Toshikazu Sekiguchi

Helicobacter pylori infection correlates with severity of reflux esophagitis : with manometry findings

Abstract: The role of Helicobacter pylori infection in the development and exacerbation of reflux esophagitis was investigated. The prevalence of Helicobacter pylori infection, the severity of atrophic gastritis, and esophageal motility (determined by esophageal manometry by an infusion catheter method) were assessed in patients with mild (n = 46) and severe (n = 27) reflux esophagitis and subjects without reflux (n = 28). Compared with the prevalence of Helicobacter pylori infection in the non-reflux group, the prevalence in the mild and severe reflux groups (60.7%, 47.8%, and 14.8%, respectively) was significantly (P < 0.05) lower. Atrophic gastritis was milder in both reflux groups than in the non-reflux group. The degree of gastritis was also milder in the severe reflux group than in the mild reflux group. The esophageal sphincter pressure was significantly (P < 0.05) lower in the reflux groups than in the non-reflux group, and the amplitude of primary peristalsis was significantly (P < 0.05) lower in the severe reflux group than in the non-reflux group. There were no significant differences between reflux patients with and without Helicobacter pylori infection in the parameters of esophageal manometry. These data imply that a low prevalence of Helicobacter pylori infection may result in a milder grade of atrophic gastritis, and consequently, exacerbate reflux esophagitis.

Interobserver and intraobserver variation in endoscopic assessment of GERD using the “Los Angeles” classification

BACKGROUND A new endoscopic classification of gastroesophageal reflux disease (GERD) has been proposed, and the term mucosal break has been introduced to describe mucosal damage. This new classification was evaluated by endoscopists with different levels of experience. METHODS Fifty endoscopic photographs for each of 20 randomly selected patients with GERD were assessed retrospectively by three groups of seven endoscopists classified by experience: group 1 (100 to 500 procedures), group 2 (500 to 3000), and group 3 (more than 3000). The new classification was modified by adding grade 0 to describe healed mucosal breaks, so that there were five grades. All photographs were assessed twice at an interval of more than 1 week, and kappa statistics were used to determine observer variation. RESULTS Interobserver variation within group 3 (kappa = 0.39, n = 21) and between groups 3 and 2 (kappa = 0.36, n = 49) was significantly different (p < 0.01) from that between groups 3 and 1 (kappa = 0.26, n = 49). Intraobserver variation in group 1 (kappa = 0.39, n = 7) was significantly different (p < 0.01) from that in group 2 (kappa = 0.51, n = 7) and group 3 (kappa = 0.54, n = 7). CONCLUSIONS Observer variation depends on level of endoscopic experience. Only experienced endoscopists should use the new classification for grading of GERD.

Effect of erythromycin on interdigestive gastrointestinal contractile activity and plasma motilin concentration in humans

The effects of erythromycin (EM) on gastrointestinal contractile activity during the interdigestive period were investigated in seven healthy subjects using an infused catheter system, and the changes in the plasma motilin concentration were also determined. Graded EM doses (0.1–1.5 mg/kg) were administered intravenously over 5 min, usually during gastric phase I. EM induced interdigestive migrating contractions (IMCs). Their induction rate was low after low doses of EM, but gradually increased as the dose increased to reach, 71.4% at an EM dose of 0.375 mg/kg. Strong contractions, which were quite similar to phase III activity of the stomach but did not migrate or migrated incompletely to the duodenum, were observed at EM doses above 0.375 mg/kg. Therefore, the optimum dose of EM for inducing an IMC was established to be 0.375 mg/kg. In comparison with spontaneous IMCs, EM-induced IMCs had a significantly longer duration in the stomach and a significantly lower amplitude in the duodenum. These observations indicate that EM induced phase III activity more intensively in the stomach than in the duodenum. The plasma motilin concentration increased significantly during EM-induced IMCs, and this suggested a close relationship between this hormone and induction of the IMC. The increase in motilin levels was also observed of the strong gastric contractions which did not migrate or migrated incompletely to the duodenum. Therefore, it seems reasonable to suggest that motilin is involved in phase III activity of the stomach rather than in that of the duodenum.

Effect of erythromycin derivative EM523L on human interdigestive gastrointestinal tract

We investigated the effect of an erythromycin derivative, EM523L, on interdigestive gastrointestinal motor activity and plasma motilin concentrations in three healthy volunteers using an infused catheter system. We administered doses of 500, 1000, and 2000 μg of EM523L to each subject as well as physiological saline. EM523L induced interdigestive migrating contractions (IMCs) that originated in the stomach and migrated to the duodenum. This response was noted in all three subjects after each dose of EM523L, while no IMCs were induced by saline. There were no significant differences in the characteristics of the EM523L-induced IMC and the spontaneous IMC. The initiation time, ie, the interval between the start of EM523L infusion and the onset of the IMC became shorter in a dose-dependent manner. Plasma motilin concentrations increased significantly after EM523L administration, suggesting that motilin is involved in the mechanism of IMC induction by this drug.

Gastric acid inhibits antral phase III activity in duodenal ulcer patients

Fourteen patients with duodenal ulcers and eight healthy volunteers were examined to measure interdigestive gastroduodenal motility and plasma motilin. In order to study the effects of gastric acid on the gastroduodenal motility, 20 mg of famotidine was administered intravenously. The motility index of the gastric antrum and the duodenum, as well as the pH in the duodenal bulb were calculated. The duodenal pH was significantly lower and the gastric motility index was significantly weaker before the duodenal interdigestive migrating complex (IMC) in the ulcer patients than in the controls. Motilin levels increased before the duodenal IMC and decreased afterwards in both groups. Famotidine significantly increased the duodenal pH and the gastric motility index before the IMC, but no changes in the motilin level were noted. We conclude that duodenal ulcer patients have duodenal hyperacidity that results from increased inflow from the antrum and antral hypomotility during the gastric IMC and that these changes are normalized by the administration of famotidine. These results suggest that gastric acid inhibits antral contraction during the gastric IMC.

Endoscopic ultrasonographic abnormalities and lower esophageal sphincter function in reflux esophagitis.

Endoscopic ultrasonography of the lower esophagus was performed in 25 patients with reflux esophagitis and 13 age-matched controls. Thickening of the esophageal wall and abnormalities of its architecture were detected. As these morphological changes became more extensive, the lower esophageal sphincter pressure and the decrease of sphincter pressure on relaxation were both progressively reduced. There was a significant correlation between morphological abnormalities and lower esophageal function. Our results suggest that inflammatory damage to the muscle layer of the lower esophagus may impair lower esophageal sphincter function further, especially in patients with advanced esophagitis.

The relationship between interdigestive gallbladder and gastroduodenal motility in man

SummaryThe relationship between interdigestive gallbladder and gastroduodenal motilty simultaneously with the behavior of plasma motilin and CCK levels in 20 subjects was investigated. We used an infusion catheter method for the measurement of gastroduodenal motility, and real-time ultrasonography for the measurement of gallbladder size. In gastric phase II, the gallbladder contracted with extension of the major axis and shrinking of the minor axis, with its minimum volume being 84% of the volume in phase I. The gallbladder then filled rapidly assuming a sphere-like shape with extension of the minor axis and shrinking of the major axis in gastric phase I. This motility was recognized only during the gastrointestinal interdigestive migrating complex (GI-IMC) cycle, originating in the stomach, and was associated with an increase of motilin levels, it was not seen before or after the intestinal IMC (I-IMC), which originated in the duodenum without contraction of the stomach or an increase of motilin levels. Furthermore no apparent relationship was recognized between CCK and gastric or gallbaldder motility. Our findings suggest that gallbladder motility in the interdigestive period has a close relationship with gastroduodenal motility and is related to the appearance of the GI-IMC.

Open Study of the Clinical Effects of Lansoprazole in the Treatment of Reflux Oesophagitis

SummaryThe clinical efficacy and safety of lansoprazole, administered in a dose of 30mg once daily after breakfast, were studied in an open trial with 38 patients with erosive/ulcerative reflux oesophagitis. In 3 of these patients, the effect on gastro-oesophageal reflux and gastroduodenal motility was also investigated by 24-hour pH and motility monitoring, performed before and 1 week after starting lansoprazole therapy.Lansoprazole almost completely reduced the total reflux (pH < 4) time and the number of reflux episodes lasting ⩾ 5 minutes, while it did not affect the induction of interdigestive migrating complex. The cumulative disappearance rate of overall subjective and objective symptoms was 66% after 1 week and 91% after 2 weeks. For individual symptoms the disappearance rate for heartburn was 79% after 1 week and 100% after 2 weeks of treatment. An endoscopic healing rate of 76% was achieved after 2 weeks, 97% after 4 weeks, and 97% after 8 weeks of lansoprazole treatment, and in poor responders to histamine H2-receptor antagonist therapy, the healing rate was 83% after 2 weeks and 100% after 4 weeks. Global improvement evaluation, as assessed by endoscopic findings and changes in symptoms and signs, showed ‘marked improvement’ in 94% and ‘moderate improvement’ in 6% of the patients.In the overall safety evaluation, no problems occurred in 33 (86.8%) of the 38 patients. Three patients had mild cases of dry mouth. No serious abnormal changes in laboratory values were detected. Lansoprazole was deemed to be ‘extremely useful’ in 31 (89%) and ‘considerably useful’ in 3 (9%) of the 35 patients.These results indicate that lansoprazole, administered in a dose of 30mg once daily after breakfast, inhibits gastro-oesophageal acid reflux almost completely, and it should prove to be a very useful therapeutic agent for reflux oesophagitis.

Comparative efficacy of acid reflux inhibition by drug therapy in reflux esophagitis.

SummaryThe advent of histamine H2 receptor antagonists (H2-RA) has allowed the treatment of reflux esophagitis (RE) to be controlled over a relatively long term. The authors have experienced some cases resistant to H2-RA, but it was revealed that these cases can be successfully treated with proton pump inhibitors. It has been suggested that esophagogastric dysmotility can lead to RE. RE has been treated for many years by using GI-prokinetic agents, which theoretically inhibit acid reflux and improve esophageal acid clearance. In order to compare the effects on acid reflux of an H2-RA (famotidine), a proton pump inhibitor (omeprazole) and a GI-prokinetic agent (cisapride), we measured the 24-hour pH in the esophagus and stomach simultaneously, before and after treatment in 17 patients with RE. It was found that the proton pump inhibitor was the most effective drug for inhibiting esophageal acidification, followed by famotidine and then cisapride. Furthermore, we found that cisapride often actually exacerbated acid reflux. The differences in inhibitory effects on acidification allowed us to draw conclusions regarding the treatment of RE. It was concluded that the stronger the inhibitory effect of a drug on acid secretion, the more useful it was in the treatment of RE. The GI-prokinetic drug did not inhibit acid reflux as much as we had expected.

Oral Erythromycin Accelerates Impaired Gastrointestinal Motility After Endoscopic Mucosal Resection

Gastrointestinal motility may be impaired after endoscopic mucosal resection of gastric lesions. We investigated whether oral erythromycin could improve motility. Twenty patients were divided randomly into groups that received oral omeprazole with or without erythromycin. Motility was recorded overnight at 3 days before and 4 days after endoscopic resection using a microtransducer probe. In the group without erythromycin, gastric phase III activity decreased significantly after endoscopic resection, while it was increased significantly by erythromycin (P < 0.01). After resection, there were significantly more gastric phase III events in the erythromycin group (P < 0.05). The interval between the start of the evening meal and the initial gastric phase III activity was significantly prolonged after resection, while this interval was significantly shortened by erythromycin (P < 0.05). The gastric phase III cycle length was also significantly shortened by erythromycin (P < 0.05). Postprandial and fasting gastrointestinal motility were impaired after endoscopic resection, and postprandial as well as fasting motility were improved by oral erythromycin.