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Biomedical subjects

Masashi Kimura

Publications and source records attributed to Masashi Kimura.

At least 19 recordsLinked to original sources
PubMed2006

Volumetric intravascular ultrasound assessment of neointimal hyperplasia and nonuniform stent strut distribution in sirolimus-eluting stent restenosis.

The neointimal hyperplasia (IH) distribution pattern of in-stent restenotic lesions after sirolimus-eluting stent (SES) implantation has not been well described. We identified 48 in-stent restenotic lesions (41 patients) after SES implantation and performed volumetric intravascular ultrasound analyses. Lumen area, stent area, and IH area at the minimal lumen area site were 2.7 +/- 1.0, 5.4 +/- 1.9, and 2.7 +/- 1.4 mm(2), respectively. IH area at the minimal lumen site was larger in the group with a stent area > or =5.0 mm(2) than the group with a stent area <5.0 mm(2) (3.7 +/- 1.3 vs 1.9 +/- 0.8 mm(2), p <0.001). There were fewer visualized stent struts in lesions with a minimum stent area > or =5.0 mm(2) at the minimum lumen site compared with those with a stent area <5.0 mm(2) (0.69 +/- 0.25 vs 0.83 +/- 0.16, p = 0.04). When we compared lesions in patients with diabetes mellitus with patients without diabetes, minimum lumen areas, percent IH at minimal lumen area, percent IH, and neointima-free stent length were identical. In conclusion, (1) lesions without SES underexpansion at the minimum lumen site had more IH and greater nonuniform stent strut distribution compared with restenotic SESs that were underexpanded, and (2) the IH response did not appear to be more aggressive in patients with diabetes mellitus than in those without diabetes mellitus.

Aged↗
PubMed2006

Ruptured high flow gastric varices with an intratumoral arterioportal shunt treated with balloon-occluded retrograde transvenous obliteration during temporary balloon occlusion of a hepatic artery.

A patient presented with hematemesis due to gastric variceal bleeding with an intratumoral arterioportal shunt. Contrast-enhanced CT revealed gastric varices and hepatocellular carcinoma with tumor thrombi in the right portal vein. Angiography and angio-CT revealed a marked intratumoral arterioportal shunt accompanied with reflux into the main portal vein and gastric varices. Balloon-occluded retrograde venography from the gastro-renal shunt showed no visualization of gastric varices due to rapid blood flow through the intratumoral arterioportal shunt. The hepatic artery was temporarily occluded with a balloon catheter to reduce the blood flow through the arterioportal shunt, and then concurrent balloon-occluded retrograde transvenous obliteration (BRTO) was achieved. Vital signs stabilized immediately thereafter, and contrast-enhanced CT revealed thrombosed gastric varices. Worsening of hepatic function was not recognized. BRTO combined with temporary occlusion of the hepatic artery is a feasible interventional procedure for ruptured high flow gastric varices with an intratumoral arterioportal shunt.

Aged↗
PubMed2006

Transhepatic catheter-directed thrombolysis for portal vein thrombosis after partial splenic embolization in combination with balloon-occluded retrograde transvenous obliteration of splenorenal shunt.

A 66-year-old woman underwent partial splenic embolization (PSE) for hypersplenism with idiopathic portal hypertension (IPH). One week later, contrast-enhanced CT revealed extensive portal vein thrombosis (PVT) and dilated portosystemic shunts. The PVT was not dissolved by the intravenous administration of urokinase. The right portal vein was canulated via the percutaneous transhepatic route under ultrasonic guidance and a 4 Fr. straight catheter was advanced into the portal vein through the thrombus. Transhepatic catheter-directed thrombolysis was performed to dissolve the PVT and a splenorenal shunt was concurrently occluded to increase portal blood flow, using balloon-occluded retrograde transvenous obliteration (BRTO) technique. Subsequent contrast-enhanced CT showed good patency of the portal vein and thrombosed splenorenal shunt. Transhepatic catheter-directed thrombolysis combined with BRTO is feasible and effective for PVT with portosystemic shunts.

Aged↗
PubMed2006

Outcome after acute incomplete sirolimus-eluting stent apposition as assessed by serial intravascular ultrasound.

We investigated the fate of postprocedural incomplete stent apposition (ISA) after sirolimus-eluting stent (SES) implantation by evaluating long-term intravascular ultrasound findings in 168 consecutive patients (182 de novo lesions). Postprocedural ISA was defined as > or = 1 stent strut that was clearly separated from the vessel wall with evidence of blood speckle behind the strut without overlapping a side branch. After SES implantation, there were 61 ISA sites in 46 stents in 31 patients (23 at the proximal edge, 7 at the distal edge, and 31 within the stent body). There were no clinical, procedural, or intravascular ultrasound measurement differences between patients and lesions with versus without ISA. At follow-up, 15 acute ISA sites (25%) in 11 patients completely resolved and 40 sites (75%) in 20 patients persisted, although 32 of 46 persisting ISA sites (70%) decreased. There was a greater decrease in effective lumen area and a greater increase in peristent plaque area in the complete-resolution group than in the persistent-ISA group. No lesion developed stent thrombosis or in-stent restenosis (angiographic diameter stenosis > 50%). Six acute ISA sites were also associated with new, late acquired ISA, only 1 of which resulted in aneurysm formation. Although most ISAs after SES implantation do not resolve completely, the incidence of restenosis or thrombosis is not affected.

Acute Disease↗
PubMed2006

Intravascular ultrasound profile analysis of ruptured coronary plaques.

Angiographic studies have shown that lesions preceding nonfatal acute events are usually not hemodynamically significant. This has led to the concept that plaque ruptures occur at minimal disease sites. We used intravascular ultrasound to create a prerupture "profile" of unstable (vulnerable) plaques. We analyzed 112 ruptured plaques detected by intravascular ultrasound. Reference and lesion external elastic membrane (EEM) and lumen areas were measured to calculate prerupture estimates of plaque area, plaque burden (plaque/EEM area), eccentricity, area stenosis, and remodeling. The narrowest coefficients of variance were for lesion EEM area, maximum plaque thickness, and plaque burden, reference lumen area, and remodeling index (coefficients of variance 0.29, 0.25, 0.12, 0.29, and 0.18, respectively); conversely, there was great variability in measurements of calcification and lumen compromise (minimum lumen area and area stenosis). When using the 5 variables with the narrowest coefficient of variance, we found that 67% of ruptured plaques fit all of following 10th or 90th percentile parameters (> 14.3 mm2 lesion EEM area, > 8.1 mm2 reference lumen area, > 1.6 mm maximum lesion plaque thickness, > 0.63 lesion plaque burden, and > 0.87 remodeling index). Further, 89% of ruptured plaques fit 4 of 5 parameters and 96% fit 3 of 5 parameters. In conclusion, plaque ruptures do not occur at minimal disease sites. Rather, vulnerable (rupture-prone) plaques predictably have significant plaque accumulation and remodeling and occur in larger arteries. It is only the degree of lumen compromise that is variable and often insignificant.

Coronary Artery Disease↗
PubMed2006

Intravascular ultrasonic differences between aorto-ostial and shaft narrowing in saphenous veins used as aortocoronary bypass grafts.

Previous studies have reported differences in interventional complication rates that depend on saphenous vein graft (SVG) lesion location. However, little is known about morphologic differences between lesions in different SVG locations. We evaluated preintervention intravascular ultrasound (IVUS) images of 75 de novo SVG lesions (aorto-ostial, n = 15; shaft, n = 60) in 63 patients. IVUS data were measured at the minimal lumen area and at 2 proximal and 2 distal references. Positive remodeling was defined as a lesion site SVG area that was larger than the average of the 2 distal references. Shaft lesions more often contained soft plaque (60.0% vs 26.7%, p = 0.02). Minimal lumen areas were identical (4.5 +/- 2.9 vs 4.3 +/- 1.5 mm2, p = 0.3); however, plaque burden at the minimal lumen area was greater in shaft locations (79.3 +/- 9.4% vs 72.1 +/- 9.2%, p = 0.01). The frequency of positive remodeling in shaft versus aorto-ostial lesions was 70.2% versus 26.7% (p = 0.002). SVG shaft lesions have more soft plaque and larger plaque burdens and undergo positive remodeling more frequently than SVG aorto-ostial lesions. These IVUS differences may account for some of the location-specific differences in interventional complications.

Aged↗
PubMed2006

Clinical results of isolated reconstruction of the medial patellofemoral ligament for recurrent dislocation and subluxation of the patella.

Complications and results of medial patellofemoral ligament (MPFL) reconstruction, performed between 2000 and 2003, were studied retrospectively in 24 randomised patients (24 knees). All procedures were performed for recurrent dislocation or subluxation of the patella, using an autogenous semitendinosus tendon. Two different methods of anchoring of the transplant were compared. After a 2-year follow-up, patellar stability was found to be similar, when the transplant was sutured to the fibrous tissue and periosteum overlying the patella or when it was fixed in a bone tunnel through the patella. The majority of the patients who had undergone MPFL reconstruction have returned to their previous level of sports activities. We had two cases of patella fracture and one case of persisting patella apprehension after surgery. Further studies must determine which measures are necessary to prevent these complications.

Adolescent↗
PubMed2006

Frequency and determinants of black holes in sirolimus-eluting stent restenosis.

BACKGROUND: In-stent neointimal hyperplasia typically has a homogenous echoreflective appearance during intravascular ultrasound (IVUS) imaging. However, the neointimal hyperplasia of some brachytherapy failure lesions contains a very echolucent, dark zone that has been termed black hole. We sought to investigate the frequency and determinants of black holes (BH) after sirolimus-eluting stent (SES) implantation. METHODS: A prospective, consecutive series of 33 intrastent SES restenosis (> 50% neointimal hyperplasia with a minimal lumen area < 4.0 mm2) was studied with IVUS. Patients were divided into 2 groups: 8 patients with BH versus 25 patients without BH. RESULTS: Fifty percent of the BH cases occurred in saphenous vein graft lesions. BH tissue was noticed in 8% of all patients with in-stent restenosis. Three patients in each group had previous vascular brachytherapy failure (p = 0.1). Compared to non-BH cases, a greater proportion of BH cases occurred after SES treatment of bare-metal stent restenosis (75% vs. 32%; p = 0.035). BH cases presented earlier (89.9 +/- 34.3 vs. 161.3 +/- 78.8 days; p = 0.001) with more severe in-stent restenosis, as indicated by greater absolute and relative amounts of neointimal hyperplasia (41.3 +/- 10.0 vs. 26.9 +/- 19.5 mm3; p = 0.012, and 19.6 +/- 6.8 vs. 10.4 +/- 7.9%; p = 0.0001, respectively). CONCLUSIONS: Echolucent restenotic tissue (black hole) is more often observed in SES restenosis after treatment of saphenous vein graft lesions or treatment of bare-metal stent restenosis. It occurs earlier and is more severe than typical SES failures.

Aged↗
PubMed2005

Association of plaque characterization by intravascular ultrasound virtual histology and arterial remodeling.

Positive remodeling is more often observed in lesions of patients who have acute coronary syndromes or vulnerable (rupture-prone) plaques. However, there are few data that correlate plaque morphology, composition, and arterial remodeling in vivo. We evaluated coronary plaque characterization of lesions with positive remodeling using intravascular ultrasound (IVUS) radiofrequency data analysis. Seventy-seven nonbifurcation native coronary lesions (in 50 patients) were imaged in vivo using 30-MHz IVUS transducers. Lesions were classified into 4 plaque types, fibrous, fibrofatty, dense calcium, and necrotic core, by using processing of the radiofrequency signal validated in vitro. The remodeling index was calculated as the lesion external elastic membrane area divided by the proximal reference external elastic membrane area. Lesions were divided into 2 groups: positive remodeling (remodeling index>1.0, 26 lesions) and intermediate/negative remodeling (remodeling index<or=1.0, 51 lesions). Total plaque volume and the volume of each plaque type were averaged over the length of the lesion. Reference segment plaque compositions were similar. Mean lesion fibrofatty plaque area was significantly larger in lesions with positive remodeling than in lesions with intermediate/negative remodeling (1.2+/-0.7 vs 0.8+/-0.4 mm2, p=0.001; 26.3+/-6.6% vs 19.8+/-5.7%, p<0.001, of total plaque volume). The same results were obtained at the minimum lumen site and in the subgroup of patients who had acute coronary syndromes. Further, there was a linear relation between remodeling index and fibrofatty plaque area (r=0.26, p=0.02). In conclusion, in vivo IVUS radiofrequency data analysis demonstrates that positive remodeling occurs in lesions with more fibrofatty plaque.

Coronary Artery Disease↗
PubMed2005

Smoking, endothelial function, and Rho-kinase in humans.

OBJECTIVE: Smoking is associated with endothelial dysfunction and activated Rho-kinase in vascular smooth muscle cells (VSMCs) in humans. The purpose of this study was to elucidate the relationship between endothelial function and Rho-kinase activity in forearm VSMCs in healthy young men. METHODS AND RESULTS: We evaluated the forearm blood flow (FBF) responses to acetylcholine (ACh), fasudil, a Rho-kinase inhibitor, and sodium nitroprusside (SNP) in male smokers (n=10) and nonsmokers (n=14). FBF was measured by using a strain-gauge plethysmography. The vasodilatory effect of ACh was significantly smaller in smokers than that in nonsmokers. The vasodilatory effect of fasudil was significantly greater in smokers than that in nonsmokers. The vasodilatory effects of SNP in the 2 groups were similar. There was a significant correlation between the maximal FBF response to fasudil and that to ACh (r=-0.67; P<0.01). There was no significant correlation between the maximal FBF response to fasudil and that to SNP. The intra-arterial coinfusion of fasudil significantly increased the FBF response to ACh in smokers but not in nonsmokers. There were no significant differences between FBF response to fasudil alone and that in combination with NG-monomethyl-L-arginine in smokers and in nonsmokers. The intra-arterial coinfusion ascorbic acid did not alter the FBF response to fasudil in both groups. CONCLUSIONS: These findings suggest that smoking is involved in not only endothelial dysfunction but also activation of Rho-kinase in VSMCs in forearm circulation, and that there is a significant correlation between endothelial function and Rho-kinase activity in VSMCs.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production.

Deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO production and increases reactive oxygen species. The purpose of this study was to elucidate the effects of aging on endothelial function and to determine whether the degree of BH4 deficiency is related to aging and oxidative stress. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after co-infusion of BH4 (500 mg/min) in 37 healthy men (mean age, 41+/-18 yr; range, 19-81 yr). FBF was measured using strain-gauge plethysmograph. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) were measured as indices of oxidative stress. Both ACh and ISDN increased the FBF in a dose-dependent manner in all subjects. Co-infusion of BH4 resulted in a significant increase in ACh-induced vasodilation (from 22.3+/-6.7 to 30.1+/-7.5 mL/min/100 mL tissue, P<0.05). Aging was found to be significantly correlated with ACh-induced vasodilation (r=-0.47, P=0.006), urinary 8-OHdG (r=0.38, P=0.02), serum MDA-LDL (r=0.36, P=0.02), and the change in ACh-induced vasodilation after co-infusion of BH4 (r=0.45, P=0.007). The FBF response to ISDN did not correlate with any parameters. Infusion of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, abolished the BH4-induced enhancement of forearm vasorelaxation evoked by ACh. The increase in FBF after ISDN was not altered by BH4. These findings suggest that a deficiency of BH4 may be involved in the pathogenesis of disturbances in endothelium-dependent vasodilation related to aging through decrease in NO production and increase in oxidative stress.

Acetylcholine↗
PubMed2005

Intravascular ultrasonic assessment of stent diameters derived from manufacturer's compliance charts.

We used intravascular ultrasound (IVUS) to assess the accuracy of manufacturers' stent balloon compliance charts. Many interventional cardiologists rely on manufacturers' compliance charts to select stent size and optimize stent diameters according to inflation pressures during percutaneous procedures. We randomly selected 212 patients who had de novo coronary lesions that had been treated with a single, bare metal, > or =3.0-mm stent (Bx velocity, NIR, TETRA/PENTA, S660/S670/S7) under IVUS guidance. Cases of stent overlap and postdilatation with another balloon were excluded. Predicted stent diameters were derived from each manufacturer's compliance charts, and stent size and final maximal deployment pressures were derived from each physician's report. IVUS-measured minimum stent diameters (range 1.4 to 4.0 mm, mean 2.79 +/- 0.48) were smaller than predicted diameters (range 3.1 to 4.57 mm, mean 3.79 +/- 0.44). The ratio of IVUS to predicted diameters ranged from 44% to 97% (mean 74 +/- 10%). This finding was common to all 3 stent sizes: 74 +/- 12% for 3.0 mm, 73 +/- 9% for 3.5 mm, and 74 +/- 9% for 4.0-mm stents (p = 0.9). This finding was also common to all 4 stent manufacturers, 72 +/- 8% for Boston Scientific, 76 +/- 11% for Guidant, 73 +/- 9% for Cordis, and 74 +/- 11% for Medtronic (p = 0.13), and to different stent lengths. Only 3.8% of the stents achieved 90% of the predicted minimum stent diameters, and only 24.6% achieved 80% of the predicted minimum stent diameters. In conclusion, in human coronary arteries, minimal stent diameter measured by IVUS is significantly smaller than that predicted by in vitro compliance charts. These differences are independent of stent manufacturer, length, diameter, and deployment pressure.

Aged↗
PubMed2005

Relationship between endothelial function in the coronary and brachial arteries.

BACKGROUND: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. HYPOTHESIS: We investigated the relationship between coronary and peripheral endothelial function. METHODS: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. RESULTS: Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. CONCLUSIONS: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.

Acetylcholine↗
PubMed2005

The nicorandil-induced vasodilation in humans is inhibited by miconazole.

Nicorandil, N-(2-hydroxyethyl)-nicotinamide nitrate, exerts its vasodilatory effects by opening ATP-sensitive potassium (K-ATP) channels and by acting as the exogenous nitric oxide (NO). It is not clear, however, whether the actions of other endothelium-dependent vasodilators, such as NO, endothelium-derived hyperpolarizing factor (EDHF), and prostaglandins, contribute to nicorandil-induced vasodilation in the vasculature in humans. We evaluated forearm blood flow (FBF) response to intraarterial infusion of nicorandil alone and in the presence of glibenclamide, a K-ATP channel inhibitor, N(G)-monomethyl-L-arginine, an NO synthase inhibitor, indomethacin, a cyclooxygenase inhibitor, or miconazol, a cytochrome P-450 inhibitor, in 24 healthy male subjects. FBF was measured using strain-gauge plethysmography. Infusion of nicorandil significantly increased the FBF response in a dose-dependent manner. Intraarterial infusion of glibenclamide attenuated nicorandil-induced vasodilation (160.9 +/- 21.2% versus 90.2 +/- 19.4%, P < 0.01), and miconazole also attenuated the FBF response to nicorandil (160.9 +/- 21.2% versus 66.1 +/- 9.2%, P < 0.001). N-monomethyl-L-arginine or indomethacin did not alter the FBF response to nicorandil. These findings suggest that nicorandil causes vasodilation in forearm circulation in humans, at least in part through a pathway that is dependent on K-ATP channels and cytochrome P-450, but not on endogenous NO and prostaglandins. EDHF may contribute to nicorandil-induced vasodilation in humans.

Adult↗
PubMed2005

Adrenomedullin causes coronary vasodilation in humans: effects of inhibition of nitric oxide synthesis.

Experimental studies have shown that adrenomedullin (AM) causes vasodilation, in part, mediated by endothelium-derived nitric oxide (NO). However, it remains to be clarified how NO is involved in AM-induced coronary vasoreactivity in humans. We examined whether NO contributes to the vasodilatory effects of adrenomedullin on human coronary arteries. In 10 patients with angiographically normal coronary arteries, adrenomedullin (low dose: 1 ng/kg/min; high dose: 10 ng/kg/min) was infused into the left coronary ostium before and after an infusion of N-monomethyl-L-arginine (L-NMMA, 40 micromol/min for 5 min), an NO synthase inhibitor. Coronary diameter and coronary blood flow (CBF) were evaluated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to adrenomedullin were expressed as percent changes from baseline values. Adrenomedullin at a high dose dilated coronary arteries (3.7+/-0.5%, P<0.001). Adrenomedullin increased the coronary blood flow at both doses (low: 55.7+/-13.9%, P<0.01; high: 48.8+/-9.8%, P<0.001). After the infusion of L-NMMA, adrenomedullin-induced coronary vasodilation and increase in coronary blood flow were attenuated. These findings suggest that adrenomedullin dilates human coronary arteries through an increase in NO production, at least in part.

Adrenomedullin↗
PubMed2005

[Aurora kinases and cancer].

Aurora kinases are highly conserved in eukaryotes and involved in many processes during cell division. Three Aurora kinases have been identified in humans and designated as Aurora-A, -B, and -C. Aurora A regulates centrosome function during M phase through its interactions with various cell cycle regulators including TACC, chTOG, Ajuba, BRCA1, LATS2, and p53. Aurora-B localizes at the kinetochore from G2 to metaphase, and relocates to the midbody after anaphase. Aurora-B plays roles in spindle dynamics, chromosome condensation, and cytokinesis by interacting with many proteins such as INCENP, Survivin, CENP-A, MgcRacGAP, and intermediate filaments. Overexpression of both Aurora-A and -B proteins is frequently observed in various human cancer tissues, and a common coding region polymorphism in aurora-A affects the risk of breast or esophageal cancer. Ectopic overexpression of Aurora-A or -B protein leads to aneuploid cells. The cells overexpressing active Aurora A or wildtype Aurora-B are tumorigenic in nude mice.

Animals↗
PubMed2005

[Results of treatment of far advanced and recurrent stomach cancer with TS-1].

We used TS-1 as first-line therapy to treat 44 patients with far advanced or recurrent gastric cancer, and assessed the results and safety. One treatment cycle consisted of TS-1, 80 mg/m2/day, for 28 days followed by a 14-day rest period. The efficacy rate in the cases capable of being evaluated was 30.1% (11/36), and 25.0%, (7/28) when TS-1 was used as monotherapy. The efficacy rate was lower than in a phase II study, however, the median survival time (MST) of 10.7 months for the patients as a whole, the 1-year survival rate of 43.2%, and the 2-year survival rate of 20.5% were favorable. There were many NC cases in which long-term therapy was possible, and they contributed to the long-term survival. The incidence of adverse events was 84.1%, but the incidence of grade 3 or more events was low at 13.6%. Since TS-1 is highly efficacious and safe, as well as convenient because of being an oral preparation, it appears that it can be ranked as the drug of first choice for chemotherapy of far advanced or recurrent gastric cancer.

Adult↗