Mariko Hojo

Pooled Analysis on the Efficacy of the Second-line Treatment Regimens for Helicobacter pylori Infection

Background: Although many of the currently available Helicobacter pylori eradication regimens fail to cure 5%-12% of patients, an optimal re-treatment therapy for eradication-failure patients has still not been established. The aim of this study was to examine all reports concerning the efficacy of re-eradication regimens for H. pylori infection, and to establish optimal re-eradication regimens. Methods: Studies concerning re-eradication regimens were retrieved from the MEDLINE database, reference lists and major congress abstract lists up through December 1999. Data from all selected reports were pooled into several groups depending on second-line or initial therapies. Pooled eradication rates of re-treatment regimens were compared using Fishers exact test (P < 0.05). Results: Sixteen articles and 24 abstracts with 75 total treatment arms were included in this study. Pooled re-eradication rates by proton-pump inhibitor (PPI)-based dual therapy, PPI-based triple therapy, ranitidine bismuth-based triple therapy and quadruple therapy were 45.8%, 69.8%, 80.2% and 75.8%, respectively. Eradication rates from studies with two new antimicobials added were higher than rates from studies with only one new antimicrobial added (P = 0.0064). Conclusion: Ranitidine bismuth-based triple therapies, as well as quadruple therapies, seem to be the most effective re-treatment therapies in all currently undertaken therapies. The strategy of adding two new antimicrobials to previous regimens was also effective in re-eradication therapy.

Treatment of functional dyspepsia with antianxiety or antidepressive agents : systematic review

BackgroundThe pathophysiology of functional dyspepsia (FD) has not been elucidated precisely; accordingly, effective management of FD has not yet been found. Until now, treatment with antianxiety or antidepressive agents has been empirically applied; however, the efficacy of these treatments has not been established. We carried out this study to estimate the efficacy of these treatment approaches by systematically reviewing the literature concerning trials with agents that are efficacious against anxiety, neurosis, or depression.MethodsArticles were searched from the MEDLINE database up to October 2003, using the terms, “antianxiety agents”, “antidepressants”, and “dyspepsia”, and from reference lists of published articles. Finally, studies in which the effectiveness of drugs was clearly stated were selected from the retrieved articles.ResultsThirteen articles, on 1717 patients, were selected from among 90 articles retrieved through our literature search. In 11 of the 13 studies, dyspeptic symptoms were improved significantly by treatment. Statistical analysis of 4 trials showed a significant benefit of treatment with antianxiety or antidepressive agents (pooled relative risk, 0.55; 95% confidence interval [CI], 0.36–0.85), although funnel plots were asymmetric.ConclusionsAntianxiety or antidepressive agents may be effective in the treatment of FD patients, though further clinical trials are necessary.

Oesophageal hypersensitivity in Japanese patients with non‐erosive gastro‐oesophageal reflux diseases

Background : Visceral hypersensitivity plays a major role in the pathogenesis of non‐erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients.

Metabolic syndrome and gastrointestinal diseases

Metabolic syndrome is a cluster of metabolic abnormalities consisting essentially of obesity, especially abdominal obesity. Metabolic syndrome has been highlighted as a risk factor for cardiovascular and other chronic diseases. Obesity has been implicated in various gastrointestinal diseases such as gastroesophageal reflux diseases and colorectal cancer. Recently, abdominal obesity has been shown to be more important than obesity as expressed by an elevated body mass index as a causative factor for the development of these diseases. In addition to the mechanical effects of obesity, such as an increase in intra-abdominal pressure from large amounts of adipose tissue, substances that adipose tissues secrete, such as tumor necrosis factor-α, interleukin-6, leptin, and insulin-like growth factor-1, have been proposed to be pathogenic links to these diseases. In this review, we discuss the association of metabolic syndrome or the individual components of metabolic syndrome, focusing on obesity and abdominal obesity, with gastrointestinal diseases.

Efficacy of the 5-HT1A Agonist Tandospirone Citrate in Improving Symptoms of Patients With Functional Dyspepsia: A Randomized Controlled Trial

OBJECTIVES:Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD.METHODS:In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals.RESULTS:Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms.CONCLUSIONS:Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.

Alteration of histological gastritis after cure of Helicobacter pylori infection

Background : It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection.

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

Objective. It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. Material and methods. Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3–5 months and 12–14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. Results. The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3–5 and 12–14 months after the end of treatment compared with those in the control group (p=0.001–0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002–0.049). No serious drug-related toxicity was observed during the trial. Conclusions. The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease

Goals To investigate the features of nonerosive reflux disease (NERD). Background NERD is not considered as a milder form of erosive gastro-esophageal reflux disease (eGERD). Although the prevalence of NERD was reported to be high in our country, there have been very few studies about NERD. Study We performed upper gastrointestinal endoscopy to confirm the diagnosis of GERD. The modified acid perfusion test and saline perfusion test were performed in 7 control subjects, 14 NERD, and 11 eGERD patients. The stimulus-response function to acid and saline was quantified by the duration of typical symptom perception (minutes), total sensory intensity rating (0 to 10), and the perfusion sensory score (SS), which was defined as the product of minutes and the sensory intensity rating. Results The mean value of SS by saline was 0 in control subjects, 12.0 in NERD patients, and 1.5 in eGERD patients (P<0.01 control vs. NERD, P<0.01 NERD vs. eGERD). The mean SS with acid was 0.9 in control subjects, 52.5 in NERD patients, and 23.0 in eGERD patients (P<0.01 control vs. NERD, control vs. eGERD, P<0.05 NERD vs. eGERD). A statistically significant association was shown between the acid and saline perfusion SSs with a correlation coefficient value of r=0.57 in the NERD group (P<0.05). Conclusions Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BackgroundThe esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis.MethodsChronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats.ResultsIn the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers.ConclusionsThe localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

Strategy for retreatment of therapeutic failure of eradication of Helicobacter pylori infection

A proton pump inhibitor (PPI)‐based triple therapy consisting of a PPI, amoxicillin (A) and clarithromycin (C) or metronidazole (M) provides an eradication rate ranging from 80 to 90%. However, there have been few controlled studies with regard to the most effective regimen to re‐treat patients after failure of the first‐line therapy. Accordingly, we retrospectively reviewed our experiences and compared regimens with different combinations of antimicrobials to determine the optimal retreatment regimen.