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Publications (7)15.86 Total impact

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    ABSTRACT: Background: Epidemiology and clinical management of acute venous thromboembolism (VTE) are not readily available in Japan. Methods and Results: The Japan VTE Treatment Registry (JAVA) is a multicenter cohort study of consecutive patients with an objectively confirmed, symptomatic acute pulmonary embolism (PE), symptomatic acute deep vein thrombosis (DVT), or asymptomatic acute proximal DVT. Of the 1,076 patients enrolled with acute VTE, 68.7% presented with an isolated DVT; 17.0% had PE alone; and 14.4% had both. VTE management was characterized by a high rate of inferior vena cava filter insertion (40.6%), frequent thrombolysis (21.1%), and sub-therapeutic unfractionated heparin-based anticoagulation, followed by warfarin prescription, mostly targeting an international normalized ratio of 2.0 (range, 1.5-2.5). During a mean observation period of 252.5 days, 29 recurrent cases of VTE were documented, yielding an incidence rate of 3.9 per 100 patient-years. A total of 123 patients died during the study period, corresponding to a rate of 16.6 deaths per 100 patient-years. The incidence of major bleeding was 3.2% per patient-year, including 2 fatal hemorrhages and 7 intracranial hemorrhages. Conclusions: VTE management in Japan is characterized by a highly aggressive strategy in the acute phase, in contrast to protocols that use low-level anticoagulation. The VTE recurrence rates in Japan and Western countries are similar, but mortality is higher in Japan, with significant variability depending on patient and management characteristics.
    Circulation Journal 01/2014; · 3.58 Impact Factor
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    ABSTRACT: Background: Peripheral arterial disease (PAD) has been recognized as an independent risk factor for vascular events and contributes to an adverse prognosis. Long-term administration of clopidogrel is recommended to prevent atherothrombotic events for patients with established PAD. We investigated the benefits of clopidogrel treatment in Japanese patients with PAD. Materials and Methods: COOPER (Clopidogrel for atherOthrombOtic event management in patients with PERipheral arterial disease) was a multicenter, randomized, double-blind study to evaluate the safety and efficacy of clopidogrel (75 mg/day) compared to ticlopidine (200 mg/day) in Japanese patients with PAD. The primary endpoint was the cumulative incidence of "safety events of interest" comprising clinically significant bleeding, blood disorders, hepatic dysfunction and other serious adverse events up to 12 weeks. The other safety events and vascular events were also assessed. Patients were followed up to 52 weeks. Results: A total of 431 patients with PAD were randomly assigned to receive either clopidogrel or ticlopidine. The cumulative incidences of "safety events of interest" at 12 weeks were 2.4% and 13.6% of patients who received clopidogrel and ticlopidine, respectively (adjusted hazard ratio, 0.161; 95% confidence interval, 0.062 to 0.416; p <0.0001). Bleeding and vascular events were similar in both groups. Conclusion: Clopidogrel demonstrated a favorable benefit/risk profile than ticlopidine in Japanese patients with PAD. (TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00862420).
    Annals of Vascular Diseases 01/2012; 5(3):364-75.
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    ABSTRACT: Hepatocyte growth factor is a potent angiogenic agent. This study investigated the efficacy and safety of intramuscular injection of naked plasmid DNA encoding the human hepatocyte growth factor gene in Japanese patients with Buerger's disease and critical limb ischemia. An open-label clinical study was performed at eight hospitals in Japan from May 2004 to April 2008. Ten patients were enrolled. They had Buerger's disease with ischemic ulcers, were not candidates for revascularization, and were unresponsive to conventional drug therapy. Treatment consisted of 8 injections (total dose: 4 mg) of hepatocyte growth factor plasmid, which were administered into the calf muscles and/or distal thigh muscles of the ischemic limbs under ultrasound guidance. Administration was done twice at an interval of 4 weeks. If there was no improvement after 2 doses, a 3rd dose could be administered. The response to treatment was evaluated from the reduction of ischemic ulcer size. The size of ischemic ulcers showed a decrease in 6/9 (66.7%) patients and the ulcers healed completely in 5/9 (55.6%) patients after gene therapy. Major amputation was not required. There were no deaths and no major safety concerns. Hepatocyte growth factor gene therapy is safe and effective for critical limb ischemia in patients with Buerger's disease.
    International angiology: a journal of the International Union of Angiology 04/2011; 30(2):140-9. · 1.46 Impact Factor
  • Circulation Journal 01/2011; 75(2):475-503. · 3.58 Impact Factor
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    ABSTRACT: Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.
    Gene Therapy 05/2006; 13(8):695-704. · 4.32 Impact Factor
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    ABSTRACT: An atherosclerotic abdominal aortic aneurysms (AAAA) differ from inflammatory abdominal aortic aneurysms (IAAA), which are characterized by a non specific inflammatory reaction leading to considerable aneurysmal wall thickness from the media to adventitia and retroperitoneal fibrosis in the surrounding tissue. Platelet-derived growth factor (PDGF) and its receptor have been localized to specific cell types within atherosclerotic plaques. Human connective tissue growth factor (CTGF) is a cysteine rich polypeptide that has similar structures to PDGF and has been implicated in connective tissue formation. PDGF and CTGF may play a role in the development of aneurysmal walls in both AAAA and IAAA. Using in situ hybridization technique with DIG-labeled RNA probes and immunostaining, we investigated CTGF gene expression, and expression of PDGF and its receptor protein, in human aneurysmal walls. Expression of CTGF mRNA was found on vascular smooth muscle cells (VSMC) in specimens from AAAA and IAAA. Strong CTGF expression was localized in VSMC around calcification in AAAA. In IAAA, strong expression of CTGF was observed around inflammatory cells. In the aneurysmal walls of AAAA, PDGF A and B chains were strongly stained on small vessels, and the PDGF beta receptor was also strongly stained on VSMC around calcification. In the aneurysmal wall of IAAA, weak expressions of PDGF A and B chains were observed in endothelial cells of vessel walls around the inflammatory cells, but the intensity of expression was much weaker than that on the vessel walls in AAAA. Such differences in fibrogenic cytokine expression may be involved in characteristic aneurysmal formation.
    The Journal of cardiovascular surgery 07/2005; 46(3):271-8. · 1.51 Impact Factor
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    ABSTRACT: Control of the ventricular assist device (VAD) for native heart preservation should be attempted, and the VAD could be one strategy for dealing with the shortage of donors in the future. In the application of nonpulsatile blood pumps for ventricular assistance from the ventricular apex to the aorta, bypass flow and hence the motor current of the pumps change in response to the ventricular pressure change. Utilizing these intrinsic characteristics of the continuous-flow pumps, in this study we investigated whether motor current could be used as an index for continuous monitoring of native cardiac function. In study 1, a centrifugal blood pump (CFP) VAD was installed between the apex and descending aorta of a mock circulatory loop. In this model, a baseline with a preload of 10 mmHg, afterload of 40 mmHg, and LV systolic pressure of 40 mmHg was used. The pump speed was fixed at 1300, 1500, and 1700 rpm, and LV systolic pressure was increased up to 140 mmHg by steps of 20 mmHg while the changes in LV pressure, motor current, pump flow, and aortic pressure were observed. In study 2, an in vivo experiment was performed using three sheep. A left heart bypass model was created using a centrifugal pump from the ventricular apex to the descending aorta. The LVP was varied through administration of dopamine while the changes in LV pressure, pump flow, and motor current at 1500 and 1700 rpm were observed. An excellent correlation was observed in both in vitro and in vivo studies in the relationship between motor current and LV pressure. In study 1, the correlation coefficients were 0.77, 0.92, and 0.99 for 1300, 1500, and 1700 rpm, respectively. In study 2, they were 0.88 (animal no. 1), 0.83 (animal no. 2), and 0.88 (animal no. 3) for 1500 rpm, and 0.95 (animal no. 2) and 0.93 (animal no. 3) for 1700 rpm. These results suggest that motor current amplitude monitoring could be useful as an index for the control of VAD for native heart preservation.
    Journal of Artificial Organs 4(4):269-272. · 1.41 Impact Factor