Increased numbers of immature plasma cells in peripheral blood specifically overexpress chemokine receptor CXCR3 and CXCR4 in patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease featuring infiltration by plasma cells producing immunoglobulins. We have reported previously the specific and significant proliferation of immature plasma cells in the inflamed colonic and pouch mucosa of UC patients. The aim of this study was to characterize peripheral blood immature plasma cells and the migration mechanisms of such immature plasma cells to inflamed sites in UC. The characteristics of peripheral blood immature plasma cells and chemokine receptor expression were examined by flow cytometry. Expression of mucosal chemokine was quantified using real-time reverse transcription-polymerase chain reaction and immunohistochemistry. The number of peripheral blood immature plasma cells was significantly higher in patients with active UC and active Crohn's disease (CD) than in healthy controls. The proportion of immature plasma cells was correlated positively with clinical activities of UC and CD. Many peripheral blood immature plasma cells were positive for CXCR3, CXCR4, CCR9 and CCR10. Expression of CXCR3 and CXCR4 in UC patients was significantly higher than in controls. CXCL9, CXCL10 and CXCL11 mRNA levels in colonic mucosa of inflamed IBD were higher than in controls. Immunofluorescence study also showed abundant CXCR3-positive immature plasma cells in the inflamed colonic mucosa of UC. Increased numbers of immature plasma cells may migrate towards inflammatory sites of UC via the CXCR3 axis, and may participate in UC pathogenesis.

The Traditional Japanese Medicine Rikkunshito Promotes Gastric Emptying via the Antagonistic Action of the 5-HT(3) Receptor Pathway in Rats.

The traditional Japanese medicine rikkunshito ameliorates the nitric oxide-associated delay in gastric emptying. Whether rikkunshito affects gastric motility associated with 5-hydroxytryptamine (serotonin: 5-HT) receptors or dopamine receptors is unknown. We examined the effects of rikkunshito on the delay in gastric emptying induced by 5-HT or dopamine using the phenol red method in male Wistar rats. 5-HT (0.01-1.0 mg kg(-1), i.p.) dose dependently delayed gastric emptying, similar to the effect of the 5-HT(3) receptor agonist 1-(3-chlorophenyl) biguanide (0.01-1.0 mg kg(-1), i.p.). Dopamine also dose dependently delayed gastric emptying. The 5-HT(3) receptor antagonist ondansetron (0.04-4.0 mg kg(-1)) and rikkunshito (125-500 mg kg(-1)) significantly suppressed the delay in gastric emptying caused by 5-HT or 1-(3-chlorophenyl) biguanide. Hesperidin (the most active ingredient in rikkunshito) suppressed the 5-HT-induced delayed gastric emptying in a dose-dependent manner, the maximum effect of which was similar to that of ondansetron (0.4 mg kg(-1)). The improvement obtained by rikkunshito or ondansetron in delaying gastric emptying was completely blocked by pretreatment with atropine. Rikkunshito appears to improve delay in gastric emptying via the antagonistic action of the 5-HT(3) receptor pathway.

Long-term efficacy of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura: 7-year follow-up prospective study.

Helicobacter pylori eradication is useful for improvement of a half of patients with idiopathic thrombocytopenic purpura (ITP), but its long-term therapeutic efficacy has not been elucidated. We investigated the long-term efficacy of H. pylori eradication in 30 cases with ITP that were included in our previous study regarding the association between H. pylori infection and ITP. Twenty-one cases were positive and nine cases were negative for H. pylori infection. H. pylori eradication therapy including secondary regimen was successful in 20 cases, half (responder) of whom showed ITP remission 1 month later. Nine responders could be followed up for a long time and did not show re-infection of H. pylori. Eight of nine needed no medication except for eradication therapy. Another case remained in remission for 1 year but thereafter needed a steroid therapy due to the recurrence. Eight nonresponders could be followed up for a long time. All these cases showed a bad clinical course even though they received the other post-treatments including steroid therapy. Three of nine H. pylori-negative cases underwent eradication therapy after obtaining the written informed consent, but none of them showed improvement. Of these three cases, two cases could be followed up. Only one case remained a remission although receiving corticosteroid as a post-treatment. Conditions of H. pylori-negative ITP cases were usually unstable for a long time. H. pylori eradication has a short-term efficacy for about half of H. pylori-positive ITP patients, and the responders to the eradication therapy may receive a long-term clinical benefit without other therapies.

A novel rat model to determine interaction between reflux oesophagitis and bronchial asthma.

BACKGROUND: Several studies have shown a strong association between reflux oesophagitis (RO) and bronchial asthma (BA). The precise mechanisms of interaction between RO and BA are uncertain, possibly due to lack of animal models. AIMS: We established a novel rat model and examined pathogenic interaction of RO and BA. METHODS: RO and BA were induced in Brown-Norway rats by ligating the transitional region between the forestomach and the glandular portion and wrapping the duodenum near the pylorus, and by ovalbumin (OVA) sensitisation and challenge with OVA aerosol. Rats were divided into four groups: control, RO, BA, and RO+BA. OVA-induced airway inflammation was assessed by the number of infiltrating cells and cytokine levels in bronchoalveolar lavage fluid (BALF). Oesophageal lesion index, histology and expression of cytokine mRNA, as determined by real-time RT-PCR, were also examined. RESULTS: Significant increases in the number of cells, especially eosinophils, and IL13 but not IFN-gamma concentration in BALF were observed in the RO+BA group compared with the BA group. These enhancements of OVA-induced airway inflammation were prevented by treatment with rabeprazole. Although the oesophagitis lesion index in the RO+BA group did not differ from that in the RO group, eosinophilic infiltration in the oesophageal submucosa and levels of mRNA expression of cytokines such as IL5, IL10, IL13, and RANTES were significantly increased. CONCLUSION: We established a novel rat model of RO and BA, and found significant interactions of the two diseases. This model thus appears to be useful for examining the association between gastro-oesophageal reflux disease and bronchial asthma.

Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent.

BACKGROUND: Enterobacteria and cytokines both play roles in the pathophysiology of NSAID-induced enteropathy. Toll-like receptor (TLR) 4 recognises lipopolysaccharide (LPS), resulting in activation of an inflammatory cascade via the accessory protein MyD88. AIMS: To investigate role of TLR4 in inflammatory responses in indomethacin-induced enteropathy. METHODS: Indomethacin was administered p.o. to non-fasting rats and mice to induce small intestinal damage. The extent of such damage was evaluated by measuring the injured area stained dark blue with Evans blue. Rats were given antibiotics (ampicillin, aztreonam or vancomycin) p.o., or intraperitoneal LPS (a TLR4 ligand) or neutralising antibodies against neutrophils, tumour necrosis factor (TNF)-alpha, or monocyte chemotactic protein (MCP)-1. Furthermore, the intestinal ulcerogenicity of indomethacin was examined in TLR4-mutant, TLR4(-/-), and MyD88(-/-) mice. RESULTS: Indomethacin induced small intestinal damage with an increase in expression of TNF-alpha and MCP-1 in both rats and mice. Antibodies against neutrophils, TNF-alpha and MCP-1 inhibited the damage by 83%, 67% and 63%, respectively, in rats. Ampicillin and aztreonam also inhibited this damage, and decreased the number of Gram-negative bacteria in the small intestinal contents of the rat. However, vancomycin, which exhibited no activity against Gram-negative bacteria, had no preventive effect against this damage. Administration of LPS 1 h after indomethacin aggravated the damage, whereas LPS pretreatment inhibited it with reduction of expression of TLR4 and cytokines. In TLR4-mutant mice, the damage and cytokine expression were markedly inhibited. TLR4(-/-) and MyD88(-/-) mice were also resistant to the damage. CONCLUSIONS: Indomethacin may injure the small intestine through a TLR4/MyD88-dependent pathway.

Famotidine vs. omeprazole: a prospective randomized multicentre trial to determine efficacy in non-erosive gastro-oesophageal reflux disease.

BACKGROUND: Several studies in Western countries showed that proton-pump inhibitors are superior to histamine2-receptor antagonists or placebo in the treatment of non-erosive gastro-oesophageal reflux disease. The efficacy of acid-suppressive drugs for non-erosive gastro-oesophageal reflux disease in Japan, in which the prevalence of Helicobacter pylori infection is higher compared with Western countries, is unknown. AIM: To compare the efficacy of famotidine and omeprazole in Japanese patients with non-erosive gastro-oesophageal reflux disease by a prospective randomized multicentre trial. METHODS: A total of 98 patients received either famotidine 20 mg b.d. (n = 48) or omeprazole once daily (n = 50). Frequency of gastro-oesophageal reflux disease symptoms and health-related quality of life were evaluated at baseline and after 4 weeks of treatment. Complete relief was defined as no gastro-oesophageal reflux disease symptoms during the 7-day interval in week 4. RESULTS: Complete relief was achieved in 23 (48%) of patients receiving famotidine and 28 (56%) of patients treated with omeprazole. In the famotidine group, complete relief rate in H. pylori-negative patients was significantly lower than H. pylori-positive patients (35% vs. 64%). Both famotidine and omeprazole improved most scales of health-related quality of life. Omeprazole significantly improved reflux score irrespective of H. pylori infection while famotidine significantly improved reflux score in H. pylori-positive patients but not in H. pylori-negative patients. CONCLUSIONS: Omeprazole is more effective than famotidine for the control of gastro-oesophageal reflux disease symptoms in H. pylori-negative patients, while similar efficacy is observed in H. pylori-positive patients with non-erosive gastro-oesophageal reflux disease.

Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease.

BACKGROUND: A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn's disease (CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell (DC) interactions, help control antigen specific T cell responses. AIMS: To investigate the Th1 response and SLC and ELC in CD pathogenesis. METHODS: Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR. RESULTS: ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. CONCLUSION: The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.

Increased expression of epidermal growth factor receptors in basal cell hyperplasia of the oesophagus after acid reflux oesophagitis in rats.

BACKGROUND: Epidermal growth factor (EGF), which binds to EGF receptors (EGF-R), stimulates oesophageal epithelial cell proliferation, enabling rapid repair after mucosal injury. In the normal human oesophageal epithelium, EGF-R expression is present and confined to the basal layer. AIM: To examine histological changes in and dynamics of EGF-R expression during healing after acid reflux oesophagitis in a rat model. METHODS: Gastric acid reflux oesophagitis was induced in Wistar rats by ligation of the pylorus and the transitional region between the forestomach and the grandular portion for 5 h, followed by release of both ligations. Rats were killed 7 and 14 days after production of oesophagitis to examine macroscopic and histological changes as well as dynamics of EGF-R expression. Epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) uptake, and expression of EGF-R mRNA and protein by RT-PCR and Western blotting or immunohistochemistry. RESULTS: Gastric acid reflux induced erosive and ulcerative mucosal lesions in the lower and middle part of the oesophagus. These lesions were healed by 14 days and histologically showed thickening of the oesophageal epithelium from 41.11 +/- 3.09 microm in controls to 142.73 +/- 11.59 microm (P < 0.001) in ligated rats, as well as elongation of papillae and basal cell hyperplasia. The number of BrdU-positive cells among basal cells on day 14 was significantly increased from 7.1 +/- 0.8/field in controls to 30.9 +/- 3.0/field in ligated rats. Expression of EGF-R mRNA and protein was significantly increased on day 14 and most basal cells were immunohistochemically positive in both BrdU and EGF-R staining. CONCLUSION: Acid reflux-induced oesophageal injury caused basal cell hyperplasia with an increase in cell proliferation and EGF-R expression. Activation of EGF-R gene and protein in response to acid reflux-induced injury may facilitate mucosal healing. These results suggest that epidermal growth factor receptors play a crucial role in healing after acid reflux oesophagitis in rats.

High molecular protein of Helicobacter pylori responsible for inhibition of ornithine decarboxylase activity of human gastric cultured cells.

BACKGROUND: Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, mediates epithelial cell proliferation and plays a critical role in the optimal repair of gastric mucosal damage. Several studies have shown that Helicobacter pylori inhibits the growth and proliferation of gastric cells in vitro. AIM: To test whether H. pylori extract affects ODC mRNA expression and its enzyme activity in gastric cells and to examine the partial characterization of the molecule responsible for this effect. METHODS: Human gastric cells (MKN-45) were used. Bacterial extracts from various E. coli or H. pylori strains, namely (1) cagA+, vacA+, CagA+, VacA+; (2) cagA+, vacA+, CagA+ VacA-; or (3) cagA-, vacA+, CagA-, VacA- were added to the cells. Cell proliferation was assessed by [3H]-thymidine incorporation, viability by MTT assay and LDH release test, ODC enzyme activity by 14CO2 counts from L-[1(14)C]ornithine, and ODC mRNA by Northern blotting. RESULTS: H. pylori and E. coli extract did not affect viability of gastric cells. H. pylori extract, especially extracts containing a protein greater than 50 kDa, significantly inhibited proliferation and ODC activity of gastric cells while E. coli extract had no effect. Inhibition of ODC activity was found in extracts of all H. pylori strains, irrespective of CagA and VacA protein expression. Serum stimulation induces an increase in ODC mRNA while H. pylori extract did not affect ODC mRNA expression. CONCLUSION: High molecular weight (greater than 50 kDa) proteins of H. pylori extract without CagA or VacA protein inhibited proliferation and ODC activity of human gastric cells, but did not affect ODC mRNA expression, suggesting that inhibition of ODC activity is regulated at the post-transcriptional level.

Prevalence of symptomatic gastro-oesophageal reflux disease in Japanese patients with peptic ulcer disease after eradication of Helicobacter pylori infection.

BACKGROUND: The association between cure of Helicobacter pylori infection and the development of gastro-oesophageal reflux disease is controversial. AIM: To examine the prevalence of symptomatic GERD (sGERD) in Japanese patients with peptic ulcer disease after successful eradication and identify associated factors affecting sGERD development. METHODS: We retrospectively examined 72 patients (40 gastric ulcer and 32 duodenal ulcer) with successful eradication. Associated factors such as age, gender, drinking and smoking habits, body mass index, presence of gastric atrophy and hiatal hernia were analysed. RESULTS: Seven (9.7%) of 72 peptic ulcer patients newly developed sGERD. There were no differences in mean age, gender, smoking habit, drinking habit, body mass index, or presence of gastric atrophy and hiatal hernia between the sGERD and non-sGERD groups, while the proportion of subjects aged over 70 was significantly higher in the sGERD than the non-sGERD group. Six of 40 patients with gastric ulcer newly developed sGERD while only one of 32 patients with duodenal ulcer developed it. CONCLUSION: Approximately 10% of Japanese patients with peptic ulcer disease newly developed sGERD after cure of H. pylori infection. Age > 70 years was associated with development of sGERD. Eradication in patients in this age group should be carefully determined.

Correlation of MAP kinases with COX-2 induction differs between MKN45 and HT29 cells.

BACKGROUND: Mitogen-activated protein (MAP) kinases, including extracellular signal-regulated kinases (ERK),c-Jun NH2-terminal kinases (JNK) and p38 MAP kinase (p38 MAPK) are important intermediates of the signal-transduction pathway from the cell surface to the nucleus. Expression of cyclooxygenase (COX)-2, associated with proliferation, apoptosis or both of gastrointestinal cancer cells, is mediated through MAP kinase families. However, the correlation between respective MAP kinase signals and COX-2 in the proliferation of gastric and colon cancer cells has not been well elucidated. AIM: We examined the effect of selective inhibitors of MAP kinases and COX-2 on serum-induced proliferation of gastric (MKN45) and colon (HT29) cancer cells. METHODS: After 24-h serum starvation, cancer cells were stimulated with 2% serum and COX-2 inhibitors (NS398 10 micromol/L, or etodolac 100 micromol/L) or 1 h after preincubation with inhibitors for ERK (PD98059 20 micromol/L) or p38 MAPK (SB203580 10 micromol/L). Phosphorylated MAP kinases and COX-2 protein were evaluated by Western blotting, and the proliferation of cancer cells was estimated by 3H-thymidine incorporation. Transcription factors nuclear factor-kappaB and CREB were assayed by an electorophoretic mobility shift assay. RESULTS: Serum increased the proliferation of MKN45 and HT29 cells by 280% and 200%, respectively, compared with the control levels (100%). In both cancer cells, phosphorylated MAP kinases were increased within 30 min after stimulation. PD98059 and SB203580 inhibited the serum-induced proliferation of MKN45 by 21% and 51% and of HT29 by 81% and 69%, respectively. NS398 and etodolac inhibited the proliferation of HT29 by 21% and 41%, respectively, but not that of MKN45. PD98059 and SB203580 also suppressed serum-induced expression of COX-2 protein in HT29 cells. In addition to the activation of MAP kinases and COX-2, activities of nuclear factor-kappaB and CREB were also increased during HT29 cell proliferation. CONCLUSIONS: These results suggest that the correlation of MAP kinases with COX-2 induction for cell proliferation differs between MKN45 and HT29 cells.

Comparison of the effects of rebamipide with those of cimetidine on chronic gastritis associated with Helicobacter pylori in Mongolian gerbils.

BACKGROUND AND AIMS: The effects of rebamipide on chronic gastritis associated with Helicobacter pylori have not been well-defined. We compared these effects of rebamipide with those of cimetidine in Mongolian gerbils infected with H. pylori. METHODS: Mongolian gerbils with or without H. pylori were divided into 10 groups 6 weeks after inoculation and fed diets containing a drug (rebamipide or cimetidine) or control diet. All animals were sacrificed 4 weeks after grouping. Their stomachs were examined for histology, colonization by H. pylori, myeloperoxidase activity (myeloperoxidase), production of neutrophil chemokine (CINC/KC) and tumour necrosis factor-alpha (TNF-alpha), and serum gastrin levels. RESULTS: H. pylori colonized all of the inoculated animals. Neither rebamipide nor cimetidine decreased myeloperoxidase activity, but each reduced wet stomach weight in H. pylori-infected animals. The amount of increase in CINC/KC and TNF-alpha in gastric tissue caused by H. pylori infection was decreased by treatment with rebamipide or cimetidine. H. pylori infection increased serum gastrin levels, and this increase was significantly enhanced by cimetidine but not rebamipide. CONCLUSIONS: Rebamipide may improve H. pylori-infected chronic gastritis by preventing the production of inflammatory cytokines and chemokines, as does cimetidine, but may be preferable to cimetidine for long-term administration for treatment of H. pylori-infected chronic gastritis due to its effect on serum gastrin levels.

Is eradication sufficient to heal gastric ulcers in patients infected with Helicobacter pylori? A randomized, controlled, prospective study.

BACKGROUND: In Helicobacter pylori infection, the effect of short-term triple therapy with proton pump inhibitor plus two antibiotics on gastric ulcer healing is not well known. AIM: To compare 1-week triple therapy with 8-week proton pump inhibitor therapy on gastric ulcer healing in infected patients. PATIENTS AND METHODS: We randomly assigned 120 patients with H. pylori and gastric ulcers to proton pump inhibitor plus amoxicillin and clarithromycin for 1 week (n = 61) or proton pump inhibitor alone for 8 weeks (n = 59), with endoscopic assessment of ulcer healing 8 weeks after the start of treatment. RESULTS: Triple therapy eradicated H. pylori in 51 patients [intention-to-treat, 84%; 95% confidence interval (CI), 75-93%]. At 8 weeks, gastric ulcers were healed in 30 patients given triple therapy (49%; 95% CI, 37-62%) and in 49 patients given proton pump inhibitor (83%; 95% CI, 73-93%, P < 0.001). Healing rates in the triple therapy and proton pump inhibitor-only groups were 89% and 100%, respectively, for ulcers of < 1.0 cm in diameter, 54% and 77% for ulcers of 1.0 to < 1.5 cm in diameter, and 5% and 77% (P < 0.001) for ulcers of > or = 1.5 cm in diameter. CONCLUSIONS: One-week triple therapy healed most ulcers of < 1.0 cm, but not ulcers of > or = 1.5 cm. Short-term therapy is effective for gastric ulcers of < 1.0 cm, but, for larger ulcers, follow-up therapy to suppress acid is needed.

Corticosteroids for the management of ulcerative colitis.

Two studies were carried out. In the first, 24 patients with severe ulcerative colitis (UC) were prospectively studied by the Research Group of Inflammatory Bowel Disease, sponsored by the Ministry of Health and Welfare of Japan. Patients were randomly assigned to two groups; one group (n = 13) was given prednisolone, 1.0 mg/kg body weight, daily, the other group (n = 11) was given prednisolone, 1.5 mg/kg body weight, daily. The 13 patients given 1.0 mg/kg prednisolone consisted of 7 with left-sided colitis and 6 with total colitis; 11 patients given 1.5 mg/kg prednisolone consisted of 5 with left-sided and 6 with total colitis. There were no statistically significant differences in clinical, endoscopic, and overall improvement between the two groups; however, 1.5 mg/kg prednisolone was significantly more effective in the treatment of the patients exhibiting the first attack. In the second study, 6 patients with severe and 7 with moderately severe UC were given megadose pulsed steroid therapy. Five hundred or 1000 mg of either hydrocortisone-21-sodium succinate or methylprednisolone was given once a day intravenously. Ten patients achieved clinical remission, 1 patient improved, and 2 patients did not respond. Endoscopically, 5 patients achieved remission, 6 patients improved, and 2 did not respond. Adverse effects severe enough to stop the medication were not noted. Steroid withdrawal syndrome also was not noted.

Drug-induced pneumonitis caused by sulfamethoxazole, trimethoprim during treatment of Pneumocystis carinii pneumonia in a patient with refractory ulcerative colitis.

We recently treated a patient with intractable ulcerative colitis complicated with Pneumocystis carinii pneumonia in whom sulfamethoxazole/trimethoprim caused pneumonitis. The pneumonitis was difficult to differentiate from worsening of the infection or the appearance of another opportunistic infection. The patient's history of sulfasalazine (sulfonamide)-induced pneumonitis made diagnosis possible. The CD4/CD8 ratio of lymphocyte subsets in bronchoalveolar lavage fluid was decreased at the diagnosis of Pneumocystis carinii pneumonia and this ratio had increased when drug-induced pneumonitis was diagnosed. Topical administration of beclomethasone dipropionate by enema was a safe and effective for the treatment of such a compromised patient with active colitis.

Effects of ecabet sodium, an antiulcer drug, on gastric adaptive relaxation in isolated guinea-pig stomachs.

Disturbances in the reservoir function of the stomach may cause epigastric fullness or early satiety, which are the main symptoms in patients with dysmotility-like functional dyspepsia. Gastric adaptive relaxation is involved in the reservoir function of the proximal stomach. Ecabet sodium, synthesized from abietic acid, is widely used in Japan as an antiulcer drug. The purpose of this study was to evaluate the effects of ecabet on gastric adaptive relaxation in isolated guinea-pig stomachs. Changes in intragastric volume and pressure were recorded in the presence of atropine and guanethidine. Gastric adaptive relaxation was triggered by luminal distention. Ecabet at the dose of 20 mmol/l in solutions at two pHs (pH 3.0 and 7.4) significantly lowered the threshold pressure needed for such relaxation and increased intragastric volume, but lower doses had little or no effect. The results suggested that this antiulcer drug might improve symptoms in patients with dysmotility-like functional dyspepsia.