Tamotsu Hata

Preliminary Trial of Rebamipide for Prevention of Low-Dose Aspirin-Induced Gastric Injury in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Study

Although low-dose aspirin is widely used, since it is a cheap and effective means of prevention of cardiovascular events, it can cause hemorrhagic gastrointestinal complications. The aim of this study was to evaluate the efficacy of rebamipide in preventing low-dose aspirin-induced gastric injury. A randomized, double-blind, placebo-controlled, crossover trial was performed in twenty healthy volunteers. Aspirin 81 mg was administered with placebo or rebamipide 300 mg three times daily for 7 consecutive days. The rebamipide group exhibited significant prevention of erythema in the antrum compared with the placebo group (p = 0.0393, respectively). Results for the body and fornix did not differ significantly between the placebo and rebamipide groups. In conclusion, short-term administration of low-dose aspirin induced slight gastric mucosal injury in the antrum, but not in the body or fornix. Rebamipide may be useful for preventing low-dose aspirin-induced gastric mucosal injury, especially which confined to the antrum.

Pathophysiological Classification of Functional Dyspepsia Using a Novel Drinking-Ultrasonography Test

Background: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD symptoms includes impaired fundic accommodation, delayed gastric emptying, and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. Method: Subjects were 60 successive FD patients according to the Rome III criteria. A drinking-ultrasonography test was performed after subjects had fasted. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. The normal range of cross-sectional area and VAS were set using average ± standard deviations of 33 healthy volunteers. Cases outside the normal range were diagnosed with a motor or sensory disorder. Results: The drinking-ultrasonography test classified FD patients into four groups without adverse effect or trouble. The distribution of each group was 27% in the normal group, 15% in the impaired relaxation group, 10% in the delayed emptying group, and 48% in the visceral hypersensitivity group. There was no significant correlation between the pathophysiological classification and subtypes of FD defined by the Rome III criteria. Conclusion: We developed a novel drinking-ultrasonography test that was effective in classifying FD patients according to pathophysiological features.

Comparison of Gastric Relaxation and Sensory Functions between Functional Dyspepsia and Healthy Subjects Using Novel Drinking-Ultrasonography Test

Background: Functional dyspepsia (FD) is a heterogeneous disease characterized by various upper abdominal symptoms. The major mechanism of FD includes impaired fundic accommodation, delayed gastric emptying and visceral hypersensitivity. We developed a novel drinking-ultrasonography test to combine a drink test with ultrasonography to assess gastric motility and sensory function of FD patients. Method: Subjects were 20 healthy volunteers and 26 successive FD patients according to the Rome III criteria. The subjects ingested 200 ml of water at 2-min intervals 4 times (total 800 ml) through a straw. The maximum cross section of the proximal stomach was visualized before water intake, after each water intake, and 5 and 10 min after the completion of drinking using extracorporeal ultrasonography. Abdominal symptoms were evaluated using the visual analog scale (VAS) a total of 5 times. Results: The mean cross-sectional area of the fornix after 800 ml of water intake was significantly lower in the FD group compared with the control group. In the FD group, marked abdominal symptoms developed immediately after initiation of water intake, and VAS score differed significantly (p <0.01) between the control and FD groups at each time point. Conclusion: We developed the novel drinking-ultrasonography test which revealed abnormalities in gastric accommodation and sensation in patients with FD compared with healthy controls. This approach can be readily performed and allows the simultaneous evaluation of gastric accommodation, emptying and sensation.

M1114 Evaluation of Gastric Mucosal Blood Flow Using Contrast-Enhanced Ultrasonography During Low-Dose Aspirin Therapy and During NSAID and Low-Dose Aspirin Combined Therapy

Background: Low-dose aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are now used extensively for prevention of vascular disorders or treatment of chronic pain. The frequency of gastric mucosal lesions is expected to increase with combined use of these medicines. A histamine-2 receptor antagonist (H2RA) suppresses development of acid secretion and is expected to prevent development of gastric mucosal lesions associated with NSAIDs and low-dose aspirin. Evaluation of gastrointestinal blood flow is important for understanding the pathogenesis of various gastrointestinal diseases. Aim: we used a noninvasive examination method, transabdominal contrast-enhanced ultrasonography (low mechanical harmonic index imaging), and assessed gastric mucosal blood flow during low-dose aspirin therapy and combined therapy with low-dose aspirin and an NSAID (loxoprofen) and then investigated the effect of an H2RA (lafutidine) on gastric mucosal blood flow. Subjects and methods: The subjects were sixteen healthy volunteers without H. pylori infection. Their mean age was 24.4 years. Subjects in the placebe took low-dose aspirin (81mg) once a day for 14 days (days 1-14), 60 mg of loxoprofen three times a day for 7 days (days 8-14), and a placebo twice a day for 14 days (days 1-14). Subjects in the lafutidine followed the same protocol for low-dose aspirin and loxoprofen but took 10 mg of lafutidine twice a day for 14 days (days 1-14). We carried out contrast-enhanced ultrasonography with perflubutane on day 1, day 8, day 15 and measured gastric mucosal blood flow of the anterior wall of the gastric antrum. A time-intensity curve (TIC) for gastric mucosal blood flow was plotted from recorded ultrasonographic images. Three values were calculated from the TIC: AUC (area under the curve), TIC peak value and TIC peak time. We used these three values to measure gastric mucosal blood flow. Results: The AUC decreased significantly after taking low-dose aspirin (day 8) in both the placebo and lafutidine groups. However, no statistically significant decrease in the AUC was found between day 8 and day 15. The results for TIC peak value were the same as those for AUC. No significant extension of TIC peak time was shown between day 1, day 8 and day 15. No significant difference in AUC, TIC peak value and TIC peak time was found between the placebo and laftidine groups. Conclusion: Low-mechanical index imaging with perflubutane enables noninvasive assessment of gastric mucosal blood flow in real time. The use of this method in a daily primary care setting is expected to lead to prevention and early detection of gastric mucosal injury caused by aspirin and NSAIDs.

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