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Articles by S Maruyama
Total Records ( 4 ) for S Maruyama
  P Li , R Shibata , S Maruyama , M Kondo , K Ohashi , N Ouchi and T. Murohara
 

Recent clinical trials demonstrated that PPAR agonist fenofibrate reduces cardiovascular events, including limb amputation in people with type 2 diabetes. Here, we investigated whether fenofibrate modulates the revascularization process in a mouse model of hindlimb ischemia. Treatment with fenofibrate led to acceleration of revascularization of ischemic hindlimb relative to the contralatereal limb in wild-type (WT) mice, as measured by laser Doppler blood flow and capillary density analyses. Treatment of WT mice with fenofibrate increased the serum levels of adiponectin, which has protective actions on the vasculature. Of importance, fenofibrate had no effects on the revascularization in ischemic limbs of adiponectin-deficient (APN-KO) mice. Fenofibrate stimulated the phosphorylation of AMPK and eNOS in the ischemic muscles in WT mice but not in APN-KO mice. AMPK inhibitor compound C suppressed fenofibrate-induced increase in limb perfusion and AMPK phosphorylation in ischemic muscle in WT mice without affecting adiponectin levels. NOS inhibitor l-NAME also blocked the increased blood flow of ischemic limbs in fenofibrate-treated WT mice. Our observations suggest that fenofibrate could promote revascularization in response to ischemia through adiponectin-dependent AMPK signaling.

  H Ishii , T Toriyama , T Aoyama , H Takahashi , T Amano , M Hayashi , M Tanaka , Y Kawamura , Y Yasuda , Y Yuzawa , S Maruyama , S Matsuo , T Matsubara and T. Murohara
 

Background— Percutaneous coronary intervention (PCI) using drug-eluting stents significantly reduces the risk of restenosis in the general population. However, in patients on hemodialysis, adverse cardiac events are frequently seen even if treated with drug-eluting stents. Recent studies suggest that C-reactive protein (CRP) reflects vascular wall inflammation and can predict adverse cardiac events. We evaluated possible prognostic values of CRP on outcomes in patients on hemodialysis undergoing PCI with drug-eluting stents.

Methods and Results— A total of 167 patients undergoing PCI with sirolimus-eluting stents for stable angina (322 lesions) were enrolled. They were divided into tertiles according to serum CRP levels. We analyzed the incidence of major adverse cardiovascular events including cardiovascular death, nonfatal myocardial infarction, and target lesion revascularization after PCI as well as quantitative coronary angiographic data. The mean follow-up was 31 months (SD, 14). Major adverse cardiac events occurred in 11 patients (19.6%) of the lowest tertile, in 22 patients (39.3%) of the middle tertile, and in 28 patients (50.9%) of the highest tertile during follow-up period (P=0.0009). There was a progressive increase in neointimal growth after sirolimus-eluting stent implantation during follow-up because preprocedural CRP levels were higher, despite similar angiographic data just after PCI. Angiographic restenosis at 6 to 8 months after PCI was seen in 10.6% in the lowest tertile, 17.9% in the middle tertile, and 32.0% in the highest tertile (P=0.0007).

Conclusions— Increased preprocedural serum CRP levels would predict higher major adverse cardiac events and restenosis rates after sirolimus-eluting stents implantation in patients on hemodialysis.

  S Yamada , H Ishii , H Takahashi , T Aoyama , Y Morita , H Kasuga , K Kimura , Y Ito , R Takahashi , T Toriyama , Y Yasuda , M Hayashi , H Kamiya , Y Yuzawa , S Maruyama , S Matsuo , T Matsubara and T. Murohara
 

Background and objectives: Cardiac failure is directly affected by left ventricular (LV) dysfunction, and particularly LV systolic dysfunction is strongly associated with survival in ESRD patients. The aim of this study was to determine the prognostic value of reduced LV ejection fraction (LVEF) measured at the time of initiation of hemodialysis (HD) in incident HD patients.

Design, setting, participants, & measurements: 1254 consecutive ESRD patients who electively started HD therapy were screened by echocardiography within 1 month after its inception. They were divided into five groups according to LVEF levels with a decrease of 0.1 each and were followed up for up to 7 years. Survival was examined with the Kaplan-Meier method and compared using the log-rank test.

Results: Among the 1254 patients, LVEF levels ≥0.6, 0.5 to 0.6, 0.4 to 0.5, 0.3 to 0.4, and <0.3 were seen in 842 (67.1%), 247 (19.7%), 107 (8.5%), 41 (3.3%), and 17 (1.4%) patients, respectively. On Kaplan-Meier analysis, 7-year event-free rates from cardiovascular death were 84.2, 83.7, 73.6, 59.4, and 30.9% in order of groups with decreasing LVEF of 0.1 each, respectively. Seven-year event-free rates from all-cause death were 69.2, 61.7, 57.1, 45.9, and 23.1% in the respective groups. Even after adjustment for other risk factors, decreasing LVEF was a strong independent predictor for cardiovascular death.

Conclusions: Reduced LVEF on starting HD therapy could stratify risk of cardiovascular and all-cause mortality in ESRD patients. Screening by echocardiography at start of HD therapy might be recommended to predict prognosis in patients with ESRD.

  N Shinohara , A Kumagai , K Kanagawa , S Maruyama , T Abe , A Sazawa and K. Nonomura
  Objective

We conducted a Phase II trial to investigate the efficacy of combined therapy with meloxicam, a cyclooxygenase-2 inhibitor and natural interferon (IFN)- in renal cell carcinoma patients with distant metastasis.

Methods

The subjects of this study were patients with untreated renal cell carcinoma who were diagnosed from the results of imaging or pathological studies and who had measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients could be enrolled in the study irrespective of whether nephrectomy had been performed. Treatment involved the subcutaneous injection of natural IFN- at 3 x 106 or 5 x 106 U three times weekly plus oral administration of meloxicam at 10 mg once daily.

Results

A total of 43 patients were enrolled in the present study, included 11 patients without nephrectomy, 23 patients with a high C-reactive protein (CRP) level and 23 patients with extrapulmonary metastasis. Four patients of complete response and 12 patients of partial response were confirmed, given an overall response rate of 37.2% (95% confidence interval, 23.0–53.3%). Stable disease for 6 months or longer was also obtained in 14 patients. The median time to progression was 14 months. Adverse events (AEs) observed were mainly flu-like symptoms due to cytokine. Although the Grade 3 or 4 AEs were fatigue, hepatic dysfunction, arthritis and gastric ulcer, all but one (gastric ulcer) were immediately improved by discontinuation of this combined therapy.

Conclusions

The combination of meloxicam and natural IFN- is considered to be an active regimen with tolerable toxicities as a first-line treatment of metastatic renal cell carcinoma.

 
 
 
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