Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter.

BACKGROUND: Recently reported normal values for esophageal motility obtained by high-resolution manometry (HRM) using a system with a Unisensor catheter were significantly different from those obtained by the ManoScan(®) , which could result in a wrong diagnosis. To clarify whether these differences were due to system or subject differences, we compared the manometric parameter values between ManoScan and a new system with a Unisensor catheter (Starlet) in the same subjects. METHODS: A total of 103 volunteers without any symptoms related to esophageal motility disorders were recruited. Esophageal HRM was performed using both the ManoScan and the Starlet in all subjects. Data from the ManoScan were analyzed using ManoView, and data from the Starlet were analyzed by a program with e-sleeve function. Integrated relaxation pressure, distal contractile integral, contractile front velocity (CFV), intrabolus pressure, and distal latency were calculated by both analyzing programs, and the values of these parameters were compared between the two systems by a signed rank test. KEY RESULTS: Data from a total of 97 participants were analyzed. The values of all parameters, except CFV, measured by the Starlet were significantly higher than those obtained by the ManoScan (p < 0.01). CONCLUSIONS & INFERENCES: Both systems can measure esophageal motility appropriately; nevertheless, we confirmed that the two systems showed different values of the parameters defined by the Chicago criteria. These differences should be recognized to evaluate esophageal motility precisely.

Changes in oxalate and some mineral concentrations of Setaria sphacelata under cutting and uncutting conditions.

Oxalate concentration in forage plants is important, because it results mineral deficiency in ruminants. Data on oxalate concentration in forage plants in conjunction with cutting and uncutting conditions throughout the growing period are limited. This study was aimed to investigate the changes in oxalate and some mineral concentrations of setaria (Setaria sphacelata). The plants were harvested at different stages (vegetative, boot, pre-flowering, flowering and seed) of maturity and at about 50 cm in length of regrowth (second to sixth cuttings) for evaluation of soluble oxalate, insoluble oxalate and some mineral concentrations. Soluble oxalate and total oxalate concentrations, as well as mineral concentrations, decreased with advancing maturity. Both oxalate concentrations (soluble or insoluble) were higher in leaf compared to stem. Soluble oxalate and total oxalate concentrations of regrowth were the highest at third cutting and lowest at sixth cutting. Insoluble oxalate concentration of regrowth was almost similar in all cuttings, except for the sixth cutting. The highest concentrations of potassium, sodium and magnesium of regrowth were observed at third cutting, while the highest concentration of calcium was observed at sixth cutting. A relationship between oxalate and mineral concentrations was partially observed. Results suggest that cutting materials of setaria from June to October could achieve oxalate levels that are toxic to ruminants.

Monosodium glutamate stimulates secretion of glucagon-like peptide-1 and reduces postprandial glucose after a lipid-containing meal.

BACKGROUND: Monosodium l-glutamate (MSG) is known to influence the endocrine system and gastrointestinal (GI) motility. The mechanism of postprandial glycemic control by food in the GI tract is mostly unknown and of great interest. AIM: To investigate the effect of MSG on glucose homeostasis, incretin secretion and gastric emptying in humans after a lipid-containing meal. METHODS: Thirteen healthy male volunteers (mean age, 25.5 years) and with no Helicobcter pylori infection were enrolled. A 400 mL (520 kcal) liquid meal with MSG (2 g, 0.5% wt:vol) or NaCl (control) was ingested in a single-blind placebo-controlled cross-over study. Blood glucose, serum insulin, plasma glucagon, plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were measured. Gastric emptying was monitored by a 13C acetate breath test. Postprandial symptoms were assessed on a visual analogue scale. RESULTS: The 30-min postprandial glucose concentration was significantly reduced by adding MSG to the test meal. The area under the glucose concentration vs. time curve (0-60 min) was also significantly reduced by adding MSG (40.6 ± 3.51 mg·1 hr/dL with MSG vs. 49.2 ± 3.86 mg·1 hr/dL with NaCl, P = 0.047), whereas, the 30-min postprandial plasma GLP-1 level was significantly increased (58.1 ± 15.8 pmol/L with MSG vs. 13.4 ± 15.8 pmol/L with NaCl, P = 0.035). MSG did not affect the half gastric emptying time or postprandial symptoms. CONCLUSIONS: Monosodium l-glutamate improved early postprandial glycaemia after a lipid-containing liquid meal. This effect was not associated with a change in gastric emptying, but was possibly related to stimulation of glucagon-like peptide-1 secretion.

Cascade stomach is associated with upper gastrointestinal symptoms: a population-based study.

BACKGROUND: Cascade stomach (CS) is recognized by characteristic findings on barium studies. We prospectively investigated the relationship between CS and upper gastrointestinal (GI) symptoms. METHODS: In subjects undergoing health screening, CS was diagnosed by barium studies. Consecutive persons (500 men and 127 women) with CS were identified and the same number of age-matched subjects without CS were selected as controls. Upper GI symptoms were classified as reflux symptoms, dyspepsia symptoms, or epigastralgia symptoms. Then, we prospectively analyzed barium studies to classify the gastric morphology and also assessed upper GI symptoms in consecutive 5008 men and 2736 women. KEY RESULTS: BMI was significantly higher in men with CS than in controls, and also in women with CS than in controls. Upper GI symptoms were significantly more frequent in the CS group than the controls among both men and women, especially reflux symptoms. In men, logistic regression analysis identified CS as an independent risk factor for upper GI symptoms (odds ratio = 1.771, P = 0.005) and for reflux symptoms (odds ratio = 2.07, P = 0.009). In women, CS was also significantly related to upper GI symptoms (odds ratio = 2.544, P = 0.020). The prevalence of CS was significantly higher (P < 0.0001) among symptomatic men than among those with no symptoms. CONCLUSIONS & INFERENCES: Gastric morphology is related to upper GI symptoms in both men and women. Cascade stomach should be reconsidered as a pathophysiological factor associated with upper GI symptoms.

Natural contamination of dietary rice straw with zearalenone and urinary zearalenone concentrations in a cattle herd.

The present study was conducted to 1) identify the natural source of feed contamination by zearalenone (ZEN), which was suspected to have caused persistently increased urinary ZEN concentrations in one of our experimental cattle herds, and 2) evaluate the effects of intervention against this source of contamination. As an experimental model, a fattening Japanese Black cattle herd showing persistently increased urinary ZEN concentrations was identified. Urinary ZEN concentrations of cows fed with new rice straw (experimental group, n = 6) vs. cows that continued to feed on the old rice straw (control group, n = 4) were measured at the start (d 1) and at 2 wk (d 14) after the onset of feeding with straw. In addition, the ZEN concentration in feed and water samples was measured by using both the ELISA and HPLC methods. Furthermore, isolation and identification of fungi from rice straw and concentrate feed samples were performed. The urinary ZEN concentration [ZEN (pg/mL)/creatinine (mg/mL) = pg/mg of creatinine] of cows fed with new rice straw was significantly (P < 0.05) less (843 pg/mg of creatinine) than that of cows fed with old rice straw (15,951 pg/mg of creatinine). On both d 1 and 14, the ZEN concentrations of old rice straw were greater than those of new rice straw. In addition, fungal colonies were observed in the culture media that was obtained from the old rice straw suspected of ZEN contamination, but not in the culture media from new rice straw or other feed samples. In conclusion, our field trials clearly indicate that the rice straw fed to the cows was naturally contaminated with ZEN, and that the monitoring of urinary ZEN concentrations could prove to be a useful tool for detecting the exposure of cattle to ZEN contamination at the farm level.

Immunoassay based on monoclonal antibodies versus LC-MS: deoxynivalenol in wheat and flour in Southern Brazil.

An indirect competitive enzyme-linked immunosorbent assay (ELISA) method using a monoclonal antibody for deoxynivalenol (DON) detection in wheat and flour was standardised and validated (detection limit = 177.1 µg kg(-1)) and its performance was compared with LC-MS, quantification limit =140 µg kg(-1)). DON recovery ranged from 88.7% to 122.6% for wheat grain and from 70.6% to 139.3% for flour. Among the 38 wheat samples evaluated, DON was detected in 29 samples (76.3%) by ic-ELISA (281.6-12 291.4 µg kg(-1)) and in 22 samples (57.9%) by LC-MS (155.3-9906.9 µg kg(-1)). The 0.93 correlation coefficient between ic-ELISA and LC-MS data in 19 positive DON wheat samples demonstrated the reliability and efficiency of ic-ELISA. Results indicated that standardised ic-ELISA was suitable for DON screening in wheat samples and the need for continuous monitoring of mycotoxin levels in foodstuffs.

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing-induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors.

BACKGROUND: Gastro-esophageal reflux disease (GERD)-related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro-esophageal reflux (GER), we studied patients with CC clearly responding to full-dose proton pump inhibitor (PPI) therapy (CC patients). METHODS: Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24-h ambulatory pharyngo-esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. KEY RESULTS: Weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing-induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05). CONCLUSIONS & INFERENCES: Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing-induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago-vagal reflex in some patients.

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome.

BACKGROUND: It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End-inspiratory intra-esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep-GER) in OSA patients. METHODS: Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. KEY RESULTS: Significantly more sleep-GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep-GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra-esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra-esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. CONCLUSIONS & INFERENCES: In OSA patients, sleep-GER was mainly caused by TLESR, but not by negative intra-esophageal pressure due to OSA.

Effect of the time interval from harvesting to the pre-drying step on natural fumonisin contamination in freshly harvested corn from the State of Parana, Brazil.

Natural mycoflora and fumonisins were analysed in 490 samples of freshly harvested corn (Zea mays L.) (2003 and 2004 crops) collected at three points in the producing chain from the Northern region of Parana State, Brazil, and correlated to the time interval between the harvesting and the pre-drying step. The two crops showed a similar profile concerning the fungal frequency, and Fusarium sp. was the prevalent genera (100%) for the sampling sites from both crops. Fumonisins were detected in all samples from the three points of the producing chain (2003 and 2004 crops). The levels ranged from 0.11 to 15.32 microg g(-1)in field samples, from 0.16 to 15.90 microg g(-1)in reception samples, and from 0.02 to 18.78 microg g(-1)in pre-drying samples (2003 crop). Samples from the 2004 crop showed lower contamination and fumonisin levels ranged from 0.07 to 4.78 microg g(-1)in field samples, from 0.03 to 4.09 microg g(-1)in reception samples, and from 0.11 to 11.21 microg g(-1)in pre-drying samples. The mean fumonisin level increased gradually from < or = 5.0 to 19.0 microg g(-1)as the time interval between the harvesting and the pre-drying step increased from 3.22 to 8.89 h (2003 crop). The same profile was observed for samples from the 2004 crop. Fumonisin levels and the time interval (rho = 0.96) showed positive correlation (p < or = 0.05), indicating that delay in the drying process can increase fumonisin levels.

High-viscosity liquid meal accelerates gastric emptying.

Adding pectin to an elemental formula increases its viscosity through gelatinization, thus presumably preventing gastro-oesophageal reflux and aspiration pneumonia. We investigated the influence of the viscosity of an elemental formula on gastric emptying. Eleven healthy volunteers underwent three tests at intervals of >1 week. After fasting for >8 h, each subject received a test meal (enteral nutrition solution, enteral solution plus pectin, or water). Then gastric emptying (continuous (13)C breath test), gastro-oesophageal intraluminal pressures, oesophageal pH, and blood levels of glucose, insulin and gastrin were all measured simultaneously. The gastric emptying coefficient was significantly increased by adding pectin to enteral nutrition (3.01 +/- 0.10 vs 2.78 +/- 0.10, mean +/- SE, P < 0.05). The antral motility index was also significantly higher with pectin than without at 45-60 min and 60-75 min after the test meal (526 +/- 237 vs 6.5 +/- 4.6 mmHg s(-1) and 448 +/- 173 vs 2.3 +/- 2.3 mmHg s(-1) respectively; P < 0.05). Plasma glucose was significantly higher with pectin than without it at 60 min after ingestion (141.5 +/- 6.03 vs 125.8 +/- 4.69 microM mL(-1), P < 0.05). In healthy individuals, pectin increased the viscosity of enteral nutrition and accelerated gastric emptying.

Association between reflux oesophagitis and features of the metabolic syndrome in Japan.

BACKGROUND: There have been many reports about the relationship between reflux oesophagitis and obesity, but not the metabolic syndrome. AIM: To review upper gastrointestinal endoscopic findings and screening data obtained in healthy subjects, and assess relations between reflux oesophagitis and features of the metabolic syndrome. METHODS: In 3599 men and 1560 women, the prevalence of reflux oesophagitis was assessed in relation to the age, body mass index, blood pressure, triglycerides and fasting blood glucose. Logistic regression analysis was used to calculate odds ratio for risk factors. RESULTS: The overall prevalence of reflux oesophagitis was 4%, and it increased with age in women. Prevalence of reflux oesophagitis increased significantly with an increase of body mass index, blood pressure, triglycerides and fasting blood glucose. On multivariate analysis, male sex (odds ratio: 2.5; 95% confidence interval: 1.6-3.8), obesity (1.9; 1.4-2.5), hyperglycaemia (1.7; 1.2-2.4) and hypertension (1.5; 1.1-2.1) were independent risk factors for reflux oesophagitis. Among both men and women, those with reflux oesophagitis were significantly more likely to have two or more of these risk factors than non-reflux oesophagitis subjects. CONCLUSIONS: Components of the metabolic syndrome are associated with the occurrence of reflux oesophagitis. Therefore, some risk factors may be common to reflux oesophagitis and the metabolic syndrome.

Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy.

OBJECTIVE: To test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Delayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. METHODS: Thirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. RESULTS: Preoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. CONCLUSIONS: Low doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.

Aflatoxins and fumonisins in corn from the high-incidence area for human hepatocellular carcinoma in Guangxi, China.

A comparative study on the natural occurrence of aflatoxins and Fusarium toxins was conducted with corn samples from high- and low-incidence areas for human primary hepatocellular carcinoma (PHC) in Guangxi, China. In samples from the high-risk area, aflatoxin B(1) was the predominant toxin detected in terms of quantity and frequency, with its concentration ranging between 9 and 2496 microg/kg and an 85% incidence of contamination. Among the samples, 13 (76%) exceeded the Chinese regulation of 20 microg/kg for aflatoxin B(1) in corn and corn-based products intended for human consumption. Significant differences in aflatoxin B(1), B(2), and G(1) and total aflatoxin concentrations in corn between the areas were found (P < 0.05). The average daily intake of aflatoxin B(1) from corn in the high-risk area was 184.1 microg, and the probable daily intake is estimated to be 3.68 microg/kg of body weight/day, 3.20 times the TD(50) in rats. Corn samples from both areas were simultaneously contaminated with fumonisins B(1), B(2), and B(3). Aflatoxin B(1) may play an important role in the development of PHC in Guangxi.

Evaluation of fumonisin-aflatoxin co-occurrence in Brazilian corn hybrids by ELISA.

The natural co-occurrence of fumonisins and aflatoxins was investigated in freshly harvested corn kernels (150 samples, 62 hybrids), acquired from the Central-Southern (27 samples, 21 hybrids), Central-Western (86 samples, 51 hybrids) and Northern (37 samples, 18 hybrids) regions of the State of Paraná, Brazil using enzyme-linked immunosorbent assay (ELISA). Fumonisins were detected in 147 (98%) samples at a concentration range of 0.096 to 22.6 microg/g, while aflatoxins were detected in 17 (11.3%). All the aflatoxin-positive samples (range 38.0-460.0 ng/g) came from the Central-Western region and were co-contaminated with fumonisins. Fumonisin contamination was higher in corn from the Northern (9.85 microg/g) and Central-Western regions (5.08 microg/g), when compared with the Central-Southern region (1.14 microg/g). The overall evaluation detected 62% samples with fumonisin levels < or = 5.0 microg/g. Regional differences affected fumonisin levels in the same hybrid, regardless of Fusarium count and moisture content, suggesting interference from climatic conditions, in addition to the local predominance of toxigenic strains of the Fusarium biotype.

A case of inability to belch.

A 22-year-old man was unable to belch. He could sense intraesophageal gas, but had no chest pain. An upper gastrointestinal X-ray series and endoscopic examination showed no abnormalities. Esophageal manometry showed normal relaxation of both the upper and lower esophageal sphincters with primary peristalsis during deglutition. However, bolus injection of air into the middle esophagus failed to initiate the belch reflex.

[Motility disorders of the esophagus, excluding achalasia].

Esophageal motor disorders can be primarily focused in the esophagus or secondarily related to a systemic disease. Based on the manometric findings, primary esophageal motor disorders can also be classified into achalasia and spastic disorders, such as diffuse esophageal spasm, nutcracker esophagus, hypertensive lower esophageal sphincter, and nonspecific esophageal motility disorders.

Measurement and evaluation of gastric emptying using radiopaque barium markers.

To simplify assessment of gastric emptying, we have developed a radiopaque barium marker method. The subjects were 11 healthy volunteers, 30 patients with progressive systemic sclerosis, 16 patients with dysmotility-like dyspepsia, 7 patients with irritable bowel syndrome, and 6 patients with diabetes mellitus. We tested three types of radiopaque markers with manometry by a three-channel strain gauge transducer. The 4.5-mm ring-shaped markers with a specific gravity of 1.2 were emptied from the stomach in correlation with the number of high-amplitude (>50 mm Hg) antral contractions. The percentage of residual markers at 2 hr was significantly (P < 0.05) lower in patients with irritable bowed syndrome than in normal controls, and at 5 hr it was significantly (P < 0.05) higher in patients with systemic sclerosis with esophageal dysmotility, dysmotility-like dyspepsia, or diabetes than in normal controls. This radiopaque barium marker method may be useful as a screening test for determining whether gastric emptying is rapid or delayed.