stomach produces the ulcerative gastric lesions in animals or humans. We carried out an experiment to study whether or not H. pylori has an ulcerogenic action in the ischemic stomach of rats, using an ex vivo gastric chamber. The rat stomachs were exposed to 1 ml of H. pylori solution (200 IU of urease/ml) and 1 ml of urea (400 mg/dl) for 60 min after the creation of ischemia in the stomach (by withdrawal of 3 ml of blood). The exposure of the stomach to both H. pylori and urea resulted in severe hemorrhagic gastric mucosal lesions with a marked decrease in potential difference (PD) with a concomitant increase in ammonia concentration in rats with ischemia, whereas gastric lesions and a fall in PD were hardly observed in rats without ischemia. These results have demonstrated that H. pylori has an ulcerogenic action on the stomach subjected to mucosal ischemia.

Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach.

We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025-0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01-0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5-1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa.

Protective effect of taurine against ammonia-induced gastric mucosal lesions in rats.

We examined the role of gastric ammonia in the development of gastric lesions in rats. Exposure of the gastric mucosa to ammonia (30 mM) produced microscopic injury, but no macroscopic lesion was observed. However, exposure of the stomach to ammonia in rats subjected to ischemia resulted in macroscopic gastric lesions. The macroscopic lesions were markedly inhibited by pretreatment with taurine, a scavenger of hypochlorous acid (HOCI) and monochloramine (NH2Cl). These results indicate that ammonia is deleterious to gastric mucosa, and monochloramine may be involved in the pathogenesis of ammonia-induced mucosal lesions.

Effects of ammonia on the gastric mucosal barrier in rats and dogs.

We examined the effect of ammonia on the gastric mucosal barrier by measuring the changes in transmucosal fluxes of H+, Na+ and K+. In rats, ammonia at concentrations of 0.1 to 0.5% increased the H+ loss from the lumen and 0.2 to 0.5% concentrations of ammonia increased both Na+ and K+ influxes into the lumen. In dogs, in an exactly similar manner to rats, ammonia at concentrations of 0.1 to 0.5% increased H+ loss, and ammonia at concentration of 0.5% increased both Na+ and K+ influxes into the lumen. These results suggest that ammonia breaks the gastric mucosal barrier.

[Evaluation of the laser-Doppler velocimetry method in the measurement of gastric blood flow in rats--spatial resolution].

In this paper, gastric blood flow in rats was measured with the laser-Doppler velocimetry method (the LDV method) to study about the tissue locus where its flow signal arises (spatial resolution). In the measurement throughout some 1 mm thickness of another nonperfused gastric wall interposed between the laser probe and gastric mucosal surface, its laser flow signal was 17% of the flow signal in the usual measurement. In the blood flow measurement with the LDV prove on the mucosal and the serosal surface of gastric wall, the laser flow signal on the mucosal surface was higher (p less than 0.05) than that on the serosal surface. These results suggested that the laser flow signal mainly arose from the tissue right under the laser probe, reflecting the total gastric blood flow of the gastric wall. In the regional blood flow measurement at corpus and antrum, the ratio between antral and corpus flow signals by the LDV method was similar to that between gastric mucosal blood flows at both sites by the hydrogen gas clearance technique. In the blood flow measurement after the intravenous infusion of each pentagastrin, isoproterenol, and vasopressin, flow signal of the LDV method could detect the each effect of these drugs on gastric mucosal blood flow as well as well as the hydrogen gas clearance technique. These results showed that the laser flow signal and gastric mucosal blood flow were mutually correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoprotective effect of plasmin inhibitor on necrotizing agent-induced gastric lesions in rats.

We studied the effect of plasmin inhibitor on ethanol and ammonia-induced gastric mucosal lesions in rats using an ex vivo chamber. Tranexamic acid and aminocaproic acid significantly inhibited macroscopic gastric hemorrhagic necrosis and attenuated the decrease of gastric transmucosal potential difference induced by 50% ethanol and 1% ammonia. The protection of gastric mucosa afforded by tranexamic acid and aminocaproic acid was not affected by pretreatment with indomethacin (5 mg/kg). These results suggest that plasmin inhibitor plays an important role in the prevention of gastric deep necrosis following exposure of the stomach to a damaging agent.

Effect of plasmin inhibitors on gastric mucosal permeability in rats.

We examined the protective effect of plasmin inhibitors on gastric mucosal vascular permeability in rats. Tranexamic acid and aminocaproic acid significantly inhibited the increase in vascular permeability and macroscopic gastric mucosal lesions induced by 50% ethanol and 1% ammonia. The protective effect afforded by plasmin inhibitors was not affected by pretreatment with indomethacin. Our results show that plasmin inhibitors inhibit the increase in gastric vascular permeability and suggest that plasmin may play an important role in the pathogenesis of gastric mucosal damage.