Role of VEGF and therapeutic strategy in Kawasaki disease
Project/Area Number |
14570725
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Chiba University |
Principal Investigator |
TERAI Masaru Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (80207472)
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Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Masaki Chiba University, University Hospital, Lecturer, 医学部附属病院, 講師 (50322764)
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Project Period (FY) |
2002 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
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Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Kawasaki disease / VEGF / gamma globulin |
Research Abstract |
Increased microvascular permeability is an initial step of Kawasaki disease (KD). We reported that vascular endothelial growth factor (VEGF) might play a role in the vascular leakage of KD. In fatal KD, plasma leakage was extensively documented at VEGF-positive microvessels. Increases in vascular leakage cause hypoalbuminemia and noncardiogenic edema. Then, we compared 76 patients who became afebrile within 5 days after starting intravenous gamma globulin (IVGG-responsive) with 27 patients who did not respond (IVGG-resistant). After IVGG, VEGF levels increased (P<0.0001) and albumin levels decreased (P<0.00001) in both groups. However, the IVGG-resistant group had higher VEGF levels (P=0.029) and severe hypoalbuminemia (P<0.00001) compared with the IVGG-responsive group. In addition, body weight gain after IVGG was documented in patients who subsequently developed coronary aneurysms (P=0.003) of IVGG resistant patients. These results suggest that vascular leakage may be a key feature of KD pathaphysiology.). Then, we studied the effects of a new regimen consisting of IVGG combined with dexamethasone (DEX) on clinical outcome and serum levels of VEGF in the initial treatment of KD. The control group consisted of 46 KD patients retrospectively treated earlier with 2 g/kg IVGG over 4 to 5 days plus higher dose acetylsalicylic acid (CONTROL). No serious adverse effect was noted in either group. Post-treatment C-reactive protein in the DEX group was lower than that in the CONTROL group (P=0.033). In addition, the mean duration of fever after the first IVGG infusion was 2.2 days in the DEX group and 2.8 days in the CONTROL group (P=0.015 Although this regimen did not affect coronary outcome, IVGG therapy combined with dexamethasone for the initial treatment of Kawasaki disease was safe and accelerated the resolution of systemic inflammation.
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Report
(3 results)
Research Products
(6 results)
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[Publications] Jibiki T, Terai M, Kurosaki T, Nakajima, H, Suzuki K, Inomata H, Terashima I, Honda T, Yasukawa K, Hamada H, Kohno, Y.: "Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease."Eur J Pediatr.
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