Generation of Gastroesophageal Reflux Disease Symptoms During Esophageal Acid Infusion With Concomitant Esophageal pH Monitoring in Healthy Adults.

BACKGROUND/AIMS: The sensitivity of the upper and lower esophageal mucosa to acid is considered to differ. We investigated the relationship between pH changes in different sites of the esophagus and generation of gastroesophageal reflux symptoms during an acid infusion test. METHODS: An acid infusion catheter was placed at 5 or 15 cm above the lower esophageal sphincter (LES) in 18 healthy volunteers, while a 2-channel pH sensor catheter was also placed in each with the sensors set at 5 and 15 cm above the LES. Solutions containing water and hydrochloric acid at different concentrations were infused through the infusion catheter. RESULTS: Acid infusion in the upper esophagus caused a pH drop in both upper and lower esophageal sites, whereas that in the lower esophagus resulted in a significant pH drop only in the lower without a corresponding pH decline in the upper esophagus. Stronger heartburn, chest pain, and chest oppression symptoms were noted when acid was infused in the upper as compared to the lower esophagus, while increased intra-esophageal acidity strengthened each symptom. Regurgitations caused by upper and lower esophageal acid infusions were similar, and not worsened by a larger drop in intra-esophageal pH. Chest pain was caused only by lowered intra-esophageal pH, while heartburn, chest oppression, and regurgitation were induced by a less acidic solution. CONCLUSIONS: Higher intra-esophageal acidity caused stronger heartburn, chest pain, and chest oppression symptoms. However, regurgitation was not significantly influenced by intra-esophageal acidity. The upper esophagus showed higher acid sensitivity than the lower esophagus.

A study on the efficacy of rebamipide for patients with proton pump inhibitor-refractory non-erosive reflux disease.

BACKGROUND AND AIM: Reflux symptoms in patients with non-erosive reflux disease (NERD) cannot be easily controlled by treatment with proton pump inhibitors (PPI). The anti-inflammatory function of rebamipide may be effective for protecting the esophageal mucosa. This prospective randomized multicenter placebo-controlled study was performed to clarify the efficacy of rebamipide for NERD patients whose reflux symptoms were refractory to PPI treatment. METHODS: One hundred forty-nine patients were enrolled on the basis of a QUEST score of over 6 and absence of endoscopically proven esophageal mucosal breaks. All the patients were initially administered 15 mg of lansoprazole for 4 weeks, and the symptoms were then assessed using QUEST and GSRS. PPI-refractory patients were randomly assigned to administration of rebamipide or placebo t.i.d. for 4 weeks. RESULTS: Three of the 149 patients were lost to follow-up, and 60 among the remaining 146 patients were found to be PPI-refractory. Among these PPI-refractory patients, 31 were randomly assigned to a rebamipide group and 29 to a placebo group. At the end of drug administration, the QUEST and GSRS scores did not differ between the rebamipide and placebo groups, although a significantly higher proportion of patients in the rebamipide group showed amelioration of abdominal pain and diarrhea. CONCLUSION: Administration of rebamipide cannot effectively control reflux symptoms in NERD patients whose symptoms are refractory to PPI therapy.

Usefulness of catheterless radiotelemetry pH monitoring system to examine the relationship between duodenal acidity and upper gastrointestinal symptoms.

BACKGROUND AND AIM: To clarify the usefulness of a newly designed method for measuring intraduodenal pH to examine the relationship between duodenal acidity and upper gastrointestinal symptoms during intragastric acid infusion. METHODS: The study subjects were six healthy volunteers. A Bravo pH capsule with thread fixed to the gastric wall was endoscopically introduced into the second portion of the duodenum, and intraduodenal acidity was measured during intragastric infusion of 300 mL of 0.1 mol/L hydrochloric acid or pure water through an elemental diet tube. The severity of several upper gastrointestinal symptoms were assessed by using a 10-cm visual analogue scale every 2 min for up to 30 min, and the area under the severity scale-time curve (cm×min.) were calculated. RESULTS: The percentage time during 30 min when the intraduodenal pH was <4.0 and was significantly greater than during water infusion (61.4±6.1% vs 24.8±6.5%). Several upper gastrointestinal symptoms were observed during acid infusion (acid vs water epigastric heaviness, 29.1±12.0 vs 2.7±1.4; dull epigastric pain, 8.8±4.9 vs 0.7±0.7 cm×min/30 min). Intraduodenal pH below 4.0 was correlated with the severity of dull pain in the stomach (R(2)=0.342, P=0.044). CONCLUSION: The newly designed intraduodenal pH monitoring by using catheterless radiotelemetry system is useful to examine the relationship between duodenal acidity and upper gastrointestinal symptoms.

Effects of mosapride on esophageal functions and gastroesophageal reflux.

BACKGROUND AND AIM: A substantial number of patients with gastroesophageal reflux disease show symptomatic resistance to high-dose proton pump inhibitors. In those cases, prokinetics are possible candidates for treatment. The aim of the present study was to determine whether mosapride, a prokinetic agent, stimulates esophageal functions, and prevents acidic and non-acidic gastroesophageal reflux. METHODS: Normal volunteers (nine and 13 for two experiments, respectively) were enrolled. Salivary secretion, esophageal peristaltic contractions, and resting lower esophageal sphincter pressure with and without mosapride administration were recorded using a cross-over protocol. Post-prandial acidic and non-acidic reflux levels were also recorded. RESULTS: Mosapride at a standard dose of 15 mg/day did not stimulate salivary secretion or any esophageal motor functions. It also failed to prevent acidic and non-acidic post-prandial gastroesophageal reflux. CONCLUSIONS: Mosapride at 15 mg/day, a standard dose in Japan, did not change the esophageal motility and salivary secretion in healthy volunteers. Future study on a larger number of individuals with higher dose of mosapride is worthwhile.

Effects of anti-hypertensive drugs on esophageal body contraction.

AIM: To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possible relationship with gastro-esophageal reflux disease. METHODS: Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine, losartan, and atenolol, as well as without any drug administration. RESULTS: Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were significantly higher than those without medication in a supine position. On the other hand, peristaltic pressures under nifedipine administration were lower than those observed without drug administration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition, while the effects of nifedipine were the opposite. CONCLUSION: Among the anti-hypertensive drugs tested, atenolol enhanced esophageal motor activity, which was in contrast to nifedipine.

Half-solidification of nutrient does not decrease gastro-esophageal reflux events in patients fed via percutaneous endoscopic gastrostomy.

BACKGROUND & AIMS: Percutaneous endoscopic gastrostomy (PEG) tube feeding is widely used for patients with swallowing dysfunction, and aspiration pneumonitis induced by reflux of gastric contents is one of the most frequent and life-threatening events in such patients. We performed this study to clarify the effect of half-solidification of nutrient on gastro-esophageal reflux (GER) of acidic and non-acidic gastric contents in patients with PEG. METHODS: The subjects were 14 elderly patients undergoing PEG feeding (female: 11, mean age 83.1 y). Twenty-four hour esophageal multichannel intraluminal impedance (MII) and pH (MII-pH) monitoring were performed during and after feeding with half-solid and liquid nutrient, respectively. The numbers of GER events during 4h after the start of feeding were compared. RESULTS: There was no significant difference in the total number of GER events between half-solid nutrient feeding and liquid nutrient feeding (5.6+/-1.5 vs. 6.6+/-1.5). The number of acid reflux events after half-solid nutrient feeding tended to be higher than that after liquid nutrient feeding (1.9+/-1.1 vs. 1.4+/-0.8). CONCLUSION: Half-solidification of nutrition does not appear to be effective for preventing GER caused by liquid PEG feeding.

Esophageal epithelial surface in patients with gastroesophageal reflux disease: an electron microscopic study.

AIM: To investigate the intercellular spaces between the most superficially located esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD). METHODS: Eighteen patients with erosive esophagitis, 10 patients with non-erosive reflux disease (NERD), and 18 normal asymptomatic volunteers were enrolled. Biopsy specimens were obtained from the lower esophageal mucosa without ulcer or erosion. Scanning electron microscopy was employed to investigate the tightness of the superficial cellular attachment. RESULTS: The intercellular space between the most superficially located epithelial cells in patients with erosive esophagitis or NERD was not different from that in asymptomatic healthy individuals. CONCLUSION: Widened luminal intercellular spaces of esophageal superficial epithelium are not responsible for the induction of reflux symptoms in patients with GERD.

[Study on the recognition of upper abdominal symptoms by Japanese adults ].

Four hundred and sixty-three cases, who visited medical center for annual check-up, were enrolled in this study. All subjects were required to answer three symptoms in the ten upper abdominal symptoms and the frequency of these symptoms by which they might visit hospital to take medical care. Upper abdominal pain, nausea and chest pain were best three symptoms, which might cause hospital visit and only a few subjects thought that they make a hospital visit by heartburn, acid regurgitation and early satiety. More than 30% of subjects think that they might visit medical center for medical care when these symptoms occur over three times per week. In contrast, upper abdominal pain, nausea, vomiting, heartburn and early satiety were frequently observed in 100 patients, who visited medical center to take medical care. In addition, about half of patients visited medical center when these symptoms occurred every day.

Five-year follow-up study of patients with reflux symptoms and reflux esophagitis in annual medical check-up field.

AIM: To clarify changes in the prevalence of reflux symptoms and reflux esophagitis over a period of 5 years. SUBJECTS AND METHODS: Five hundred thirty-nine study subjects (male: 408, mean age 47.3 years) were assessed using a reflux symptom questionnaire and endoscopic examinations conducted twice, 5 years apart. RESULTS: At enrollment, 88 patients had reflux symptoms and 44 had reflux esophagitis (RE). After 5 years, 58 and 53 patients were diagnosed as having reflux symptoms and RE, respectively. Only 26% of the patients with reflux symptoms at enrollment had the symptoms after 5 years. The presence of reflux symptoms and an increase of BMI were significant risk factors for the presence of reflux symptoms after 5 years. CONCLUSION: Reflux symptoms frequently disappear after 5 years. It is difficult to identify individuals who will still have symptoms after 5 years on the basis of clinical characteristics.

Study of arteriosclerosis in patients with hiatal hernia and reflux esophagitis.

BACKGROUND AND AIM: It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE. METHODS: We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check-ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart-carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart-ankle PWV (HAPWV). RESULTS: The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE. CONCLUSION: Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.

[QOL of Japanese patients with GERD].

Gastroesophageal reflux disease(GERD) has been reported to be a pathological condition that decreases quality of life(QOL) of patients because of the various troublesome symptoms. To measure QOL, generic and disease specific instruments have been used in western countries. In Japan, some of these instruments are translated into the Japanese and are used for the measurement of QOL of various diseases. QOL of the Japanese patients with GERD are measured with the Japanese version of SF-36 and GSRS. As reported in western countries, QOL of the Japan patients with GERD are reported to be significantly decreased in comparison with those of healthy individuals.

Difference in localization of esophageal mucosal breaks among grades of esophagitis.

BACKGROUND: Gastroesophageal reflux occurs mainly during the daytime in patients with Los Angeles grade A esophagitis, but predominantly during the night in patients with grade C and D esophagitis. The purpose of the present paper was to investigate whether this difference in the pattern of gastroesophageal reflux influences the circumferential localization of erosions in the esophageal wall. METHODS: The subjects were 394 consecutive patients diagnosed endoscopically as having reflux esophagitis (grade A, n = 223; B, n = 93; C, n = 53; D, n = 25 cases). Their endoscopic films were reviewed retrospectively to determine the circumferential location of esophageal mucosal breaks, and also the prevalence and size of hiatal hernia (HH). RESULTS: The numbers of mucosal breaks analyzed in patients with grade A, B and C esophagitis were 321, 173 and 54, respectively. Patients with grade A and B esophagitis had longitudinal mucosal breaks mainly in the right-anterior wall of the lower esophagus, whereas patients with grade C esophagitis had transverse mucosal breaks mainly in the posterior wall. The prevalence and size of HH was significantly higher and larger, respectively, in patients with grade C or D esophagitis than in those with grade A and B esophagitis. CONCLUSION: The circumferential location of esophageal mucosal breaks differs significantly among different grades of esophagitis.

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease.

BACKGROUND AND AIM: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION: The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.

Consumption of uncooked deer meat as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study.

It was reported previously food-borne transmission of hepatitis E virus (HEV) to humans from deer meat. The present study attempted to clarify whether eating uncooked deer meat is a major epidemiological risk factor for HEV infection in Kasai, a city in western Japan. In total, 45 volunteer subjects with experience of eating raw deer meat were enrolled. An equivalent number of people from the same area who had never eaten raw deer meat served as controls. The subjects and controls had comparable age and sex distributions. Serum anti-HEV IgG and anti-hepatitis A virus (HAV) IgG levels were measured in all 90 volunteers. There was no significant difference in age, overseas travel history, or rate of anti-HAV antibody positivity between the subjects and controls. Eight (17.7%) of the subjects but only one (2.2%) of the controls had measurable serum anti-HEV IgG levels (P = 0.014). Anti-HAV prevalence did not differ between the anti-HEV-positive and negative groups. The results suggest that eating uncooked deer meat is an epidemiological risk factor for HEV infection in the studied area. In countries such as Japan where deer meat is sometimes eaten raw, attention must be paid to this route of HEV infection.