Long Term Follow-up after Drug-eluting Stent Implantation and Early Experience with Endothelial Progenitor Cell Capture Stent

Intracoronary stent replacement is being used increasingly for the treatment of atherosclerotic coronary artery disease and has gained widespread acceptance. Although stent implantation itself has been shown to reduce restenosis compared to balloon angioplasty, in-stent restenosis still occurs in 10-40% of patients. In-stent restenosis has long been considered the main limitation hampering the long-term efficacy of coronary stenting. Restenosis after stent occurs secondary to the accumulation of smooth muscle cells and extracellular matrix which consists of proteoglycans, hyaluronan and collagen. To overcome this major limitation, drug-eluting stents were developed. Drug-eluting stents consist of a drug (immunosuppressive, antiproliferative, or anti-inflammatory drug), a polymer, and a stent platform. Several drugs with durable or erodable polymers were tested in clinical trials and showed that drug-eluting stents significantly inhibit neointimal growth compared with bare metal stents. Currently, drug-eluting stents have been widely distributed all over the world and become main-stream of percutaneous coronary intervention. However, (1) long-term efficacy and chronic vascular response after drug-eluting stents implantation in humans (Part 1 of this thesis) (2) effect of drugeluting stents for patients with high in-stent resteonsis risk factors, such as diffuse lesion, diabetes mellitus, left main coronary artery lesion, chronic total occlusion or bifurcation lesion (Part 2 of this thesis), have not been fully investigated. Furthermore, problem of stent thrombosis is still observed in drug-eluting stent era. Drug-eluting stents interferes with the natural healing response by preventing or significantly delaying the formation of a functional endothelial lining over stent. The early establishment of a functional endothelial layer after stent implantation may resolve this issue. Recently, the existence of circulating endothelial progenitor cells has been identified as a key factor for re-endothelialization. 8,9 New concept stent using immobilized antibodies targeted at endothelial progenitor cell surface antigens has been developed. (Part 3 of this thesis)

Cluster size effect on reactive sputtering by fluorine cluster impact using molecular dynamics simulation

Computer Simulation of Radiation Effects in SolidsThe mechanism of high-yield sputtering induced by reactive cluster impact was investigated using molecular dynamics (MD) simulations. Various sizes of fluorine clusters were radiated on clean silicon surface. At an incident energy of 1 eV/atom, F atom and F2 molecule are only adsorbed on the surface and sputtering of Si atom does not occur. However, fluorine cluster, which consists of more than several tens molecules causes sputtering. In this case, most of Si atoms are sputtered as fluorinated material such as SiFx. This effect is due to the fact that cluster impact induces high-density particle and energy deposition, which enhances both formation of precursors and desorption of etching products. The deposition of atoms and energy becomes denser as the incident cluster size increases, so that larger clusters have shown higher sputtering yield.Articl

Evaluation of Four-Year Coronary Artery Response After Sirolimus-Eluting Stent Implantation Using Serial Quantitative Intravascular Ultrasound and Computer-Assisted Grayscale Value Analysis for Plaque Composition in Event-Free Patients

ObjectivesThis study sought to evaluate the long-term arterial response after sirolimus-eluting stent implantation.BackgroundSirolimus-eluting stents are effective in inhibiting neointimal hyperplasia without affecting plaque volume behind the stent struts at six months.MethodsSerial quantitative intravascular ultrasound and computer-assisted grayscale value analysis over four years were performed in 23 event-free patients treated with sirolimus-eluting stents.ResultsIn the first two years, the mean plaque volume (155.5 ± 42.8 mm3post-procedure and 156.8 ± 57.7 mm3at two years, p = 0.86) and plaque compositional change expressed as mean percent hypoechogenic tissue of the plaque behind the stent struts (78.9 ± 8.6% post-procedure and 78.2 ± 8.9% at two years, p = 0.67) did not significantly change. However, significant plaque shrinking (change in plaque volume = −18.4 mm3, p = 0.02) with an increase in plaque echogenicity (change in percent hypoechogenic tissue = −7.8%, p < 0.0001) was observed between two and four years. The mean neointimal volume increased over four years from 0 to 8.4 ± 5.8 mm3(p < 0.0001). However, no further statistically significant change occurred between two and four years (7.0 ± 6.7 mm3vs. 8.4 ± 5.8 mm3, p = 0.25).ConclusionsBetween two and four years after sirolimus-eluting stent implantation, peri-stent tissue shrank with a concomitant increase in echogenicity. These intravascular ultrasound findings suggest that late chronic artery responses may evolve for up to four years after sirolimus-eluting stent implantation. In addition, the fact that the neointima does not significantly change from two to four years may suggest that the biological phenomenon of a delayed healing response has begun to subside

Effect of olmesartan on the levels of circulating endothelial progenitor cell after drug-eluting stent implantation in patients receiving statin therapy

AbstractBackgroundThe endothelial progenitor cell (EPC) plays an important role in repairing vascular injury. Statins and angiotensin II receptor blockers increase the level of circulating EPCs. However, it is unknown whether the angiotensin II receptor blocker olmesartan synergistically acts with statins to increase the levels of circulating EPCs. Moreover, the association between the levels of circulating EPCs and endothelial dysfunction after implantation of drug-eluting stents (DESs) has not been evaluated.MethodsNine patients with stable coronary artery disease underwent percutaneous coronary intervention (PCI) and received DES implantation. All patients received olmesartan in addition to statin therapy after PCI. The dose of olmesartan was based on the physician's discretion as per the patients’ blood pressure. The levels of circulating EPCs were analyzed at baseline, post-PCI, and 1, 2, 3, and 8 months after PCI. Coronary angiography and the acetylcholine provocation test were performed on all patients at 8 months.ResultsAlthough the angiotensin II level significantly changed, the levels of circulating EPCs did not change during 8 months of olmesartan treatment (3.1±0.6cells/ml, 2.5±0.8cells/ml, 2.0±0.6cells/ml, 2.9±0.9cells/ml, 3.0±0.4cells/ml, 3.4±0.8cells/ml, p=0.64). The patients were subsequently divided into two groups based on whether the level of circulating EPCs was less or greater than 4cells/ml at 8 months. There were no significant differences in the mean vessel diameter of each segment (proximal, proximal edge, distal edge, and distal) after the acetylcholine provocation test between the two groups.ConclusionsLow-to-moderate doses of olmesartan might not increase the level of circulating EPCs in patients receiving statin therapy. There might be no association between the levels of circulating EPCs and the degree of coronary vasospasm in the acetylcholine provocation test 8 months after DES implantation

Relationship between lymph node metastasis and E-cadherin expression in submucosal invasive gastric carcinomas with gastric-phenotype

Background : Recent advances in immunohistochemical staining have led to the proposition of a classification of gastric carcinomas based on cellular phenotypes, and the degree of biological malignancy of gastric-phenotype carcinomas has attracted particular attention. Subjects and Methods : One hundred and seven submucosal (SM) invasive carcinomas encountered in our center were examined for their histological type, cellular phenotype, and E-cadherin expression status to clarify their relationships with lymph node metastasis. Results : Eleven (10.3%) of 107 SM gastric carcinomas were lymph node metastasis-positive. Gastric-phenotype carcinomas accounted for 20.6%, with a lymph node metastasis rate of 27.3% (6/22), which was significantly higher (p<0.05) than those of intestinal-phenotype carcinomas (5.9%) and mixed-phenotype carcinomas (2.9%). In terms of E-cadherin expression, only carcinomas with reduced E-cadherin expression showed lymph node metastasis at a rate significantly higher than that of carcinomas with normal E-cadherin expression (p<0.05). The lymph node metastasis rate (46.2%) of gastric-phenotype carcinomas with reduced E-cadherin expression was significantly higher than those of carcinomas of other phenotypes (p<0.05). Conclusion : Since gastric-phenotype differentiated carcinomas with reduced E-cadherin expression have the potential for becoming undifferentiated, the risk of lymph node metastasis should be considered

A different distribution of corticotropin releasing factor and arginine vasopressin contents in the hypothalamic nuclei after estrogen administration.

The distribution of corticotropin releasing factor (CRF) and arginine vasopressin (AVP) in hypothalamic nuclei were examined in control and estrogen-treated female rats. CRF activity was measured using monolayer cultured rat anterior pituitary cells and AVP by radioimmunoassay. Hypothalamic nuclei were punched out according to the method of Palkovits. The distribution of CRF activity in 5 different hypothalamic nuclei was similar to that of AVP in intact female rats. CRF activity in hypothalamic nuclei, pituitary ACTH content and plasma ACTH levels in estrogen-treated rats were not significantly different from those in control rats. However, significant elevation of AVP content was observed in the supraoptic and paraventricular nuclei of estrogen-treated rats. These results indicate that CRF and AVP are distributed in similar hypothalamic nuclei, but that they are not identical.</p

In vivo variability in quantitative coronary ultrasound and tissue characterization measurements with mechanical and phased-array catheters

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials. Methods and results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3 ± 2.0 mm2 vs. 6.7 ± 1.8 mm2, p = 0.001) and vessel (11.8 ± 3.3 mm2 vs. 11.0 ± 2.9 mm2, p = 0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4 ± 2.3 mm2 vs. 4.4 ± 2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7 ± 2.38 vs. 88.4 ± 5.53, p < 0.0001). Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/ regression studies