Diarrhea caused by proton pump inhibitor administration: comparisons among lansoprazole, rabeprazole, and omeprazole.

BACKGROUND: The number of patients who require treatment with proton pump inhibitors (PPIs) is increasing in Japan. One of their adverse effects is diarrhea. OBJECTIVES: We investigated the incidence of diarrhea caused by 3 different PPIs: lansoprazole, rabeprazole, and omeprazole. METHODS: Patients using PPIs for >1 month were enrolled. Enrolled patients recorded daily stool frequency, stool consistency using the Bristol Stool Scale Form, and impaired quality of life caused by diarrhea for 1 month. Their attending physicians described the types and dosages, and duration of PPI administration, as well as other necessary information. RESULTS: A total of 255 patients participated. Mean age of the patients was 70.7 years old. During the 1-month observation period, 3.5% of the patients complained of diarrhea. There was no significant difference for the incidence of diarrhea among the 3 types of PPIs. Furthermore, no correlations between diarrhea and length and dosage of PPI administration were found. CONCLUSIONS: The incidence of diarrhea in patients receiving long-term therapy did not differ among 3 different PPIs. ClinicalTrials.gov identifier: UMIN ID 000005300.

Primary hyperparathyroidism with duodenal ulcer and H. pylori infection.

A patient with duodenal ulcer and primary hyperparathyroidism was found to have an abnormally high intragastric pH. The pH level returned to normal after surgical removal of the parathyroid adenoma followed by normalization of parathyroid hormone (PTH) and serum calcium concentrations. The patient was positive for Helicobacter pylon (H. pylori) infection. Although the exact mechanism by which chronic hypercalcemia or high PTH level inhibited gastric acid secretion in this case remains unclear, our findings suggest that hypercalcemia may play some role in H. pylori associated gastroduodenal diseases through induction of proinflammatory cytokines or by enhancing the attachment of H. pylori to gastric epithelial cells.

Effects of omeprazole on sleep disturbance: randomized multicenter double-blind placebo-controlled trial.

OBJECTIVES: Gastroesophageal reflux is considered to cause sleep disturbance, whereas proton pump inhibitor (PPI) administration is reported to improve insomnia associated with gastroesophageal reflux disease (GERD). The majority of patients with gastroesophageal reflux are asymptomatic and a significant number with erosive esophagitis are also reported to be asymptomatic. We examined whether PPI administration has a therapeutic effect for improving insomnia in patients without reflux symptoms in the same manner as patients with reflux symptoms. METHODS: We performed a randomized multicenter double-blind placebo-controlled trial using 176 patients with insomnia regardless of the presence of reflux symptoms. The patients were divided into those administered omeprazole (20 mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J (Japanese translation of Quality of Life in Reflux and Dyspepsia), Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a sleep diary, were used for evaluating GERD-related quality of life (QOL) and sleep disturbance. RESULTS: We evaluated 171 patients with insomnia, of whom 69 had typical reflux symptoms. Omeprazole statistically significantly improved GERD-related QOL from 30.8±0.7 to 33.0±0.5 (P<0.01) (QOLRAD-J, total) and from 6.0±0.2 to 6.6±0.1 (P<0.01) (QOLRAD-J, sleep-related) when administrated to patients with reflux symptoms. Omeprazole also improved insomnia significantly better than the placebo in patients with reflux symptoms; PSQI, from 9.3±0.5 to 7.9±0.5 (P<0.01) and sleep diary, from 2.1±0.1 to 1.8±0.1 (P<0.01). On the other hand, the therapeutic effects of omeprazole and the placebo were not different in patients without reflux symptoms. CONCLUSIONS: Our results showed that PPI administration is effective only for insomnia in patients with reflux symptoms.

Morphological changes of pancreatic ducts in Otsuka Long-evans Tokushima Fatty rats.

OBJECTIVE: To determine if pancreatic ductal changes characteristic of chronic pancreatitis occur in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and to elucidate the 3-dimensional structure of the pancreatic ducts in those rats. METHODS: Male OLETF rats aged 10, 20, and 40 weeks were used. The pancreas was injected with a 120% barium sulfate suspension into the pancreatic ducts, after which radiograph images of the injected pancreas were taken using radiography of the soft parts. Conventional fixed pancreatic tissues were observed by the use of light and scanning electron microscopy, whereas corrosion casts of the pancreatic ducts were observed by the use of scanning electron microscopy. RESULTS: In 20- and 40-week-old male OLETF rats, deletion of acini and formation of tubular complexes and tortuous or helical, deformed, dilated pancreatic ducts were found, whereas the inner surfaces of pancreatic ducts had many craterlike depressions and long cilia. CONCLUSIONS: Male OLETF rats demonstrated the same morphological changes in pancreatic ductal lumina and histological changes in pancreatic tissues as the rats were subjected to pancreatic duct ligation. These results suggested that increased pancreatic duct pressure occurs in male OLETF rats and induces the chronic pancreatitis-like lesions, including the above-mentioned findings.

Changes in serum lipid concentrations in patients with chronic hepatitis C virus positive hepatitis responsive or non-responsive to interferon therapy.

BACKGROUND: Changes in serum lipid concentrations during the administration of interferon to patients with chronic hepatitis C virus (HCV) infection have not been fully investigated. The present study was designed to compare changes in serum lipid concentrations before, during and after interferon therapy in responders and non-responders to treatment. METHODS: In total, 101 patients with chronic HCV positive hepatitis were enrolled in this study. High dose interferon alpha was given on alternate days for 6 months. Six months after the end of treatment patients were assessed for the presence or absence of HCV RNA to determine the results of interferon treatment. The time courses of changes in serum lipid concentrations were measured in all patients. RESULTS: The total cholesterol level increased gradually during and after interferon therapy, and its pattern of change coincided with that of serum cholinesterase activity. Pretreatment serum cholesterol concentrations did not differ between responders and non-responders to interferon therapy. The serum triglyceride concentration, conversely, showed a sharp increase during interferon administration and returned to its basal level after the end of treatment. Responders to interferon therapy tended to have higher pretreatment triglyceride concentrations than did non-responders. CONCLUSIONS: We clarified that serum cholesterol and triglyceride levels showed different patterns of change during interferon therapy.

Comparative study of nizatidine and famotidine for maintenance therapy of erosive esophagitis.

BACKGROUND: The therapeutic effect of combined administration of prokinetics and histamine H2 receptor antagonists (H2RA) in gastroesophageal reflux disease is reported to be superior to that of monotherapy with H2RA alone. In addition to its acid-suppressing effect, the H2RA nizatidine also has a prokinetic action by suppressing acetylcholine esterase. The present multicenter, randomized controlled study was performed to investigate whether nizatidine is superior to famotidine, which does not suppress acetylcholine esterase activity, in maintenance therapy for erosive esophagitis. In addition, the question as to whether the grade of erosive esophagitis affects the non-recurrence rate during the maintenance therapy with H2RA was also investigated. METHODS: Seventy-two patients with endoscopically healed erosive esophagitis after 8 weeks of initial treatment with proton pump inhibitors were randomly divided into two groups. Patients in the nizatidine group were treated with 150 mg nizatidine twice a day (b.i.d.), while patients in the famotidine group were treated with 20 mg famotidine b.i.d. for 6 months. At the end of therapy, and at the time when patients complained of symptoms, endoscopic investigations were repeated to find out whether the esophagitis had recurred. RESULTS: Nizatidine produced a significantly higher non-recurrence rate than famotidine (P = 0.049 in intention-to-treat [ITT] analysis). This difference of remission rate between nizatidine and famotidine was observed mainly in grade B esophagitis (P = 0.016 in ITT analysis). CONCLUSION: Nizatidine is a more effective H2RA than famotidine in the maintenance therapy of patients with reflux esophagitis.

Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation.

Adherence of Helicobacter pylori to the gastric epithelium is believed to be an important step in the induction of active inflammation of the mucosal layer. However, structural evidence showing a quantitative relationship between the adherence of H. pylori and severity of gastric mucosal inflammation is lacking. We therefore investigated the correlations between severity of gastritis and adherence of morphologically different forms of H. pylori. Fifty-seven biopsy specimens from the gastric bodies of patients with H. pylori-induced gastritis were examined. The severity of gastritis and the adherence and structure of H. pylori were determined with the use of light and scanning electron microscopy. We also investigated the ability of H. pylori organisms with different structural features to induce interleukin-8 secretion by human gastric adenocarcinoma (AGS) cells in vitro because production of interleukin-8 is related to H. pylori-associated gastritis. Furthermore, serum pepsinogen concentrations and cytotoxin-associated protein status in relation to adherence of H. pylori to the epithelial surface were examined. The results indicated that H. pylori organisms, which adhered firmly to the epithelial surface, were consistently long, tightly coiled bacilli. Histologically, those gastric mucosa samples with H. pylori firmly attached showed severe gastritis. H. pylori bacilli of greater length induced higher levels of interleukin-8 secretion. The serum pepsinogen I/II ratio showed a significant negative correlation with the grade of H. pylori adhesion (r = -0.401, P <.01). We also noted a significant correlation between cytotoxin-associated protein status and the adherence of H. pylori (r = 0.344, P <.05). A quantitative correlation was found between adherence of H. pylori and gastric inflammation. Both adherence and the induction of inflammation were found to be related to the structure of H. pylori.

A new water instillation method for colonoscopy without sedation as performed by endoscopists-in-training.

BACKGROUND: Colonoscopy may be associated with discomfort when performed without sedation. A study was conducted to determine whether instillation of water into the colon at the beginning of the procedure reduces intubation time as well as patient discomfort and pain. METHODS: Colonoscopy was performed in 259 patients by 3 endoscopists-in-training with limited experience. Patients were randomly allocated to 2 groups. In one, a technique was used in which 500 to 1000 mL of water is instilled into the colon by enema at the beginning of the procedure (instillation group, n = 130). In the other, patients underwent a conventional colonoscopy (control group, n = 129). Intubation time was measured and compared between the groups, and subjective discomfort experienced by the patients was measured upon completion of the examination. RESULTS: Success rates for insertion to the cecum were similar, (95.4%, instillation group; 96.1%, control group). Detection rates for any colorectal diseases were not different between the groups (30.0% vs. 32.6%). Mean time to cecal intubation was 10.5 minutes in the instillation group and 16.2 minutes in the control group (p < 0.0001). The proportion of patients who complained of abdominal pain during the procedure was 17.1% in the instillation group and 33.3% in the control group (p < 0.001). CONCLUSIONS: When used by endoscopists-in-training, the water-instillation colonoscopy technique was associated with less discomfort and faster cecal intubation with no decrease in the rate of detection of colorectal diseases.

Symptom relief in patients with reflux esophagitis: comparative study of omeprazole, lansoprazole, and rabeprazole.

BACKGROUND AND AIM: Rabeprazole has a faster onset of antisecretory activity than omeprazole and lansoprazole. The aim of the present study was to clarify whether there is any difference in the speed of symptom relief in patients with reflux esophagitis following the administration of these three proton pump inhibitors (PPI). METHODS: Eighty-five patients with erosive reflux esophagitis were randomized to receive 8 weeks of 20 mg of omeprazole (n = 30), 30 mg of lansoprazole (n = 25), or 20 mg of rabeprazole (n = 30) once a morning. Daily changes in heartburn and acid reflux symptoms in the first 7 days of administration were assessed using a six-point scale (0: none, 1: mild, 2: mild-moderate, 3: moderate, 4: moderate-severe, 5: severe). RESULTS: The mean heartburn score in patients administered rabeprazole decreased more rapidly than those given the other PPI. Complete heartburn remission also occurred more rapidly in patients administered rabeprazole (compared with omeprazole: P = 0.035, compared with lansoprazole: P = 0.038 by log-rank test). No differences were seen in the rate of endoscopic healing of reflux esophagitis at 8 weeks between the three treatment regimens. CONCLUSION: Rabeprazole may be more effective than omeprazole and lansoprazole for the rapid relief of heartburn symptoms in patients with reflux esophagitis.