| Project/Area Number |
16390514
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Chiba University |
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Principal Investigator |
ODA Shigeto Chiba University, Graduate School of Medicine, professor, 大学院・医学研究院, 教授 (90204205)
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| Co-Investigator(Kenkyū-buntansha) |
HIRASAWA Hiroyuki Chiba University, School of Medicine, Professor Emeritus, 名誉教授 (80114320)
SADAHIRO Tomohito Chiba University, School of Medicine, Assitant Professo, 医学部附属病院, 講師 (00436437)
NAKAMURA Masataka Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 医員 (30315436)
MORITA Yasumasa Chiba University, School of Medicine, Research Associate, 医学部附属病院, 医員 (20400971)
OSHIMA Taku Chiba University, School of Medicine, Research Associate (50375789)
志賀 英敏 千葉大学, 医学部附属病院, 講師 (20282478)
松田 兼一 千葉大学, 医学部附属病院, 講師 (60282480)
渡辺 圭祐 千葉大学, 医学部附属病院, 助手 (10375800)
渡邉 栄三 千葉大学, 医学部附属病院, 助手 (40375639)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | genetic polymorphism / cytokine / hypercytokinemia / septic multiple organ failure / genetic high resk / cytokine adsorbing column / tailor-made therapy / 多臓器不全 / サイトカイン吸着 / 個別化診療 / 血液浄化法 |
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| Research Abstract |
This study was conducted to establish a novel tailor-made therapy for prevention of septic multiple organ failure (MOF) with anti-cytokine strategy, such as an cytokine adsorbing column, based on the screening of genetically high risk patients of hypercytokinemia using an genetic analysis of cytokine-related genes. To identify the highly related genetic polymorphisms with hypercytokinemia, various reported genetic polymorphisms were analyzed in patients with hypercytokinemia in relation to their clinical course and outcome. Among genetic polymorphisms tested, TNF α-308G/A, IL-1β-511T/A, IL-1ra VNTR polymorphisms were identified to be highly related with uncontrolled hypercytokinemia and poor outcome. We established the screening system to analyze these polymorphisms using real-time PCR in the laboratory within 4-6 hours. To develop a more effective cytokine modulator than PMMA-CHDF, the phase II clinical trial of a newly developed cytokine adsorbing column, CYT-860, in patients with persistent and severe hypercytokinemia was conducted and has been completed. CYT-860-DHP showed significant reduction in cytokine blood levels and resulted in improvement of P/F ratio. Four of 7 enrolled patients were survived and no adverse effect was observed. Further study is needed for clinical approval of this device. As the realistic approach of more potent cytokine modulation, double PMMA-CHDF, in which 2 series of PMMA-CHDF was simultaneously performed, and PMMA-CHDF using a large sized PMMA dialyzer, in which membrane area is double of conventional hemofilter, were evaluated and their efficacy was confirmed clinically. Therefore, we conducted a prospective study to treat patients with hypercytokinemia based on the genetic analysis of cytokine related genes. This tailor-made therapy for hypercytokinemia based on genetic analysis of cytokine-related gene polymorphism has been approved by institute's ethics committee and now on going in our ICU.
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