Effect of different proton pump inhibitors, differences in CYP2C19 genotype and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin and clarithromycin.

AIM: To investigate the effect of different proton pump inhibitors, S-mephenytoin 4'-hydroxylase (CYP2C19) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori. METHODS: One hundred and eighty-seven H. pylori-infected peptic ulcer patients were randomly treated with either rabeprazole (10 mg b.d.) or lansoprazole (30 mg b.d.) plus amoxicillin (750 mg b.d.) and clarithromycin (400 mg b.d.) for 1 week. The antibiotic susceptibility and CYP2C19 genotype (extensive or poor metabolizer) were investigated. RESULTS: The eradication rates in the rabeprazole-amoxicillin-clarithromycin (RAC) and lansoprazole-amoxicillin-clarithromycin (LAC) groups were 75% and 69%, respectively, on an intention-to-treat basis, and 80% and 75%, respectively, on a per protocol basis. The eradication rate for clarithromycin-resistant strains was significantly lower than that for clarithromycin-sensitive strains (24% vs. 86%, P < 0.05). For clarithromycin-sensitive strains in the LAC group, there was a tendency for a lower eradication rate in extensive than poor metabolizers. The eradication rate in extensive metabolizers in the RAC group tended to be higher than that in extensive metabolizers in the LAC group (89% vs. 78%, P = 0.079726). CONCLUSIONS: The success of the 1-week proton pump inhibitor-amoxicillin-clarithromycin regimen depends on the susceptibility of H. pylori to clarithromycin. Moreover, differences in CYP2C19 genotype influence the eradication rates of lansoprazole-based therapy, and the rabeprazole-based regimen has an advantage especially in extensive metabolizers.

[Acute isoniazid poisoning presenting convulsion and liver dysfunction].

A-19-year-old girl ingested 7.4 g of Isoniazid (INH) and 14.5 g of Ethambutol (EB) intentionally. She presented repetitive generalized convulsions with metabolic acidosis, treated with diazepam and 7.5 g of Pyridoxine (Vitamin B6). During day 4 and 5, liver dysfunction worsened and prothrombin time declined below 5%. She was treated with infusion of fresh frozen plasma and fully recovered on day 13. Serum concentration of INH and EB at 5 hours after ingestion was 7.6, 0.94 micrograms/ml respectively.

Localization of recombination activating gene 1/green fluorescent protein (RAG1/GFP) expression in secondary lymphoid organs after immunization with T-dependent antigens in rag1/gfp knockin mice.

Secondary rearrangements of immunoglobulin gene segments that generate a new antibody repertoire in peripheral B cells have been described as receptor revision and occur by as yet unknown mechanisms. To determine the importance of recombination activating gene (RAG) expression in receptor revision, heterozygous rag1/green fluorescent protein (gfp) knockin mice were used to examine the location of RAG1 expression in the germinal centers (GCs) of lymphoid follicles after immunization with a variety of T-cell-dependent antigens. Immunization of rag1/gfp heterozygous mice or rag1 homozygous knockout mice reconstituted with rag1/gfp heterozygous spleen cells caused the down-regulation of RAG1/GFP signal in GCs. Although some RAG1/GFP(+) cells appeared in regions surrounding the peanut agglutinin (PNA)(+)GL-7(+) GC area, RAG1/GFP(+) cells did not accumulate in the central region. In addition, the stimulation of spleen B cells with anti-mu antibody plus interleukin-4 (IL-4) or with anti-CD40 monoclonal antibody plus IL-7 did not induce GFP signals at detectable levels in vitro. These results clearly demonstrate that RAG1 re-expression either does not occur or is at extremely low levels in antigen-driven B cells in GCs of secondary lymphoid follicles, suggesting that other mechanisms may mediate the gene rearrangements observed in receptor revision.

[Cost-effectiveness of the treatment of reflux esophagitis: proton pump inhibitor versus histamine-2-receptor antagonist].

Gastroesophageal reflux disease(GERD) is a common condition and acid-suppressing agents are the mainstays of treatment. A clinical decision analysis comparing a proton pump inhibitor(PPI), lansoprazole and a histamine H2-receptor antagonist (H2RA), ranitidine for the treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The PPI was consistently superior to the H2RA with regard to both clinical effectiveness and cost-effectiveness. Prescription of PPIs for a one-month period would further enhance the cost-effectiveness of PPI treatment. The PPI first strategy is the preferred therapeutic approach for medical treatment of reflux esophagitis. We also recommend that prescription of PPIs for a one-month period be approved by the Japanese health insurance scheme.

[The clinical evaluation of structured questionnaire for reflux esophagitis].

Reflux esophagitis is suspected on clinical grounds and confirmed by a variety of endoscopical, roentgenological and physiological investigations, which are obviously inapplicable to an epidemiological survey. Questionnaire for the diagnosis of reflux disease(QUEST) can reduce bias introduced by observer variability, is practical, inexpensive, and noninvasive. QUEST also has good sensitivity and specificity for reflux esophagitis, so it's one of the useful diagnostic tools for reflux esophagitis. It, however, needs to be modified for the diagnosis of gastroesophageal reflux disease (GERD). Questionnaires to measure Quality of Life(QOL) quantitatively can be applied to the assessment of the severity of diseases or drug efficacy, and they are useful especially for the evaluation of endoscopy-negative GERD.

[Evaluation of the efficacy and the cost-effectiveness of proton pump inhibitor-based dual and triple therapy regimens for H. pylori eradication in peptic ulcer disease].

To evaluate the efficacy and the cost-effectiveness of H. pylori eradication for the treatment of peptic ulcer disease, a randomized controlled trial to compare the efficacy of proton pump inhibitor-based dual and triple regimens was conducted. A decision analysis was also performed to assess H. pylori eradication compared to the conventional maintenance strategy. Two hundred and thirty-four peptic ulcer patients suffering from H. pylori infection were randomly treated with either omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) or with omeprazole 20 mg bid + clarithromycin 400 mg bid (OC) for 14 days. The eradication rate with OAC was 87.6% (92/105) (95% Confidence Interval (CI): 81-94%), which was significantly higher than that with OC (61.9% (60/97) (95% CI: 52-72%)) (p < 0.001, chi 2 test). Both regimens were safe and well tolerated. H. pylori eradication was more effective and less costly than conventional strategy in a long term perspective. OAC was more cost-effective than OC. In conclusion, H. pylori eradication is a cost-effective alternative to conventional treatment. We recommend 2 weeks triple regimen with omeprazole 20 mg bid + amoxicillin 500 mg qid + clarithromycin 400 mg bid (OAC) as a first-line treatment in all patients with peptic ulcers associated with H. pylori infection.

Comparison of 1-week and 2-week triple therapy with omeprazole, amoxicillin, and clarithromycin in peptic ulcer patients with Helicobacter pylori infection: results of a randomized controlled trial.

This study was a comparison of 1-week and 2-week triple therapies with omeprazole, amoxicillin, and clarithromycin (OAC) in patients with peptic ulcer disease and Helicobacter pylori infection. A total of 147 peptic ulcer patients with H. pylori infection assessed by histology and culture were randomly treated with omeprazole 20mg bid + amoxicillin 1000mg bid + clarithromycin 400mg bid for either 1 week (OAC1w) or 2 weeks (OAC2w). Both groups then received omeprazole 20mg daily for 2 weeks followed by ranitidine 300mg daily for 4 weeks. Eradication of H. pylori was assessed by histology, culture, and the 13C-urea breath test (13C-UBT) at least 6 weeks after cessation of antimicrobial therapy. Intention-to-treat eradication rates were 78.2% (95%CI 69%-87%) with OAC1w and 88.4% (95%CI 81%-96%) with OAC2w. Per-protocol eradication rates were 86.0% (95%CI 78%-94%) with OAC1w, 97.0% (95%CI 93%-100%) with OAC2w. There was no significant difference in the eradication rates between OAC1w and OAC2w. Side effects were mild and self-limiting in both groups. In conclusion, both 1- and 2-week triple therapy with OAC are well tolerated and provide good eradication rates in peptic ulcer patients in Japan. The eradication rate of the 2-week regimen was higher than that of the 1-week regimen, but the difference was not statistically significant. Further studies including long-term economic considerations are required to determine the optimal duration of treatment.

Triple therapy with omeprazole, amoxicillin and clarithromycin is effective against Helicobacter pylori infection in gastric ulcer patients as well as in duodenal ulcer patients. Results of a randomized controlled trial in Japan.

BACKGROUND/AIMS: There have been few reliable published studies permitting assessment of therapeutic regimens for Helicobacter pylori infection in gastric ulcer (GU) patients. The aim of the present study was to evaluate the efficacy of omeprazole-based dual and triple therapy regimens, both including clarithromycin, for the cure of H. pylori infection in active GU and duodenal ulcer (DU) patients. The study was conducted in Japan, a country in which GU is more prevalent than DU. METHODS: Two hundred and thirty-four consecutive peptic ulcer patients (GU: n = 124; DU: n = 103; GDU: n = 7) suffering from H. pylori infection were randomly treated with either omeprazole 20 mg b.i.d. + amoxicillin 500 mg q.i.d. + clarithromycin 400 mg b.i.d. (OAC) or with omeprazole 20 mg b.i.d. + clarithromycin 400 mg b.i.d. (OC) for 14 days. H. pylori infection was evaluated by histology and culture from antral and corpus biopsies 6 weeks after completing antimicrobial therapy. RESULTS: Follow-up data were available in 202 patients. The cure rates of H. pylori infection in GU patients were 83.9% (47/56) with OAC and 59. 2% (29/49) with OC. Corresponding rates in DU patients were 91.5% (43/47) and 70.5% (31/44), respectively. The cure rates with OAC were significantly higher than those with OC (p < 0.001, chi2 test). The cure rates in GU patients were lower than those in DU patients for both regimens, but these differences were not statistically significant. Side effects were generally mild and did not interfere with compliance. One patient in the OAC group and 2 patients in the OC group complained of severe side effects that led to therapy discontinuation. CONCLUSIONS: Triple therapy with omeprazole, amoxicillin and clarithromycin is a safe and effective regimen for the cure of H. pylori infection in GU patients as well as in DU patients. We recommend this triple regimen as a first-line treatment in all patients with peptic ulcers associated with H. pylori infection in Japan.

Economic evaluation of Helicobacter pylori eradication for the treatment of duodenal ulcer disease in Japan: a decision analysis to assess eradication strategy in comparison with a conventional strategy.

To evaluate the socio-economic effects of Helicobacter pylori eradication in the treatment of duodenal ulcer disease in Japan, a clinical decision analysis was performed to assess H. pylori eradication therapy compared with the conventional strategy of maintenance with histamine-2 receptor antagonists. A decision tree-based state transition model (Markov chain approach) implemented to simulate a 5 year period of follow up was constructed. The H. pylori eradication strategy was found to be superior to the conventional maintenance strategy with regard to clinical effectiveness and other dimensions of a patient's outcome. Furthermore, in a long-term perspective, the eradication strategy was less costly than the maintenance strategy. Helicobacter pylori eradication should be recommended as the first choice treatment of H. pylori-positive duodenal ulcer patients. The clinical implication of H. pylori eradication entails an improvement in clinical effectiveness and other dimensions of a patient's outcome and a significant reduction in the costs of duodenal ulcer treatment. The long-term total costs do not depend on the initial drug cost of an eradication regimen. Pursuing a high eradication rate of H. pylori is essential in improving the patient's outcome and the cost-effectiveness of treatment.

[Validation of the hospital anxiety and depression scale in a gastro-intestinal clinic].

This study examined the validity of the Japanese version of the hospital anxiety and depression scale (HAD) in a gastro-intestinal outpatient clinic. One hundred and twenty-three men and 142 women consulting a gastro-intestinal outpatient clinic at a primary care hospital in Kyoto during 1995 were surveyed. Item-remainder correlation and internal consistency were examined for reliability. Concurrent validities were examined using the stait-trait anxiety inventory (STAI) and Zung's self-rating depression scale (SDS). The prevalence of psychiatric disorder in this population ranged from 27% to 39%. Cronbach's coefficients were greater than 0.8 for the anxiety subscale and more than 0.7 for the depression subscale. Spearman's correlation of the anxiety subscale scores and the STAI were r = 0.678 for men, and r = 0.717 for women. The correlation of depression subscale scores and SDS were r = 0.457 for men, and r = 0.565 for women. It is suggested that the use of the HAD to general hospital outpatients clinic would facilitate detecting emotional disorders in outpatients.

Reevaluation of clinical features of ischemic colitis. Analysis of 68 consecutive cases diagnosed by early colonoscopy.

BACKGROUND: Ischemic colitis (IC) is generally considered a disease of elderly patients who have associated diseases. The aim of the present study was to reevaluate the clinical features of IC. METHODS: We retrospectively analyzed the clinical characteristics, background, and endoscopic and histologic changes in 68 consecutive patients (16 men and 52 women) with this disease diagnosed by early colonoscopy. RESULTS: The patients' age ranged from 22 to 98 years (mean, 55 years). Twenty-three patients (34%, including 19 women) were less than 50 years of age. The classical predisposing factors were not discernible in patients younger than 50. Chronic constipation and prior history of abdominal surgery were common in both young and old patients. Early colonoscopy (especially by the 3rd day from onset) showed endoscopic and histologic findings consistent with the characteristics of IC. CONCLUSIONS: IC is not limited only to the elderly, and it should be considered in the differential diagnosis of colitis with melena in younger patients, especially females, who do not have any predisposing factors. Chronic constipation and prior history of abdominal surgery were commonly associated in both young and old patients. Early colonoscopy, especially by the 3rd day from the clinical onset, is essential for the accurate diagnosis of IC.

[A preliminary study of percutaneous ethanol injection therapy for hepatocellular carcinoma: evaluation of the ethanol diffusion area by the ethanol mixed with gadolinium].

To evaluate the ethanol diffusion area after Lipoidalization in 3 patients with advanced HCC treated by Lipoidalization-PEIT combination therapy, 99.9% ethanol mixed with Gadolinium was used for PEIT (Gd-PEIT). T1-weighted MR images wear obtained 1 hr after Gd-PEIT. The area of homogeneous hyperintense change on T1-weighted MR images was taken to be the ethanol diffusion area. In all 3 patients, homogeneous hyperintensity throughout the tumor over the capsule was recognized on T1-weighted MR images after treatment. The results suggests that T1-weighted MR images after Gd-PEIT provide a valuable tool by which to directly evaluate the ethanol diffusion area for advanced HCC treated by Lipoidalization followed by PEIT.

[Measurement of gastric emptying by magnetic resonance imaging].

The purpose of the study was to establish a new method of measuring gastric emptying using MR Imaging in human. Gastric emptying was measured in 6 healthy male volunteers aged from 28 to 43 years, using MR imaging and RI. The measurements were performed after the oral administration of liquid meal containing glucose, protein and fat. The MR imaging was performed with 0.5T superconducting magnet machine, and consecutive 12 transaxial T1 weighted spin echo images (TR/TE = 300/17) of the upper abdomen were recorded every 10 minutes for more than 1 hour. Gastric emptying curves and their T1/2 values obtained by MR imaging and RI method were correlated well in 5 of 6 cases. We concluded that a non invasive and radiation free method using MR imaging was proved to be a useful tool for measuring gastric emptying.

Vein of Galen aneurysmal malformation in an adult: a case report.

We report a 19-year old woman with a choroidal-type vein of Galen aneurysmal malformation who presented with hydrocephalus. This venous malformation was fed by multiple fistulas and drained into the superior sagittal sinus through a persistent falcine sinus (precursor of the straight sinus). The hydrocephalus was treated by ventriculoperitioneal shunting, and the patient remained well for 9 years. At this time, magnetic resonance imaging (MRI) and magnetic resonance angiography demonstrated a vein of Galen aneurysmal malformation in the right thalamus, with a Chiari I appearance. This case may provide valuable data regarding the natural history of such venous malformations.

[Epidemiology of non-ulcer dyspepsia (NUD) in Japan].

The purpose of this study is to investigate the incidence of NUD in Japan and to describe the clinical presentation of NUD. The population of this study consisted of the patients initially visited to our gastroenterology clinic during the period of one year from Feb. 1990 to Jan. 1991. Out of the total population, 106 patients with dyspepsia were suspected of NUD according to the definition of AGA, and have received the endoscopy and ultrasonography to find the existence of organic disease. While 50 cases presented organic diseases (19 peptic ulcers, 16 gastritis, 7 carcinoma, 4 gall stone, 4 esophageal disease), 56 cases were with no organic diseases and were regarded as NUD. NUD was more common in younger generation and was especially so in women under 40 years old. There was no significant difference in symptoms between NUD and organic diseases. On the other hand, peptic ulcer disease was frequently associated with sever epigastralgia, and smoking habit as a external factor, while abdominal fullness was predominant feature observed in NUD.