The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Hiroshi Shionoya - One of the best experts on this subject based on the ideXlab platform.
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Supplemental treatment of rheumatoid arthritis with natural milk antibodies against enteromicrobes and their toxins: results of an open-labelled pilot study
Nutrition Journal, 2011Co-Authors: Kou Katayama, Takeo Matsuno, Takaki Waritani, Kuniaki Terato, Hiroshi ShionoyaAbstract:Background Environmental factors, particularly commensal bacteria in the gastrointestinal tract, may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to evaluate whether natural milk antibodies against a wide spectrum of pathogenic enteromicobes and their toxins modify the disease activity in RA. Methods Twenty patients with RA, whose disease activity was uncontrolled by authentic medications due to drug resistance, complications and/or risk factors were treated for 3 months with an oral administration of a whey protein concentrate (WPC) containing high levels of natural milk antibodies. Eighteen background-matched RA patients, not supplemented with milk antibody adjunct, were used as controls. Results Statistically significant reduction of arthritis symptoms and improvement of intestinal disorders were observed only in the test group: effective in 8 (44%), possibly effective in 2 (12%) and not effective in 8 (44%) of 18 patients treated (2 patients withdrew) based on an ad hoc "Evaluation Point", the sum of variables that are improved more than 20% among the 8 core variables used for the American College of Rheumatology (ACR) response criteria. This disease modifying effect of the WPC disappeared upon cessation of treatment, but was reappeared upon reintroduction of it. Importantly, 7 of 8 non-responders carry DR15 haplotype (DRB1-1501 and 1502), whereas only 1 of 7 responders was DR15 positive (risk ratio: 6.1). Furthermore, the pre-clinical serum anti-LPS and anti-type II collagen antibody levels in the responders were higher or tended to be higher than those in the non-responders, suggesting that there are 2 sub-types of RA based on an interaction between gastrointestinal pathogens and MHC class II haplotypes. Conclusions The natural milk antibody preparation containing high levels antibodies against pathogenic enteromicrobes and their toxins seems to be effective in a certain RA subset, and deserves more attention as a potential adjunct in the treatment of RA. Trial Registration Number UMIN000003128
Shin Fukudo - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the irritable bowel syndrome severity index in Japanese male patients with irritable bowel syndrome with diarrhea
BioPsychoSocial Medicine, 2017Co-Authors: Akito Nishida, Hiraku Akiho, Yoshihiro Nakashima, Kei Matsueda, Shin FukudoAbstract:Background Previous studies have indicated that ramosetron, a 5-hydroxytryptamine-3 receptor antagonist, achieves global improvement in irritable bowel syndrome (IBS) symptoms in male patients with IBS with diarrhea (IBS-D). However, in addition to global assessment it was deemed important to assess “clinically meaningful improvements, focusing on the patient’s chief complaint and the severity of major IBS symptoms”. We performed a randomized, placebo-controlled, phase IV pilot study to explore and examine efficacy variables that allow such Evaluation of ramosetron in male patients with IBS-D. Methods We performed a prospective study of 115 male outpatients with IBS-D (according to the Rome III criteria), from June 2009 to December 2009 at 25 centers in Japan. After a one-week baseline period, subjects received either 5 μg of ramosetron ( n = 47) or placebo ( n = 51) once daily for 12 weeks. To evaluate “clinically meaningful improvements focusing on the severity of major IBS symptoms,” the Japanese version of the IBS severity index (IBSSI-J) was used. Results Change in IBSSI-J overall score from baseline was −133.5 ± 110.72 in the ramosetron 5 μg group and −108.2 ± 94.44 in the placebo group ( P = 0.228) at the last Evaluation Point. Differences in responder rates for at least a 50% reduction from baseline in IBSSI-J between the ramosetron 5 μg group and the placebo group were over 10%, except Month 1. The monthly responder rate for global assessment of relief of overall IBS symptoms in the ramosetron 5 μg group showed a statistically significant improvement compared to placebo at the second month (44.4% vs 18.4%, P = 0.012). The proportion of patients who had a ≥ 50% reduction in IBSSI-J overall score was 24/37 (64.9%) in the responder group on global assessment and 18/54 (33.3%) in the non-responder group at Week 12. Conclusions Further examination will be needed before IBSSI-J can be used in clinical trials of agents for IBS-D. However, this study revealed that response on global assessment was correlated with improvement in the IBSSI-J, suggesting that global assessment reflects improvement of the symptom severity of patients with IBS-D. (Clinicaltrials.gov ID: NCT00918411 Registered 9 June 2009).
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Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study
Journal of Gastroenterology, 2016Co-Authors: Shin Fukudo, Hiraku Akiho, Yoshihiro Nakashima, Yoshikazu Kinoshita, Toshikatsu Okumura, Kenta Hayashi, Ken HarumaAbstract:Background The long-term safety of administration of ramosetron in female patients with irritable bowel syndrome with diarrhea (IBS-D) is unknown. The aim of this study was to assess the long-term safety, tolerability, and outcomes with the use of ramosetron in female patients with IBS-D. Methods This was a phase III, open-label, uncontrolled, long-term safety trial of the treatment of female Japanese patients with IBS-D, diagnosed according to the Rome III criteria. A total of 151 patients were given 2.5 μg of ramosetron for 4 weeks, and responders continued the same dose for another 48 weeks. Non-responders at 4 weeks were given 5 μg of ramosetron for 48 weeks. At the end of week 52, 106 patients receiving 2.5 μg and 17 patients receiving 5 μg had completed the study. Safety and efficacy including symptoms and quality of life (QOL) were evaluated. Results Concerning safety, no serious adverse event related to ramosetron, specifically ischemic colitis, was observed in patients with either dose of ramosetron. However, constipation occurred in 19.7 % of patients given 2.5 μg and 10.5 % of patients given 5 μg of ramosetron. Ramosetron-treated patients showed high rates of global improvement. Stool consistency, abdominal pain and discomfort, and IBS-QOL were also improved at the last Evaluation Point. Conclusions The results provide evidence of the long-term safety and efficacy of treatment with 2.5 and 5 μg of ramosetron in female patients with IBS-D. Clinicians should be aware that one-fifth of women with IBS-D receiving ramosetron may suffer from constipation during treatment (ClinicalTrials.gov ID: NCT01736423).
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Ramosetron Reduces Symptoms of Irritable Bowel Syndrome With Diarrhea and Improves Quality of Life in Women
Gastroenterology, 2015Co-Authors: Shin Fukudo, Hiraku Akiho, Akito Nishida, Yoshihiro Nakashima, Yoshikazu Kinoshita, Toshikatsu Okumura, Ken HarumaAbstract:Background & Aims Previous studies have indicated that serotonin-3–receptor antagonists might have a sex-specific effect in patients with irritable bowel syndrome with diarrhea (IBS-D). Alosetron has been approved for the treatment of only women, and ramosetron has been approved for the treatment for only men. We performed a randomized, placebo-controlled, phase 3 study to determine whether ramosetron reduces symptoms of IBS-D in women. Methods We performed a prospective study of 576 female outpatients with IBS-D (according to the Rome III criteria), from February 2013 through February 2014, at 70 academic Gastroenterology Departments in Japan. After a 1-week baseline period, subjects received either 2.5 μg ramosetron (n = 292) or placebo (n = 284) once daily for 12 weeks. Primary end Points were the monthly rates of response for relief from overall IBS symptoms and increased stool consistency at the last Evaluation Point. Quality of life (QOL) also was quantified. Results A significantly higher proportion of patients given ramosetron reported global improvement (50.7%; 95% confidence interval [CI], 44.8–56.6) than patients given placebo (32.0%; 95% CI, 26.7–37.8)—a difference of 18.6% (95% CI, 10.7–26.5; P P P = .001) and greater improvement in QOL ( P = .002) compared with placebo. Ramosetron induced constipation in 11.0% of patients. Conclusions In a randomized, placebo-controlled study of 576 women with IBS-D, 2.5 μg ramosetron per day reduced symptoms and increased stool consistency and QOL. Clinicaltrials.gov no: NCT01870895.
Kou Katayama - One of the best experts on this subject based on the ideXlab platform.
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Supplemental treatment of rheumatoid arthritis with natural milk antibodies against enteromicrobes and their toxins: results of an open-labelled pilot study
Nutrition Journal, 2011Co-Authors: Kou Katayama, Takeo Matsuno, Takaki Waritani, Kuniaki Terato, Hiroshi ShionoyaAbstract:Background Environmental factors, particularly commensal bacteria in the gastrointestinal tract, may be involved in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to evaluate whether natural milk antibodies against a wide spectrum of pathogenic enteromicobes and their toxins modify the disease activity in RA. Methods Twenty patients with RA, whose disease activity was uncontrolled by authentic medications due to drug resistance, complications and/or risk factors were treated for 3 months with an oral administration of a whey protein concentrate (WPC) containing high levels of natural milk antibodies. Eighteen background-matched RA patients, not supplemented with milk antibody adjunct, were used as controls. Results Statistically significant reduction of arthritis symptoms and improvement of intestinal disorders were observed only in the test group: effective in 8 (44%), possibly effective in 2 (12%) and not effective in 8 (44%) of 18 patients treated (2 patients withdrew) based on an ad hoc "Evaluation Point", the sum of variables that are improved more than 20% among the 8 core variables used for the American College of Rheumatology (ACR) response criteria. This disease modifying effect of the WPC disappeared upon cessation of treatment, but was reappeared upon reintroduction of it. Importantly, 7 of 8 non-responders carry DR15 haplotype (DRB1-1501 and 1502), whereas only 1 of 7 responders was DR15 positive (risk ratio: 6.1). Furthermore, the pre-clinical serum anti-LPS and anti-type II collagen antibody levels in the responders were higher or tended to be higher than those in the non-responders, suggesting that there are 2 sub-types of RA based on an interaction between gastrointestinal pathogens and MHC class II haplotypes. Conclusions The natural milk antibody preparation containing high levels antibodies against pathogenic enteromicrobes and their toxins seems to be effective in a certain RA subset, and deserves more attention as a potential adjunct in the treatment of RA. Trial Registration Number UMIN000003128
Ken Haruma - One of the best experts on this subject based on the ideXlab platform.
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Effect of ramosetron in female patients with irritable bowel syndrome with diarrhea: a phase III long-term study
Journal of Gastroenterology, 2016Co-Authors: Shin Fukudo, Hiraku Akiho, Yoshihiro Nakashima, Yoshikazu Kinoshita, Toshikatsu Okumura, Kenta Hayashi, Ken HarumaAbstract:Background The long-term safety of administration of ramosetron in female patients with irritable bowel syndrome with diarrhea (IBS-D) is unknown. The aim of this study was to assess the long-term safety, tolerability, and outcomes with the use of ramosetron in female patients with IBS-D. Methods This was a phase III, open-label, uncontrolled, long-term safety trial of the treatment of female Japanese patients with IBS-D, diagnosed according to the Rome III criteria. A total of 151 patients were given 2.5 μg of ramosetron for 4 weeks, and responders continued the same dose for another 48 weeks. Non-responders at 4 weeks were given 5 μg of ramosetron for 48 weeks. At the end of week 52, 106 patients receiving 2.5 μg and 17 patients receiving 5 μg had completed the study. Safety and efficacy including symptoms and quality of life (QOL) were evaluated. Results Concerning safety, no serious adverse event related to ramosetron, specifically ischemic colitis, was observed in patients with either dose of ramosetron. However, constipation occurred in 19.7 % of patients given 2.5 μg and 10.5 % of patients given 5 μg of ramosetron. Ramosetron-treated patients showed high rates of global improvement. Stool consistency, abdominal pain and discomfort, and IBS-QOL were also improved at the last Evaluation Point. Conclusions The results provide evidence of the long-term safety and efficacy of treatment with 2.5 and 5 μg of ramosetron in female patients with IBS-D. Clinicians should be aware that one-fifth of women with IBS-D receiving ramosetron may suffer from constipation during treatment (ClinicalTrials.gov ID: NCT01736423).
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Ramosetron Reduces Symptoms of Irritable Bowel Syndrome With Diarrhea and Improves Quality of Life in Women
Gastroenterology, 2015Co-Authors: Shin Fukudo, Hiraku Akiho, Akito Nishida, Yoshihiro Nakashima, Yoshikazu Kinoshita, Toshikatsu Okumura, Ken HarumaAbstract:Background & Aims Previous studies have indicated that serotonin-3–receptor antagonists might have a sex-specific effect in patients with irritable bowel syndrome with diarrhea (IBS-D). Alosetron has been approved for the treatment of only women, and ramosetron has been approved for the treatment for only men. We performed a randomized, placebo-controlled, phase 3 study to determine whether ramosetron reduces symptoms of IBS-D in women. Methods We performed a prospective study of 576 female outpatients with IBS-D (according to the Rome III criteria), from February 2013 through February 2014, at 70 academic Gastroenterology Departments in Japan. After a 1-week baseline period, subjects received either 2.5 μg ramosetron (n = 292) or placebo (n = 284) once daily for 12 weeks. Primary end Points were the monthly rates of response for relief from overall IBS symptoms and increased stool consistency at the last Evaluation Point. Quality of life (QOL) also was quantified. Results A significantly higher proportion of patients given ramosetron reported global improvement (50.7%; 95% confidence interval [CI], 44.8–56.6) than patients given placebo (32.0%; 95% CI, 26.7–37.8)—a difference of 18.6% (95% CI, 10.7–26.5; P P P = .001) and greater improvement in QOL ( P = .002) compared with placebo. Ramosetron induced constipation in 11.0% of patients. Conclusions In a randomized, placebo-controlled study of 576 women with IBS-D, 2.5 μg ramosetron per day reduced symptoms and increased stool consistency and QOL. Clinicaltrials.gov no: NCT01870895.
Mark J Ratain - One of the best experts on this subject based on the ideXlab platform.
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successful implementation of the randomized discontinuation trial design an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma calgb 69901
Journal of Clinical Oncology, 2005Co-Authors: Walter M Stadler, Gary L Rosner, Eric J Small, Donna Hollis, Brian I Rini, Donald S Zaentz, John Mahoney, Mark J RatainAbstract:Purpose To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design. Patients and Methods Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week Evaluation Point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end Point was the stable disease rate in the randomized groups. Results A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatenin...
