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The 24-hr gastric and duodenal pressure measurement was performed in 5 patients with non-ulcer dyspepsia (NUD). The reduction of incidence of IMC and prolongation of the first appearance of IMC after evening meal were observed in NUD patients. The gastroprokinetic agent, cisapride 5 mg, 3 times a day for 7 days significantly increased the incidence of IMC and shortened the time before the first appearance of IMC after evening meal. This result indicates that in NUD patients impaired gastrointestinal motility is present in fasting phases and cisapride may be useful for correcting motility disorders.

Free glutamate activates the taste receptors in the oral cavity and excites taste nerves to elicit a unique taste eumami. Recently the receptors sensitive to free glutamate were also found in the upper gastrointestinal (GI) tract. These reports suggest that glutamate acts as a modulator of gastric function. Therefore, we examined its effect on gastric emptying and the postprandial sensation for protein-rich meal in healthy volunteers. The base liquid meal (400 kcal/400 ml) consisted of 12.5% dextrin and 12.5% casein-calcium. To enrich free glutamate, monosodium L -glutamate (0.5% w/v) was supplemented. The following two studies comparing glutamate-enriched meal with control one were performed separately. Gastric emptying was measured by 13C breath test. The intensities of postprandial sensations were assessed at 15 min intervals for 4 h using a questionnaire with visual analogue scales (VAS). Glutamate significantly reduced gastric half-emptying time (153+34.6 /212.7+102.6 min, glutamate +/−, mean+S.D., n =10, p p =0.202) of the subjects older than 45 years old ( n =14). These data suggest that glutamate may affect the subject with declined GI function by aging.

Manometric study was performed to investigate the effects of cisapride, a new nonantidopaminergic gastrointestinal prokinetic compound, on interdigestive lower esophageal sphincter pressure (LESP) and gastroduodenal motility using infused catheter technique. The subjects consisted of 9 healthy volunteers and 29 patients with progressive systemic sclerosis (19), reflux esophagitis (8) and others (2). 4 mg of cisapride was given by bolus injection, continuous infusion or oral administration.The following results were obtained:1) Intravenous and oral cisapride increased LESP compared with basal pressure. Especially, bolus injection of cisapride caused a significant elevation of LESP during 30 minutes after administration.2) After administration of cisapride, gastroduodenal motility was accelerated gradually, then inducing IMC-like contractions. By bolus injection, IMC-like contractions were induced in healthy subjects more frequently than in patients group.On the other hand, motility index of stomach and duodenum showed persistent increase in patients group compared with healthy subjects.3) Cisapride-induced IMC-like contractions initiated from LES and upper part of stomach and mediated to duodenum, though aborad migration was not confirmed in the present study.

Manometric study was performed to compare the inhibitory effect of glucagon and secretin on the gastroduodenal motor activity by infused catheter method. The subjects consisted of 3 healthy volunteers and 7 patients with peptic ulcer and other diseases. The following results were obtained. After the intravenous administration of glucagon (1 mg), the motor activity of the stomach and duodenum was inhibited promptly. According to statistic evaluation, the contraction numbers and motility index decreased significantly during 25 minutes compared with the basal values in both stomach and duodenum. After the administration of secretin (100 units), gastric motor activity was markedly inhibited, although duodenal motility increased during 10 minutes due to the initiation of secretin-induced migrating motor complex. The contraction numbers and motility index in stomach decreased significantly during 20 minutes after the administration. The inhibitory effect of glucagon was more remarkable in duodenum than in stomach. On the other hand, secretin was more effective in stomach than in duodenum.

An open-labeled study of once-daily administration of 40 mg famotidine was conducted in 24 patients with endoscopically confirmed reflux esophagitis. The mean age of the patients was 62.8 years. Most had stage I or stage II esophagitis of 1 years' duration or less. After 4, 8, 12, and 16 weeks of treatment, endoscopically documented healing was reported in 50%, 75%, 82%, and 83% of patients, respectively. Among specific endoscopic findings documented at the start of the study there was clearing of white exudate in 83% of patients, and redness cleared in 50% of patients after 16 weeks of treatment. Symptomatic improvement was observed in 73% of patients after 2 weeks, and this increased to 81% and 85% after 4 and 8 weeks of treatment, respectively. Painful symptoms cleared within 2 weeks in 68% of patients, and this increased to 77% after 8 weeks of once-daily therapy. Famotidine was well tolerated. Historically, reflux esophagitis has not responded satisfactorily to drug treatment. The reported symptomatic response and the response documented by endoscopy after therapy with 40 mg famotidine once daily at bedtime are encouraging. Further studies should be conducted to define the role of famotidine in the treatment of reflux esophagitis.

The incidence and severity of gastroesophageal reflux disease (GERD) in Japan tends to increase in elderly women. Rikkunshito (RKT), a traditional Japanese medicine, acts as a prokinetic agent and improves gastric emptying and gastric accommodation. Our previous prospective randomized placebo-controlled study showed that RKT combined with a standard-dose of rabeprazole (RPZ) significantly improved the acid-related dysmotility symptoms (ARD) in elderly patients with proton pump inhibitor (PPI)-refractory non-erosive reflux disease (NERD). This study aimed to evaluate clinical characteristics of elderly PPI-refractory NERD patients with ARD symptoms who responded to RKT. Two hundred forty-two patients with PPI-refractory NERD were randomly assigned to 8 weeks of either RPZ (10 mg/q.d.) + RKT (7.5 g/t.i.d.) (RKT group) or RPZ + placebo (PL group). Among them, 95 were elderly (≥65 years) with ARD (RKT group: n = 52; PL group: n = 43). We analyzed the changes using the 12 subscale score of frequency scale for the symptoms of GERD (FSSG) and 15 items of the Gastrointestinal Symptom Rating Scale at 4 and 8 weeks and compared the therapeutic efficacy between the 2 groups. There were no marked differences in baseline demographic or clinical characteristics in the 2 groups except for rate of current smoking. The FSSG score (mean ± SD at 0, 4, and 8 weeks) in both the RKT (16.0 ± 7.0; 9.9 ± 8.4; 7.0 ± 6.4) and PL (15.1 ± 6.4; 10.9 ± 6.7, 11.1 ± 8.5) groups significantly decreased after treatment. However, the degree of improvement of total and ARD scores of FSSG after the 8-week treatment was significantly greater in the RKT group than in the PL group. Combination therapy with RKT for 8 weeks showed significant improvement in 3 subscale scores (abdominal bloating, heavy feeling in stomach and sick feeling after meals) of the ARD domain and 1 subscale score (heartburn after meals) of the reflux symptom domain. RKT may be useful for improving GERD symptoms in elderly PPI-refractory NERD patients with ARD. Thus, RKT was particularly effective for resolving postprandial GERD symptoms (heavy feeling in stomach, sick feeling, and heartburn after meals). ( UMIN000005880 )