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Sample records for generation drug eluting

  1. XIENCE V everolimus-eluting coronary stent system: a novel second generation drug-eluting stent

    NARCIS (Netherlands)

    Beijk, Marcel A. M.; Piek, Jon J.

    2007-01-01

    Drug-eluting stents (DES) have been shown to be safe and significantly reduce clinical events and angiographic restenosis in the percutaneous treatment of coronary artery disease. Currently, three DES have been approved in Europe and Northern America: the sirolimus-eluting stent (SES), the

  2. Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

    Science.gov (United States)

    El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

    2017-03-13

    The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (6 months), the strut thickness of the BP-DES (thin 100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

  3. Incidence of periprocedural myocardial infarction following stent implantation: Comparison between first- and second-generation drug-eluting stents

    NARCIS (Netherlands)

    Tandjung, Kenneth; Basalus, Mounir W.Z.; Muurman, Esther; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Jansen, Hanneke; Huisman, Jennifer; Linssen, Gerard C.M.; Droste, Herman T.; Nienhuis, Mark B.; von Birgelen, Clemens

    2012-01-01

    Background: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). Objective: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research

  4. Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.

    Science.gov (United States)

    Lee, Joo Myung; Kang, Jeehoon; Lee, Euijae; Hwang, Doyeon; Rhee, Tae-Min; Park, Jonghanne; Kim, Hack-Lyoung; Lee, Sang Eun; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Na, Sang-Hoon; Kang, Hyun-Jae; Koo, Bon-Kwon; Kim, Hyo-Soo

    2016-10-24

    The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR adjust ]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR adjust 2.44; 95% CI: 1.54 to 3.86; HR adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m 2 . Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR adjust : 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All

  5. Safety and efficacy of everolimus-eluting stents compared with first-generation drug-eluting stents in patients undergoing primary percutaneous coronary intervention

    Energy Technology Data Exchange (ETDEWEB)

    Escárcega, Ricardo O.; Baker, Nevin C.; Magalhaes, Marco A.; Lipinski, Michael J.; Minha, Sa’ar; Torguson, Rebecca; Satler, Lowell F.; Pichard, Augusto D.; Suddath, William O.; Waksman, Ron, E-mail: ron.waksman@medstar.net

    2014-09-15

    Objective: To assess the safety and efficacy everolimus-eluting stents (EES) compared with first-generation drug-eluting stents (DES) in patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Background: EES have been associated with improved clinical outcomes compared to paclitaxel-eluting stents (PES) and with similar outcomes compared to sirolimus-eluting stents (SES). Methods: A total of 520 patients who presented with ST-elevation myocardial infarction (STEMI) from 2003 to 2013, who underwent primary PCI with DES, were retrospectively analyzed. Of these, 247 received SES, 136 PES, and 137 EES. Patients were followed up to 2 years for major adverse cardiac events (MACE). Univariate and multivariate models detected correlates to outcome. Results: EES implantation, compared with PES and SES, resulted in comparable rates of MACE (8.8% vs. 16.2%, p = 0.06 and 8.8% vs. 12.6%, respectively, p = 0.26), stent thrombosis, MI, and target lesion revascularization. Patients who received EES had lower rates of all-cause mortality (3.7% vs. 12.6% vs. 9.4%, p = 0.03) at 1-year follow up. However, in the univariate and multivariate analyses, stent type was not independently associated with the primary outcome or with all-cause mortality. Diabetes mellitus and number of stents implanted were independently associated with the primary outcome. Conclusion: While EES seem to be associated with better outcome when compared to PES, the main correlates of STEMI patients are the presence of diabetes and number of stents implanted, and not the type of stent used for intervention.

  6. Impact of stent length on clinical outcomes of first-generation and new-generation drug-eluting stents.

    Science.gov (United States)

    Konishi, Hirokazu; Miyauchi, Katsumi; Dohi, Tomotaka; Tsuboi, Shuta; Ogita, Manabu; Naito, Ryo; Kasai, Takatoshi; Tamura, Hiroshi; Okazaki, Shinya; Isoda, Kikuo; Daida, Hiroyuki

    2016-04-01

    The aim of this study is to compare first- and new-generation drug-eluting stents (DESs) which are implanted in long lesion. Stent length is known to be a predictor of adverse events after percutaneous coronary intervention (PCI), even with the first-generation DESs. The introduction of new-generation DESs has reduced the rates of adverse clinical events. However, the impact of stent length on long-term clinical outcomes is not well known. A total of 1181 consecutive patients who underwent PCI using either a first-generation DES (n = 885) or a new-generation DES (n = 296) between 2004 and 2011 were investigated. In each of the stent groups, the patients were divided into two groups by stent length (>32 and ≤32 mm) and compared. During the follow-up period, the incidence of major adverse cardiac events (MACEs) was significantly higher for patients with long stents implanted than with short stents (P stent groups in the new-generation DES group (P = 0.24; log-rank test). On multivariate Cox regression analysis, stent length was not associated with adverse events in the new-generation DES groups [hazard ratio (HR) 0.87; 95 % confidence interval (95 % CI) 0.71-1.04; P = 0.14]. Implanted stent length was significantly associated with a higher risk of MACEs in patients who received first-generation DESs, but not in patients who received the new-generation DESs.

  7. Next generation drug-eluting stents: focus on bioabsorbable platforms and polymers

    Directory of Open Access Journals (Sweden)

    Brendan Doyle

    2009-11-01

    Full Text Available Brendan Doyle, David R Holmes JrDivision of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USAAbstract: The success of drug-eluting stents in preventing restenosis has shifted the focus of new stent development toward enhancing long term safety and efficacy of these devices, while simultaneously eliminating the need for indefinite dual antiplatelet therapy. A technical advance fulfilling these aims would hold tremendous potential to reduce morbidity, mortality and economic costs associated with the percutaneous treatment of coronary artery disease. An attractive approach is the use of bioabsorbable stent designs. These may include stents with different bioabsorbable drugs, bioabsorbable polymers or even bioabsorbable metallic backbones. A device that could achieve excellent acute and long-term results, but disappear completely within months (thereby avoiding the need for prolonged dual antiplatelet therapy, would be a tremendous advance. Too good to be true? We explore here the scientific rationale and prospects for success with this exciting concept.Keywords: percutaneous coronary intervention, biodegradable, bioabsorbable, polymer, stent

  8. First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

    Directory of Open Access Journals (Sweden)

    Jong-Hwa Ahn

    Full Text Available Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES versus first-generation DES in patients with coronary chronic total occlusion (CTO who undergo percutaneous coronary intervention (PCI. The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557 or second-generation DES (n = 449 were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72 or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99. After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86 and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71 were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

  9. Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients.

    Science.gov (United States)

    Tada, Tomohisa; Byrne, Robert A; Simunovic, Iva; King, Lamin A; Cassese, Salvatore; Joner, Michael; Fusaro, Massimiliano; Schneider, Simon; Schulz, Stefanie; Ibrahim, Tareq; Ott, Ilka; Massberg, Steffen; Laugwitz, Karl-Ludwig; Kastrati, Adnan

    2013-12-01

    This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES. The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery

    DEFF Research Database (Denmark)

    Mangione, Fernanda Marinho; Biering-Sørensen, Tor; Nochioka, Kotaro

    2017-01-01

    OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to b...

  11. Drug-Eluting Balloon versus New-Generation Drug-Eluting Stent for the Treatment of In-Stent Restenosis: An Updated Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Kong-Yong Cui

    2018-01-01

    Conclusions: The current meta-analysis showed that DEB and new-generation DES had comparable safety and efficacy for the treatment of ISR in RCTs. However, treatment with DEB was associated with higher risk of all-cause mortality in the real-world nonrandomized studies.

  12. Current manufacturing processes of drug-eluting sutures.

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    Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

    2017-11-01

    Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

  13. Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

    Science.gov (United States)

    Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

    2015-11-01

    The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Gorny, B.; Koltowski, L.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; Schaaf, R.J. van der; Kelm, M.; Kubica, J.; Suryapranata, H.

    2014-01-01

    BACKGROUND: First-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to their long-term safety. Second-generation DES were designed to overcome

  15. In-stent neoatherosclerosis and tissue characteristics of restenotic lesions following implantation of second generation drug-eluting stents in unrestricted coronary lesions: Optical frequency domain imaging study.

    Science.gov (United States)

    Sabbah, Mahmoud; Kadota, Kazushige; El-Eraky, Azza; Kamal, Hanan M; Abdellah, Ahmed-Tageldien; El Hawary, Ahmed

    2017-06-01

    Differences in stent platform, polymer coatings, and antirestenotic drugs among the current in use second-generation drug-eluting stents (G2-DESs) may induce significant variations in neointimal response and vascular healing, which may impact the prevalence of neoatherosclerosis (NA) and morphological appearance of the restenotic tissue. Utilizing Optical frequency domain imaging, two independent reviewers, retrospectively compared the prevalence of neoatherosclerosis (NA), and the morphological differences, and tissue characteristics of 50 G2-DESs in-stent restenosis (ISR) lesions (35 everolimus-eluting stent [22 cobalt-chromium (CoCr), 13 platinum-chromium (PtCr)], and 15 biolimus-eluting stent [BES]) implanted liberally in unrestricted coronary lesions. More than half of the stents were implanted in type C lesions, while 40% of the stents were implanted primarily in lesions with recanalized chronic total occlusion. NA, defined as a neointima formation with the presence of lipids or calcification, was observed in fewer than half (24/50) of all ISR lesions with no significant in-between group differences (41%, 69%, and 40% in CoCr, PtCr, and BES respectively, P = 0.22), nor were there any significant differences in the morphological appearance or tissue characteristics between all G2-DESs subtypes. Acknowledging some limitations, our results may suggest that the prevalence of NA and the morphological appearance of restenotic lesions might not differ when G2-DESs are implanted in unrestricted, rather complex, coronary lesions. © 2017, Wiley Periodicals, Inc.

  16. Two-Year Clinical Outcomes of Newer-Generation Drug-Eluting Stent Implantation Following Rotational Atherectomy for Heavily Calcified Lesions.

    Science.gov (United States)

    Jinnouchi, Hiroyuki; Kuramitsu, Shoichi; Shinozaki, Tomohiro; Kobayashi, Yohei; Hiromasa, Takashi; Morinaga, Takashi; Mazaki, Toru; Sakakura, Kenichi; Soga, Yoshimitsu; Hyodo, Makoto; Shirai, Shinichi; Ando, Kenji

    2015-01-01

    Clinical outcomes of implantation of the newer-generation drug-eluting stent (DES) following rotational atherectomy for heavily calcified lesions remain unclear in the real-world setting. We enrolled 252 consecutive patients (273 lesions) treated with newer-generation DES following rotational atherectomy. The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular events (MACE), defined as cardiac death, myocardial infarction, clinically-driven target lesion revascularization, and definite stent thrombosis. Complete clinical follow-up information at 2-year was obtained for all patients. The mean age was 73.2±9.0 years and 155 patients (61.5%) were male. Cumulative 2-year incidence of MACE (cardiac death, myocardial infarction, clinically-driven target lesion revascularization and definite stent thrombosis) was 20.3% (7.0%, 2.1%, 18.1% and 2.1%, respectively). Predictors of MACE were presenting with acute coronary syndrome (hazard ratio [HR]: 3.80, 95% confidence interval [CI]: 1.29-11.2, P=0.02), hemodialysis (HR: 1.93, 95% CI: 1.04-3.56, P=0.04) and previous coronary artery bypass graft (HR: 2.26, 95% CI: 1.02-5.00, P=0.045). PCI for calcified lesions requiring rotational atherectomy is still challenging even in the era of newer-generation DES.

  17. Drug-eluting stents to prevent stent thrombosis and restenosis.

    Science.gov (United States)

    Im, Eui; Hong, Myeong-Ki

    2016-01-01

    Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results of new generation DES and bioresorbable scaffolds are described.

  18. Ultra-hydrophilic stent platforms promote early vascular healing and minimise late tissue response: a potential alternative to second-generation drug-eluting stents.

    Science.gov (United States)

    Kolandaivelu, Kumaran; Bailey, Lynn; Buzzi, Stefano; Zucker, Arik; Milleret, Vincent; Ziogas, Algirdas; Ehrbar, Martin; Khattab, Ahmed A; Stanley, James R L; Wong, Gee K; Zani, Brett; Markham, Peter M; Tzafriri, Abraham R; Bhatt, Deepak L; Edelman, Elazer R

    2017-04-20

    Simple surface modifications can enhance coronary stent performance. Ultra-hydrophilic surface (UHS) treatment of contemporary bare metal stents (BMS) was assessed in vivo to verify whether such stents can provide long-term efficacy comparable to second-generation drug-eluting stents (DES) while promoting healing comparably to BMS. UHS-treated BMS, untreated BMS and corresponding DES were tested for three commercial platforms. A thirty-day and a 90-day porcine coronary model were used to characterise late tissue response. Three-day porcine coronary and seven-day rabbit iliac models were used for early healing assessment. In porcine coronary arteries, hydrophilic treatment reduced intimal hyperplasia relative to the BMS and corresponding DES platforms (1.5-fold to threefold reduction in 30-day angiographic and histological stenosis; p<0.04). Endothelialisation was similar on UHS-treated BMS and untreated BMS, both in swine and rabbit models, and lower on DES. Elevation in thrombotic indices was infrequent (never observed with UHS, rare with BMS, most often with DES), but, when present, correlated with reduced endothelialisation (p<0.01). Ultra-hydrophilic surface treatment of contemporary stents conferred good healing while moderating neointimal and thrombotic responses. Such surfaces may offer safe alternatives to DES, particularly when rapid healing and short dual antiplatelet therapy (DAPT) are crucial.

  19. Very late stent thrombosis with second generation drug eluting stents compared to bare metal stents: Network meta-analysis of randomized primary percutaneous coronary intervention trials.

    Science.gov (United States)

    Philip, Femi; Stewart, Susan; Southard, Jeffrey A

    2016-07-01

    The relative safety of drug-eluting stents (DES) and bare-metal stents (BMS) in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) continues to be debated. The long-term clinical outcomes between second generation DES and BMS for primary percutaneous coronary intervention (PCI) using network meta-analysis were compared. Randomized controlled trials comparing stent types (first generation DES, second generation DES, or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second generation DES to BMS) and indirect evidence (first generation DES with BMS and second generation DES) from the randomized trials. Twelve trials comparing all stents types including 9,673 patients randomly assigned to treatment groups were analyzed. Second generation DES was associated with significantly lower incidence of definite or probable ST (OR 0.59, 95% CI 0.39-0.89), MI (OR 0.59, 95% CI 0.39-0.89), and TVR at 3 years (OR 0.50: 95% CI 0.31-0.81) compared with BMS. In addition, there was a significantly lower incidence of MACE with second generation DES versus BMS (OR 0.54, 95% CI 0.34-0.74) at 3 years. These were driven by a higher rate of TVR, MI and stent thrombosis in the BMS group at 3 years. There was a non-significant reduction in the overall and cardiac mortality [OR 0.83, 95% CI (0.60-1.14), OR 0.88, 95% CI (0.6-1.28)] with the use of second generation DES versus BMS at 3 years. Network meta-analysis of randomized trials of primary PCI demonstrated lower incidence of MACE, MI, TVR, and stent thrombosis with second generation DES compared with BMS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Functional Nanoarchitectures For Enhanced Drug Eluting Stents

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    Saleh, Yomna E.; Gepreel, Mohamed A.; Allam, Nageh K.

    2017-01-01

    Different strategies have been investigated to allow for optimum duration and conditions for endothelium healing through the enhancement of coronary stents. In this study, a nanoarchitectured system is proposed as a surface modification for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a new Ni-free biocompatible Ti-based alloy, as a potential material for self-expandable stents. The fabricated nanotubes were self-grown from the potential stent substrate, which are also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder Vascular Smooth Muscle Cells (VSMC) proliferation. Two morphologies were synthesized to investigate the effect of structure homogeneity on the intended application. The material was characterized by field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were performed and compared for the two fabricated nanoarchitectures, versus smooth untextured samples, using in-vitro cultured endothelial cells. Finally, the drug loading capacity was experimentally studied and further supported by computational modeling of the release profile.

  1. Optimization of Drug Delivery by Drug-Eluting Stents.

    Directory of Open Access Journals (Sweden)

    Franz Bozsak

    Full Text Available Drug-eluting stents (DES, which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours or very slowly (over periods of several months up to one year at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

  2. Production of 99Tc generators with automatic elution

    International Nuclear Information System (INIS)

    Mengatti, J.; Yanagawa, S.T.I.; Mazzarro, E.; Gasiglia, H.T.; Rela, P.R.; Silva, C.P.G. da; Pereira, N.P.S. de.

    1983-10-01

    The improvements performed on the routine production of sup(99m) Tc-generators at the Instituto de Pesquisas Energeticas e Nucleares-CNEN/SP, are described. The old model generators (manual elution of sup(99m) Tc) were substituted by automatically eluted generators (Vacuum system). The alumina column, elution system and acessories were modified; the elution time was reduced from 60 to 20-30 seconds. The new generators give 80-90% elution yields using six mililiters of sodium chloride 0,9% as sup(99m) Tc eluant instead of the 10 mililiters necessary to eluate the old generators. So, the radioactive concentrations are now 70% higher. The radioactive, radiochemical, chemical and microbiological criteria were examinated for sup(99m) Tc solutions. Like old generators, automatic generators were considered safe for medical purpose. (Author) [pt

  3. Percutaneous coronary intervention with second-generation drug-eluting stent versus bare-metal stent: Systematic review and cost-benefit analysis.

    Science.gov (United States)

    Poder, Thomas G; Erraji, Jihane; Coulibaly, Lucien P; Koffi, Kouamé

    2017-01-01

    Drug-eluting stents (DESs) were considered as ground-breaking technology promising to eradicate restenosis and the necessity to perform multiple revascularization procedures subsequent to percutaneous coronary intervention. Soon after DESs were released on the market, however, there were reports of a potential increase in mortality and of early or late thrombosis. In addition, DESs are far more expensive than bare-metal stents (BMSs), which has led to their limited use in many countries. The technology has improved over the last few years with the second generation of DESs (DES-2). Moreover, costs have come down and an improved safety profile with decreased thrombosis has been reported. Perform a cost-benefit analysis of DES-2s versus BMSs in the context of a publicly funded university hospital in Quebec, Canada. A systematic review of meta-analyses was conducted between 2012 and 2016 to extract data on clinical effectiveness. The clinical outcome of interest for the cost-benefit analysis was target-vessel revascularization (TVR). Cost units are those used in the Quebec health-care system. The cost-benefit analysis was based on a 2-year perspective. Deterministic and stochastic models (discrete-event simulation) were used, and various risk factors of reintervention were considered. DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e., 0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and in-stent thrombosis than BMSs, but results are rarely significant, with the exception of the cobalt-chromium everolimus DES. The rate ratio of myocardial infraction is systematically in favor of DES-2s and very often significant. Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings (i.e., -$479 to -$769 per patient). Moreover, the higher a patient's risk of reintervention, the higher the savings associated with the use of DES-2s. Despite the higher purchase cost of DES-2s compared to BMSs

  4. Drug-eluting versus bare-metal stents in large coronary arteries

    DEFF Research Database (Denmark)

    Kaiser, Christoph; Galatius, Soeren; Erne, Paul

    2010-01-01

    Recent data have suggested that patients with coronary disease in large arteries are at increased risk for late cardiac events after percutaneous intervention with first-generation drug-eluting stents, as compared with bare-metal stents. We sought to confirm this observation and to assess whether...

  5. From drug eluting stents to bioresorbable scaffolds; to new horizons in PCI

    NARCIS (Netherlands)

    Tenekecioglu, Erhan; Bourantas, Christos; Abdelghani, Mohammad; Zeng, Yaping; Silva, Rafael Cavalcante; Tateishi, Hiroki; Sotomi, Yohei; Onuma, Yoshinobu; Yılmaz, Mustafa; Serruys, Patrick W.

    2016-01-01

    Drug eluting stents and particularly the fully bioresorbable drug-eluting scaffolds herald a new era in percutaneous treatment of coronary artery disease. There has been tremendous progress in drug eluting stents with fully biodegradable coating polymers and polymer-free devices with reservoir

  6. Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mina, George S; Watti, Hussam; Soliman, Demiana; Shewale, Anand; Atkins, Jessica; Reddy, Pratap; Dominic, Paari

    2018-01-05

    Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI. Copyright © 2018. Published by Elsevier Inc.

  7. Thrombosis of second-generation drug-eluting stents in real practice results from the multicenter Spanish registry ESTROFA-2 (Estudio Español Sobre Trombosis de Stents Farmacoactivos de Segunda Generacion-2).

    Science.gov (United States)

    de la Torre Hernández, José M; Alfonso, Fernando; Gimeno, Federico; Diarte, Jose A; Lopez-Palop, Ramón; Pérez de Prado, Armando; Rivero, Fernando; Sanchis, Juan; Larman, Mariano; Diaz, Jose F; Elizaga, Jaime; Moreiras, Javier Martín; Gomez Jaume, Alfredo; Hernández, José M; Mauri, Josepa; Recalde, Angel Sánchez; Bullones, Juan A; Rumoroso, Jose R; Del Blanco, Bruno García; Baz, Jose A; Bosa, Francisco; Botas, Javier; Hernández, Felipe

    2010-09-01

    This study sought to evaluate second-generation drug-eluting stent (DES) thrombosis in clinical practice. First-generation DES are associated with a significant incidence of late thrombosis. There is paucity of data regarding real practice late thrombosis incidence and predictors with second-generation DES, zotarolimus-eluting stent (ZES), and everolimus-eluting stents (EES). A prospective, large-scale, non-industry-linked multicenter registry was designed. Complete clinical-procedural data and systematic follow-up of all patients treated with these stents was reported in a dedicated registry supported by the Spanish Working Group on Interventional Cardiology. From 2005 to 2008, 4,768 patients were included in 34 centers: 2,549 treated with ZES, and 2,219 with EES. The cumulative incidence of definite/probable thrombosis for ZES was 1.3% at 1 year and 1.7% at 2 years and for EES 1.4% at 1 year and 1.7% at 2 years (p = 0.8). The increment of definite thrombosis between the first and second year was 0.2% and 0.25%, respectively. In a propensity score analysis, the incidence remained very similar. Ejection fraction (adjusted hazard ratio [HR]: 0.97; 95% confidence interval [CI]: 0.95 to -0.99; p = 0.008), stent diameter (adjusted HR: 0.37; 95% CI: 0.17to 0.81; p = 0.01) and bifurcations (adjusted HR: 2.1; 95% CI: 1.14 to 3.7; p = 0.02) emerged as independent predictors of thrombosis. In the subgroup of patients with bifurcations, the use of ZES was independently associated with a higher thrombosis rate (adjusted HR: 4; 95% CI: 1.1 to 13; p = 0.03). In a real practice setting, the incidence of thrombosis at 2 years with ZES and EES was low and quite similar. The incidence of very late thrombosis resulted lower than was reported in registries of first-generation DES. In the subset of bifurcations, the use of ZES significantly increased the risk of thrombosis. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation

    DEFF Research Database (Denmark)

    Thim, Troels; Johansen, Martin Berg; Chisholm, Gro Egholm

    2014-01-01

    BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug-eluting ......BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug......-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. RESULTS: Discontinuation of clopidogrel within the first 3 months after...... stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were...

  9. [Drug-eluting stent thrombosis and its pharmacological prevention].

    Science.gov (United States)

    Pershukov, I V; Batyraliev, T A

    2007-01-01

    The problem of drug eluting stents (DES) safety has been actively discussed throughout 2006 because of increase of frequency of development of late stent thromboses which were noted during almost 2 years after stenting. In December 2006 US Food and Drug Administration (FDA) advisory panel acknowledged increase of development of late stent thrombosis. At the same time FDA accepted new definition of stent-thrombosis suggested by the Academic Research Consortium. According to this definition thrombosis can be definite, probable and possible. Any unexplained death before end of follow-up in a trial should be considered thrombosis related. Recalculation of thrombosis rate using this definition caused pronounced increase of this parameter in previously conducted trials. Thrombosis rate rose from 0,6 to 3,3% for bare metal stents, from 0,8 to 3,6% for sirolimus eluting stents and from 1,3 to 3,5% for paclitaxel eluting stents. Professional cardiological and angiographical societies (ACC, AHA, SCAI) responding to FDA advisory panel published their proofs and vision of the problem of stent thrombosis. In February 2007 ACC, AHA, SCAI, American College of Surgeons and Association of Dentists published scientific bulletin in which described preventive measures aimed at lowering of risk of thrombosis development. This document contains strict recommendation to continue double antithrombotic therapy with aspirin and clopidogrel for 12 months after implantation of DES or abandonment of the use of this type of stents when long term double antithrombotic therapy is not possible.

  10. Recent developments in drug eluting devices with tailored interfacial properties.

    Science.gov (United States)

    Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon

    2017-11-01

    Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Advantages and disadvantages of biodegradable platforms in drug eluting stents.

    Science.gov (United States)

    Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

    2011-03-26

    Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.

  12. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

    Science.gov (United States)

    Nam, Hee Chul; Jang, Bohyun; Song, Myeong Jun

    2016-01-01

    Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities. PMID:27833376

  13. Comparison of newer-generation drug-eluting with bare-metal stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of the EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) and COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trials.

    Science.gov (United States)

    Sabaté, Manel; Räber, Lorenz; Heg, Dik; Brugaletta, Salvatore; Kelbaek, Henning; Cequier, Angel; Ostojic, Miodrag; Iñiguez, Andrés; Tüller, David; Serra, Antonio; Baumbach, Andreas; von Birgelen, Clemens; Hernandez-Antolin, Rosana; Roffi, Marco; Mainar, Vicente; Valgimigli, Marco; Serruys, Patrick W; Jüni, Peter; Windecker, Stephan

    2014-01-01

    This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS. Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up. Copyright © 2014 American

  14. REUSABILITY OF BOND ELUT CERTIFY COLUMNS FOR THE EXTRACTION OF DRUGS FROM PLASMA

    NARCIS (Netherlands)

    CHEN, XH; FRANKE, JP; WIJSBEEK, J; DEZEEUW, RA

    1993-01-01

    The reusability of Bond Elut Certify columns for the extraction of toxicologically relevant drugs from plasma has been evaluated. Pentobarbital, hexobarbital, mepivacaine, trimipramine and clonazepam were selected as test drugs to represent various classes of drugs. The columns were regenerated

  15. Towards Hypoxia-responsive Drug-eluting Embolization Beads.

    Science.gov (United States)

    Ashrafi, Koorosh; Heaysman, Clare L; Phillips, Gary J; Lloyd, Andrew W; Lewis, Andrew L

    2017-05-30

    Drug release from chemoembolization microspheres stimulated by the presence of a chemically reducing environment may provide benefits for targeting drug resistant and metastatic hypoxic tumours. A water-soluble disulfide-based bifunctional cross-linker bis(acryloyl)-(l)-cystine (BALC) was synthesised, characterised and incorporated into a modified poly(vinyl) alcohol (PVA) hydrogel beads at varying concentrations using reverse suspension polymerisation. The beads were characterised to confirm the amount of cross-linker within each formulation and its effects on the bead properties. Elemental and UV/visible spectroscopic analysis confirmed the incorporation of BALC within the beads and sizing studies showed that in the presence of a reducing agent, all bead formulations increased in mean diameter. The BALC beads could be loaded with doxorubicin hydrochloride and amounts in excess of 300mg of drug per mL of hydrated beads could be achieved but required conversion of the carboxylic acid groups of the BALC to their sodium carboxylate salt forms. Elution of doxorubicin from the beads demonstrated a controlled release via ionic exchange. Some formulations exhibited an increase in size and release of drug in the presence of a reducing agent, and therefore demonstrated the ability to respond to an in vitro reducing environment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Bioresorbable polymer coated drug eluting stent: a model study.

    Science.gov (United States)

    Rossi, Filippo; Casalini, Tommaso; Raffa, Edoardo; Masi, Maurizio; Perale, Giuseppe

    2012-07-02

    In drug eluting stent technologies, an increased demand for better control, higher reliability, and enhanced performances of drug delivery systems emerged in the last years and thus offered the opportunity to introduce model-based approaches aimed to overcome the remarkable limits of trial-and-error methods. In this context a mathematical model was studied, based on detailed conservation equations and taking into account the main physical-chemical mechanisms involved in polymeric coating degradation, drug release, and restenosis inhibition. It allowed highlighting the interdependence between factors affecting each of these phenomena and, in particular, the influence of stent design parameters on drug antirestenotic efficacy. Therefore, the here-proposed model is aimed to simulate the diffusional release, for both in vitro and the in vivo conditions: results were verified against various literature data, confirming the reliability of the parameter estimation procedure. The hierarchical structure of this model also allows easily modifying the set of equations describing restenosis evolution to enhance model reliability and taking advantage of the deep understanding of physiological mechanisms governing the different stages of smooth muscle cell growth and proliferation. In addition, thanks to its simplicity and to the very low system requirements and central processing unit (CPU) time, our model allows obtaining immediate views of system behavior.

  17. Incidence, predicting factors, and clinical outcomes of periprocedural myocardial infarction after percutaneous coronary intervention for chronic total occlusion in the era of new-generation drug-eluting stents.

    Science.gov (United States)

    Kim, Jin-Ho; Kim, Byeong-Keuk; Kim, Seunghwan; Ahn, Chul-Min; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Hong, Myeong-Ki; Jang, Yangsoo

    2017-12-20

    This study aimed to examine predictors and clinical outcomes of periprocedural myocardial infarction (PMI) after chronic total occlusion (CTO) intervention. There are limited data on the clinical implications of PMI after CTO intervention in the new-generation drug-eluting stent (DES) era. We enrolled 337 patients who underwent CTO intervention and met the study criteria. We evaluated the incidence and predictors of PMI, defined as an increase in creatine kinase-MB ≥3× the upper limit of normal (ULN) after intervention and compared the occurrence rates of major adverse cardiac and cerebrovascular events (MACCE, defined as the composite of cardiac death, myocardial infarction, stent thrombosis, target-vessel revascularization, or cerebrovascular accidents) between the PMI and non-PMI groups. PMI occurred in 23 (6.8%) patients after CTO intervention. Significant independent predictors were previous bypass surgery [odds ratio (OR) = 5.52, 95% confidence interval (CI) = 1.17-25.92; P = 0.03], Japan-CTO score ≥3 (OR = 7.06, 95%CI = 2.57-19.39; P PMI group had a significantly higher MACCE rate than the non-PMI group (23.7 vs. 5.6%, P = 0.008 by log-rank test). PMI was an independent predictor of MACCE (HR = 4.26, 95%CI = 1.35-13.43; P = 0.01). The MACCE rate gradually increased in a CK-MB-dependent fashion and was highest in patients with ≥10× ULN (P = 0.005). Previous bypass surgery, high Japan-CTO score, side branch occlusion, and longer procedure time were strongly related to PMI occurrence after CTO intervention. PMI was significantly associated with worse clinical outcomes in the new-generation DES era. © 2017 Wiley Periodicals, Inc.

  18. Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Lishan Wang

    Full Text Available Drug-eluting stents (DES are increasingly used for treatment of acute coronary syndrome (ACS. However, clinical efficacy and safety of various types of DES is not well established in these subjects. We therefore evaluated clinical utility of second-generation and first-generation DES in patients with ACS by conducting a meta-analysis.A search of Medline, Embase, the Cochrane databases, and Web of Science was made. Randomized controlled trials (RCTs which compared second-generation DES (everolimus-eluting stents [EES] or zotarolimus-eluting stents [ZES] versus first-generation DES (sirolimus-eluting stents [SES] or paclitaxe-eluting stents [PES] in patients with ACS and provided data on clinical efficacy or safety endpoints were included. Pooled estimates were calculated using random-effects model.A total of 2,757 participants with ACS in 6 RCTs were included. Compared with first-generation one, second-generation DES trended to be associated with the decreased incidence of definite or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95% confidence intervals [CI] 0.33 to 1.07, p = 0.09. However, the rate of target lesion revascularization (TLR significantly increased in second-generation DES (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005. There were no significant differences in the incidence of major adverse cardiac events (MACEs, all-cause death, cardiac death, and recurrent myocardial infarction between the two arms (all p>0.10. The second-generation EES showed a tendency towards lower risk of MACEs (p = 0.06 and a beneficial effect on reducing stent thrombosis episodes (p = 0.009, while the second-generation ZES presented an increased occurrence of MACEs (p = 0.02 and TLR (p = 0.003.Second-generation DES, especially EES, appeared to present a lower risk of stent thrombosis, whereas second-generation ZES might increase the need for repeat revascularization in ACS patients. During coronary

  19. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Tóth, S.; Koós, M.; Beiler, B.

    2009-01-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)

  20. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Tóth, S.; Koós, M. [Research Institute for Solid State Physics and Optics, Budapest (Hungary); Beiler, B. [Institute of Isotopes, HAS, Budapest (Hungary)

    2009-07-01

    Drug-eluting stents have several advantages over bare metal implants. They eliminate restenosis, the main drawback of bare metal stents. In addition the locally delivered drug is more effective and causes less side-effects. However in some cases dangerous stent thrombosis, inflammatory and allergy reactions were observed after their implantation, which first of all related to the drug-eluting coating. This project is aimed to develop a novel biocompatible nanoporous polymer layer by radiation induced polymerization that is capable of holding and eluting drugs and promotes endothelization after the release of the drug. (author)

  1. All-cause mortality after drug-eluting stent implantation in African-Americans.

    Science.gov (United States)

    Poludasu, Shyam; Cavusoglu, Erdal; Khan, Waqas; Marmur, Jonathan D

    2008-12-01

    Recent studies have questioned the safety of drug-eluting stents because of a higher incidence of late stent thrombosis, raising the possibility that drug-eluting stents may be associated with an increased mortality. The effect of drug-eluting stents on mortality in African-Americans is unknown. We evaluated 628 African-American patients (354 patients treated with drug-eluting stents and 274 patients treated with bare metal stents) between January 2003 and August 2005, using data from our bolus-only platelet glycoprotein IIb/IIIa inhibitor database. The primary end point was all-cause mortality obtained using social security death index. After a mean follow-up of 3+/-0.9 years, the mortality rate in the bare metal stents group was 12.8% compared with 7.1% in the drug-eluting stents group [adjusted P value=0.19; hazard ratio (HR) for bare metal stents group compared with drug-eluting stents group for death=1.4; 95% confidence interval (CI): 0.8-2.4]. In a subgroup analysis, patients presenting with acute coronary syndrome had a higher mortality when treated with bare metal stents compared with drug-eluting stents (17.1 vs. 6.3%, P=0.022; HR=2.2; 95% CI: 1.1-4.4). Patients with chronic kidney disease (all patients with creatinine >1.5 mg/dl) also had a higher mortality with bare metal stents compared with drug-eluting stents (36.7 vs. 20.4%, P=0.044; HR=2.3; 95% CI: 1.02-5.2). Drug-eluting stents seem to be safe in African-Americans and may improve survival in certain subgroups such as patients with acute coronary syndromes and chronic kidney disease.

  2. Drug-eluting stents studies in mice: Do we need atherosclerosis to study restenosis?

    NARCIS (Netherlands)

    Pires, N.M.M.; Jukema, J.W.; Daemen, M.J.A.P.; Quax, P.H.A.

    2006-01-01

    In 2001, the first human study with drug-eluting stents (DES) was published showing a nearly complete abolition of restenosis by using a sirolimus-eluting stent. This success was very encouraging to test new compounds in combination with the DES platform. Nevertheless, several other anti-restenotic

  3. The stenting strategy of drug-eluting stents for coronary artery disease in patients on dialysis

    Directory of Open Access Journals (Sweden)

    Hiroshi Fujita

    2014-12-01

    Full Text Available Background: Reports regarding the relationship between the length and diameter of implanted drug-eluting stents and clinical and angiographic outcomes in dialysis patients are limited. Aim: We investigated the efficiency of drug-eluting stents for coronary artery disease in patients on dialysis from the viewpoint of stent sizing. Methods: Sirolimus-eluting stents were implanted in 88 lesions and bare metal stents were implanted in 43 lesions. We compared stenting strategy, major adverse cardiac events, and angiographic results between sirolimus-eluting stent and bare metal stent groups. Results: Stent diameter was smaller and stent length was longer in the sirolimus-eluting stent group than in the bare metal stent group in our routine practices. There was no significant between-group difference in late diameter loss. Rates of angiographic restenosis and target lesion revascularization were significantly higher in the sirolimus-eluting stent group than in the bare metal stent group. Although stent length was significantly longer and stent diameter was smaller in the sirolimus-eluting stent group, sirolimus-eluting stents did not improve the subsequent clinical and angiographic results compared with bare metal stents in dialysis patients. Conclusion: In dialysis patients, a longer length and/or smaller diameter sirolimus-eluting stent implantation was associated with high rates of restenosis and target lesion revascularization compared with bare metal stents.

  4. Use of drug-eluting stents in Victorian public hospitals.

    Science.gov (United States)

    Yan, Bryan P; Ajani, Andrew E; Duffy, Stephen J; New, Gishel; Horrigan, Mark; Szto, Gregory; Walton, Antony; Eccleston, David; Lefkovits, Jeffery; Black, Alexander; Sebastian, Martin; Brennan, Angela L; Reid, Christopher M; Clark, David J

    2006-10-02

    We aimed to assess the pattern of use of drug-eluting stents (DESs) in patients undergoing percutaneous coronary interventions (PCIs) in Victorian public hospitals. Prospective study comparing the use of one or more DESs versus bare-metal stents (BMSs) only, in consecutive patients undergoing 2428 PCIs with stent implantation from 1 April 2004 to 31 December 2005 at seven Victorian public hospitals. Adherence to current Victorian Department of Human Services guidelines which recommend DES use in patients with high-risk features for restenosis (diabetes, small vessels, long lesions, in-stent restenotic lesions, chronic total occlusions and bifurcation lesions). Of the 2428 PCIs performed, at least one DES was implanted in 1101 (45.3%) and BMSs only were implanted in 1327 (54.7%). In 87.7% (966/1101) of PCI with DESs, there was at least one criterion for high risk of restenosis. DESs were more likely to be used in patients with diabetes (risk ratio [RR], 2.45; 95% CI, 2.02-2.97), small vessels (RR, 3.35; 95%CI, 2.35-4.76), long lesions (RR, 3.87; 95% CI, 3.23-4.65), in-stent restenotic lesions (RR, 3.98; 95%CI, 2.67-6.06), chronic total occlusions (RR, 1.30; 95% CI, 0.51-2.88) and bifurcation lesions (RR, 2.23; 95%CI, 1.57-3.17). However, 66.2% (1608/2428) of all PCIs were in patients eligible for DESs according to Victorian guidelines, and in 39.9% (642/1608) of these PCIs, a BMS was used. In Victorian public hospitals, DESs have been largely reserved for patients at high risk of restenosis in accordance with Department of Human Services guidelines. However, many patients with high-risk criteria for restenosis did not receive DESs. Greater use of DESs in these patients may improve outcomes by reducing the need for repeat revascularisation.

  5. Mechanisms of Very Late Drug-Eluting Stent Thrombosis Assessed by Optical Coherence Tomography

    DEFF Research Database (Denmark)

    Taniwaki, Masanori; Radu, Maria D; Zaugg, Serge

    2016-01-01

    BACKGROUND: The pathomechanisms underlying very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are incompletely understood. Using optical coherence tomography, we investigated potential causes of this adverse event. METHODS AND RESULTS: Between August 2010 and Decemb...

  6. Meta-analysis comparing efficacy and safety of first generation drug-eluting stents to bare-metal stents in patients with diabetes mellitus undergoing primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    De Luca, Giuseppe; Dirksen, Maurits T; Spaulding, Christian

    2013-01-01

    revascularization (hazard ratio 0.42, 95% confidence interval 0.29 to 0.59, p 1 year) with DES. In conclusion, this meta-analysis, based on individual patients' data from 11 randomized trials, showed that among patients with diabetes with STEMIs who undergo primary percutaneous coronary intervention, sirolimus...... with high rates of target vessel revascularization after bare-metal stent (BMS) implantation but also higher rates of ST after DES implantation. Therefore, the aim of this study was to perform a meta-analysis of individual patients' data to evaluate the long-term safety and effectiveness of DES compared......Several concerns have emerged regarding the higher risk for stent thrombosis (ST) after drug-eluting stent (DES) implantation, especially in the setting of ST-segment elevation myocardial infarction (STEMI). Few data have been reported so far in patients with diabetes mellitus, which is associated...

  7. Long-Term Safety of Drug-Eluting and Bare-Metal Stents

    DEFF Research Database (Denmark)

    Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

    2015-01-01

    BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

  8. Studies of post-elution concentration of 99m-Tc eluted from a gel type chromatographic generator

    International Nuclear Information System (INIS)

    Suzuki, Katia N.; Osso Junior, Joao Alberto

    2007-01-01

    The radiopharmaceuticals most used in Diagnostic Nuclear Medicine are those labeled with the metastable technetium ( 99m Tc) due to its ideal physical properties of decay (t 1/2 6.01 h, Eγ 140 keV), low cost and availability facilitated through the commercial generator 99 Mo / 99m Tc. This radionuclide is formed by the β - decay of 99 Mo adsorbed on an alumina column of the generator and collected in the form of sodium pertechnetate (Na 99m TcO 4 ) by elution with saline solution (0.9%). The Radiopharmacy Center (CR) of the IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with 99 Mo produced by 98 Mo(n, γ) 99 Mo reaction that occurs in IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 ml with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (34 mCi) / ml. The fission generator gives a higher radioactive concentration around 1850 MBq (69 mCi) / ml. The aim of this work is to study a system of post-elution concentration using ion exchange cartridges in tandem (cation - anion) for the attainment of a high enough radioactive concentration to meet the demand of market, with a proved quality. This system of concentration will be made based in the technique of solid phase extraction (SPE) using commercial cartridges of extraction, which contains the solid phase and eluent saline solution (0.9%). As the eluent results of this system used in the gel generator of MoZr will be compared with the fission generator currently produced by IPEN-CNEN/SP. (author)

  9. Studies of post-elution concentration of {sup 99m}-Tc eluted from a gel type chromatographic generator

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Katia N.; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: norisuzuki6@yahoo.com.br; jaosso@ipen.br

    2007-07-01

    The radiopharmaceuticals most used in Diagnostic Nuclear Medicine are those labeled with the metastable technetium ({sup 99m}Tc) due to its ideal physical properties of decay (t{sub 1/2} 6.01 h, E{gamma} 140 keV), low cost and availability facilitated through the commercial generator {sup 99}Mo /{sup 99m}Tc. This radionuclide is formed by the {beta}{sup -} decay of {sup 99}Mo adsorbed on an alumina column of the generator and collected in the form of sodium pertechnetate (Na{sup 99m}TcO{sub 4}) by elution with saline solution (0.9%). The Radiopharmacy Center (CR) of the IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with {sup 99}Mo produced by {sup 98}Mo(n, {gamma}){sup 99}Mo reaction that occurs in IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 ml with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (34 mCi) / ml. The fission generator gives a higher radioactive concentration around 1850 MBq (69 mCi) / ml. The aim of this work is to study a system of post-elution concentration using ion exchange cartridges in tandem (cation - anion) for the attainment of a high enough radioactive concentration to meet the demand of market, with a proved quality. This system of concentration will be made based in the technique of solid phase extraction (SPE) using commercial cartridges of extraction, which contains the solid phase and eluent saline solution (0.9%). As the eluent results of this system used in the gel generator of MoZr will be compared with the fission generator currently produced by IPEN-CNEN/SP. (author)

  10. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention

    OpenAIRE

    Baschet, Louise; Bourguignon, Sandrine; Marque, S?bastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    Objective To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. Methods A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117?762 patient-years with 76 randomised trials. The main effectiveness criterion was major c...

  11. Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V)

    DEFF Research Database (Denmark)

    Christiansen, Evald Høj; Jensen, Lisette Okkels; Thayssen, Per

    2013-01-01

    Third-generation biodegradable polymer drug-eluting stents might reduce the risk of stent thrombosis compared with first-generation permanent polymer drug-eluting stents. We aimed to further investigate the effects of a biodegradable polymer biolimus-eluting stent compared with a durable polymer......-coated sirolimus-eluting stent in a population-based setting....

  12. Percutaneous coronary intervention with second-generation paclitaxel-eluting stents versus everolimus-eluting stents in United States contemporary practice (REWARDS TLX Trial).

    Science.gov (United States)

    Waksman, Ron; Ghali, Magdi; Goodroe, Randy; Ryan, Thomas; Turco, Mark; Ring, Michael; McGarry, Thomas; Dobies, David; Shammas, Nicolas; Steinberg, Daniel H; Swymelar, Stacy; Kaneshige, Kimberly; Torguson, Rebecca

    2012-10-15

    Registry Experience at the Washington Hospital Center, DES - Taxus Liberte Versus Xience V (REWARDS TLX) is a physician-initiated, retrospective, real-world, multicenter, observational study for all patients >18 years of age subjected to percutaneous coronary intervention with everolimus-eluting stents (EESs) or paclitaxel-eluting stents (PESs). Outcomes of patients receiving a TAXUS Liberté or XIENCE V drug-eluting stent were compared. Baseline clinical, procedural, and follow-up data at 12 months were collected from 10 clinical centers by an electronic data capture system. The study's primary end point was major adverse cardiac events: a composite of all-cause death, Q-wave myocardial infarction, target vessel revascularization, and stent thrombosis. The trial is registered with http://www.clinicaltrials.gov (NCT01134159). Data were entered for 1,195 patients (PES, n = 595; EES, n = 600). Baseline clinical characteristics were similar except for higher dyslipidemia, systemic hypertension, and family history of coronary artery disease in the EES group. In-hospital outcome was similar between groups, with an overall in-hospital stent thrombosis rate of 0.2%. The primary end point at 12 months was similar (EES 7.8% vs 10.8%, p = 0.082). Overall stent thrombosis rate was lower in the EES group (0.3% vs 1.2%, respectively, p = 0.107); however, target lesion revascularization was similar (PES, hazard ratio 1.46, 95% confidence interval 0.98 to 2.19, p = 0.064). There was no difference in overall mortality between groups. In conclusion, second-generation EESs and PESs demonstrated similar efficacy and safety profiles for broadened patient and lesion subsets compared to a selected population from the pivotal trials. However, for composite efficacy and safety end points, EESs outperformed second-generation PESs. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Drug diffusion and biological responses of arteries using a drug-eluting stent with nonuniform coating

    Directory of Open Access Journals (Sweden)

    Saito N

    2016-03-01

    Full Text Available Noboru Saito, Yuhei Mori, Sayaka Uchiyama Terumo Corporation R&D Center, Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa, Japan Abstract: The purpose of this study was to determine the effect of a nonuniform coating, abluminal-gradient coating (AGC, which leaves the abluminal surface of the curves and links parts of the stent free from the drug coating, on the diffusion direction of the drug and the biological responses of the artery to drug-eluting stent (DES by comparing the AGC-sirolimus stent and the conventional full-surface coating (CFC sirolimus stent. The study aimed to verify whether the AGC approach was appropriate for the development of a safer DES, minimizing the risks of stent thrombosis due to delayed endothelialization by the drug and distal embolization due to cracking of the coating layer on the hinge parts of the DES on stent expansion. In the in vitro local drug diffusion study, we used rhodamine B as a model drug, and rhodamine B released from the AGC stent diffused predominantly into the abluminal side of the alginate artery model. Conversely, rhodamine B released from the CFC stent quickly spread to the luminal side of the artery model, where endothelial cell regeneration is required. In the biological responses study, the luminal surface of the iliac artery implanted with the AGC-sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with endothelial-like cells. On the other hand, the luminal surface of the iliac artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial coverage with endothelial-like cells. While thrombosis was observed in two of the three CFC-sirolimus stents, it was observed in only one of the three AGC-sirolimus stents. Taken together, these findings indicate that the designed nonuniform coating (AGC is an appropriate approach to ensure a safer DES. However, the number of studies is limited and a larger study should be conducted to reach a statistically

  14. study on 113 Sn-113m In generator of the chromatographic column elution mode

    International Nuclear Information System (INIS)

    Abdel-Halim, A.A.

    2002-01-01

    this work has been carried out to study the optimum conditions required for local preparation of 113 Sn- 113m In radioisotope generator based on 12- molybdocerate- 113 Sn column matrix. this work was directed to: 1- investigate the optimum conditions of the tin target irradiation and dissolution processes. 2- study the different preparative conditions which affect the loading of 113 Sn radionuclide onto 12- molybdocerate (IV) columns and the elution of the generated 113m In radionuclide. 3- study the effect of generator life- time on the elution performance and quality control of the generated 113m In radionuclide over a period of 190 days

  15. Enhanced performance of magnesium alloy for drug-eluting vascular scaffold application

    Science.gov (United States)

    Dong, Hongzhou; Li, Daikun; Mao, Daoyong; Bai, Ningning; Chen, Yashi; Li, Qing

    2018-03-01

    Bio-absorbable magnesium alloys drug-eluting vascular scaffold was developed to resolve the defect of permanent metal and drug-eluting stents, most notably a chronic vessel wall inflammation and the risk of stent thrombosis. Nevertheless, violent chemical reaction and rapid degradation under physiological conditions limits their application. Furthermore, multifunctional drug-eluting stents which could reduce the formation of thrombus and repair the damaged vessels need more attention to fundamentally cure the coronary artery disease. Herein, a drug delivery system (Mg/MgO/PLA-FA) which can realize sustainable release of ferulaic acid was designed via anodic oxidation process and dip coating process. Electrochemical tests and immersion experiments showed that the superior anticorrosion behavior, it is due to the dense MgO-PLA composite layer. The released ferulaic acid can effectively decrease platelets adhesion and aggregation during the early stage of implantation. Besides, hemolysis tests showed that the composite coatings endowed the Mg alloy with a low hemolysis ratio. The Mg/MgO/PLA-FA composite materials may be appropriate for applications on biodegradable Mg alloys drug-eluting stents.

  16. Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents.

    Science.gov (United States)

    Yazdani, Saami K; Sheehy, Alexander; Pacetti, Stephen; Rittlemeyer, Brandon; Kolodgie, Frank D; Virmani, Renu

    2016-10-01

    Coatings consisting of a polymer and drug are widely used in drug-eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. The aim of this study was to investigate the short-term (7 and 28 days) and long-term (90 and 180 days) coating integrity of the Xience Prime Everolimus-Eluting Stent (EES), Resolute Zotarolimus-Eluting Stent (ZES), Taxus Paclitaxel-Eluting Stent (PES), and Nobori Biolimus A9-Eluting Stent (BES) in a rabbit ilio-femoral stent model. Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking. Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long-term durability of these drug-eluting stent coatings in vivo. © 2016, Wiley Periodicals, Inc.

  17. Drug-eluting stents: from bench-top to clinical research

    NARCIS (Netherlands)

    Basalus, Mounir Welson Zakhary

    2013-01-01

    The development of drug-eluting stents (DES) has improved the invasive treatment of obstructive coronary artery disease by reducing both, restenosis rate and need for reinterventions. This success resulted in a widespread utilization of DES in clinical practice and entailed many clinical research

  18. Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions

    DEFF Research Database (Denmark)

    Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert

    2016-01-01

    Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used...

  19. Impaired health status in Type D patients following PCI in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Denollet, Johan; Ong, Andrew T L

    2007-01-01

    Drug-eluting stenting reduces restenosis post-percutaneous coronary intervention (PCI), but subgroups of patients may not benefit optimally from this procedure. We examined the impact of Type D personality on health status over time and the clinical relevance of Type D as a predictor of impaired...... health status at 12 months in unselected post-PCI patients....

  20. In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris - DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial.

    Science.gov (United States)

    Garcia-Garcia, Hector M; Haude, Michael; Kuku, Kayode; Hideo-Kajita, Alexandre; Ince, Hüseyin; Abizaid, Alexandre; Tölg, Ralph; Lemos, Pedro Alves; von Birgelen, Clemens; Christiansen, Evald Høj; Wijns, William; Escaned, Javier; Dijkstra, Jouke; Waksman, Ron

    2018-03-15

    Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall. We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G). The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed. There was hardly any difference in curvature between pre-procedure and 12months (-0.0019; p=0.48). The change in angulation from pre- to 12months was negligible (-3.58°; 95% CI [-5.97, -1.20]), but statistically significant. At 6months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of -0.489; p=0.055) and with fibrous volume a positive relationship (estimate of 0.53, p=0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6months (Δ 6months vs. post-proc. is -13.5 [95% CI -14.6, -12.4]) and at 12months (Δ 12months vs. post-proc. is -14.0 [95% CI -15.4, -12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6months and at 12months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6months; thereafter, they remained unchanged. Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12months; importantly, these changes occurred with

  1. Transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma: its research progress

    International Nuclear Information System (INIS)

    Zhao Yan; Han Guohong; Bai Wei; Fan Daiming

    2012-01-01

    Transarterial chemoembolization (TACE) has been the main treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). However, the clinical application of TACE is limited due to the technical deficiencies, such as uncontrolled local drug delivery and systemic toxicity. Recently, the new drug-eluting beads (DEB), loading with doxorubicin, have be used in the TACE procedures. This new technique can not only maintain the local drug level for quite a long time and thus get a higher objective response, but also decrease the systemic toxicity. Transarterial chemoembolization with drug-eluting beads (DEB-TACE) have already been widely used abroad, and more related clinical trials are underway to clarify its advantages. This paper aims to make a comprehensive review in the respects of its characteristics and the latest research progress in DEB-TACE. (authors)

  2. Three-Dimensional Printing of Drug-Eluting Implants

    DEFF Research Database (Denmark)

    Water, Jorrit Jeroen; Bohr, Adam; Bøtker, Johan Peter

    2015-01-01

    The aim of the present work was to investigate the potential of three-dimensional (3D) printing as a manufacturing method for products intended for personalized treatments by exploring the production of novel polylactide-based feedstock materials for 3D printing purposes. Nitrofurantoin (NF......) and hydroxyapatite (HA) were successfully mixed and extruded with up to 30% drug load with and without addition of 5% HA in polylactide strands, which were subsequently 3D-printed into model disc geometries (10 × 2 mm). X-ray powder diffraction analysis showed that NF maintained its anhydrate solid form during...... of custom-made, drug-loaded feedstock materials for 3D printing of pharmaceutical products for controlled release....

  3. Study to modify the elution system in a sup(99m)Tc generator

    International Nuclear Information System (INIS)

    Delgado S, Baldomero.

    1979-01-01

    The sup(99m)Tc generator is a system that allows us to obtain sup(99m)Tc through the radioactive desintegration of 99 Mo, a radionuclide absorbed in an alumine chromatographic column, the sup(99m)Tc extraction is accomplished by elution and the 99 Mo remains at the column. In this work we try to modify the elution procedure of the generator. At present after eluating the generator, it must be dried with air, in order to support the column in an oxidant atmosphere to avoid the reduction of the technetiate. This reduction causes a low yield of elution, since the reduced species of the technetium can not be eluated. The drying of the column with air complicates a little the elution procedure, and we look to simplify it, the employed methods to resolve the problem were: a) adding an oxidant agent to the elution saline solution, b) adsorbing an oxidant in the alumina chromatographic column, after that the 99 Mo was settled. In the case a) the used oxidant agents were KMnO 4 , K 2 Cr 2 O 7 , NaNo 2 , etc. At concentration rates of 10 -7 M the obtained yields in high activity generators were of the 25-30%. In the case b) variable amounts of a disolution of 2.5 mg/ml of K 2 CrO 4 were adsorbed, the obtained yields in high activity generators were about 85-90%, this second procedure was better, it lets us keep the column wet and it is not necessary to dry it with air, and in this way it can be carried out more easily and efficiently the elution procedure. (author)

  4. Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives.

    Science.gov (United States)

    Rapetto, Claudio; Leoncini, Massimo

    2017-08-01

    Drug-eluting stents (DES) have reached a high safety and efficacy profile, becoming the best option for percutaneous coronary interventions (PCI) based revascularization. However, despite their optimal performance, a few concerns remain regarding their use, mainly due to permanent caging of the vessels and its consequences, first of all late stent thrombosis (ST). Bioresorbable scaffolds (BRS) aim to overcome these issues. The results achieved in randomized controlled trials (RCT) by the first generation of poly-L-lactic acid (PLLA) based scaffolds were promising at 1 year, but the first long term reports (albeit flawed by non-optimal implantation technique) have been disappointing, showing, for instance, an increased risk of ST and target vessel myocardial infarction (TV-MI). In such a scenario the advent of a newer generation magnesium (Mg) based BRS is welcome, mainly because of its innovative mechanical and chemical features coupled with well proven biocompatibility. Despite being in its infancy, this technology seems to promise a great potential. In our article, we review the Magmaris (Biotronik AG, Bülach, Switzerland) Mg BRS development from animal models to human use, underscore its best qualities and weaknesses, and provide hints of its possible future perspectives.

  5. Hepatic Arterial Chemoembolization Using Drug-Eluting Beads in Gastrointestinal Neuroendocrine Tumor Metastatic to the Liver

    International Nuclear Information System (INIS)

    Gaur, Shantanu K.; Friese, Jeremy L.; Sadow, Cheryl A.; Ayyagari, Rajasekhara; Binkert, Christoph A.; Schenker, Matthew P.; Kulke, Matthew; Baum, Richard

    2011-01-01

    Purpose: This study was designed to evaluate short ( 3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. Methods: Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100–300 or 300–500 μm drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50–100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RECIST) or European Association for the Study of the Liver (EASL) criteria. Short-term ( 3 months) imaging response was determined and Kaplan–Meier survival curves were plotted. Results: Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163–1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. Conclusions: Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver.

  6. Posterior reversible leukoencephalopathy syndrome secondary to hepatic transarterial chemoembolization with doxorubicin drug eluting beads

    Science.gov (United States)

    Kistler, C. Andrew; McCall, Joseph Caleb; Ghumman, Saad Sultan; Ali, Ijlal Akbar

    2014-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a rare complication of transarterial chemoembolization (TACE) used to treat liver metastases and has never been reported in a patient with metastatic uveal melanoma (UM) to the liver. We report the first case of PRES secondary to TACE with drug eluting beads (DEBs) loaded with doxorubicin in a 56-year-old woman with metastatic UM to the liver. PMID:24772346

  7. Histologic Assessment of Drug-Eluting Grafts Related to Implantation Site

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Tille

    2016-02-01

    Full Text Available Drug-eluting vascular prostheses represent a new direction in vascular surgery to reduce early thrombosis and late intimal hyperplasia for small calibre grafts. Subcutaneous implantation in rats is a rapid and cost-effective screening model to assess the drug-elution effect and could, to some extent, be useful to forecast results for vascular prostheses. We compared biological and histological responses to scaffolds in different implantation sites. Polycaprolactone (PCL, paclitaxel-loaded PCL (PCL-PTX and dexamethasone-loaded PCL (PCL-DXM electrospun scaffolds were implanted subcutaneously and in an infrarenal abdominal aortic model in rats for up to 12 weeks. At the conclusion of the study, a histological analysis was performed. Cellular graft invasion revealed differences in the progression of cellular infiltration between PCL-PTX and PCL/PCL-DXM groups in both models. Cell infiltration increased over time in the aortic model compared to the subcutaneous model for all groups. Cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation in all groups and models over time. Macrophages and giant cells increased in the PCL aortic model; whereas in the subcutaneous model these cell types increased only after three weeks or even decreased in the drug-eluting PCL groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. The subcutaneous implant model can be used for screening, especially when drug-eluting effects are studied. However, major histological differences were observed in cell type reaction and depth of cell penetration compared to the aortic model. Our results demonstrate that the implantation site is a critical determinant of the biological response.

  8. Clinical benefits of drug-eluting stent implantation in septuagenarians with coronary artery disease

    International Nuclear Information System (INIS)

    Fang Yuehua; Shen Weifeng; Zhang Ruiyan; Zhang Jiansheng; Hu Jian; Zhang Xian; Zheng Aifang

    2005-01-01

    Objective: This study evaluated the safety and long-term outcomes of drug-eluting stents in septuagenarians with coronary artery disease. Methods: Two hundred and thirty-nine consecutive patients with coronary artery disease underwent drug-eluting stenting, including 88 patients aged ≥70 years (group A) and 151 aged <70 years (group B). Baseline clinical characteristics, procedural success rate, occurrence of cardiac events during follow-up were recorded and compared between the two groups. Results: Procedural success rate and complications were similar for the two groups. During follow-up, group A had higher recurrence rate of chest pain than group B (23.9% vs. 7.3%, P<0.001), and occurrence of cardiac events was higher in group A than in group B (5.7% vs. 2.7%, P<0.296). There was no significant difference in the frequency of restenosis between the two groups. Conclusions: Drug-eluting stent implantation for septuagenarians with coronary artery disease is safe but may have more recurrence of angina than younger ones during long-term follow-up. (authors)

  9. Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection

    Science.gov (United States)

    Gulati, Karan; Aw, Moom Sinn; Losic, Dusan

    2011-10-01

    Current bone fixation technology which uses stainless steel wires known as Kirschner wires for fracture fixing often causes infection and reduced skeletal load resulting in implant failure. Creating new wires with drug-eluting properties to locally deliver drugs is an appealing approach to address some of these problems. This study presents the use of titanium [Ti] wires with titania nanotube [TNT] arrays formed with a drug delivery capability to design alternative bone fixation tools for orthopaedic applications. A titania layer with an array of nanotube structures was synthesised on the surface of a Ti wire by electrochemical anodisation and loaded with antibiotic (gentamicin) used as a model of bone anti-bacterial drug. Successful fabrication of TNT structures with pore diameters of approximately 170 nm and length of 70 μm is demonstrated for the first time in the form of wires. The drug release characteristics of TNT-Ti wires were evaluated, showing a two-phase release, with a burst release (37%) and a slow release with zero-order kinetics over 11 days. These results confirmed our system's ability to be applied as a drug-eluting tool for orthopaedic applications. The established biocompatibility of TNT structures, closer modulus of elasticity to natural bones and possible inclusion of desired drugs, proteins or growth factors make this system a promising alternative to replace conventional bone implants to prevent bone infection and to be used for targeted treatment of bone cancer, osteomyelitis and other orthopaedic diseases.

  10. Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives

    OpenAIRE

    Rapetto, Claudio; Leoncini, Massimo

    2017-01-01

    Drug-eluting stents (DES) have reached a high safety and efficacy profile, becoming the best option for percutaneous coronary interventions (PCI) based revascularization. However, despite their optimal performance, a few concerns remain regarding their use, mainly due to permanent caging of the vessels and its consequences, first of all late stent thrombosis (ST). Bioresorbable scaffolds (BRS) aim to overcome these issues. The results achieved in randomized controlled trials (RCT) by the firs...

  11. Drug-eluting stents versus bare-metal stents for acute coronary syndrome

    DEFF Research Database (Denmark)

    Feinberg, Joshua; Nielsen, Emil Eik; Greenhalgh, Janette

    2017-01-01

    -EXPANDED, and BIOSIS from their inception to January 2017. We also searched two clinical trials registers, the European Medicines Agency and the US Food and Drug Administration databases, and pharmaceutical company websites. In addition, we searched the reference lists of review articles and relevant trials. SELECTION...... CRITERIA: Randomised clinical trials assessing the effects of drug-eluting stents versus bare-metal stents for acute coronary syndrome. We included trials irrespective of publication type, status, date, or language. DATA COLLECTION AND ANALYSIS: We followed our published protocol and the methodological...

  12. The role of drug-eluting balloons alone or in combination with drug-eluting stents in the treatment of de novo diffuse coronary disease.

    Science.gov (United States)

    Costopoulos, Charis; Latib, Azeem; Naganuma, Toru; Sticchi, Alessandro; Figini, Filippo; Basavarajaiah, Sandeep; Carlino, Mauro; Chieffo, Alaide; Montorfano, Matteo; Naim, Charbel; Kawaguchi, Masanori; Giannini, Francesco; Colombo, Antonio

    2013-11-01

    This study sought to investigate the role of drug-eluting balloons (DEB) alone or in combination with drug-eluting stents (DES) in the treatment of diffuse de novo coronary artery disease (CAD) (>25 mm). The use of DEB in diffuse CAD, either alone or in combination with DES, offers an alternative to stenting alone. Data regarding DEB in this context are limited. We retrospectively evaluated all patients treated with DEB for diffuse CAD between June 2009 and October 2012. Endpoints analyzed were major adverse cardiac events, defined as all-cause death, myocardial infarction, and target vessel revascularization (TVR), as well as TVR and target lesion revascularization separately. Results were compared with those obtained from a cohort of patients with similar characteristics treated with DES alone. A total of 69 patients (93 lesions) were treated with DEB ± DES, and 93 patients with DES alone (93 lesions). A high proportion of patients were diabetic (46.4% vs. 44.1%, p = 0.77). Of the DEB-treated lesions, 56.0% were treated with DEB alone, 7.4% with DEB and DES as bail out, and 36.6% with DES and DEB as part of a hybrid approach for very long disease. Outcome rates with DEB ± DES were comparable to those with DES alone at 2-year follow-up (major adverse cardiac events = 20.8% vs. 22.7%, p = 0.74; TVR = 14.8% vs. 11.5%, p = 0.44; target lesion revascularization = 9.6% vs. 9.3%, p = 0.84). DEB may have a role in the treatment of diffuse de novo CAD, either alone in smaller vessels or in combination with DES in very long disease. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Comparison of clinical outcomes after drug-eluting balloon and drug-eluting stent use for in-stent restenosis related acute myocardial infarction: a retrospective study

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Fang

    2018-04-01

    Full Text Available Background Good results of drug-eluting balloon (DEB use are achieved in in-stent restenosis (ISR lesions, small vessel disease, long lesions, and bifurcations. However, few reports exist about DEB use in acute myocardial infarction (AMI with ISR. This study’s aim was to evaluate the efficacy of DEB for AMI with ISR. Methods Between November 2011 and December 2015, 117 consecutive patients experienced AMI including ST-segment elevation MI, and non-ST-segment elevation MI due to ISR, and received percutaneous coronary intervention (PCI. We divided our patients into two groups: (1 PCI with further DEB, and (2 PCI with further drug-eluting stent (DES. Clinical outcomes such as target lesion revascularization, target vessel revascularization, recurrent MI, stroke, cardiovascular mortality, and all-cause mortality were analyzed. Results The patients’ average age was 68.37 ± 11.41 years; 69.2% were male. A total of 75 patients were enrolled in the DEB group, and 42 patients were enrolled in the DES group. The baseline characteristics between the two groups were the same without statistical differences except for gender. Peak levels of cardiac biomarker, pre- and post-PCI cardiac function were similar between two groups. The major adverse cardiac cerebral events rate (34.0% vs. 35.7%; p = 0.688 and cardiovascular mortality rate (11.7% vs. 12.8%; p = 1.000 were similar in both groups. Conclusions DEB is a reasonable strategy for AMI with ISR. Compared with DES, DEB is an alternative strategy which yielded acceptable short-term outcomes and similar 1-year clinical outcomes.

  14. Progress in the study of drug-eluting intra-stent thrombosis

    International Nuclear Information System (INIS)

    Guo Zhifu; Zheng Xing; Qin Yongwen

    2007-01-01

    Durg-eluting stent has been regarded as the milestone in the history of PCI for their efficiency in the prevention of coronary arterial restenosis after percutaneous coronary intervention. But unfortunately intra-stent thrombosis continues to be a serious complication of contemporary DES use. The incidence of drug-eluting stents thrombosis is at least not lower than that of bare metal stents at present. The clinical consequences of stent thrombosis are frequently catastrophic, including death in 40% to 50% of the cases or major myocardial infarction in 60% to 70%. Premature discontinuation of standard antiplatelet therapy is by far the most important predictor of stent thrombosis with DES and other predictors included renal failure, diabetes, bifurcation lesions, multiple lesions or multivessel disease, long stents, female, advanced age, stent underexpansion and residual stenosis etc. The delayed endothelialization may be the underling mechanism of DES thrombosis. (authors)

  15. Clinical outcomes with drug-eluting and bare-metal stents in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Palmerini, Tullio; Biondi-Zoccai, Giuseppe; Della Riva, Diego

    2013-01-01

    The authors investigated the relative safety and efficacy of different drug-eluting stents (DES) and bare metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) using a network meta-analysis.......The authors investigated the relative safety and efficacy of different drug-eluting stents (DES) and bare metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) using a network meta-analysis....

  16. Studies on the production of technetium-99m generators based on gel elution

    International Nuclear Information System (INIS)

    Castro, M.

    1993-12-01

    Technetium-99m generator based on Ti Mo elution has been carried out. The gel matrix was prepared by mixing non-irradiated molybdate with Titanium Chloride solution. Conditions of preparing and drying Ti Mo were evaluated as a function of elution yield. Thus, pH and water content were found highly critical for reproductiveness of the results. Non-elutable form of Tc-99m can be oxidized treating the target after irradiation with K 2 Cr 2 O 7 0.001M solution. During several experiments the columns were soaked with this oxidizing solution for one hour and afterwards the Ti Mo was washed with 150 ml physiological saline. Daily elutions were done with 10 ml of NaCl 0.9%. Cooling water reactor during irradiation quartz ampoules has been studied. To study this effect, one group of samples were irradiated in aluminium caps air-tight screw and another one was irradiated in drilled caps with six holes to permit water reactor recirculation around quartz ampoules. By combination K 2 Cr 2 O 7 target treatment and cooling Ti Mo during irradiation is possible to get yields of Tc-99m near to 76%. The radiochemical purity was > 99% and Al content < 10ppm , Cr < 0.05ppm , Mo <20ppm, Ti was no detected. Biological scans practiced in animals have been considered satisfactory. (author). 8 refs., 7 tabs., 3 figs

  17. Direct comparison of coronary bare metal vs. drug-eluting stents: same platform, different mechanics?

    Science.gov (United States)

    Schmidt, Wolfram; Lanzer, Peter; Behrens, Peter; Brandt-Wunderlich, Christoph; Öner, Alper; Ince, Hüseyin; Schmitz, Klaus-Peter; Grabow, Niels

    2018-01-08

    Drug-eluting stents (DES) compared to bare metal stents (BMS) have shown superior clinical performance, but are considered less suitable in complex cases. Most studies do not distinguish between DES and BMS with respect to their mechanical performance. The objective was to obtain mechanical parameters for direct comparison of BMS and DES. In vitro bench tests evaluated crimped stent profiles, crossability in stenosis models, elastic recoil, bending stiffness (crimped and expanded), and scaffolding properties. The study included five pairs of BMS and DES each with the same stent platforms (all n = 5; PRO-Kinetic Energy, Orsiro: BIOTRONIK AG, Bülach, Switzerland; MULTI-LINK 8, XIENCE Xpedition: Abbott Vascular, Temecula, CA; REBEL Monorail, Promus PREMIER, Boston Scientific, Marlborough, MA; Integrity, Resolute Integrity, Medtronic, Minneapolis, MN; Kaname, Ultimaster: Terumo Corporation, Tokyo, Japan). Statistical analysis used pooled variance t tests for pairwise comparison of BMS with DES. Crimped profiles in BMS groups ranged from 0.97 ± 0.01 mm (PRO-Kinetic Energy) to 1.13 ± 0.01 mm (Kaname) and in DES groups from 1.02 ± 0.01 mm (Orsiro) to 1.13 ± 0.01 mm (Ultimaster). Crossability was best for low profile stent systems. Elastic recoil ranged from 4.07 ± 0.22% (Orsiro) to 5.87 ± 0.54% (REBEL Monorail) including both BMS and DES. The bending stiffness of crimped and expanded stents showed no systematic differences between BMS and DES neither did the scaffolding. Based on in vitro measurements BMS appear superior to DES in some aspects of mechanical performance, yet the differences are small and not class uniform. The data provide assistance in selecting the optimal system for treatment and assessment of new generations of bioresorbable scaffolds. not applicable.

  18. A SINGLE-COLUMN PROCEDURE ON BOND ELUT CERTIFY FOR SYSTEMATIC TOXICOLOGICAL ANALYSIS OF DRUGS IN PLASMA AND URINE

    NARCIS (Netherlands)

    CHEN, XH; WIJSBEEK, J; FRANKE, JP; DEZEEUW, RA

    A single-column solid-phase extraction procedure was developed for the screening of acidic, neutral, and basic drugs from plasma. The recoveries of all 25 tested drugs exceeded 82%. After the plasma had been diluted with phosphate buffer (pH 6.0), the drugs were extracted using a single Bond Elut

  19. Spectral Analysis Related to Bare-Metal and Drug-Eluting Coronary Stent Implantation

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Rose Mary Ferreira Lisboa da, E-mail: roselisboa@cardiol.br [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil); Silva, Carlos Augusto Bueno [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil); Belo Horizonte, Hospital São João de Deus, Divinópolis, MG (Brazil); Greco, Otaviano José [Belo Horizonte, Hospital São João de Deus, Divinópolis, MG (Brazil); Moreira, Maria da Consolação Vieira [Faculdade de Medicina da UFMG, Divinópolis, MG (Brazil)

    2014-08-15

    The autonomic nervous system plays a central role in cardiovascular regulation; sympathetic activation occurs during myocardial ischemia. To assess the spectral analysis of heart rate variability during stent implantation, comparing the types of stent. This study assessed 61 patients (mean age, 64.0 years; 35 men) with ischemic heart disease and indication for stenting. Stent implantation was performed under Holter monitoring to record the spectral analysis of heart rate variability (Fourier transform), measuring the low-frequency (LF) and high-frequency (HF) components, and the LF/HF ratio before and during the procedure. Bare-metal stent was implanted in 34 patients, while the others received drug-eluting stents. The right coronary artery was approached in 21 patients, the left anterior descending, in 28, and the circumflex, in 9. As compared with the pre-stenting period, all patients showed an increase in LF and HF during stent implantation (658 versus 185 ms2, p = 0.00; 322 versus 121, p = 0.00, respectively), with no change in LF/HF. During stent implantation, LF was 864 ms2 in patients with bare-metal stents, and 398 ms2 in those with drug-eluting stents (p = 0.00). The spectral analysis of heart rate variability showed no association with diabetes mellitus, family history, clinical presentation, beta-blockers, age, and vessel or its segment. Stent implantation resulted in concomitant sympathetic and vagal activations. Diabetes mellitus, use of beta-blockers, and the vessel approached showed no influence on the spectral analysis of heart rate variability. Sympathetic activation was lower during the implantation of drug-eluting stents.

  20. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    International Nuclear Information System (INIS)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M.

    2010-01-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings

  1. Porous Polymer Drug-Eluting Coating Prepared by Radiation Induced Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Veres, M.; Beiler, B.; Himics, L.; Tóth, S.; Koós, M., E-mail: vm@szfki.hu [Hungarian Academy of Sciences, Research Institute for Solid State Physics and Optics, Department of Laser Applications, Konkoly Thege Miklós ut 29-33, 1121 Budapest, P.O. Box 49, 1525 Budapest (Hungary)

    2010-07-01

    Many areas of modern medicine are almost unimaginable without the use of different kinds of implants. They used as replacements, supports, auxiliary devices etc. for various parts or functions of the body. Their use has many advantages, however there could be some drawbacks too, like the possibility of rejection, inflammation and other side-effects. Many of these drawbacks are directly related to the materials used for the implant fabrication. Coatings are widely used to eliminate the unwanted effects appearing after the implantation. In addition to the protection and separation of tissues from the implant material they could also enhance the functionality and the acceptance of the artificial device and also promote the regeneration of the tissues after the intervention. Drug-eluting coatings are a good example for the latter. By delivery and controlled elution of drugs they could actively suppress inflammatory reactions, allergy and rejection of the implant, and their activity is localized to the place where these effects could mainly occur – to the region of the implant. This project is aimed to develop a drug-eluting porous polymer coating by radiation induced polymerization that can be used in different medical implants. The primary objects for this research are coronary stents however these porous layers could have perspective in other types of medical devices too. The main objectives are to develop a method for coating the surface of medical grade metallic alloy wires, plates and tubes with a porous polymer nanocomposite layer prepared by radiation induced polymerization and to characterize the obtained coatings.

  2. Application of rotational atherectomy in the drug-eluting stent era

    Science.gov (United States)

    Chen, Chun-Chi; Hsieh, I-Chang

    2013-01-01

    Rotational atherectomy (RA) was introduced in the interventional arena in 1988 as a dedicated device for calcified lesions. Due to the complexity of the technique, the development of alternative methods such as the cutting balloon procedure, and the high restenosis rate of subsequent bare metal stenting in long lesions, its use had later declined. However, with the increasing use of drug-eluting stents (DES) and the aggressive treatment of longer lesions, the number of procedure performed with RA has increased significantly again in recent years. In this article, we reviewed the application of RA in DES era. PMID:24133506

  3. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    International Nuclear Information System (INIS)

    Pua, Uei

    2013-01-01

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192–198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960–966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  4. Drug eluting stents and modern stent technologies for in-stent restenosis.

    Science.gov (United States)

    Werner, Martin

    2017-08-01

    The implantation of metallic stents has become a standard procedure to improve the outcome after angioplasty of peripheral vessels. However, the occurrence of in-stent restenosis is hampering the long-term efficacy of these procedures and is associated with re-occurrence of symptoms. The optimal treatment modality for in-stent-restenosis in the peripheral vasculature is not well examined. This review discusses the existing evidence for the treatment of in-stent restenosis with drug eluting stents and modern stent technologies.

  5. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

    2013-06-15

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  6. 3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents.

    Science.gov (United States)

    Alfonso, Fernando; Pérez-Vizcayno, María José; Cuesta, Javier; García Del Blanco, Bruno; García-Touchard, Arturo; López-Mínguez, José Ramón; Masotti, Mónica; Zueco, Javier; Cequier, Angel; Velázquez, Maite; Moreno, Raúl; Mainar, Vicente; Domínguez, Antonio; Moris, Cesar; Molina, Eduardo; Rivero, Fernando; Jiménez-Quevedo, Pilar; Gonzalo, Nieves; Fernández-Pérez, Cristina

    2018-05-28

    This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). Treatment of patients with DES-ISR remains a challenge. The RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p 1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940). Published by Elsevier Inc.

  7. DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

    International Nuclear Information System (INIS)

    Asmis, Lars; Tanner, Felix C.; Sudano, Isabella; Luescher, Thomas F.; Camici, Giovanni G.

    2010-01-01

    Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents. Methods and results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54 ± 0.9427%, n = 5, P < 0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0% ± 4.031, n = 9, P = 0.0004 versus control) as well as a decreased maximal aggregation (-6.388 ± 2.212%, n = 6, P = 0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.

  8. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Denise Oliveira, E-mail: dennizmo@yahoo.com.br; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo [Hospital São Lucas PUC, Porto Alegre, RS (Brazil)

    2014-09-15

    Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. To evaluate the efficacy and safety of drug-eluting stents in the real world. We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the 'real world' may benefit from drug-eluting stenting with excellent, long-term results.

  9. Irinotecan drug eluting beads used as a treatment of advanced intra hepatic cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Jean Amede Roch

    2008-10-01

    Full Text Available

    This report describes a 74-year-old male with unresectable intrahepatic cholangiocarcinoma (ICC. However surgical procedure is the only curative treatment, it often seems to be ineffective because of the aggressive behaviour of the disease. The role of systemic chemotherapy in the ICC is undefined with a median survival between 6.43 to 12.17 months obtained by using the combination chemotherapy of gemcitabine with cisplatin. In the present case, we performed a targeted treatment using drug eluting beads (DEB with irinotecan (IRI administered as transarterial-chemoembolization (TACE. After one session, the tumour vascularity decreased significantly at the one month evaluation on computed tomography (CT scan of the liver.  This case report suggested that minimally invasive transcatheter DEB embolization could be a promising, safe and effective treatment for selective patients with unresectable ICC.

  10. Successful drug-eluting stent implantation in a male patient with dextrocardia: a case report

    Directory of Open Access Journals (Sweden)

    Long Wenjie

    2017-12-01

    Full Text Available Situs inversus with dextrocardia is a rare condition, with complete transposition of all the body organs, including the heart. Percutaneous coronary intervention (PCI in these patients is technically difficult because of the mirror image of organs. Here, we describe a 56-year-old man with coronary heart disease with known situs inversus with dextrocardia and coronary percutaneous intervention was performed for stenosis in the right coronary artery. A drug eluting stent was implanted at this site successfully. This case suggested that the interventional management of such patients follows the same general rules as for non-dextrocardia patients, but the manipulation of the catheter and projection position choices need to be taken into consideration to obtain optimal benefits for the patient.

  11. Patient-Centered Tablet Application for Improving Medication Adherence after a Drug-Eluting Stent.

    Science.gov (United States)

    Shah, Vicki; Dileep, Anandu; Dickens, Carolyn; Groo, Vicki; Welland, Betty; Field, Jerry; Baumann, Matthew; Flores, Jose D; Shroff, Adhir; Zhao, Zhongsheng; Yao, Yingwei; Wilkie, Diana J; Boyd, Andrew D

    2016-01-01

    This study's objective was to evaluate a patient-centered educational electronic tablet application, "My Interventional Drug-Eluting Stent Educational App" (MyIDEA) to see if there was an increase in patient knowledge about dual antiplatelet therapy (DAPT) and medication possession ratio (MPR) compared to treatment as usual. In a pilot project, 24 elderly (≥50 years old) research participants were recruited after a drug-eluting stent. Eleven were randomized to the control arm and 13 to the interventional arm. All the participants completed psychological and knowledge questionnaires. Adherence was assessed through MPR, which was calculated at 3 months for all participants who were scheduled for second and third follow-up visits. Relative to control, the interventional group had a 10% average increase in MPR. As compared to the interventional group, more patients in the control group had poor adherence (<80% MPR). The psychological data revealed a single imbalance in anxiety between the control and interventional groups. On average, interventional participants spent 21 min using MyIDEA. Consumer health informatics has enabled us to engage patients with their health data using novel methods. Consumer health technology needs to focus more on patient knowledge and engagement to improve long-term health. MyIDEA takes a unique approach in targeting DAPT from the onset. MyIDEA leverages patient-centered information with clinical care and the electronic health record highlighting the patients' role as a team member in their own health care. The patients think critically about adverse events and how to solve issues before leaving the hospital.

  12. Patient Centered Tablet Application for improving medication adherence after a Drug Eluting Stent

    Directory of Open Access Journals (Sweden)

    Vicki Shah

    2016-12-01

    Full Text Available Background/Aims: This study’s objective was to evaluate a patient-centered educational electronic tablet application, My Interventional Drug-Eluting Stent Educational App (MyIDEA to see if there was an increase in patient knowledge about dual antiplatelet therapy (DAPT and medication possession ratio (MPR compared to treatment as usual. Methods: In a pilot project, 24 elderly (≥50 years-old research participants were recruited after a Drug Eluting Stent. 11 were randomized to the control arm and 13 to the interventional arm. All participants completed psychological and knowledge questionnaires. Adherence was assessed through MPR, which was calculated at three months for all participants who were scheduled for a second and third follow-up visit.Results: Relative to control, the interventional group had a 10% average increase in MPR. As compared to the interventional group, more patients in the control group had poor adherence (<80% MPR. The psychological data revealed a single imbalance in anxiety between the control and interventional groups. On average interventional participants spent 21 minutes using MyIDEA. Discussion: Consumer health informatics has enabled us to engage patients with their health data using novel methods. Consumer health technology needs to focus more on patient knowledge and engagement to improve long term health. MyIDEA takes a unique approach in targeting DAPT from the onset.Conclusion: MyIDEA leverages patient centered information with clinical care and the electronic health record highlighting the patients’ role as a team member in their own healthcare. The patients think critically about adverse events and how to solve issues before leaving the hospital.

  13. The Role Of Inflammation In Stent Restenosis More Than 1 Year Afetr Drug Eluting Stent Implantation

    Directory of Open Access Journals (Sweden)

    Hasan Shemirani

    2011-09-01

    Full Text Available Background: In stent restenosis (ISR following endovascular interventions is the main limitation of their long-term success. Despite advances have been made during recent years to decrease restenosis, it remains a challenging clinical problem.The aim of this study was to evaluate the relationship between angiographic coronary in stent restenosis, inflammation after successful stent implantation. Methods: This study included 78 patients, 35year old and higher who underwent coronary angiography more than 1 year after drug-eluting stent (DES implantation because of symptoms suggestive ischemia. Patients were divided into ISR group (case and patent stent group (control according to angiography results. For all patients blood lipids and high sensitivity C-Reactive Protein (hsCRP were measured simultaneously. Results: Age, sex, hypertension, current smoking, and lipid profile other than High Density Lipoprotein (HDL-C of patients in the case and control groups were similar .However, HDL-C < 40mg/L was more prevalent with ISR (66.7% vs. 30.8%, p=0.002. The hsCRP level was 2.98±2.06 mg/L in the case group and 2.50±1.80 mg/L in the control group. There were no significant differences in mean hsCRP concentration between the two groups (p=0.14, however mean hsCRP level was significantly higher in men of case group than control group (3.35mg/L vs. 2.21mg/L, p<0.05. Conclusion: This study demonstrates that in men but not in women inflammation may be a predictor of in stent restenosis more than 1 year after drug eluting stent implantation. Also, high-density lipoprotein (HDL probably has protective effect against stent restenosis.

  14. Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study.

    Science.gov (United States)

    Bagust, A; Grayson, A D; Palmer, N D; Perry, R A; Walley, T

    2006-01-01

    To assess the cost effectiveness of drug eluting stents (DES) compared with conventional stents for treatment of symptomatic coronary artery disease in the UK. Cost-utility analysis of audit based patient subgroups by means of a simple economic model. Tertiary care. 12 month audit data for 2884 patients receiving percutaneous coronary intervention with stenting at the Cardiothoracic Centre Liverpool between January 2000 and December 2002. Risk of repeat revascularisation within 12 months of index procedure and reduction in risk from use of DES. Economic modelling was used to estimate the cost-utility ratio and threshold price premium. Four factors were identified for patients undergoing elective surgery (n = 1951) and two for non-elective surgery (n = 933) to predict risk of repeat revascularisation within 12 months. Most patients fell within the subgroup with lowest risk (57% of the elective surgery group with 5.6% risk and 91% of the non-elective surgery group with 9.9% risk). Modelled cost-utility ratios were acceptable for only one group of high risk patients undergoing non-elective surgery (only one patient in audit data). Restricting the number of DES for each patient improved results marginally: 4% of stents could then be drug eluting on economic grounds. The threshold price premium justifying 90% substitution of conventional stents was estimated to be 112 pound sterling (212 USD, 162 pound sterling) (sirolimus stents) or 89 pound sterling (167 USD, 130 pound sterling) (paclitaxel stents). At current UK prices, DES are not cost effective compared with conventional stents except for a small minority of patients. Although the technology is clearly effective, general substitution is not justified unless the price premium falls substantially.

  15. Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds: Evidence From a Network Meta-Analysis of 147 Trials.

    Science.gov (United States)

    Kang, Si-Hyuck; Chae, In-Ho; Park, Jin-Joo; Lee, Hak Seung; Kang, Do-Yoon; Hwang, Seung-Sik; Youn, Tae-Jin; Kim, Hyo-Soo

    2016-06-27

    This study sought to perform a systematic review and network meta-analysis to compare the relative safety and efficacy of contemporary DES and BVS. To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS). Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus-eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP)-EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP-BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year. A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP-BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization. Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices. Copyright © 2016 American College of Cardiology Foundation. Published by

  16. Factors that affect mass transport from drug eluting stents into the artery wall

    Directory of Open Access Journals (Sweden)

    Walsh Michael T

    2010-03-01

    Full Text Available Abstract Coronary artery disease can be treated by implanting a stent into the blocked region of an artery, thus enabling blood perfusion to distal vessels. Minimally invasive procedures of this nature often result in damage to the arterial tissue culminating in the re-blocking of the vessel. In an effort to alleviate this phenomenon, known as restenosis, drug eluting stents were developed. They are similar in composition to a bare metal stent but encompass a coating with therapeutic agents designed to reduce the overly aggressive healing response that contributes to restenosis. There are many variables that can influence the effectiveness of these therapeutic drugs being transported from the stent coating to and within the artery wall, many of which have been analysed and documented by researchers. However, the physical deformation of the artery substructure due to stent expansion, and its influence on a drugs ability to diffuse evenly within the artery wall have been lacking in published work to date. The paper highlights previous approaches adopted by researchers and proposes the addition of porous artery wall deformation to increase model accuracy.

  17. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    International Nuclear Information System (INIS)

    Hamlekhan, Azhang; Shokuhfar, Tolou; Sinha-Ray, Suman; Yarin, Alexander L; Takoudis, Christos; Mathew, Mathew T; Sukotjo, Cortino

    2015-01-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT. (paper)

  18. Local perivascular delivery of anti-restenotic agents from a drug-eluting poly(ε-caprolactone) stent cuff

    NARCIS (Netherlands)

    Pires, N.M.M.; Hoeven, B.L. van der; Vries, M.R. de; Havekes, L.M.; Vlijmen, B.J. van; Hennink, W.E.; Quax, P.H.A.; Jukema, J.W.

    2005-01-01

    The introduction of drug-eluting stents (DES) to prevent in-stent restenosis is one of the major advances in interventional cardiology. Currently many types of DES are under evaluation for effectiveness and safety, a time-consuming and difficult procedure in humans. An animal model that allows rapid

  19. Natural history of optical coherence tomography-detected non-flow-limiting edge dissections following drug-eluting stent implantation

    DEFF Research Database (Denmark)

    Radu, Maria D; Räber, Lorenz; Heo, Jungho

    2014-01-01

    history and clinical implications remain unclear. The objectives of the present study were to assess the morphology, healing response, and clinical outcomes of OCT-detected edge dissections using serial OCT imaging at baseline and at one year following drug-eluting stent (DES) implantation. METHODS...

  20. Correlates and Impact of Coronary Artery Calcifications in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Mastoris, Ioannis; Baber, Usman

    2016-01-01

    OBJECTIVES: The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES). BACKGROUND: The clinical correlates and the prognostic significance of CAC...

  1. Determination of 99Mo contamination in 99mTc elute obtained from 99Mo/99mTc- generator

    International Nuclear Information System (INIS)

    Momennezhad, M.; Zakavi, S. R.; Sadeghi, R.

    2010-01-01

    99m Tc is a widely used radioisotope in nuclear medicine centers which is obtained by elution from Mo-99/Tc-99m generators. Usually the generators are either supplied by the Iran Atomic Energy Agency or by private companies from foreign countries. In this study we have measured 99 Mo contamination in 99m Tc elute from different generators in a period of one year. Materials and Methods: The radionuclide impurity of the 99m Tc elute were studied in two types of radionuclide generators (A: produced in Iran and B: Imported from other country). In-vitro measurements were performed using dose calibrator. Direct measurements were made, using a standard canister at the time of milking of the generators and also in Subsequent hours after milking. Results: The results showed a mean of 99 Mo impurity in generators A and B to be 0.00932±0.0043 and 0.0170±0.0127 respectively. Although the results showed that the 99 Mo contamination in 99 mTc elute was lesser than the maximum accepted activity limit of 0.015%, the difference in these two types may reflect different methods of productions of generator, as well as the quality control procedures. Conclusion: The mean of 99 Mo contamination in generators produced in Iran Atomic Energy Organization was lesser than generators imported from foreign origin.

  2. Sustained multiple organ ischaemia after transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

    Science.gov (United States)

    Kim, Young Woon; Kwon, Jung Hyun; Nam, Soon Woo; Jang, Jeong Won; Jung, Hyun Suk; Shin, Yu Ri; Park, Eun Su; Shim, Dong Jae

    2018-02-01

    Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads) may enhance drug delivery to tumours and reduce systemic toxicity. TACE with DC beads leads to significantly fewer serious side-effects compared with conventional TACE. A 66-year-old man with hepatocellular carcinoma (HCC) complained of continuous abdominal pain 1 month after TACE with DC beads. At the time of TACE, angiography revealed severe stenosis of both hepatic arteries. The diagnostic work up on admission suggested severe bile duct injury with regional bile duct dilatation, segmental liver and spleen infarction, necrotizing pancreatitis, as well as gastric and duodenal ulcers. The pathology specimens of the duodenum contained DC beads that had passed through small vessels in the connective tissue. The patient's condition appeared to improve after 2 weeks of antibiotic treatment and supportive care, but new multifocal liver and spleen infarction subsequently developed. After 2 months, he was well enough to be discharged. His HCC partially responded to the TACE with DC beads but eventually progressed and he died after 11 months. The present case report highlights unexpected ongoing multiple organ ischaemia in a 66-year-old man treated for HCC using TACE with DC beads. The use of TACE with DC beads should be carefully considered in patients with vascular strictures or aberrant blood supply.

  3. The study of drug eluting biodegradable intravascular stent with antiproliferation agent-paclitaxel in preventing vascular restenosis

    International Nuclear Information System (INIS)

    Xiao Yueyong; Zhang Jinshan; Cui Fuzhai; Meng Bo

    2004-01-01

    Objective: To define the effect of drug eluting BIS with antiproliferation agent-paclitaxel in preventing vascular restenosis. Methods: Bare BIS and drug BIS with 60 μg paclitaxel were prepared. Both types of the BIS were implanted into the infrarenal restenosis aortas in canine models, and the animals were euthanized 6 weeks after implantation for histopathological, morphometric and immunohistochemical assessment. Results: The mean lumen area of bare BIS group was (77 586.5 ± 66.0) μm 2 , and lumen of paclitaxel eluting BIS group was (113 435.9 ±71.0) μm 2 . The mean neointima area of bare BIS group was (24 803 ± 56) μm 2 , and paclitaxel eluting BIS group was (12 931 ± 63) μm 2 . The PCNA-positive ratio was (38 ± 15)% in bare BIS group and (11 ± 0.31)% in paclitaxel eluting BIS group. The statistically significant difference between the two groups were noted (P<0.01). Conclusion: BIS as a vehicle of loading and releasing drugs could significantly inhibit the VSMC and neointimal hyperplasia with antiproliferation agent-paclitaxel. BIS is a promising and new strategy in preventing the restenosis

  4. Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

    International Nuclear Information System (INIS)

    Moscarella, Elisabetta; Varricchio, Attilio; Stabile, Eugenio; Franzone, Anna; Granata, Francesco; Rapacciuolo, Antonio; Galasso, Gennaro; Capozzolo, Claudia; Cirillo, Plinio

    2015-01-01

    Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

  5. Bioabsorbable drug-eluting vascular scaffold for the treatment of coronary in-stent restenosis: A two center registry

    Energy Technology Data Exchange (ETDEWEB)

    Moscarella, Elisabetta [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Varricchio, Attilio [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Stabile, Eugenio, E-mail: geko50@hotmail.com [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Franzone, Anna [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Granata, Francesco [Division of Cardiology, Seconda Università degli studi di Napoli, AO Dei cColli, PO Monaldi (Italy); Rapacciuolo, Antonio; Galasso, Gennaro [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); Capozzolo, Claudia [Division of Cardiology, Department of Advanced Biomedical Sciences, University of Napoli “Federico II”, Napoli (Italy); Cirillo, Plinio [Laboratory of Invasive Cardiology, Dipartimento di Cardiologia, Presidio Ospedaliero “Monaldi”, Azienda Ospedaliera “Dei Colli”, Napoli (Italy); and others

    2015-10-15

    Background/purpose: Coronary in-stent restenosis (ISR) is a clinical problem for which a satisfactory solution has not been found yet. Bioabsorbable drug eluting vascular scaffolds (BVSs) provide transient vessel scaffolding combined with prolonged drug delivery capability. The aim of this study was to investigate the safety of BVS for the treatment of coronary ISR. Methods/materials: Between January 2013 and June 2013, 27 patients (31 lesions), presenting with either stable or unstable angina due to coronary ISR, were enrolled in a single arm, prospective, open label registry. Primary end point was the occurrence of target vessel revascularization (TVR) at 12 months. Secondary end point was the composite of death, myocardial infarction and TVR at 12 months. Results: A diffuse ISR pattern was present in 70% of the lesions; mean lesion length was 34.6 ± 15. BVS was successfully implanted in all patients with no in hospital MACE. At twelve months of follow up, MACE rate was 18.5%. One patient died for non-cardiac reason, one patient died due to a possible stent thrombosis and TVR was necessary in 3 patients (11.1%). Conclusions: Our data suggest that BVS is safe and technically feasible for treatment of long and diffuse coronary ISR. These data could be considered hypothesis generator for a randomized clinical trial. - Highlights: • A safe therapeutic option for the treatment of diffuse ISR; • Technically feasible; • Associated to a low rate of restenosis recurrence at nine month.

  6. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis.

    Science.gov (United States)

    Palmerini, Tullio; Biondi-Zoccai, Giuseppe; Della Riva, Diego; Stettler, Christoph; Sangiorgi, Diego; D'Ascenzo, Fabrizio; Kimura, Takeshi; Briguori, Carlo; Sabatè, Manel; Kim, Hyo-Soo; De Waha, Antoinette; Kedhi, Elvin; Smits, Pieter C; Kaiser, Christoph; Sardella, Gennaro; Marullo, Antonino; Kirtane, Ajay J; Leon, Martin B; Stone, Gregg W

    2012-04-14

    The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare

  7. Patient-rated health status predicts prognosis following percutaneous coronary intervention with drug-eluting stenting

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Versteeg, Henneke; Denollet, Johan

    2011-01-01

    In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events.......In patients treated with percutaneous coronary intervention (PCI) with the paclitaxel-eluting stent, we examined whether patient-rated health status predicts adverse clinical events....

  8. Attitudes towards drug-eluting stent use and the distribution of motivation type among interventional cardiologists.

    Science.gov (United States)

    Qian, Feng; Phelps, Charles E; Ling, Frederick S; Hannan, Edward L; Veazie, Peter J

    2012-06-01

    The safety of drug-eluting stent (DES) use was called into question in 2006. However, the attitudes towards DES use after DES safety concerns were expressed and the distribution of chronic motivation type among interventional cardiologists are unknown. This study aims to examine the current attitudes towards DES use among interventional cardiologists and to investigate the distribution of chronic motivation type among these doctors. A questionnaire survey of interventional cardiologists was conducted in New York State from October 2008 to April 2009. The questionnaire included face valid items to measure the attitudes towards DES use, valid Regulatory Focus Questionnaire to measure the chronic motivation type, and items collecting demographic information. A total of 119 valid responses were received (response rate: 47%). There were no statistically significant differences regarding the demographic factors between the respondents and the non-respondents. The vast majority of interventional cardiologists (92%) agreed that 'DES is a revolutionary technology' and that 'DES use will increase in the future' (70%). The chronic motivation type of the respondents was predominantly sensitive to positive outcomes (89%). Interventional cardiologists had a very positive attitude regarding DES technology and predicted future growth of DES use. The vast majority of interventional cardiologists were found to be concerned about achieving positive outcomes and wanted to prevent errors of omission. To the best of our knowledge, this is the first study to report the distribution of chronic motivation type among doctors. © 2011 Blackwell Publishing Ltd.

  9. Disappearing and reappearing differences in drug-eluting stent use by race.

    Science.gov (United States)

    Federspiel, Jerome J; Stearns, Sally C; Reiter, Kristin L; Geissler, Kimberley H; Triplette, Matthew A; D'Arcy, Laura P; Sheridan, Brett C; Rossi, Joseph S

    2013-04-01

    Drug-eluting coronary stents (DES) rapidly dominated the marketplace in the United States after approval in 2003, but utilization rates were initially lower among African American patients. We assess whether racial differences persisted as DES diffused into practice. Medicare claims data were used to identify coronary stenting procedures among elderly patients with acute coronary syndromes (ACS). Regression models of the choice of DES versus bare mental stent controlled for demographics, ACS type, co-morbidities and hospital characteristics. Diffusion was assessed in the short run (2003-2004) and long run (2007), with the effect of race calculated to allow for time-varying effects. The sample included 381,887 Medicare beneficiaries treated with stent insertion; approximately 5% were African American. Initially (May 2003-February 2004), African American race was associated with lower DES use compared to other races (44.3% versus 46.5%, P differences were not significant (79.8% versus 80.3%, P = 0.45). Subsequent concerns regarding DES safety caused reductions in DES use, with African Americans having lower use than other racial groups in 2007 (63.1% versus 65.2%, P differences in race reflect decisions regarding treatment appropriateness. © 2011 Blackwell Publishing Ltd.

  10. Clinical evaluation of domestic biodegradable drug-eluting stents in the treatment of coronary heart disease

    International Nuclear Information System (INIS)

    Yu Hongying; Suo Chuantao; Shang Ruiping

    2009-01-01

    Objective: To evaluate the safety and efficacy of domestic biodegradable drug-eluting stent, EXCEL, in clinical treatment of coronary heart disease. Methods: During the period of Jan. 2008-Oct. 2008, 100 patients with coronary heart disease who consented to PCI and postoperative coronary angiography were selected and enrolled in the study. The patients were divided into EXCEL group (n = 58) and Cypher group (n = 42). The immediate successful rate of interventional therapy and the complications occurred during hospitalization were observed. Postoperative follow-up and checkup coronary angiography were conducted. Results: No significant difference in the relevant clinical data, in the number and type of diseased coronary branch and in the mean length of implanted stents existed between two groups. Also, no statistically significant difference in the occurrence of major adverse cardiac event (MACE), in-stent restenosis and thrombosis was present between two groups. Conclusion: Compared with Cypher stenting, EXCEL stenting carries similar, i.e. rather low, occurrence of MACE and in-stent restenosis. (authors)

  11. Drug-eluting stent implantation for the percutaneous treatment of vertebro-basilar arterial stenosis

    International Nuclear Information System (INIS)

    Ma Rujun; Liu Jianmin; Huang Haiqing; Hong Bo; Xu Yi; Zhao Wenyuan; Zhao Rui; Chen Jun

    2006-01-01

    Objective: To evaluate the early results and mid-term outcomes following angioplasty of vertebro-basilar arterial stenosis with drug-eluting stents. Methods: All of the patients presented with recurrent TIA or ceretral infarction with >50% stenoses in vertebro-basilar arteries, and having failure in maximal medical therapy. All of the lesions were treated with primary stenting under local or general anesthesia and followed by continual anticoagulant therapy of clopidogrel and aspirin together with clinical follow-up and vascular imagings. Results: Of 28 stenoses (27 patients), 27 lesions were successfully treated with implantation of 24 Cypher stents, 2 Taxus stents and one Firebird stent. The mean stenotic severity reduced from (74 ± 6.7)% to (8.7 ± 4.4)%. Two patients had inchemic events relating to penetration vascular obstruction. During 2-14 months follow-up, the patients were clinically asymptomatic with no recurrent TIA/stoke. Angiographic follow-up was obtained in 14 patients at a mean of 7.2 months. Proximal restenosis (<50%) occurred in one patient (3.3%), and corrected with restenting, while others were free of intra-stent restenoses. Conclusion: Using DES in cerebrovascular stenosis is safe and effective with lowing the risk of intra-stent restenosis in comparison with bare stent. Further study for long term efficiency is still in need. (authors)

  12. Bioerodible drug/eluting stent coating with highly controllable drug release rate and excellent vascular biocompatibility

    Czech Academy of Sciences Publication Activity Database

    Rypáček, František; Mulinková, Katarína; Bernátková, Markéta; Machová, Luďka; Lapčíková, Monika; Otsuka, Y.; Robinson, K. A.; Mulkey, S. P.; Baranowski, C.; Zablocki, J.; Blackburn, B. K.; Chronos, N.

    2005-01-01

    Roč. 96, 7A (2005), 209H-210H ISSN 0002-9149. [Annual Conference of Transcathetral Cardiovascular Therapeutics /17./. Washington, 16.10.2005-21.10.2005] R&D Projects: GA AV ČR IAA4050202 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug delivery * polymer coating * stent Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.059, year: 2005

  13. In vitro haematic proteins adsorption and cytocompatibility study on acrylic copolymer to realise coatings for drug-eluting stents

    International Nuclear Information System (INIS)

    Gagliardi, Mariacristina

    2012-01-01

    In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synthesised acrylic copolymers is reported. In particular, with the aim to obtain coatings for drug-eluting stents, blood protein absorption and cytocompatibility were studied. For protein absorption tests, bovine serum albumin and bovine plasma fibrinogen were considered. Cytocompatibility was tested using C2C12 cell line as model, analysing the behaviour of polymeric matrices and of drug-eluting systems, obtained loading polymeric matrices with paclitaxel, an anti-mitotic drug, in order to evaluate the efficacy of a pharmacological treatment locally administered from these materials. Results showed that the amount of albumin absorbed was greater than the amount of fibrinogen (comprised in the range of 70%–85% and 10%–22% respectively) and it is a good behaviour in terms of haemocompatibility. Cell culture tests showed good adhesion properties and a relative poor proliferation. In addition, a strong effect related to drug elution and a correlation with the macromolecular composition were detected. In this preliminary analysis, tested materials showed good characteristics and can be considered possible candidates to obtain coatings for drug-eluting stents. Highlights: ► Preliminary evaluation of haemo- and cytocompatibility of newly-synthesised acrylic copolymers ► Materials adsorb higher amounts of albumin and with a faster rate than fibrinogen. ► Protein adsorption depended on the macromolecular composition and surface properties. ► Cell viability on pure samples and efficacy of paclitaxel release were verified in C2C12 cultures.

  14. In vitro haematic proteins adsorption and cytocompatibility study on acrylic copolymer to realise coatings for drug-eluting stents

    Energy Technology Data Exchange (ETDEWEB)

    Gagliardi, Mariacristina, E-mail: mariacristina.gagliardi@iit.it

    2012-12-01

    In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synthesised acrylic copolymers is reported. In particular, with the aim to obtain coatings for drug-eluting stents, blood protein absorption and cytocompatibility were studied. For protein absorption tests, bovine serum albumin and bovine plasma fibrinogen were considered. Cytocompatibility was tested using C2C12 cell line as model, analysing the behaviour of polymeric matrices and of drug-eluting systems, obtained loading polymeric matrices with paclitaxel, an anti-mitotic drug, in order to evaluate the efficacy of a pharmacological treatment locally administered from these materials. Results showed that the amount of albumin absorbed was greater than the amount of fibrinogen (comprised in the range of 70%-85% and 10%-22% respectively) and it is a good behaviour in terms of haemocompatibility. Cell culture tests showed good adhesion properties and a relative poor proliferation. In addition, a strong effect related to drug elution and a correlation with the macromolecular composition were detected. In this preliminary analysis, tested materials showed good characteristics and can be considered possible candidates to obtain coatings for drug-eluting stents. Highlights: Black-Right-Pointing-Pointer Preliminary evaluation of haemo- and cytocompatibility of newly-synthesised acrylic copolymers Black-Right-Pointing-Pointer Materials adsorb higher amounts of albumin and with a faster rate than fibrinogen. Black-Right-Pointing-Pointer Protein adsorption depended on the macromolecular composition and surface properties. Black-Right-Pointing-Pointer Cell viability on pure samples and efficacy of paclitaxel release were verified in C2C12 cultures.

  15. Cost-effectiveness analysis of biodegradable polymer versus durable polymer drug-eluting stents incorporating real-world evidence.

    Science.gov (United States)

    Teng, Monica; Zhao, Ying Jiao; Khoo, Ai Leng; Ananthakrishna, Rajiv; Yeo, Tiong Cheng; Lim, Boon Peng; Chan, Mark Y; Loh, Joshua P

    2018-06-05

    Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over one year and five years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent four years were derived from a meta-analysis of published studies. At one year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20,503 per quality-adjusted life-year (QALY) gained. At five years, BP-DES yielded an ICER of USD4,062 per QALY gained. At the willingness-to-pay threshold of USD50,400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with one-year of follow-up. BP-DES were cost-effective compared with DP-DES in patients with coronary artery disease at one year and five years after PCI. It is worth noting that the cost of stents had a significant impact on the findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Preparation of paclitaxel/chitosan co-assembled core-shell nanofibers for drug-eluting stent

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jing; Liu, Yongjia [Instrumental Analysis Center, Shanghai Jiao Tong University, 200240 Shanghai (China); State Key Laboratory of Metal Matrix Composites, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 200240 Shanghai (China); Zhu, Bangshang, E-mail: bshzhu@sjtu.edu.cn [Instrumental Analysis Center, Shanghai Jiao Tong University, 200240 Shanghai (China); State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, 201620 Shanghai (China); Su, Yue; Zhu, Xinyuan [State Key Laboratory of Metal Matrix Composites, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 200240 Shanghai (China)

    2017-01-30

    Highlights: • The core-shell nanofibers (NFs) were made by the co-assembly of paclitaxel (PTX) and chitosan(CS). • The PTX/CS NFs have high PTX loading content, slow drug release and low adherence of platelets. • The PTX/CS NFs have low cytotoxicity and good haemocompatibility. • The PTX/CS NFs which could be easily coated on stents could have potential application for drug eluting stents. - Abstract: The paclitaxel/chitosan (PTX/CS) core-shell nanofibers (NFs) are easily prepared by co-assembly of PTX and CS and used in drug-eluting stent. The mixture solution of PTX (dissolved in ethanol) and CS (dissolved in 1% acetic acid water solution) under sonication will make the formation of NFs, in which small molecule PTX co-assembles with biomacromolecular CS through non-covalent interactions. The obtained NFs are tens to hundreds nanometers in diameter and millimeter level in length. Furthermore, the structure of PTX/CS NFs was characterized by confocal laser scanning microscopy (CLSM), zeta potential, X-ray photoelectron spectroscopy (XPS) and nanoscale infra-red (nanoIR), which provided evidences demonstrated that PTX/CS NFs are core-shell structures. The ‘shell’ of CS wrapped outside of the NFs, while PTX is located in the core. Thus it resulted in high drug loading content (>40 wt.%). The well-controlled drug release, low cytotoxicity and good haemocompatibility were also found in drug carrier system of PTX/CS NFs. In addition, the hydrophilic and flexible properties of NFs make them easily coating and filming on stent to prepare drug-eluting stent (DES). Therefore, this study provides a convenient method to prepare high PTX loaded NFs, which is a promising nano-drug carrier used for DES and other biomedical applications. The possible molecular mechanism of PTX and CS co-assembly and core-shell nanofiber formation is also explored. Statement of significance: We develop a convenient and efficient approach to fabricate core-shell nanofibers (NFs) through

  17. Response rates of hepatocellular carcinoma and hepatic colorectal cancer metastases to drug eluting bead regional liver therapy

    Institute of Scientific and Technical Information of China (English)

    Glenn W. Stambo; Deborah Cragan

    2017-01-01

    Aim: The purpose of this study was to evaluate and compare how hepatocellular carcinoma (HCC) and colorectal metastases respond to LC Bead chemoembolization using doxorubicin and irinotecan. Methods: The authors report their experience with doxorubicin and irinotecan eluting beads to treat 13 patients with primary HCC and 25 patients with colorectal metastases over a 1-year period at a single community based oncology practice. Within the colorectal cancer group they compared irinotecan eluting beads to doxorubicin eluting beads. Results:Nine of the 11 (81.8%) doxorubicin treated HCC patients had either complete response or partial response. All of the HCC lesions showed reduction in size and tumor enhancement and 10/11 (91%) HCC patients were alive at 24 months post treatment. Fisher's exact test revealed that among the 22 with colorectal metastases for whom follow-up data were available, those 11 who were treated with doxorubicin were significantly more likely to demonstrate complete or partial response compared to the 11 in the irinotecan treated group (P < 0.001). Conclusion:Overall, HCC and colon metastasis patients clearly demonstrated the effectiveness of drug eluting beads with 91% of the HCC patients alive 24 months after treatment.

  18. Simple balloon dilation for drug-eluting in-stent restenosis: An optical coherent tomography analysis

    Energy Technology Data Exchange (ETDEWEB)

    Arikawa, Ryo [Division of Cardiology, Tenyoukai Central Hospital, Izumi-cho, Kagoshima City, Kagoshima (Japan); Yamaguchi, Hiroshi, E-mail: hyamaguchi@tsm.bbiq.jp [Division of Cardiology, Tenyoukai Central Hospital, Izumi-cho, Kagoshima City, Kagoshima (Japan); Takaoka, Junichiro; Miyamura, Akihiro; Atsuchi, Nobuhiko; Ninomiya, Toshiko; Atsuchi, Yoshihiko [Division of Cardiology, Tenyoukai Central Hospital, Izumi-cho, Kagoshima City, Kagoshima (Japan); Ohishi, Mitsuru [Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Science, Kagoshima University, Kagoshima (Japan); Terashima, Mitsuyasu [Department of Cardiology, Toyohashi Heart Center, Toyohashi (Japan); Kaneda, Hideaki [Okinaka Memorial Institute for Medical Research, Tokyo (Japan)

    2015-01-15

    Background: Although drug-eluting stent (DES) has significantly reduced restenosis, the treatment of DES-in-stent restenosis (ISR) remains a challenge with high restenosis rate. Methods: We examined whether morphologic appearance of restenosis tissue by optical coherent tomography (OCT) had an impact on outcomes after balloon angioplasty for DES-ISR. The morphologic appearance of restenosis tissue was qualitatively assessed for tissue structures such as homogeneous, layered, and heterogeneous patterns. Results: Using OCT, 50 patients with DES-ISR were divided into 2 groups: 25 lesions with homogeneous or layered patterns (homo/layered group) and 25 lesions with heterogeneous patterns (hetero group). Acute gain was larger in the hetero group (1.33 ± 0.41 mm vs. 1.06 ± 0.32 mm in the homo/layered group, P = 0.03). On intravascular ultrasound analysis, post-procedural percent neointimal area was smaller in the hetero group (27.4 ± 9.2% vs. 34.0 ± 11.2% in the homo/layered group, P = 0.05). Angiographic follow-up was performed in 37 lesions (74%). Follow-up minimal lumen diameter was larger in the hetero group (1.75 ± 0.89 mm vs. 1.01 ± 0.81 mm in the homo/layered group, P = 0.04). Target lesion revascularization rates tended to be lower in the hetero group (20% vs. 43% in the homo/layered group, P = 0.12). Conclusions: Balloon angioplasty was more effective for DES-ISR with heterogeneous tissue appearance than DES-ISR with homogeneous/layered tissue appearance. OCT assessment of DES-ISR morphology may be a useful adjunct in determining clinical strategies. Simple balloon dilatation is a possible treatment strategy for DES-ISR lesions with a heterogeneous appearance on OCT images.

  19. Drug elution from high-dose antibiotic-loaded acrylic cement: a comparative, in vitro study.

    Science.gov (United States)

    Gasparini, Giorgio; De Gori, Marco; Calonego, Giovanni; Della Bora, Tommaso; Caroleo, Benedetto; Galasso, Olimpio

    2014-11-01

    High-dose antibiotic-loaded acrylic cement (ALAC) is used for managing peri-prosthetic joint infections (PJIs). The marked increase in resistant high-virulence bacteria is drawing the attention of physicians toward alternative antimicrobial formulations loaded into acrylic bone cement. The aim of this in vitro study was to determine the elution kinetics of 14 different high-dose ALACs. All ALAC samples showed a burst release of antibiotics in the first hour, progressively decreasing over time, and elution curves strictly adhered to a nonlinear regression analysis formula. Among aminoglycosides, commonly seen as the most appropriate antibiotics to be loaded into the bone cement, the highest elution rate was that of tobramycin. Among the glycopeptides, a class of antibiotics that should be considered to treat PJIs because of the prevalence of aminoglycoside resistance, vancomycin showed better elution than teicoplanin. Clindamycin, which can be associated with aminoglycosides to prepare ALACs and represents a useful option against the most common pathogens responsible for PJIs, showed the highest absolute and relative elutions among all the tested formulations. A noticeable elution was also detected for colistin, an antibiotic of last resort for treating multidrug-resistant bacteria. The current study demonstrates theoretical advantages in the preparation of ALAC for some antibiotics not routinely used in the clinical setting for PJIs. The use of these antibiotics based on the infecting bacteria sensitivity may represent a useful option for physicians to eradicate PJIs. In vivo testing should be considered in the future to confirm the results of this study. Copyright 2014, SLACK Incorporated.

  20. Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

    Science.gov (United States)

    Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

    2015-01-01

    Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

  1. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention.

    Science.gov (United States)

    Baschet, Louise; Bourguignon, Sandrine; Marque, Sébastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations.

  2. Drug-eluting stents and bare metal stents in patients with NSTE-ACS

    DEFF Research Database (Denmark)

    Pedersen, Sune Haahr; Pfisterer, Matthias; Kaiser, Christoph

    2014-01-01

    the randomised BASKET-PROVE trial (sirolimus-eluting stent vs. everolimus-eluting stent vs. bare metal stent in large-vessel stenting). The primary endpoint was the combined two-year rate of cardiovascular death or non-fatal myocardial infarction (MI). Secondary endpoints were each component of the primary...... implantation in large vessels was associated with a reduction in both TVR and the combined endpoint consisting of cardiovascular death/MI. Thus, DES use improves both efficacy and safety. These findings support the use of DES in NSTE-ACS patients....

  3. Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries

    DEFF Research Database (Denmark)

    Hansen, K W; Kaiser, C; Hvelplund, A

    2013-01-01

    To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels.......To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels....

  4. Impact of Age on Long-Term Outcome After Primary Angioplasty With Bare-Metal or Drug-Eluting Stent (From the DESERT Cooperation)

    DEFF Research Database (Denmark)

    De Luca, Giuseppe; Dirksen, Maurits T; Spaulding, Christian

    2013-01-01

    Despite mechanical reperfusion, elderly patients with ST-segment elevation myocardial infarction (STEMI) still experience unsatisfactory outcomes. Drug-eluting stents (DES) have significantly reduced target-vessel revascularization (TVR), but concerns have emerged about the higher risk of late st...... angioplasty and stent implantation included in the Drug-Eluting Stent in Primary Angioplasty (DESERT) Cooperation database. Age was significantly associated with female gender (p...

  5. Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Holmvang, Lene; Kelbæk, Henning; Kaltoft, Anne Kjer

    2013-01-01

    This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention.......This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention....

  6. Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

    Energy Technology Data Exchange (ETDEWEB)

    Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Spiliopoulos, Stavros [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Diamantopoulos, Athanasios [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Karnabatidis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Sabharwal, Tarun [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Siablis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece)

    2013-06-15

    IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall

  7. Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

    International Nuclear Information System (INIS)

    Katsanos, Konstantinos; Spiliopoulos, Stavros; Diamantopoulos, Athanasios; Karnabatidis, Dimitris; Sabharwal, Tarun; Siablis, Dimitris

    2013-01-01

    IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration’s tool. Primary endpoint was primary patency defined as absence of ≥50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford–Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel–Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18–1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford–Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002–1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28–0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02–1.62, p = 0.04; NNT = 5.9), and better

  8. Study of the elution {sup 99}Mo-{sup 99m}Tc generators produced at IPEN-CNEN/SP

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Paula Regina Corain [Pontificia Univ. Catolica de Sao Paulo, SP (Brazil); Instituto de Pesquisas Energeticas e Nucleares IPEN/CNEN-SP, Sao Paulo, SP (Brazil)]. E-mail: corain.lopes@uol.com.br; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: jaosso@ipen.br

    2007-07-01

    Over the last years {sup 99m}Tc has become a very important asset in modern nuclear medicine, due to the emission of gamma ray of optimal energy (140 keV) and a suitable half-life (6.04 h). A further attribute of {sup 99m}Tc is its formation from the decay of {sup 99}Mo and the availability from {sup 99}Mo-{sup 99m}Tc generator systems. The most common and practical generator types consist of a chromatographic column packed with aluminium oxide, onto which the highly purified fission product {sup 99}Mo (imported from Canada) is adsorbed in the form of molybdate. {sup 99m}Tc is further eluted with saline solution. The objective of this work is to study the performance and the elution profile of {sup 99m}Tc from high activity generators in order to decrease molybdenum and aluminium concentration. The experiments involved the use of paper filters and Sep Pak columns and also the changing in the time interval between elutions. {sup 99}Mo breakthrough was measured using a dose calibrator and aluminium by UV-Vis spectrophotometry. The best results were achieved using a Sep Pak column containing neutral aluminium oxide. (author)

  9. Study of the elution 99Mo-99mTc generators produced at IPEN-CNEN/SP

    International Nuclear Information System (INIS)

    Lopes, Paula Regina Corain; Osso Junior, Joao Alberto

    2007-01-01

    Over the last years 99m Tc has become a very important asset in modern nuclear medicine, due to the emission of gamma ray of optimal energy (140 keV) and a suitable half-life (6.04 h). A further attribute of 99m Tc is its formation from the decay of 99 Mo and the availability from 99 Mo- 99m Tc generator systems. The most common and practical generator types consist of a chromatographic column packed with aluminium oxide, onto which the highly purified fission product 99 Mo (imported from Canada) is adsorbed in the form of molybdate. 99m Tc is further eluted with saline solution. The objective of this work is to study the performance and the elution profile of 99m Tc from high activity generators in order to decrease molybdenum and aluminium concentration. The experiments involved the use of paper filters and Sep Pak columns and also the changing in the time interval between elutions. 99 Mo breakthrough was measured using a dose calibrator and aluminium by UV-Vis spectrophotometry. The best results were achieved using a Sep Pak column containing neutral aluminium oxide. (author)

  10. Association of Adventitial Vasa Vasorum and Inflammation With Coronary Hyperconstriction After Drug-Eluting Stent Implantation in Pigs In Vivo.

    Science.gov (United States)

    Nishimiya, Kensuke; Matsumoto, Yasuharu; Shindo, Tomohiko; Hanawa, Kenichiro; Hasebe, Yuhi; Tsuburaya, Ryuji; Shiroto, Takashi; Takahashi, Jun; Ito, Kenta; Ishibashi-Ueda, Hatsue; Yasuda, Satoshi; Shimokawa, Hiroaki

    2015-01-01

    The importance of adventitial inflammation has been implicated for the pathogenesis of coronary artery disease. However, the roles of adventitial changes in drug-eluting stent (DES)-induced coronary hyperconstriction remain largely unknown. In the present study, this issue in pigs in vivo with a special reference to adventitial vasa vasorum (VV) formation and Rho-kinase activation, a central mechanism of coronary vasospasm, was examined. Each animal received a sirolimus-eluting stent (SES) and a biolimus A9-eluting stent (BES), one in the left anterior descending and another in the left circumflex coronary arteries in a randomized manner (n=18). After 1, 3 and 6 months, coronary vasomotion was examined. At 1 month, coronary vasoconstriction to serotonin was significantly enhanced at the SES edges as compared with the BES edges (SES, 52±7% vs. BES, 22±3%, Pmicro-CT showed VV augmentation at the SES site, extending to the proximal and distal edges. Immunostainings demonstrated that VV formation, macrophage infiltration in the adventitia and Rho-kinase expressions/activation were significantly enhanced at the SES edges as compared with the BES edges. The DES with durable polymers enhances VV formation and inflammation in the adventitia, associating with the pathogenesis of DES-induced coronary hyperconstriction through Rho-kinase activation in pigs in vivo.

  11. Unenhanced and Contrast-Enhanced Ultrasonography During Hepatic Transarterial Embolization and Chemoembolization With Drug-Eluting Beads

    International Nuclear Information System (INIS)

    Moschouris, Hippocrates; Malagari, Katerina; Kornezos, Ioannis; Papadaki, Marina Georgiou; Gkoutzios, Panagiotis; Matsaidonis, Dimitrios

    2010-01-01

    The purpose of this study was to describe and evaluate the findings of unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) when these modalities are applied during transarterial embolization (TAE) or transarterial chemoembolization (TACE) of liver tumors. Sixteen tumors (9 hepatocellular carcinomas, 5 metastases from colorectal cancer, and 2 hemangiomas) were treated with TAE with microspheres and/or TACE with drug-eluting beads. All of these lesions were studied with intraprocedural unenhanced US and 12 were studied with intraprocedural CEUS. For the latter, a second-generation echo-enhancer (SonoVue; Bracco, Milan, Italy) and a low mechanical index technique were used. Intraprocedural findings were classified according to an arbitrary scale and were compared with pretreatment imaging (CEUS and computed tomography or CEUS and magnetic resonance imaging), with postembolization angiography, and with follow-up results. On unenhanced intraprocedural US, 13 of 16 tumors demonstrated intralesional high-level echoes of varying extent. These feature correlated poorly (r = 0.33, p = 0.097) with and generally underestimated the actual extent of necrosis. Exceptionally, high-level echoes that occupied the largest part of the treated lesions were associated with >50% tumor necrosis. Intraprocedural CEUS clearly depicted immediate partial or complete disappearance of tumor enhancement as a result of TAE/TACE. Three of 6 tumors with complete devascularization on postembolization angiogram showed residual enhancement on intraprocedural CEUS. Intraprocedural CEUS findings correlated closely (r = 0.91, p = 0.002) with follow-up findings. Intraprocedural sonography, particularly with echo-enhancers, could be used for intraprocedural monitoring in selected cases of liver tumors that undergo TAE or TACE.

  12. Intimal hyperplasia and vascular remodeling after everolimus-eluting and sirolimus-eluting stent implantation in diabetic patients the randomized diabetes and drug-eluting stent (DiabeDES) IV intravascular ultrasound trial

    DEFF Research Database (Denmark)

    Antonsen, Lisbeth; Maeng, Michael; Thayssen, Per

    2013-01-01

    OBJECTIVE: To evaluate the effects of the everolimus-eluting Xience™/Promus™ stent (EES) and the sirolimus-eluting Cypher™ stent (SES) on intimal hyperplasia (IH) in diabetic patients. BACKGROUND: Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent...... implantation due to intimal hyperplasia (IH). METHODS: In a sub study of the Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated with Percutaneous Coronary Intervention (SORT OUT IV trial), serial intravascular ultrasound (IVUS) 10-month follow-up data were available...... in 88 patients, including 48 EES and 40 SES treated patients. IVUS endpoints included IH volume, in-stent % volume obstruction and changes in external elastic membrane (EEM) volume. RESULTS: Compared with the SES group, IH volume was increased in the EES group [median (interquartile range): 2.8 mm(3) (0...

  13. Everolimus-induced Pneumonitis after Drug-eluting Stent Implantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, Susumu, E-mail: susumu1029@gmail.com; Kikuchi, Naoshi; Ichikawa, Atsuo; Sano, Go; Satoh, Keita; Sugino, Keishi; Isobe, Kazutoshi; Takai, Yujiro [Toho University School of Medicine, Department of Respiratory Medicine (Japan); Shibuya, Kazutoshi [Toho University School of Medicine, Department of Pathology (Japan); Homma, Sakae [Toho University School of Medicine, Department of Respiratory Medicine (Japan)

    2013-08-01

    Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

  14. Late lumen loss and intima hyperplasia after sirolimus-eluting and zotarolimus-eluting stent implantation in diabetic patients: the diabetes and drug-eluting stent (DiabeDES III) angiography and intravascular ultrasound trial

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Mæng, Michael; Thayssen, Per

    2011-01-01

    Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects...... of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients....

  15. Drug-eluting stents vs. coronary artery bypass-grafting in coronary heart disease

    Directory of Open Access Journals (Sweden)

    Hagen, Anja

    2008-12-01

    Full Text Available Background: Coronary artery bypass graft (CABG and percutaneous revascularisations with implantation of drug-eluting stents (DES are important treatment methods in coronary heart disease (CHD. Research questions: The evaluation addresses questions on medical efficacy, health economic parameters as well as ethic, social and legal implications in the use of DES vs. CABG in CHD patients. Methods: A systematic literature search was conducted in December 2006 in the most important electronic databases beginning from 2004. Register data and controlled clinical studies were included in the evaluation. Additionally, a health economic modelling was conducted. Results: Medical evaluation: The literature search yielded 2,312 hits. 14 publications about six controlled clinical studies and five publications about two registers were included into the evaluation. Register data showed low mortality (0.2% to 0.7% and low rates of myocardial infarction (0.5% to 1.4% during hospital stay. In patients with stenosis of the left anterior descending coronary artery one study showed in several analyses a significantly higher rate of reinterventions and a significantly higher rate of repeated angina pectoris for DES up to two years after the implantation (16.8% vs. 3.6% and 35% vs. 8%. In patients with left main coronary artery stenosis two studies revealed a significantly higher survival without myocardial infarction and stroke for DES up to one year (96% vs. 79% and 95% vs. 91% and two studies a significantly higher rate of revascularisations up to two years (20% vs. 4% and 25% vs. 5% after the primary intervention. In patients with multivessel disease, one study found a significantly higher mortality and myocardial infarction rate for CABG at one year (2.7% vs. 1.0% and 4.2% vs. 1.3%. The rate of revascularisations was significantly higher in two studies up to two years after DES implantation (8.5% vs. 4.2% and 14.2% vs. 5.3%. The rate at repeated angina pectoris was

  16. Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease

    DEFF Research Database (Denmark)

    Raungaard, Bent; Christiansen, Evald H; Bøtker, Hans Erik

    2017-01-01

    artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion......OBJECTIVES: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BACKGROUND: Biodegradable-polymer biolimus-eluting stents are superior to first......-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. METHODS: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary...

  17. Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 3-year follow-up of the randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) Trial

    DEFF Research Database (Denmark)

    Kaltoft, Anne; Kelbaek, Henning; Thuesen, Leif

    2010-01-01

    The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).......The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI)....

  18. Differential clinical outcomes after 1 year versus 5 years in a randomised comparison of zotarolimus-eluting and sirolimus-eluting coronary stents (the SORT OUT III study)

    DEFF Research Database (Denmark)

    Maeng, Michael; Tilsted, Hans Henrik; Jensen, Lisette Okkels

    2014-01-01

    received two different types of drug-eluting stents. METHODS: We undertook this multicentre, open-label, randomised superiority trial at five percutaneous coronary intervention centres in Denmark. We randomly allocated 2332 eligible adult patients (≥18 years of age) with an indication for drug......-eluting stent implantation to the zotarolimus-eluting Endeavor Sprint stent (Medtronic, Santa Rosa, CA, USA) or the sirolimus-eluting Cypher Select Plus stent (Cordis, Johnson & Johnson, Warren, NJ, USA). Randomisation of participants was achieved by computer-generated block randomisation and a telephone...

  19. Histological assessment of the efficacy of drug-eluting beads in portal tumor thrombosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yusuke Imai, MD

    2017-03-01

    Full Text Available A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT. The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.

  20. Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Maeng, Michael; Kaltoft, Anne

    2007-01-01

    OBJECTIVES: The aim of the study was to examine outcomes subsequent to implantation of drug-eluting stents (DES) and bare-metal stents (BMS). BACKGROUND: Use of DES might be associated with increased risk of stent thrombosis (ST), myocardial infarction (MI), and death. METHODS: From January 2002...... through June 2005, data from all percutaneous coronary interventions in western Denmark were prospectively recorded in the Western Denmark Heart Registry; 12,395 consecutive patients (17,152 lesions) treated with stent implantation were followed for 15 months. Data on death and MI were ascertained from...... within 15 months after implantation of DES seems unlikely to outweigh the benefit of these stents. Udgivelsesdato: 2007-Jul-31...

  1. Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

    International Nuclear Information System (INIS)

    Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis; Matsaidonis, Dimitrios

    2010-01-01

    The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

  2. The effect of solvents and hydrophilic additive on stable coating and controllable sirolimus release system for drug-eluting stent.

    Science.gov (United States)

    Kim, Seong Min; Park, Sung-Bin; Bedair, Tarek M; Kim, Man-Ho; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2017-09-01

    Various drug-eluting stents (DESs) have been developed to prevent restenosis after stent implantation. However, DES still needs to improve the drug-in-polymer coating stability and control of drug release for effective clinical treatment. In this study, the cobalt-chromium (CoCr) alloy surface was coated with biodegradable poly(D,L-lactide) (PDLLA) and sirolimus (SRL) mixed with hydrophilic Pluronic F127 additive by using ultrasonic spray coating system in order to achieve a stable coating surface and control SRL release. The degradation of PDLLA/SRL coating was studied under physiological solution. It was found that adding F127 reduced the degradation of PDLLA and improved the coating stability during 60days. The effects of organic solvent such as chloroform and tetrahydrofuran (THF) on the coating uniformity were also examined. It was revealed that THF produced a very smooth and uniform coating compared to chloroform. The patterns of in vitro drug release according to the type of organic solvent and hydrophilic additive proposed the possibility of controllable drug release design in DES. It was found that using F127 the drug release was sustained regardless of the organic solvent used. In addition, THF was able to get faster and controlled release profile when compared to chloroform. The structure of SRL molecules in different organic solvents was investigated using ultra-small angle neutron scattering. Furthermore, the structure of SRL is concentration-dependent in chloroform with tight nature under high concentration, but concentration-independent in THF. These results strongly demonstrated that coating stability and drug release patterns can be changed by physicochemical properties of various parameters such as organic solvents, additive, and coating strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Long-Term Results of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With Bare-Metal In-Stent Restenosis: 3-Year Follow-Up of the RIBS V Clinical Trial.

    Science.gov (United States)

    Alfonso, Fernando; Pérez-Vizcayno, María José; García Del Blanco, Bruno; Otaegui, Imanol; Masotti, Mónica; Zueco, Javier; Veláquez, Maite; Sanchís, Juan; García-Touchard, Arturo; Lázaro-García, Rosa; Moreu, José; Bethencourt, Armando; Cuesta, Javier; Rivero, Fernando; Cárdenas, Alberto; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Fernández, Cristina

    2016-06-27

    The aim of this study was to compare the long-term efficacy of everolimus-eluting stents (EES) and drug-eluting balloons (DEB) in patients with bare-metal stent in-stent restenosis (ISR). The relative long-term clinical efficacy of current therapeutic modalities in patients with ISR remains unknown. The 3-year clinical follow-up (pre-specified endpoint) of patients included in the RIBS V (Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent Implantation) randomized clinical trial was analyzed. All patients were followed yearly using a pre-defined structured questionnaire. A total of 189 patients with bare-metal stent ISR were allocated to either EES (n = 94) or DEB (n = 95). Clinical follow-up at 1, 2, and 3 years was obtained in all patients (100%). Compared with patients treated with DEB, those treated with EES obtained better angiographic results, including larger minimal luminal diameter at follow-up (primary study endpoint; 2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm; p 1 year) target vessel (3 [3.2%] vs. 3 [3.2%]; p = 0.95) and target lesion (1 [1%] vs. 2 [2.1%]; p = 0.54) revascularization was low and similar in the 2 arms. Rates of definite or probable stent thrombosis (1% vs. 0%) were also similar in the 2 arms. The 3-year clinical follow-up of the RIBS V clinical trial confirms the sustained safety and efficacy of EES and DEB in patients treated for bare-metal stent ISR. In this setting, EES reduce the need for target lesion revascularization at very long-term follow-up. (RIBS V [Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent] [RIBS V]; NCT01239953). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. Long-Term Follow-up of the PADI Trial : Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia

    NARCIS (Netherlands)

    Spreen, Marlon I; Martens, Jasper M; Knippenberg, Bob; van Dijk, Lukas C; De Vries, Jean-Paul P. M.; Vos, Jan Albert; de Borst, Gert Jan; Vonken, Evert-Jan P A; Bijlstra, Okker D; Wever, Jan J; Statius van Eps, Randolph G; Mali, Willem P Th M; van Overhagen, Hendrik

    2017-01-01

    BACKGROUND: Clinical outcomes reported after treatment of infrapopliteal lesions with drug-eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (PTA-BMS) through midterm follow-up in patients with critical limb ischemia.

  5. Risk factors for impaired health status differ in women and men treated with percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Pedersen, Susanne S.; Ong, Andrew T L; Lemos, Pedro A

    2006-01-01

    In patients treated with percutaneous coronary intervention (PCI) in the drug-eluting stent era, we compared women's and men's health status 6 and 12 months post-PCI and investigated whether predictors of poor health status at 12 months are similar for women and men....

  6. Intravascular ultrasound assessed incomplete stent apposition and stent fracture in stent thrombosis after bare metal versus drug-eluting stent treatment the Nordic Intravascular Ultrasound Study (NIVUS)

    DEFF Research Database (Denmark)

    Kosonen, Petteri; Vikman, Saila; Jensen, Lisette Okkels

    2012-01-01

    This prospective multicenter registry used intravascular ultrasound (IVUS) in patients with definite stent thrombosis (ST) to compare rates of incomplete stent apposition (ISA), stent fracture and stent expansion in patients treated with drug-eluting (DES) versus bare metal (BMS) stents. ST...... is a rare, but potential life threatening event after coronary stent implantation. The etiology seems to be multifactorial....

  7. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease A Meta-Analysis of Individual Patient Data

    NARCIS (Netherlands)

    Lee, Cheol Whan; Ahn, Jung-Min; Cavalcante, Rafael; Sotomi, Yohei; Onuma, Yoshinobu; Suwannasom, Pannipa; Tenekecioglu, Erhan; Yun, Sung-Cheol; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Serruys, Patrick W.; Park, Seung-Jung

    2016-01-01

    OBJECTIVES The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD).

  8. Stent implantation into the tracheo-bronchial system in rabbits: histopathologic sequelae in bare metal vs. drug-eluting stents.

    Science.gov (United States)

    Sigler, Matthias; Klötzer, Julia; Quentin, Thomas; Paul, Thomas; Möller, Oliver

    2015-12-01

    Stent implantation into the tracheo-bronchial system may be life-saving in selected pediatric patients with otherwise intractable stenosis of the upper airways. Following implantation, significant tissue proliferation may occur, requiring re-interventions. We sought to evaluate the effect of immunosuppressive coating of the stents on the extent of tissue proliferation in an animal model. Bare metal and sirolimus-coated stents (Bx Sonic and Cypher Select, Johnson & Johnson, Cordis) were implanted into non-stenotic lower airways of New Zealand white rabbits (weight 3.1 to 4.8 kg). Three stents with sirolimus coating and six bare metal stents could be analyzed by means of histology and immunohistochemistry 12 months after implantation. On a macroscopic evaluation, all stents were partially covered with a considerable amount of whitish tissue. Histologically, these proliferations contained fiber-rich connective tissue and some fibromuscular cells without significant differences between both stent types. The superficial tissue layer was formed by typical respiratory epithelium and polygonal cells. Abundant lymphocyte infiltrations and moderate granulocyte infiltrations were found in both groups correspondingly, whereas foreign-body reaction was more pronounced around sirolimus-eluting stents. After stent implantation in the tracheo-bronchial system of rabbits, we found tissue reactions comparable to those seen after stent implantation into the vascular system. There was no difference between coated and uncoated stents with regard to quality and quantity of tissue proliferation. We found, however, a significantly different inflammatory reaction with a more pronounced foreign-body reaction in sirolimus-coated stents. In our small series, drug-eluting stents did not exhibit any benefit over bare metal stents in an experimental setting.

  9. Long-term clinical outcome in STEMI patients treated with primary PCI and drug-eluting or bare-metal stents: insights from a high-volume single-center registry

    DEFF Research Database (Denmark)

    Pedersen, Sune; Galatius, Soren; Mogelvang, Rasmus

    2011-01-01

    Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial.......Use of drug-eluting stents (DES) in patients with ST-elevation myocardial infarction (STEMI) during routine primary percutaneous coronary intervention (pPCI) is controversial....

  10. Outcome of everolimus eluting bioabsorbable vascular scaffold (BVS) compared to non BVS drug eluting stent in the management of ST-segment elevation myocardial infarction (STEMI) — A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Rabin; Patra, Soumya, E-mail: dr_soumyapatra@rediffmail.com; Banerjee, Suvro; Pande, Arindam; Khan, Aftab; Mandol, Prakash Chandra; Ghosh, Debashish; De, Swapan Kumar; Das, Sankha Subhro; Nag, Raja

    2016-04-15

    Background: The safety and efficacy of everolimus eluting bioabsorbable vascular scaffold (BVS) in the management of “ST” segment elevation myocardial infarction (STEMI) are yet to be established. Aims: To evaluate immediate and short term safety and efficacy of the everolimus-eluting ABSORB BVS compared with non BVS drug eluting stent (DES) in patients with STEMI. Methods: From December 2013 to December 2014, 220 patients with STEMI were included in this study. Among them, 35 patients treated with BVS were compared with a control group composed of 180 patients who underwent non BVS DES implantation in the same time period. The incidence of major adverse cardiac events (MACE: stent thrombosis: death, non-fatal myocardial infarction, or target vessel/lesion revascularization) before discharge and up to six months was evaluated. Results: 1 vessel disease was more frequent whereas, 2 and 3 vessel disease was less frequent in BVS group. Procedural characteristics were also similar between groups, except for the use of post dilation (p = 0.04). Procedural success, in-hospital, and up to six-month MACE rates were similar between both groups. Definite or probable stent thrombosis did not occur (according to the ARC criteria) in BVS patients, though two patients during the index admission and another two patients in the first month after DES implantation had stent thrombosis. Conclusion: The use of the ABSORB BVS for STEMI is feasible and associated with good procedural safety, and angiographic success rate.

  11. Outcome of everolimus eluting bioabsorbable vascular scaffold (BVS) compared to non BVS drug eluting stent in the management of ST-segment elevation myocardial infarction (STEMI) — A comparative study

    International Nuclear Information System (INIS)

    Chakraborty, Rabin; Patra, Soumya; Banerjee, Suvro; Pande, Arindam; Khan, Aftab; Mandol, Prakash Chandra; Ghosh, Debashish; De, Swapan Kumar; Das, Sankha Subhro; Nag, Raja

    2016-01-01

    Background: The safety and efficacy of everolimus eluting bioabsorbable vascular scaffold (BVS) in the management of “ST” segment elevation myocardial infarction (STEMI) are yet to be established. Aims: To evaluate immediate and short term safety and efficacy of the everolimus-eluting ABSORB BVS compared with non BVS drug eluting stent (DES) in patients with STEMI. Methods: From December 2013 to December 2014, 220 patients with STEMI were included in this study. Among them, 35 patients treated with BVS were compared with a control group composed of 180 patients who underwent non BVS DES implantation in the same time period. The incidence of major adverse cardiac events (MACE: stent thrombosis: death, non-fatal myocardial infarction, or target vessel/lesion revascularization) before discharge and up to six months was evaluated. Results: 1 vessel disease was more frequent whereas, 2 and 3 vessel disease was less frequent in BVS group. Procedural characteristics were also similar between groups, except for the use of post dilation (p = 0.04). Procedural success, in-hospital, and up to six-month MACE rates were similar between both groups. Definite or probable stent thrombosis did not occur (according to the ARC criteria) in BVS patients, though two patients during the index admission and another two patients in the first month after DES implantation had stent thrombosis. Conclusion: The use of the ABSORB BVS for STEMI is feasible and associated with good procedural safety, and angiographic success rate.

  12. Visible Light Irradiation-Mediated Drug Elution Activity of Nitrogen-Doped TiO2 Nano tubes

    International Nuclear Information System (INIS)

    Oh, S.; Moon, K.S.; Bae, J.M.; Moon, J.H.; Jin, S.

    2013-01-01

    We have developed nitrogen-doped TiO 2 nano tubes showing photo catalytic activity in the visible light region and have investigated the triggered release of antibiotics from these nano tubes in response to remote visible light irradiation. Scanning electron microscopy (SEM) observations indicated that the structure of TiO 2 nano tubes was not destroyed on the conditions of 0.05 and 0.1 M diethanolamine treatment. The results of X-ray photoelectron spectroscopy (XPS) confirmed that nitrogen, in the forms of nitrite (TiO 2 ) and nitrogen monoxide (NO), had been incorporated into the TiO 2 nano tube surface. A drug-release test revealed that the antibiotic-loaded TiO 2 nano tubes showed sustained and prolonged drug elution with the help of polylactic acid. Visible light irradiation tests showed that the antibiotic release from nitrogen-doped nano tubes was significantly higher than that from pure TiO 2 nano tubes (ρ ≨ 0.05).

  13. Rapid Globalization of Medical Device Clinical Development Programs in Japan - The Case of Drug-Eluting Stents.

    Science.gov (United States)

    Murakami, Madoka; Suzuki, Yuka; Tominaga, Toshiyoshi

    2018-02-23

    Delays in the introduction to the Japanese market of drug-eluting stents (DES) developed overseas (i.e., "device lag") decreased sharply between 2004 and 2012. The reduction accompanied a shift in clinical development from a succession pattern (initial product development and approval overseas followed by eventual entrance into the Japanese market) to parallel development (employing multiregional clinical trials (MRCTs)). Although resource-intensive in the short-term, MRCTs are proving to be an effective tool in simultaneous global product development. Creative study designs and the absence of significant ethnic differences in Japanese subjects regarding DES safety and efficacy and the pharmacokinetic behavior of their coating drugs propel this process. More general factors such as medical need and industry incentivization also encourage this shift. Physicians' preference for DES over other percutaneous coronary interventions, the expanding global DES market, and streamlined development and approval prospects each motivate industry to continue investing in DES product development. The efforts of various stakeholders were also integral to overcoming practical obstacles, and contributions by 'Harmonization by Doing' and a premarket collaboration initiative between the USA and Japan were particularly effective. Today, USA/Japan regulatory cooperation is routine, and Japan is now integrated into global medical device development. MRCTs including Japanese subjects, sites, and investigators are now commonplace.

  14. In vitro biologic efficacy of sunitinib drug-eluting beads on human colorectal and hepatocellular carcinoma-A pilot study.

    Directory of Open Access Journals (Sweden)

    Steven Lahti

    Full Text Available Sunitinib drug eluting beads (DEB are a novel anti-angiogenic bead preparation for use in transarterial chemoembolization. However, systematic studies of sunitinib DEB's effect on cancer cells have not been reported. Herein, we assess their direct biologic efficacy against carcinoma cell lines and correlate cell viability with drug release in vitro.Sunitinib-HCl (10mg/mL in Milli-Q water was mixed with LC Bead® 300-500μm (Biocompatibles UK Ltd.. Loading and release were assessed by measurement of drug UV absorbance using UV-visible spectrophotometer. Viability of human colorectal cancer (CRC, HCT116 and HT29 and hepatocellular carcinoma (HCC, HepG2 cells upon exposure to sunitinib DEB was measured using a bioluminescent assay. Drug concentration during exposure was quantified using HPLC.When added to cultured HepG2 cells, sunitinib DEB rapidly inhibited viability with a significant decrease observed within 1 hour of incubation. Viability of HCT116 and HT29 cells decreased relatively slower, with significant reductions observed after 8 and 24 hours, respectively. After 24 hours there was nearly complete inhibition of all three cell lines. There was no difference in viability observed between cells treated with 5 μl, 10 μL, or 20 μL of sunitinib DEB. HPLC analysis of the cell culture supernatant demonstrated saturation of the cell medium within approximately 4 hours for each amount added, with sunitinib achieving a final concentration of 17.61 μM (SE ±1.01.Sunitinib can be efficiently loaded to and released from LC beads, and the resulting sunitinib DEB demonstrate strong in vitro inhibition of human CRC and HCC cells.

  15. Comparison between Exclusive and Selective Drug-Eluting Stent Strategies in Treating Patients with Multivessel Coronary Artery Disease.

    Science.gov (United States)

    Tung, Ying-Chang; Hsiao, Ping-Gune; Hsu, Lung-An; Kuo, Chi-Tai; Chang, Chi-Jen

    2014-05-01

    The expanded usage of drug-eluting stents (DES) in treating patients with multivessel coronary artery disease (CAD) may sometimes be limited in real-world practice due to cost concerns. We compared the clinical outcomes of exclusive and selective DES use in treating patients with multivessel CAD. From November 2004 to December 2011, 110 patients with multivessel CAD who received four or more stents were enrolled into this study, and divided into two groups according to the DES strategy employed: exclusive DES (n = 52), or selective DES (n = 58). In the selective DES group, DES was reserved for complex lesions only, such that the incidence and predictors of clinical events were assessed. At a mean follow-up of 41.4 ± 26.5 months, there were no significant differences between the two strategies in terms of baseline characteristics, all-cause mortality (exclusive vs. selective: 1.9% vs. 6.9%, p = 0.21), cardiac death (1.9% vs. 1.7%, p = 0.94) and nonfatal myocardial infarction (3.8% vs. 5.2%, p = 0.74). Despite the presence of more ostial lesions in the exclusive DES group, there was a trend such that major adverse cardiac events (MACE) and target lesion revascularization (TLR) rates were higher in the selective DES group (MACE: 17.3% vs. 31%, p = 0.16; TLR: 11.5% vs. 24.1%, p = 0.08). The higher MACE rate in the selective DES group was mainly driven by a higher target vessel revascularization (TVR) rate (15.4% vs. 29.3%, p = 0.08). In the exclusive DES group, SYNTAX score was an independent predictor of MACE [Haxard ratio (HR): 1.09, 95% confidence internal (CI): 1.02-1.16, p = 0.01] and TVR (HR 1.08, 95% CI 1.01-1.15, p = 0.04). Compared to the exclusive DES strategy, the selective DES strategy with reservation of DES for complex lesions is associated with numerically higher, but not statistically significant, rates of MACE and all-cause mortality in this small group of patients with multivessel CAD receiving four or more stents. Bare metal stent; Drug-eluting

  16. Studies of techniques for the post-elution concentration of 99mTc obtained from gel type 99Mo/99mTc generators

    International Nuclear Information System (INIS)

    Suzuki, Katia Noriko

    2009-01-01

    On average 80% of the radiopharmaceuticals used in Nuclear Medicine are labeled with 99 mTc due to its physical properties and easy attainment through of 99 Mo/ 99 mTc generators. The Directory of Radiopharmacy (DIRF) of IPEN-CNEN/SP developed a gel type chromatographic generator of MoZr with 99 Mo produced by 98 Mo(n,γ) 99 Mo reaction that occurs at the IEA-R1 Nuclear Reactor. The gel is composed of zirconium molybdate with elution volume of 12 mL with an activity of 11100 MBq (300 mCi) producing a radioactive concentration of 925 MBq (25 mCi)/mL. The fission generator gives a higher radioactive concentration around 1850 MBq (50 mCi)/mL. The aim of this work is to study a system of post-elution concentration of 99 mTc for the attainment of a high enough radioactive concentration to meet the demands of the market, with a proved quality. Two types of systems of post-elution concentration were developed: the single and the tandem. The most appropriate system for the gel generator of 99 Mo/ 99 mTc, being at the same time sterile and vacuum automated, was the tandem system using Dionex 2.5 cc/QMA cartridges. The gel generator is eluted with 10 mL of solution of 0.1% NaCl and the pertechnetate anion is retained in the QMA cartridge and further eluted with 4 mL of saline. The process takes no more than 30 minutes. The elution efficiency of the system of concentration was 90 %. At the beginning of 2009 a global crisis in the supply of 99 Mo took place making it necessary the development of alternative technologies for the production of 99 Mo/ 99 mTc generators using fission produced 99 Mo and the development of an appropriate method to extend the useful life of this generator. The results of this study showed that the same system developed for the post- concentration of the gel generator can be employed for the fission generator, using the tandem system, giving a concentration factor of 3 for the elution of 99 mTc. (author)

  17. Modifying release characteristics from 3D printed drug-eluting products

    DEFF Research Database (Denmark)

    Boetker, Johan; Water, Jorrit; Aho, Johanna

    2016-01-01

    Abstract This work describes an approach to modify the release of active compound from a 3D printed model drug product geometry intended for flexible dosing and precision medication. The production of novel polylactic acid and hydroxypropyl methylcellulose based feed materials containing...... nitrofurantoin for 3D printing purposes is demonstrated. Nitrofurantoin, Metolose® and polylactic acid were successfully co-extruded with up to 40% Metolose® content, and subsequently 3D printed into model disk geometries (ø10 mm, h = 2 mm). Thermal analysis with differential scanning calorimetry and solid phase...... identification with Raman spectroscopy showed that nitrofurantoin remained in its original solid form during both hot-melt extrusion and subsequent 3D printing. Rheological measurements of the different compositions showed that the flow properties were sensitive to the amount of undissolved particles present...

  18. Stent underexpansion in angiographic guided percutaneous coronary intervention, despite adjunctive balloon post-dilatation, in drug eluting stent era

    Directory of Open Access Journals (Sweden)

    Mehrdad Taherioun

    2014-01-01

    Full Text Available BACKGROUND: Stent underexpansion is the most powerful predictor of long-term stent patency and clinical outcome. The purpose of this study was to evaluate the incidence and predictors of stent underexpansion despite adjunctive post-dilatation with non-compliant balloon. METHODS: After elective coronary stent implantation and adjunctive post-dilatation with non-compliant balloon and optimal angiographic result confirmed by the operator, intravascular ultrasound (IVUS was performed for all the treated lesions. If the treated lesions fulfilled the IVUS criteria, they are considered as the optimal stent group; if not, they are considered as the suboptimal group. RESULTS: From 50 patients enrolled in this study 39 (78% had optimal stent deployment and 11 (22% had suboptimal stent deployment. In the suboptimal group 7 (14% had underexpansion, 2 (4% malposition, and 2 (4% had asymmetry. There were no stent edge dissections detected by IVUS. We did not find any correlation between lesion calcification, ostial lesions, stent length, and stent underexpansion. Stent diameter ≤ 2.75 mm had a strong correlation with stent underexpansion. CONCLUSION: Despite adjunctive post-dilatation with noncompliant balloon, using a relatively small stent diameter was a strong predictor for underexpansion. IVUS guided percutaneous coronary intervention (PCI may be considered for drug eluting stent (DES implantation in relatively small vessels.   Keywords: Stent, Percutaneous Coronary Intervention, Ultrasound, Post-dilatation 

  19. Association Between Helicobacter Pylori Infection and Long-term Outcome in Patients with Drug-eluting Stent Implantation

    Science.gov (United States)

    Wang, Rui; Chen, Lei-Lei; Wang, De-Zhao; Chen, Bu-Xing

    2017-07-01

    To investigate the relationship between Helicobacter pylori (Hp) infection and the long-term outcome in acute coronary syndrome (ACS) patients with drug-eluting stent (DES) implantation and so as to explore the significance of Hp eradication therapy in preventing major adverse cardiac events (MACE) and upper gastrointestinal bleeding (UGIB). 539 ACS patients with DES implantation from January 1, 2010 to December 31, 2012 were analyzed. All the patients were divided into two groups according to the result of 13C urea breath test. 253 patients with Hp infection were put into group A (Hp+), and 286 cases without Hp infection were put into group B (Hp-). Demographic data was collected and all patients went through biochemical indicators and other routine blood examinations. We explored the correlations of Hp infection with MACE and UGIB after 3 to 5 years of follow-up using survival analysis. Survival analysis showed that Hp infection was a predictor of MACE and UGI. Sub-group analysis showed that patients with Hp eradication therapy had no relationship with MACE but had a lower rate of UGIB than those without Hp eradication therapy.

  20. Rapid determination of 90Sr impurities in freshly 'generator eluted'90Y for radiopharmaceutical preparation

    International Nuclear Information System (INIS)

    Bonardi, Mauro L.; Martano, Luigi; Groppi, Flavia; Chinol, Marco

    2009-01-01

    90 Y is one of the most useful radionuclides for radioimmunotherapeutic applications and has a half-life (t 1/2 =64.14 h) suitable for most therapeutic applications, beta particles of high energy and decays to a stable daughter. It is significant that 90 Y is available conveniently and inexpensively from a radionuclide 'generator' by decay of its parent, 90 Sr. Nevertheless, current and planned clinical applications with [ 90 Y] labelled compounds employ activity levels that cannot be readily obtained from an in-house generator, but from commercial sources. We have evaluated Eichrom's Sr-resin, either as an 'in-house' generator or as a fast QC method for analysis of 90 Y solutions. In particular, for the development as a generator, we investigated the percentage of the radio-Sr in the first 8 M HNO 3 eluate: in this fraction the concentration of 90 Sr must be smaller than 10 -5 % (recommendations of the International Commission on Radiological Protection). For evaluation as a rapid QC method, we analyzed the concentration of 90 Y in all the fractions containing 'only' radio-Sr: 90 Y should not be present in these eluates. After the collection of β - and γ spectra and analysis of them, we concluded that commercial Sr-resin minicolumn cannot give us the results expected; we developed an in-house system loaded with 4 mL of Sr-resin which gave better results as a generator and a rapid QC method.

  1. Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI)

    DEFF Research Database (Denmark)

    Raungaard, Bent; Jensen, Lisette Okkels; Tilsted, Hans-Henrik

    2015-01-01

    BACKGROUND: New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety...... and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. METHODS: This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All......-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat...

  2. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  3. The Relationship Between Neutrophil–Lymphocyte Ratio and Primary Patency of Percutaneous Transluminal Angioplasty in Hemodialysis Arteriovenous Fistula Stenosis When Using Conventional and Drug-Eluting Balloons

    Energy Technology Data Exchange (ETDEWEB)

    Çildağ, Mehmet Burak, E-mail: mbcildag@yahoo.com [Adnan Menderes University, Department of Diagnostic and Interventional Radiology (Turkey); Çildağ, Songül, E-mail: songulcildag@yahoo.com [Adnan Menderes University, Department of Immunology and Allergy (Turkey); Köseoğlu, Ömer Faruk Kutsi, E-mail: kutsikoseoglu@yahoo.com [Adnan Menderes University, Department of Diagnostic and Interventional Radiology (Turkey)

    2016-12-15

    ObjectiveThe aim of this study is to investigate the potential association of neutrophil–lymphocyte ratio (NLR) between primary patency of percutaneous transluminal angioplasty (PTA) in hemodialysis arteriovenous fistula stenosis and type (Conventional and Drug-Eluting) of balloons used in PTA.Material-MethodThis retrospective study consists of 78 patients with significant arteriovenous fistulas stenosis who were treated with PTA by using Drug-Eluting Balloon (DEB) (n = 29) or Conventional Balloon (CB) (n = 49). NLR was calculated from preinterventional blood samples. All patients were classified into two groups. Group A; primary patency <12 months (43/78), Group B; primary patency ≥12 months (35/78). Cox regression analysis and Kaplan–Meier method were used to determine respectively independent factors affecting the primary patency and to compare the primary patency for the two balloon types.ResultsNLR ratio and balloon type of the two groups were significantly different (p = 0.002, p = 0.010). The cut-off value of NLR was 3.18 for determination of primary patency, with sensitivity of 81.4 % and specificity of 51.4 %. Primary patency rates between PTA with DEB and CB displayed statistically significant differences (p < 0.05). The cut-off value was 3.28 for determination of 12-month primary patency with the conventional balloon group; sensitivity was 81.8 % and specificity was 81.3 %. There was no statistical relation between NLR levels and the drug-eluting balloon group in 12-month primary patency (p = 0.927).ConclusionIncreased level of NLR may be a risk factor in the development of early AVF restenosis after successful PTA. Preferring Drug-Eluting Balloon at an increased level of NLR can be beneficial to prolong patency.

  4. Combined Directional Atherectomy and Drug-Eluting Balloon Angioplasty for Isolated Popliteal Artery Lesions in Patients With Peripheral Artery Disease.

    Science.gov (United States)

    Stavroulakis, Konstantinos; Bisdas, Theodosios; Torsello, Giovanni; Stachmann, Arne; Schwindt, Arne

    2015-12-01

    To evaluate the midterm results of combined directional atherectomy (DA) and drug-eluting balloon (DEB) angioplasty for atherosclerotic lesions of the popliteal artery. In a single-arm, prospective study, 21 patients (mean age 63±16 years; 16 men) with isolated popliteal artery lesions were enrolled and underwent treatment with combined DA and DEB angioplasty under filter protection between October 2009 and February 2014. The majority (18, 86%) presented with lifestyle-limiting intermittent claudication and 3 with critical limb ischemia. Fifteen (71%) target sites were de novo lesions; 4 were occlusions. The main outcome was primary patency; secondary outcomes were technical success, secondary patency, and early and midterm morbidity and mortality. The TurboHawk atherectomy device was used in 15 (71%) patients and the SilverHawk peripheral plaque excision system in the remaining 6 patients. The In.Pact Admiral/Pacific DEB was used in the majority of cases (15, 71%). The technical success rate was 90% (n=19). One flow-limiting dissection was treated with bailout stenting. Complications included a perforation of the popliteal artery and 2 puncture site hematomas; there was no distal embolic event. The mean follow-up was 18±12 months. Two restenoses were retreated successfully. Kaplan-Meier estimates of primary patency at 12 and 18 months were 95% and 90%, respectively; the secondary patency was 100%. One (5%) patient died in follow-up. None of the patients had an amputation. In this prospective single-arm study, the combined therapy of DA and DEB angioplasty for popliteal artery lesions showed promising midterm performance. The combination of DA and DEB may, in highly selected patients, overcome the challenges presented by the mobility of the knee joint. © The Author(s) 2015.

  5. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

    Energy Technology Data Exchange (ETDEWEB)

    Monier, Arnaud; Duran, Rafael; Bize, Pierre; Dunet, Vincent; Denys, Alban [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Guiu, Boris [Lausanne University Hospital, Department of Diagnostic and Interventional Radiology, Lausanne (Switzerland); Montpellier University Hospital, Department of Diagnostic and Interventional Radiology, Montpellier (France); Aho, Serge [University Hospital, Department of Epidemiology, Dijon (France); Deltenre, Pierre [Lausanne University Hospital, Department of Gastroenterology, Lausanne (Switzerland)

    2017-04-15

    To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma. In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model. Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025). DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis. (orig.)

  6. IVUS Findings in Late and Very Late Stent Thrombosis. A Comparison Between Bare-metal and Drug-eluting Stents.

    Science.gov (United States)

    Fuentes, Lara; Gómez-Lara, Josep; Salvatella, Neus; Gonzalo, Nieves; Hernández-Hernández, Felipe; Fernández-Nofrerias, Eduard; Sánchez-Recalde, Ángel; Alfonso, Fernando; Romaguera, Rafael; Ferreiro, José Luis; Roura, Gerard; Teruel, Luis; Gracida, Montserrat; Marcano, Ana Lucrecia; Gómez-Hospital, Joan-Antoni; Cequier, Ángel

    2018-05-01

    Stent thrombosis (ST) is a life-threatening complication after stent implantation. Intravascular ultrasound is able to discern most causes of ST. The aim of this study was to compare intravascular ultrasound findings between bare-metal stents (BMS) and drug-eluting stents (DES) in patients with late (31 days to 1 year) or very late ST (> 1 year). Of 250 consecutive patients with late or very late ST in 7 Spanish institutions, 114 patients (45.5% BMS and 54.5% DES) were imaged with intravascular ultrasound. Off-line intravascular ultrasound analysis was performed to assess malapposition, underexpansion, and neoatherosclerosis. The median time from stent implantation to ST was 4.0 years with BMS and 3.4 years with DES (P = .04). Isolated malapposition was similarly observed in both groups (36.5% vs 46.8%; P = .18) but was numerically lower with BMS (26.6% vs 48.0%; P = .07) in patients with very late ST. Isolated underexpansion was similarly observed in both groups (13.5% vs 11.3%; P = .47). Isolated neoatherosclerosis occurred only in patients with very late ST and was more prevalent with BMS (22.9%) than with DES (6.0%); P = .02. At 2.9 years' follow-up, there were 0% and 6.9% cardiac deaths, respectively (P = .06) and recurrent ST occurred in 4.0% and 5.2% of patients, respectively (P = .60). Malapposition was the most common finding in patients with late and very late ST and is more prevalent with DES in very late ST. In contrast, neoatherosclerosis was exclusively observed in patients with very late ST and mainly with BMS. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Prognostic Value of Plasma Pentraxin-3 Levels in Patients with Stable Coronary Artery Disease after Drug-Eluting Stent Implantation

    Directory of Open Access Journals (Sweden)

    Liu Haibo

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP. Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD after drug eluting stent (DES implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5 for major adverse cardiovascular events (MACEs. We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.

  8. Association of localized hypersensitivity and in-stent neoatherosclerosis with the very late drug-eluting stent thrombosis.

    Directory of Open Access Journals (Sweden)

    Kyohei Yamaji

    Full Text Available Localized hypersensitivity reaction, delayed arterial healing, and neoatherosclerosis inside the stent have been suggested as the underlying pathologic mechanisms of very late stent thrombosis (VLST of drug-eluting stent (DES. The present study sought to explore the prevalence of inflammatory cell infiltrates and evidence for fragments of atherosclerotic plaques in the aspirated thrombi in patients with DES VLST.From April 2004 to September 2012, 48 patients with stent thrombosis (ST of DES underwent thrombus aspiration with retrieved material sufficient for the histopathologic analysis; early ST (EST, within 30 days: N = 17, late ST (LST, between 31 and 365 days: N = 7, and very late ST (VLST, >1 year: N = 24. Eosinophil fraction in the aspirated thrombi was significantly higher in patients with VLST (8.2±5.7% as compared with those with EST (4.3±3.0% and LST (5.5±3.8% (P = 0.03. Eosinophil fraction in the aspirated thrombi was significantly higher in 12 VLST patients with angiographic peri-stent contrast staining (PSS and/or incomplete stent apposition (ISA by intravascular ultrasound than in 12 VLST patients without PSS or ISA (10.6±6.1% versus 5.8±4.1%, P = 0.03. Evidences for fragments of atherosclerotic plaques in the aspirated thrombi were observed only in 3 (13% out of 24 patients with DES VLST.Eosinophil fraction in the aspirated thrombi was significantly higher in patients with DES VLST as compared with those with EST and LST. Evidences for fragments of atherosclerotic plaques were relatively uncommon in patients with DES VLST.

  9. Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR

    Directory of Open Access Journals (Sweden)

    Zhongxia Wang

    2016-01-01

    Full Text Available The inflammatory response after polymer-based drug-eluting stent (DES placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ activators thiazolidinedione (TZD remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO on circulating peripheral blood mononuclear cells (MNCs in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO or placebo (control; Con treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and matrix metalloproteinase-9 (MMP-9 were significantly decreased in PIO group compared to the Con group (P=0.035, 0.011, 0.008, and 0.012, resp.. DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P=0.031, 0.012, and 0.007, resp.. In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era.

  10. Type D personality predicts chronic anxiety following percutaneous coronary intervention in the drug-eluting stent era

    DEFF Research Database (Denmark)

    Spindler, Helle; Pedersen, Susanne S.; Serruys, Patrick W.

    2007-01-01

      Background: Anxiety is an often overlooked risk factor in coronary artery disease (CAD). Hence, little is known about predictors of unremitting chronic anxiety in CAD patients. This study examined whether the distressed personality (Type D) predicts chronic anxiety post percutaneous coronary...... months post-PCI. Results: Of 167 patients anxious at 6 months, 108 (65%) were still anxious 12 months post-PCI. Significant univariable predictors of chronic anxiety were Type D personality (OR:3.17: 95% CI:1.64-6.14) and sirolimus-eluting stents (OR:0.51; 95% CI:0.27-0.98), with sirolimus-eluting stents...... showing a protective effect. In multivariable analyses, Type D personality (OR:3.31; 95% CI:1.59-6.87) and sirolimus-eluting stents (OR:0.44; 95% CI:0.21-0.92) remained significant independent predictors of chronic anxiety adjusting for depressive symptoms at 6 months, and demographic and clinical risk...

  11. Discretionary decisions and disparities in receiving drug-eluting stents under a universal healthcare system: A population-based study.

    Directory of Open Access Journals (Sweden)

    Raymond N Kuo

    Full Text Available One of the main objectives behind the expansion of insurance coverage is to eliminate disparities in health and healthcare. However, researchers have not yet fully elucidated the reasons for disparities in the use of high-cost treatments among patients of different occupations. Furthermore, it remains unknown whether discretionary decisions made at the hospital level have an impact on the administration of high-cost interventions in a universal healthcare system. This study investigated the adoption of drug-eluting stents (DES versus bare metal-stents (BMS among patients in different occupations and income levels, with the aim of gauging the degree to which the inclination of health providers toward treatment options could affect treatment choices at the patient-level within a universal healthcare system.We adopted a cross-sectional observational study design using hierarchical modeling in conjunction with the population-based National Health Insurance database of Taiwan. Patients who received either a BMS or a DES between 2007 and 2010 were included in the study.During the period of study, 42,124 patients received a BMS (65.3% and 22,376 received DES (34.7%. Patients who were physicians or the family members of physicians were far more likely to receive DES (OR: 3.18, CI: 2.38-4.23 than were patients who were neither physicians nor in other high-status jobs (employers, other medical professions, or public service. Similarly, patients in the top 5% income bracket had a higher probability of receiving a DES (OR: 2.23, CI: 2.06-2.47, p 50% or between 25% and 50% was shown to be strongly associated with the selection of DESs (OR: 3.64 CI: 3.24-4.09 and OR: 2.16, CI: 2.01-2.33, respectively.Even under the universal healthcare system in Taiwan, socioeconomic disparities in the use of high-cost services remain widespread. Differences in the care received by patients of lower socioeconomic status may be due to the discretionary decisions of healthcare

  12. Multifunctional surfaces with biomimetic nanofibres and drug-eluting micro-patterns for infection control and bone tissue formation

    Directory of Open Access Journals (Sweden)

    XN Chen

    2012-09-01

    Full Text Available For long-term orthopaedic implants, the creation of a surface that is repulsive to bacteria while adhesive to tissue cells represents a promising strategy to control infection. To obtain such multifunctional surfaces, two possible approaches were explored to incorporate a model antibiotic, rifampicin (Rf, into the osteogenic polycaprolactone (PCL/chitosan (CHS biomimetic nanofibre meshes by (1 blending Rf into the electrospinning solutions and then electrospinning into nanofibres (i.e., Rf-incorporating fibres, or (2 depositing Rf-containing poly(D,L-lactic-co-glycolic acid (PLGA micro-patterns onto the PCL/chitosan nanofibre meshes via ink-jet printing (i.e., Rf-eluting micro-pattern/fibre. Rapid release of Rf from both meshes was measured even though a relatively slower release rate was obtained from the Rf-eluting micro-pattern ones. Antibacterial assay with Staphylococcus epidermidis showed that both mesh surfaces could effectively kill bacteria and prevent biofilm formation. However, only Rf-eluting micro-pattern meshes favoured the attachment, spreading and metabolic activity of preosteoblasts in the cell culture study. Furthermore, the Rf-eluting micro-pattern meshes could better support the osteogenic differentiation of preosteoblasts by up-regulating the gene expression of bone markers (type I collagen and alkaline phosphatase. Clearly, compared to Rf-incorporating nanofibre meshes, Rf-eluting micro-patterns could effectively prevent biofilm formation without sacrificing the osteogenic properties of PCL/chitosan nanofibre surfaces. This finding provides an innovative avenue to design multifunctional surfaces for enhancing bone tissue formation while controlling infection.

  13. The sirolimus-eluting Cypher Select coronary stent for the treatment of bare-metal and drug-eluting stent restenosis: insights from the e-SELECT (Multicenter Post-Market Surveillance) registry.

    Science.gov (United States)

    Abizaid, Alexandre; Costa, J Ribamar; Banning, Adrian; Bartorelli, Antonio L; Dzavik, Vladimir; Ellis, Stephen; Gao, Runlin; Holmes, David R; Jeong, Muyng Ho; Legrand, Victor; Neumann, Franz-Josef; Nyakern, Maria; Orlick, Amy; Spaulding, Christian; Worthley, Stephen; Urban, Philip M

    2012-01-01

    This study sought to compare the 1-year safety and efficacy of Cypher Select or Cypher Select Plus (Cordis Corporation, Bridgewater, New Jersey) sirolimus-eluting stents (SES) with the treatment of bare-metal stents (BMS) and drug-eluting stent (DES) in-stent restenosis (ISR) in nonselected, real-world patients. There is paucity of consistent data on DES for the treatment of ISR, especially, DES ISR. The e-SELECT (Multicenter Post-Market Surveillance) registry is a Web-based, multicenter and international registry encompassing virtually all subsets of patients and lesions treated with at least 1 SES during the period from 2006 to 2008. We enrolled in this pre-specified subanalysis all patients with at least 1 clinically relevant BMS or DES ISR treated with SES. Primary endpoint was major adverse cardiac events and stent thrombosis rate at 1 year. Of 15,147 patients enrolled, 1,590 (10.5%) presented at least 1 ISR (BMS group, n = 1,235, DES group, n = 355). Patients with DES ISR had higher incidence of diabetes (39.4% vs. 26.9%, p target lesion revascularization and definite/probable late stent thrombosis were higher in patients with DES ISR (6.9% vs. 3.1%, p = 0.003, and 1.8% vs. 0.5%, p = 0.04, respectively). Use of SES for either BMS or DES ISR treatment is safe and associated with low target lesion revascularization recurrence and no apparent safety concern. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Predictive Ability of the SYNergy Between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery Score II for Long-term Mortality in Patients with Three-vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated with Second-generation Drug-eluting Stents

    Directory of Open Access Journals (Sweden)

    Ji-Qiang He

    2015-01-01

    Conclusion: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.

  15. Efectos biológicos de los stents medicados en la circulación coronaria Biological effects of drug-eluting stents in the coronary circulation

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-04-01

    Full Text Available Los stents medicados ofrecen la mejor alternativa disponible no quirúrgica para el tratamiento de la enfermedad coronaria gracias a su demostrada eficacia. Sin embargo, estos excelentes resultados han sido opacados en términos de seguridad, principalmente por la presencia de trombosis de stents de manera tardía o muy tardía. La comprensión de los efectos biológicos que ejercen a nivel de la arteria coronaria luego de su implante, se debe al efecto de la plataforma utilizada, el polímero y la droga que liberan. Los trastornos de reparación vascular inducidos favorecen la trombosis de stents y sus consecuencias clínicas. Se hace una revisión de los diferentes efectos biológicos de los stents medicados en las arterias coronarias, que permite comprender como han surgido rápidamente nuevas versiones en materiales, diseños, polímeros y medicamentos que reducen los efectos adversos a nivel coronario, mejorando su eficacia y seguridad.Drug-eluting stents offer the best available non-surgical alternative for the treatment of coronary disease, thanks to its demonstrated efficacy. However, in terms of security, these excellent results have been overshadowed by the late or very late appearance of stent thromboses.The biological effects they have in the coronary artery after its implantation are due to the effect of the platform used, the polymer and the medication released. The vascular healing disorders induced by drug-eluting stents favor stent thrombosis and its clinical consequences. This is a review of the different biological effects of drug-eluting stents in coronary arteries that allows to understand how the rapid onset of new versions of materials, designs, polymers and medications diminish adverse coronary effects and improve its efficacy and safety.

  16. Comparison of elution efficiency of 99Mo/99mTc generator using theoretical and a free web based software method

    International Nuclear Information System (INIS)

    Kiran Kumar, J.K.; Sharma, S.; Chakraborty, D.; Singh, B.; Bhattacharaya, A.; Mittal, B.R.; Gayana, S.

    2010-01-01

    Full text: Generator is constructed on the principle of decay growth relationship between a long lived parent radionuclide and short lived daughter radionuclide. Difference in chemical properties of daughter and parent radionuclide helps in efficient separation of the two radionuclides. Aim and Objectives: The present study was designed to calculate the elution efficiency of the generator using the traditional formula based method and free web based software method. Materials and Methods: 99 Mo/ 99m Tc MON.TEK (Monrol, Gebze) generator and sterile 0.9% NaCl vial and vacuum vial in the lead shield were used for the elution. A new 99 Mo/ 99m Tc generator (calibrated activity 30GBq) calibrated for thursday was received on monday morning in our department. Generator was placed behind lead bricks in fume hood. The rubber plugs of both vacuum and 0.9% NaCl vial were wiped with 70% isopropyl alcohol swabs. Vacuum vial placed inside the lead shield was inserted in the vacuum position simultaneously 10 ml NaCl vial was inserted in the second slot. After 1-2 min vacuum vial was removed without moving the emptied 0.9%NaCl vial. The vacuum slot was covered with another sterile vial to maintain sterility. The RAC was measured in the calibrated dose calibrator (Capintec, 15 CRC). The elution efficiency was calculated theoretically and using free web based software (Apache Web server (www.apache.org) and PHP (www.php.net). Web site of the Italian Association of Nuclear Medicine and Molecular Imaging (www.aimn.it). Results: The mean elution efficiency calculated by theoretical method was 93.95% +0.61. The mean elution efficiency as calculated by the software was 92.85% + 0.89. There was no statistical difference in both the methods. Conclusion: The free web based software provides precise and reproducible results and thus saves time and mathematical calculation steps. This enables a rational use of available activity and also enabling a selection of the type and number of

  17. Drug-eluting stents with biodegradable polymer for the treatment of patients with diabetes mellitus: clinical outcome at 2 years in a large population of patients

    Directory of Open Access Journals (Sweden)

    Wiemer M

    2015-02-01

    Full Text Available Marcus Wiemer,1 Gian Battista Danzi,2 Nick West,3 Vassilios Voudris,4 René Koning,5 Stefan Hoffmann,6 Mario Lombardi,7 Josepa Mauri,8 Rade Babic,9 Fraser Witherow10On behalf of the NOBORI 2 Investigators 1Department of Cardiology, Heart and Diabetes Center North Rhine–Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany; 2Ospedale Maggiore Policlinico, Milan, Italy; 3Papworth Hospital, Cambridge, UK; 4Onassis Cardiac Surgery Center, Athens, Greece; 5Clinique Saint Hilaire, Rouen, France; 6Vivantes Netzwerk für Gesundheit GmbH, Berlin, Germany; 7Azienda Ospedaliera Villa Sofia, Palermo, Italy; 8Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 9Institute for Cardiovascular Diseases Dedinje, Belgrade, Serbia; 10Dorset County Hospital, Dorchester, UK Objective: This study investigates the safety and efficacy of a third-generation drug-eluting stent (DES with biodegradable polymer in the complex patient population of diabetes mellitus (DM. Clinical trial registration: ISRCTN81649913. Background: Percutaneous coronary interventions in patients with DM are associated with a higher incidence of death, restenosis, and stent thrombosis as compared to non-diabetic patients. The use of a DES has been shown to improve outcomes in diabetic patients. Methods: Out of 3,067 patients, enrolled in 126 centers worldwide in the NOBORI 2 registry, 888 patients suffered from DM, 213 of them (14% being insulin-dependent DM (IDDM. Two years’ follow-up has been completed in this study. Results: At 1- and 2-year follow-up, 97% and 95% of the patients, respectively, were available. The reported target lesion failure (TLF rates at 1- and 2-year follow-up were 6.0% and 7.2% in the DM group, respectively, and 3.0% and 4.2% in the non-DM group, respectively (P<0.001 for both years. Inside the DM group, the TLF rates of 9.9% and 11.7% at the 1- and 2-year follow-ups, respectively, in patients with IDDM were significantly higher than the TLF rates of 4

  18. Determination of Chemical Compounds Generated from Second-generation E-cigarettes Using a Sorbent Cartridge Followed by a Two-step Elution Method.

    Science.gov (United States)

    Uchiyama, Shigehisa; Senoo, Yui; Hayashida, Hideki; Inaba, Yohei; Nakagome, Hideki; Kunugita, Naoki

    2016-01-01

    We developed an analytical method for analyzing electronic cigarette (E-cigarette) smoke, and measured the carbonyl compounds and volatile organic compounds generated by 10 brands of second-generation E-cigarettes. A glass filter (Cambridge filter pad) for particulate matter and a solid sorbent tube packed with Carboxen-572 for gaseous compounds were used to collect E-cigarette smoke. These were then analyzed using a two-step elution method with carbon disulfide and methanol, followed by high-performance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC/MS). Formaldehyde (FA), acetaldehyde (AA), acetone (AC), acrolein (ACR), propanal (PA), acetol (AT), glyoxal (GO), and methyl glyoxal (MGO) were detected by HPLC in some E-cigarettes. Propylene glycol (PG), glycerol (GLY), and some esters were detected by GC/MS. GO and MGO exist mainly as particulate matter. AA, AC, ACR, PA, and AT exist mainly as gaseous compounds. FA exists as both particulate matter and gaseous compounds. These carbonyl compounds have carbon numbers C1 - C3. The main components of E-liquid are PG (C3) and GLY (C3). Therefore, the oxidation of liquids, such as PG and GLY in E-cigarettes upon incidental contact with the heating element in E-cigarette, is suggested as being a possible cause for carbonyl generation. When the puff number exceeds a critical point, carbonyl generation rapidly increases and then remains constant. The results of this study are now being used to determine the following E-cigarette smoking protocol: puff volume, 55 mL; puff duration, 2 s; and puff number, 30. E-cigarette analysis revealed very large variation in carbonyl concentration among not only different brands, but also different samples of the same product. Typical distributions of carbonyl concentration were not observed in any of the E-cigarettes tested, and the mean values greatly differed from median values.

  19. The effect of stent coating on stent deliverability: direct randomised comparison of drug eluting and bare metal stents using the same stent platform.

    Science.gov (United States)

    Siminiak, Tomasz; Link, Rafał; Wołoszyn, Maciej; Kałmucki, Piotr; Baszko, Artur

    2012-01-01

    There is certain experimental and clinical evidence indicating that the covering of bare metal stents (BMS) with drug eluting polymers to produce drug eluting stents (DES) results in increased stent stiffness and modifies the mechanical properties of the stent platform. In addition, it has been speculated that the mechanical performance of DES, compared to BMS, may be related to the type of polymer used to cover stents. We aimed at evaluating the deliverability of DES with a lactate based biodegradable polymer and BMS in patients with stable coronary artery disease in a prospective randomised study. One hundred eleven consecutive patients (age: 36-77, mean 58.8 years) scheduled for routine angioplasty due to stable coronary disease were randomised to receive BMS (Chopin II(TM), Balton, Poland) or paclitaxel eluting stent (Chopin Luc(TM), Balton, Poland) using the same metal platform. Only patients scheduled for angioplasty using the direct implantation technique of a single stent were randomised. The exclusion criteria included patients 〉 80 years, multivessel disease and reference diameter of the target vessel 〉 3.5 mm. In the BMS group (n = 55; 35 males and 20 females), the mean diameter of implanted stents was 3.09 ± 0.40 and the mean length was 11.37 ± 2.80, whereas in the DES group (n = 56; 34 males and 22 females) the mean stent sizes were 3.02 ± 0.34 and 17.90 ± 7.38 mm, respectively (p 〉 0.05 for length). The groups did not significantly differ regarding the frequency of stent implantation to particular coronary vessels. The direct stenting technique was attempted and failed, leading to the stents' implantation after predilatation in five patients in the BMS group and six patients in the DES group. Failure of stent implantation and subsequent implantation of another stent type was observed in no BMS patients and in one DES patient (NS). Although stent covering with lactate based drug eluting polymer may increase its stiffness, it does not affect

  20. Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry.

    Science.gov (United States)

    Baber, Usman; Mehran, Roxana; Kirtane, Ajay J; Gurbel, Paul A; Christodoulidis, Georgios; Maehara, Akiko; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Xu, Ke; Parise, Helen; Brodie, Bruce R; Stuckey, Thomas D; Stone, Gregg W

    2015-06-01

    Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (Pimpact of HPR on ischemic and bleeding events is similar irrespective of CKD status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794. © 2015 American Heart Association, Inc.

  1. Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study)

    DEFF Research Database (Denmark)

    Schoos, Mikkel M.; Dangas, George D.; Mehran, Roxana

    2016-01-01

    An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether Hb...... With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c 8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208...... >208 (42.5%, 50.2%, and 62.3%, p definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models...

  2. Endothelial cell repopulation after stenting determines in-stent neointima formation: effects of bare-metal vs. drug-eluting stents and genetic endothelial cell modification.

    Science.gov (United States)

    Douglas, Gillian; Van Kampen, Erik; Hale, Ashley B; McNeill, Eileen; Patel, Jyoti; Crabtree, Mark J; Ali, Ziad; Hoerr, Robert A; Alp, Nicholas J; Channon, Keith M

    2013-11-01

    Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function. Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043). Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.

  3. Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: an in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Chan EC

    2012-02-01

    Full Text Available Dave Wei-Chih Chen1,2, Jun-Yi Liao3, Shih-Jung Liu2, Err-Cheng Chan41Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 2Department of Mechanical Engineering, 3Graduate Institute of Medical Mechatronics, 4School of Medical Technology, Chang Gung University, Kwei-San, Tao-Yuan, TaiwanBackground: The purpose of this study was to develop novel sandwich-structured nanofibrous membranes to provide sustained-release delivery of vancomycin, gentamicin, and lidocaine for repair of infected wounds.Methods: To prepare the biodegradable membranes, poly(D, L-lactide-co-glycolide (PLGA, collagen, and various pharmaceuticals, including vancomycin, gentamicin, and lidocaine, were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into sandwich-structured membranes with PLGA/collagen as the surface layers and PLGA/drugs as the core. An elution method and a high-pressure liquid chromatography assay were used to characterize in vivo and in vitro drug release from the membranes. In addition, repair of infected wounds in rats was studied. Histological examination of epithelialization and granulation at the wound site was also performed.Results: The biodegradable nanofibrous membranes released large amounts of vancomycin and gentamicin (well above the minimum inhibition concentration and lidocaine in vivo for more than 3 weeks. A bacterial inhibition test was carried out to determine the relative activity of the antibiotics released. The bioactivity ranged from 40% to 100%. The nanofibrous membranes were functionally active in treating infected wounds, and were very effective as accelerators in early-stage wound healing.Conclusion: Using the electrospinning technique, we will be able to manufacture biodegradable, biomimetic, nanofibrous, extracellular membranes for long-term delivery of various drugs.Keywords: nanofibrous, sandwich-structured, drug-eluting membranes, electrospinning, release characteristics, repair, wound

  4. Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm

    Directory of Open Access Journals (Sweden)

    Oliver P. Guttmann

    2016-05-01

    Full Text Available BackgroundResearch trials have shown improved short-term outcome with drug-eluting stents (DES over bare metal stents (BMS in saphenous vein graft (SVG percutaneous coronary intervention (PCI, primarily by reducing target vessel revascularization (TVR for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter.MethodsData were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE out to a median of 3.3 years (interquartile range: 2.1-4.1. MACE was defined as all-cause mortality, myocardial infarction (MI, TVR and stroke.ResultsThere was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017 over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI 0.52-0.94, with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68. However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES.ConclusionsOverall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen.

  5. Application of Snyder-Dolan classification scheme to the selection of "orthogonal" columns for fast screening of illicit drugs and impurity profiling of pharmaceuticals--I. Isocratic elution.

    Science.gov (United States)

    Fan, Wenzhe; Zhang, Yu; Carr, Peter W; Rutan, Sarah C; Dumarey, Melanie; Schellinger, Adam P; Pritts, Wayne

    2009-09-18

    Fourteen judiciously selected reversed phase columns were tested with 18 cationic drug solutes under the isocratic elution conditions advised in the Snyder-Dolan (S-D) hydrophobic subtraction method of column classification. The standard errors (S.E.) of the least squares regressions of logk' vs. logk'(REF) were obtained for a given column against a reference column and used to compare and classify columns based on their selectivity. The results are consistent with those obtained with a study of the 16 test solutes recommended by Snyder and Dolan. To the extent these drugs are representative, these results show that the S-D classification scheme is also generally applicable to pharmaceuticals under isocratic conditions. That is, those columns judged to be similar based on the 16 S-D solutes were similar based on the 18 drugs; furthermore those columns judged to have significantly different selectivities based on the 16 S-D probes appeared to be quite different for the drugs as well. Given that the S-D method has been used to classify more than 400 different types of reversed phases the extension to cationic drugs is a significant finding.

  6. Country report: Vietnam. Setting Up of a 90Sr/90Y Generator System Based on Supported Liquid Membrane (SLM) Technique and Radiolabeling of Eluted 90Y with Biomolecules

    International Nuclear Information System (INIS)

    Nguyen Thi Thu; Duong Van Dong; Bui Van Cuong; Chu Van Khoa

    2010-01-01

    In the course of participating in the IAEA-CRP during the last two years, Vietnam has achieved the goal of setting up a 90 Sr/ 90 Y generator system based on Supported Liquid Membrane (SLM) technique and also radiolabeling of the eluted 90 Y with antibody, peptides and albumin. A two stage SLM based 90 Sr- 90 Y generator was set up in-house to generate carrier-free 90 Y at different activity levels viz. 5, 20, 50 mCi. The generator system was operated in sequential mode in which 2-ethylhexyl 2-ethylhexyl phosphonic acid (PC88A) based SLM was used in the first stage for the transport 90 Y in 4.0 M nitric acid from source phase where 90 Sr- 90 Y equilibrium mixture is placed in nitric acid medium at pH to 1-2. In the second stage, octyl (phenyl)-N,N-diisobutylcarbamoylmethyl phosphine oxide (CMPO) based SLM was used for the transport of 90 Y selectively to 1.0 M acetic acid which is the best medium for radiolebeling. The eluted 90 Y from the generator was tested for the presence of any traces of 90 Sr using the Extraction Paper Chromatography (EPC) and was found suitable for radiolabeling. The generator system could be upgraded to 100 mCi level successfully due to an expert mission from India through IAEA. The 90 Y product obtained from the generator system was used for radiolabeling of antibody and peptides viz. Rituximab, DOTATATE and albumin particles under different experimental conditions. A new chromatography system could be developed for analyzing 90 Y labeled albumin using the TAE buffer as mobile phase in PC and ITLC

  7. Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).

    Science.gov (United States)

    Lee, Joo Myung; Park, Kyung Woo; Han, Jung-Kyu; Yang, Han-Mo; Kang, Hyun-Jae; Koo, Bon-Kwon; Bae, Jang-Whan; Woo, Sung-Il; Park, Jin Sik; Jin, Dong-Kyu; Jeon, Dong Woon; Oh, Seok Kyu; Park, Jong-Seon; Kim, Doo-Il; Hyon, Min Su; Jeon, Hui-Kyung; Lim, Do-Sun; Kim, Myeong-Gon; Rha, Seung-Woon; Her, Sung-Ho; Hwang, Jin-Yong; Kim, Sanghyun; Choi, Young Jin; Kang, Jin Ho; Moon, Keon-Woong; Jang, Yangsoo; Kim, Hyo-Soo

    2014-11-01

    Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and

  8. In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

    Science.gov (United States)

    Buchanan, Kyle D; Torguson, Rebecca; Rogers, Toby; Xu, Linzhi; Gai, Jiaxiang; Ben-Dor, Itsik; Suddath, William O; Satler, Lowell F; Waksman, Ron

    2018-03-13

    Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p stent technique and should motivate the continued development of fully bioresorbable scaffolds. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Effects of amphiphilic chitosan-g-poly(ε-caprolactone) polymer additives on paclitaxel release from drug eluting implants

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Weibin [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Gu, Chunhua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Jiang, Han [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Zhang, Mengru [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-12-01

    Bioresorbable polymer stents have been proposed as promising medical implants to avoid long-term safety concerns and other potential issues caused by traditional materials. As an important member, poly(ε-caprolactone) (PCL) was used as the implant matrix with different drug loadings. To better regulate drug release rate, the hydrophilicity of PCL was adjusted by addition of amphiphilic graft copolymers, chitosan-g-poly(ε-caprolactone) (CP). The in vitro release results indicated that the improvement of bulk hydrophilicity could accelerate drug release better than that of surface coating. The optimum additive amount was 25% with CP9. Further study showed that the effect of aspirin molecules displayed no obvious difference to that of CP macromolecules on drug release rate. Moreover, these release profiles were fitted with mathematical models. The similarities were evaluated with similarity factors. Scanning electron microscopy (SEM) images displayed surface/cross-section morphologies of pure PCL and modified implants before and after release. - Highlights: • The improvement of bulk hydrophilicity better accelerated drug release. • The higher weight ratio of CP implants had, the faster the drug released. • The shorter PCL chain in CP graft coploymers, the faster the drug released. • The optimum additive amount was 25% with CP9. • Drug release profile conformed to controllable Fick diffusional release mechanism.

  10. Factors Associated with the Use of Drug-Eluting Stents in Patients Presenting with Acute ST-Segment Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Jose F. Chavez

    2015-01-01

    Full Text Available Background. Drug-eluting stents (DES have proven clinical superiority to bare-metal stents (BMS for the treatment of patients with ST-segment elevation myocardial infarction (STEMI. Decision to implant BMS or DES is dependent on the patient’s ability to take dual antiplatelet therapy. This study investigated factors associated with DES placement in STEMI patients. Methods. Retrospective analysis was performed on 193 patients who presented with STEMI and were treated with percutaneous coronary intervention at an urban, tertiary care hospital. Independent factors associated with choice of stent type were determined using stepwise multivariate logistic regression. Odds ratio (OR was used to evaluate factors significantly associated with DES and BMS. Results. 128 received at least one DES, while 65 received BMS. BMS use was more likely in the setting of illicit drug or alcohol abuse ([OR] 0.15, 95% CI 0.05–0.48, p≤0.01, cardiogenic shock (OR 0.26, 95% CI 0.10–0.73, p=0.01, and larger stent diameter (OR 0.28, 95% CI 0.11–0.68, p≤0.01. Conclusions. In this analysis, BMS implantation was associated with illicit drug or alcohol abuse and presence of cardiogenic shock. This study did not confirm previous observations that non-White race, insurance, or income predicts BMS use.

  11. Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Cortese, B.; Kandzari, D.; Dias, S.; Wojakowski, W.; Buffon, A.; Lansky, A.; Angelini, P.; Torguson, R.; Kubica, J.; Kelm, M.; Boer, M.J. de; Waksman, R.; Suryapranata, H.

    2014-01-01

    BACKGROUND: The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy

  12. Incidence of definite stent thrombosis or in-stent restenosis after drug-eluting stent implantation for treatment of coronary in-stent restenosis. From western denmark heart registry

    DEFF Research Database (Denmark)

    Jensen, Jesper; Jensen, Lisette Okkels; Terkelsen, Christian Juhl

    2012-01-01

    There are limited data on the optimal management of in-stent restenosis after percutaneous coronary intervention (PCI) with bare metal stent (BMS) or drug-eluting stent (DES) implantations. We assessed the clinical presentation, the incidence, and prognosis of definite stent thrombosis...

  13. Novel management strategy for coronary steal syndrome: case report of occlusion of a LIMA graft side branch with a combination of drug-eluting and covered-stent deployment.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2009-11-01

    We report a novel percutaneous therapeutic approach to the management of suspected coronary artery steal syndrome resulting from a large side branch of the left internal mammary artery bypass graft, using a combination of coated and drug-eluting stents. We demonstrate the feasibility and long-term efficacy of this strategy in a case report.

  14. Direct implantation of rapamycin-eluting stents with bioresorbable drug carrier technology utilising the Svelte coronary stent-on-a-wire: the DIRECT II study.

    Science.gov (United States)

    Verheye, Stefan; Khattab, Ahmed A; Carrie, Didier; Stella, Pieter; Slagboom, Ton; Bartunek, Jozef; Onuma, Yoshinobu; Serruys, Patrick W

    2016-08-05

    Our aim was to demonstrate the safety and efficacy of the Svelte sirolimus-eluting coronary stent-on-a-wire Integrated Delivery System (IDS) with bioresorbable drug coating compared to the Resolute Integrity zotarolimus-eluting stent with durable polymer in patients with de novo coronary artery lesions. Direct stenting, particularly in conjunction with transradial intervention (TRI), has been associated with reduced bleeding complications, procedure time, radiation exposure and contrast administration compared to conventional stenting with wiring and predilatation. The low-profile Svelte IDS is designed to facilitate TRI and direct stenting, reducing the number of procedural steps, time and cost associated with coronary stenting. DIRECT II was a prospective, multicentre trial which enrolled 159 patients to establish non-inferiority of the Svelte IDS versus Resolute Integrity using a 2:1 randomisation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at six months. Target vessel failure (TVF), as well as secondary clinical endpoints, will be assessed annually up to five years. At six months, in-stent LLL was 0.09±0.31 mm in the Svelte IDS group compared to 0.13±0.27 mm in the Resolute Integrity group (p<0.001 for non-inferiority). TVF at one year was similar across the Svelte IDS and Resolute Integrity groups (6.5% vs. 9.8%, respectively). DIRECT II demonstrated the non-inferiority of the Svelte IDS to Resolute Integrity with respect to in-stent LLL at six months. Clinical outcomes at one year were comparable between the two groups.

  15. Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

    Science.gov (United States)

    Stefanović, Srđan; Janković, Slobodan M; Novaković, Milan; Milosavljević, Marko; Folić, Marko

    2018-02-01

    Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

  16. Lab-on-fiber optofluidic platform for in situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers

    Czech Academy of Sciences Publication Activity Database

    Tian, F.; Min, J.; Kaňka, Jiří; Li, X.; Hammond, P. T.; Du, H.

    2015-01-01

    Roč. 23, č. 15 (2015), s. 20132-20142 ISSN 1094-4087 R&D Projects: GA MŠk(CZ) LH11038 Institutional support: RVO:67985882 Keywords : long-period grating * drug release * thin film Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 3.148, year: 2015

  17. Long-term prognostic value of risk scores after drug-eluting stent implantation for unprotected left main coronary artery: A pooled analysis of the ISAR-LEFT-MAIN and ISAR-LEFT-MAIN 2 randomized clinical trials.

    Science.gov (United States)

    Xhepa, Erion; Tada, Tomohisa; Kufner, Sebastian; Ndrepepa, Gjin; Byrne, Robert A; Kreutzer, Johanna; Ibrahim, Tareq; Tiroch, Klaus; Valgimigli, Marco; Tölg, Ralf; Cassese, Salvatore; Fusaro, Massimiliano; Schunkert, Heribert; Laugwitz, Karl L; Mehilli, Julinda; Kastrati, Adnan

    2017-01-01

    To evaluate the long-term prognostic value of risk scores in the setting of drug-eluting stent (DES) implantation for uLMCA. Data on the prognostic value of novel risk scores developed to select the most appropriate revascularization strategy in patients undergoing DES implantation for uLMCA disease are relatively limited. The study represents a patient-level pooled analysis of the ISAR-LEFT-MAIN (607 patients randomized to paclitaxel-eluting or sirolimus-eluting stents) and the ISAR-LEFT-MAIN-2 (650 patients randomized to everolimus-eluting or zotarolimus-eluting stents) randomized trials. The Syntax Score (SxScore) as well the Syntax Score II (SS-II), the EuroSCORE and the Global Risk Classification (GRC) were calculated. The primary outcome was all-cause mortality. At a mean follow-up of 3 years there were 160 deaths (12.7%). The death-incidence was significantly higher in the upper tertiles than in the intermediate or lower ones for all risk scores (log-rank test P risk scores were able to stratify the mortality risk at long-term follow-up. EuroSCORE was the only risk score that significantly improved the discriminatory power of a multivariable model to predict long-term mortality. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. TIDES-ACS Trial: comparison of titanium-nitride-oxide coated bio-active-stent to the drug (everolimus)-eluting stent in acute coronary syndrome. Study design and objectives.

    Science.gov (United States)

    Colkesen, E B; Eefting, F D; Rensing, B J; Suttorp, M J; Ten Berg, J M; Karjalainen, P P; Van Der Heyden, J A

    2015-02-01

    Drug-eluting stents (DES), delivering antiproliferative drugs from a durable polymer, have shown to reduce in-stent restenosis after percutaneous coronary intervention (PCI) compared to bare-metal stents (BMS). However, they have been associated with a hypersensitivity reaction, delayed healing, and incomplete endothelialization, which may contribute to an increased risk of late stent thrombosis. Consequently, a prolonged duration of dual antiplatelet therapy (DAPT) is needed, with an increased risk of bleeding complication. A number of stent technologies are being developed in an attempt to modify late thrombotic events and DAPT duration. The Optimax™ stent is such a novel, next generation bioactive stent (BAS), in which a thicker layer of titanium-nitride-oxide coating is inserted over the stent struts. The rationale of this is to obtain more efficient and rapid vascular healing at the site of the stent implantation. The aim of TIDES-ACS Trial is to compare clinical outcome in patients presenting with ACS, treated with PCI using Optimax-BAS versus Synergy™-EES. Second objective is to explore whether the Optimax™-BAS use is superior compared with Synergy™-EES use with respect of hard end points (cardiac death, myocardial infarction [MI] and major bleeding). A prospective, randomized, multicenter trial (ClinicalTrials.gov Identifier: NCT02049229), will be conducted in interventional centres in Finland (six centres), France (five centres) and Holland (two centres), including a total of 1800 patients.

  19. Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents

    DEFF Research Database (Denmark)

    Wein, Bastian; Coslovsky, Michael; Jabbari, Reza

    2017-01-01

    BACKGROUND: Clinical and cost-effectiveness of prasugrel vs. clopidogrel in acute coronary syndrome (ACS) was only evaluated using TRITON-TIMI 38 event rates. A comparative analysis of both drugs in contemporary European ACS patients is lacking. METHODS: To address this issue, cardiac and bleedin......=0.255), but more major bleedings (4.0% vs. 1.7%, pexpenditures per patient: 1116.3 (DNK), 1063.5 (GER) and 880.8 (SUI) EURO, respectively. Accordingly, incremental cost...

  20. Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

    Science.gov (United States)

    Giustino, Gennaro; Kirtane, Ajay J; Baber, Usman; Généreux, Philippe; Witzenbichler, Bernhard; Neumann, Franz-Josef; Weisz, Giora; Maehara, Akiko; Rinaldi, Michael J; Metzger, Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Brodie, Bruce R; Stuckey, Thomas D; Gurbel, Paul A; Dangas, George D; Francese, Dominic P; Ozan, Ozgu; Mehran, Roxana; Stone, Gregg W

    2016-06-15

    Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with drug-eluting stents for patients with multivessel coronary artery disease.

    Science.gov (United States)

    Javaid, Aamir; Steinberg, Daniel H; Buch, Ashesh N; Corso, Paul J; Boyce, Steven W; Pinto Slottow, Tina L; Roy, Probal K; Hill, Peter; Okabe, Teruo; Torguson, Rebecca; Smith, Kimberly A; Xue, Zhenyi; Gevorkian, Natalie; Suddath, William O; Kent, Kenneth M; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

    2007-09-11

    Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a "real-world" evaluation of current technology in the treatment of multivessel coronary artery disease. A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19). Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes

  2. The OCT-ORION Study: A Randomized Optical Coherence Tomography Study Comparing Resolute Integrity to Biomatrix Drug-Eluting Stent on the Degree of Early Stent Healing and Late Lumen Loss.

    Science.gov (United States)

    Lee, Stephen W L; Tam, Frankie C C; Lam, Simon C C; Kong, Shun-Ling; Shea, Catherine P; Chan, Kelvin K W; Wong, Michael K L; Chan, Michael P H; Wong, Anthony Y T; Yung, Arthur S Y; Lam, Yui-Ming; Zhang, Lei-Wei; Wu, Karl K Y; Mintz, Gary S; Maehara, Akiko

    2018-04-01

    Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer. Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months ( P <0.001) and less variance of percent coverage at 9 months, 99.7% (interquartile range, 99.1-100) versus 99.6% (interquartile range, 96.8-99.9; difference, 0.10; 95% confidence interval, 0.00-1.05; P <0.001). No significant difference was observed in major adverse cardiac events or angiographic end points. Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small

  3. Determining clinical benefits of drug-eluting coronary stents according to the population risk profile: a meta-regression from 31 randomized trials.

    Science.gov (United States)

    Moreno, Raul; Martin-Reyes, Roberto; Jimenez-Valero, Santiago; Sanchez-Recalde, Angel; Galeote, Guillermo; Calvo, Luis; Plaza, Ignacio; Lopez-Sendon, Jose-Luis

    2011-04-01

    The use of drug-eluting stents (DES) in unfavourable patients has been associated with higher rates of clinical complications and stent thrombosis, and because of that concerns about the use of DES in high-risk settings have been raised. This study sought to demonstrate that the clinical benefit of DES increases as the risk profile of the patients increases. A meta-regression analysis from 31 randomized trials that compared DES and bare-metal stents, including overall 12,035 patients, was performed. The relationship between the clinical benefit of using DES (number of patients to treat [NNT] to prevent one episode of target lesion revascularization [TLR]), and the risk profile of the population (rate of TLR in patients allocated to bare-metal stents) in each trial was evaluated. The clinical benefit of DES increased as the risk profile of each study population increased: NNT for TLR=31.1-1.2 (TLR for bare-metal stents); prisk profile of each study population, since the effect of DES in mortality, myocardial infarction, and stent thrombosis, was not adversely affected by the risk profile of each study population (95% confidence interval for β value 0.09 to 0.11, -0.12 to 0.19, and -0.03 to-0.15 for mortality, myocardial infarction, and stent thrombosis, respectively). The clinical benefit of DES increases as the risk profile of the patients increases, without affecting safety. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  4. Clinical outcome after primary percutaneous coronary intervention with drug-eluting and bare metal stents in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Maeng, Michael; Thayssen, Per

    2008-01-01

    BACKGROUND: The use of drug-eluting stents (DESs) versus bare metal stents (BMSs) in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction is a matter of debate. Therefore, we examined the risk of target lesion revascularization (TLR), stent thrombosis...... Registry from January 2002 through June 2005, were followed up for 2 years. We used Cox regression analysis to control for confounding. The 2-year incidence of definite stent thrombosis was 1.9% in the DES group and 1.1% in the BMS group (adjusted relative risk [RR]=1.53; 95% CI=0.84 to 2.78; P=0.17). Very...... late definite stent thrombosis (> or =12 months) was seen in 0.4% in the DES group and 0.06% in the BMS group (adjusted RR=6.74; 95% CI=1.23 to 37.00; P=0.03). The 2-year incidence of myocardial infarction was similar in the 2 groups, 5.2% in the DES group versus 6.3% in the BMS group (P=0.28; adjusted...

  5. Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts.

    Science.gov (United States)

    Harrison, Robert W; Radhakrishnan, Vaishnavi; Lam, Peter S; Allocco, Dominic J; Brar, Sandeep; Fahy, Martin; Fisher, Rebecca; Ikeno, Fumiaki; Généreux, Philippe; Kimura, Takeshi; Liu, Minglei; Lye, Weng Kit; Mintz, Gary S; Nagai, Hirofumi; Suzuki, Yuka; White, Roseann; Allen, John C; Krucoff, Mitchell W

    2016-12-01

    The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization. The mechanistic response to DES has not been directly compared across predominantly Asian or Western populations, whereas understanding their comparability across geographic populations could enhance global DES evaluation. The East-West late lumen loss study is designed to demonstrate whether the residual differences in late lumen loss, as assessed by QCA, is different between Eastern and Western DES recipients from studies with protocol angiography at 8-13 months of follow-up. Data from independent core laboratories that have characterized angiographic late lumen loss in DES clinical trials with protocol follow-up angiography will be compiled and dichotomized into Eastern and Western populations. A prospectively developed propensity score model incorporating clinical and anatomic variables affecting late lumen loss will be used to adjust comparisons of QCA measurements. Documentation of whether there are clinically meaningful differences in mechanistic response to DES implantation across genetically unique geographies could facilitate both the quality and efficiency of global device evaluation requiring invasive follow-up for novel stent designs. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. [Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].

    Science.gov (United States)

    Chen, Shao-liang; Zhang, Jun-jie; Ye, Fei; Chen, Yun-dai; Lü, Shu-zheng; Tan, Huaycheem; Patel, Tejas; Kenji, Kawajiri; Tamari, Israel; Shan, Shou-jie; Zhu, Zhong-sheng; Lin, Song; Tian, Nai-liang; Li, Xiao-bo; Liu, Zhi-zhong; Lee, Michael; Wei, Meng; Xu, Ya-wei; Yuan, Zheng-bai; Qian, Jun; Sun, Xue-wen; Yang, Song; Chen, Jin-guo; He, Ben; Sumit, Suji

    2008-02-01

    To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions. 311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE). Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique. DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

  7. Minimizing Molybdenum 99 contamination in Technetium 99m Pertechnetate from the elution of 99Mo/ 99m Tc Generator

    International Nuclear Information System (INIS)

    Zakaria Ibrahim; Zulkifli Hashim; Bohari Yaacob

    2011-01-01

    Radioisotope Tc-99m is widely used for variety of nuclear medicine diagnostic procedures. For many commercial applications, it is prepared in a portable type generator. Nuclear Malaysia has been producing a dry type alumina chromatographic column generator utilizing fission Mo-99. This injectable Tc-99m must meet the British Pharmacopeia [1] product specification prior to be apply on patient. This paper provides a method to minimize the up to acceptable level Mo-99 in the final product. Purposely made pertechnetate contaminated with Mo-99 and re-eluate by using old generator. Excellent removal of Mo-99 impurity was achieved and more than 80 % of Tc-99m total activity was recovered. (author)

  8. Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Seki, Akihiko; Hori, Shinich

    2012-01-01

    Purpose: There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE). Methods: Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50–100-μm superabsorbent polymer microspheres loaded with 1 mg cisplatin/1 mg microspheres together with hepatic arterial infusion of 25 mg cisplatin and 500 mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria. Results: The median number of CLM-TACE treatment sessions was 1.8 (range, 1–5), and the mean total dose of cisplatin per session was 42.8 mg (range, 30.0–59.0). After 6 months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2 months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events. Conclusions: witching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.

  9. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

    Science.gov (United States)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe; Aquino, Melissa; Stone, Gregg W; Sartori, Samantha; Steg, Philippe Gabriel; Wijns, William; Smits, Pieter C; Jeger, Raban V; Leon, Martin B; Windecker, Stephan; Serruys, Patrick W; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Kandzari, David; Dangas, George D; Mastoris, Ioannis; Von Birgelen, Clemens; Galatius, Soren; Kimura, Takeshi; Mikhail, Ghada; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Valgimigli, Marco; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

    2015-09-15

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women. Published by Elsevier Inc.

  10. Feasibility study of solidification for low-level liquid waste generated by sulfuric acid elution treatment of spent ion exchange resin

    International Nuclear Information System (INIS)

    Asano, Takashi; Kawasaki, Tooru; Higuchi, Natsuko; Horikawa, Yoshihiko

    2007-01-01

    Low-level liquid waste with relatively high levels of radioactivity is generated by the sulfuric acid elution treatment of spent ion exchange resin used in water purification systems of nuclear power plants. We studied cement-like solidification process for this type waste that contains a high concentration of sodium sulfate. For this type waste, it is important that the sulfate ion should not dissolve from the solid waste because it forms ettringite on reaction with minerals in the concrete, and this leads to cracking during repository storage. It is also preferable that the pH of pore water of the solid waste be low, because the bentonite of the repository changes in quality on exposure to alkaline solution. Our solidification process has two procedures: conversion into insoluble sulfate from sodium sulfate (CIS) and formation of low pH cement-like solid (FLS). In the CIS procedure, BaSO 4 precipitation occurs with addition of Ba(OH) 2 ·8H 2 O to the liquid waste when the Ba/SO 4 molar ratio > 1. In the FLS procedure, silica fume and blast furnace slag are added to the liquid wastes containing Ba S O 4 precipitate. The CIS reaction yield is over 98% and the pH of pore water of the solid waste is 11.5 or less. Therefore, we think that our solidification process is one of the best methods for treating liquid waste that contains a high concentration of sodium sulfate. (author)

  11. Impact of lesion morphology on angiographic and clinical outcomes in patients with chronic total occlusion after recanalization with drug-eluting stents: a multislice computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tsuyoshi [Toyohashi Heart Center, Toyohashi (Japan); Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan); Tsuchikane, Etsuo; Nasu, Kenya; Kimura, Masashi; Terashima, Mitsuyasu; Kinoshita, Yoshihisa; Habara, Maoto; Suzuki, Takahiko [Toyohashi Heart Center, Toyohashi (Japan); Suzuki, Yoriyasu; Ehara, Mariko [Nagoya Heart Center, Nagoya (Japan); Ohte, Nobuyuki [Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan)

    2015-10-15

    The aim of this study was to investigate the multislice computed tomography (MSCT) parameters associated with adverse outcomes after chronic total occlusion percutaneous coronary intervention (CTO-PCI) with drug-eluting stents. A total of 285 patients who underwent MSCT before CTO-PCI were analyzed. Lesion morphology was assessed with MSCT. Angiographic restenosis, reocclusion, and MACE (a composite of cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization) were analyzed. MACE was observed in 36 patients (13.6 %). Occlusion length was greater (39.5 ± 19.9 mm vs. 22.3 ± 13.7 mm, p < 0.01), minimal vessel area smaller (11.2 ± 5.7 mm{sup 2} vs. 14.5 ± 5.6 mm{sup 2}, p < 0.01), and severe calcification more common (36 % vs. 12 %, p < 0.01) in the MACE group compared to the non-MACE group. We defined occluded length >25.4 mm, minimal vessel area <11.9 mm{sup 2}, which were identified by receiver operating characteristic analysis, and severe calcification as CT-derived risk factors. Angiographic restenosis (60 % vs. 12 % vs. 7 %, p < 0.01), reocclusion (29 % vs. 2 % vs. 2 %, p < 0.01), and MACE (43 % vs. 6 % vs. 3 %, p < 0.01) were more common in patients with 2 or more risk factors than in those with 1 or 0. MSCT characteristics associated with adverse outcomes after CTO-PCI were occlusion length, minimal vessel area, and severe calcification. (orig.)

  12. Differential Clinical Outcomes Between Angiographic Complete Versus Incomplete Coronary Revascularization, According to the Presence of Chronic Kidney Disease in the Drug-Eluting Stent Era.

    Science.gov (United States)

    Kim, Jihoon; Lee, Joo Myung; Choi, Ki Hong; Rhee, Tae-Min; Hwang, Doyeon; Park, Jonghanne; Ahn, Chul; Park, Taek Kyu; Yang, Jeong Hoon; Song, Young Bin; Choi, Jin-Ho; Hahn, Joo-Yong; Choi, Seung-Hyuk; Gwon, Hyeon-Cheol

    2018-02-15

    There are limited data regarding the prognostic impact of angiographic complete revascularization (CR) in patients with chronic kidney disease (CKD). We sought to investigate the differential prognostic impact of angiographic CR over incomplete revascularization (IR), according to the presence of CKD in the drug-eluting stent era. Between 2003 and 2011 at Samsung Medical Center, consecutive patients with multivessel disease were stratified by the presence of CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m 2 ) and classified according to angiographic CR (residual SYNTAX score=0) or IR. Clinical outcomes were compared between angiographic CR and IR, stratified by the presence of CKD. Primary outcome was patient-oriented composite outcomes (POCO, a composite of all-cause death, myocardial infarction, any revascularization) at 3 years. Inverse probability weighting was performed between the CR and IR groups. A total of 3224 patients were eligible for analysis: 2295 without CKD; 929 with CKD. Among non-CKD patients, angiographic CR showed a significantly lower risk of POCO than IR (17.2% versus 21.7%, adjusted hazard ratio 0.76, 95% confidence interval, 0.62-0.95, P =0.014), mainly driven by a significantly lower risk of any revascularization. Among CKD patients, however, angiographic CR was associated with a significantly higher risk of POCO than IR (37.7% versus 28.4%, adjusted hazard ratio 1.42, 95% confidence interval, 1.08%-1.85%, P =0.011), mainly driven by a significantly higher risk of nonfatal target vessel myocardial infarction. Angiographic CR was associated with reduced risk of POCO than IR in patients without CKD; however, it was associated with a significantly higher risk of POCO and nonfatal myocardial infarction in CKD patients. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  13. Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus 90Y-radioembolization for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Ludwig, Johannes M.; Xing, Minzhi; Zhang, Di; Kim, Hyun S.

    2017-01-01

    To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 ( 90 Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus 90 Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus 90 Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. Fourteen studies comparing DEB-TACE or 90 Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over 90 Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and 90 Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to 90 Y-radioembolization but direct comparison is warranted for further evaluation. (orig.)

  14. Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Akinwande, Olaguoke K., E-mail: gokeakin@gmail.com [University of Louisville Hospital, Department of Interventional Radiology (United States); Philips, Prejesh, E-mail: prejesh.philips@louisville.edu [University of Louisville, Division of Surgical Oncology, Department of Surgery (United States); Duras, Petr, E-mail: durasp@seznam.cz [Fakultní nemocnice Plzeň (Czech Republic); Pluntke, Stefan, E-mail: stefan.pluntke@t-online.de [Onkologe bei Kliniken Essen-Mitte (Germany); Scoggins, Charles, E-mail: charles.scoggins@louisville.edu; Martin, Robert C. G., E-mail: Robert.Martin@louisville.edu [University of Louisville, Division of Surgical Oncology, Department of Surgery (United States)

    2015-04-15

    PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02) in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity.

  15. Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

    International Nuclear Information System (INIS)

    Akinwande, Olaguoke K.; Philips, Prejesh; Duras, Petr; Pluntke, Stefan; Scoggins, Charles; Martin, Robert C. G.

    2015-01-01

    PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02) in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity

  16. Meta-analysis: adjusted indirect comparison of drug-eluting bead transarterial chemoembolization versus {sup 90}Y-radioembolization for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Johannes M.; Xing, Minzhi [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Zhang, Di [University of Pittsburgh Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA (United States); Kim, Hyun S. [Yale School of Medicine, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Yale School of Medicine, Yale Cancer Center, New Haven, CT (United States)

    2017-05-15

    To investigate comparative effectiveness of drug-eluting bead transarterial chemoembolization (DEB-TACE) versus Yttrium-90 ({sup 90}Y)-radioembolization for hepatocellular carcinoma (HCC). Studies comparing conventional (c)TACE versus {sup 90}Y-radioembolization or DEB-TACE for HCC treatment were identified using PubMed/Medline, Embase, and Cochrane databases. The adjusted indirect meta-analytic method for effectiveness comparison of DEB-TACE versus {sup 90}Y-radioembolization was used. Wilcoxon rank-sum test was used to compare baseline characteristics. A priori defined sensitivity analysis of stratified study subgroups was performed for primary outcome analyses. Publication bias was tested by Egger's and Begg's tests. Fourteen studies comparing DEB-TACE or {sup 90}Y-radioembolization with cTACE were included. Analysis revealed a 1-year overall survival benefit for DEB-TACE over {sup 90}Y-radioembolization (79 % vs. 54.8 %; OR: 0.57; 95 %CI: 0.355-0.915; p = 0.02; I-squared: 0 %; p > 0.5), but not for the 2-year (61 % vs. 34 %; OR: 0.65; 95%CI: 0.294-1.437; p = 0.29) and 3-year survival (56.4 % vs. 20.9 %; OR: 0.713; 95 % CI: 0.21-2.548; p = 0.62). There was significant heterogeneity in the 2- and 3-year survival analyses. The pooled median overall survival was longer for DEB-TACE (22.6 vs. 14.7 months). There was no significant difference in tumour response rate. DEB-TACE and {sup 90}Y-radioembolization are efficacious treatments for patients suffering from HCC; DEB-TACE demonstrated survival benefit at 1-year compared to {sup 90}Y-radioembolization but direct comparison is warranted for further evaluation. (orig.)

  17. Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy.

    Science.gov (United States)

    Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Driscoll-Shempp, Priscilla; Cutlip, Donald E; Steg, P Gabriel; Gershlick, Anthony H; Darius, Harald; Meredith, Ian T; Ormiston, John; Tanguay, Jean-François; Windecker, Stephan; Garratt, Kirk N; Kandzari, David E; Lee, David P; Simon, Daniel I; Iancu, Adrian Corneliu; Trebacz, Jaroslaw; Mauri, Laura

    2015-10-01

    This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS. Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES. Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months. Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Prevention of Intracranial In-stent Restenoses: Predilatation with a Drug Eluting Balloon, Followed by the Deployment of a Self-Expanding Stent

    Energy Technology Data Exchange (ETDEWEB)

    Vajda, Zsolt, E-mail: Z.Vajda@klinikum-stuttgart.de; Guethe, Thomas, E-mail: T.Guethe@klinikum-stuttgart.de; Perez, Marta Aguilar, E-mail: M.Aguilar@klinikum-stuttgart.de; Kurre, Wiebke, E-mail: w.kurre@klinikum-stuttgart.de [Klinikum Stuttgart, Katharinenhospital, Klinik fuer Neuroradiologie, Neurozentrum (Germany); Schmid, Elisabeth, E-mail: ESchmid@klinikum-stuttgart.de; Baezner, Hansjoerg, E-mail: H.Baezner@klinikum-stuttgart.de [Klinikum Stuttgart, Klinik fuer Neurologie, Neurozentrum (Germany); Henkes, Hans, E-mail: hhhenkes@aol.com [Klinikum Stuttgart, Katharinenhospital, Klinik fuer Neuroradiologie, Neurozentrum (Germany)

    2013-04-15

    Stenting in intracranial atherosclerotic disease (ICAD) is increasingly debated, due to issues of procedural safety, technical efficacy, and in-stent recurrent stenoses (ISR). In the present study, feasibility, safety, and efficacy of angioplasty using a drug-eluting balloon (DEB) followed by the implantation of a self-expanding stent (Enterprise) were evaluated for the treatment of ICAD lesions. Fifty-two patients (median age: 71 years; range: 54-86 years; male/female ratio 37:15) underwent stenting of high-grade ICAD lesions between February 2010 and November 2011 in a single center. Angioplasty using a paclitaxel coated SeQuent Please (B. Braun, Germany) or DIOR (Eurocor, Germany) coronary PTCA balloon, followed by the implantation of a self-expanding stent (Enterprise, Codman, USA) was performed in 54 lesions. Angiographic and clinical follow-up was performed at 6 and 12 weeks, 6 and 12 months, and yearly thereafter. Technical success rate, periprocedural complications, occurrence of recurrent ischemic symptoms, and the development of an ISR were analyzed. Angioplasty using a DEB followed by stent implantation was successfully performed in 44 (81 %) cases. DEB insertion failed in 19 % of the cases and angioplasty was finally performed using a conventional PTCA balloon. The combined procedure related permanent neurologic morbidity and mortality rate (stroke, ICH, and subarachnoid hemorrhage) at 30 days and beyond was 5 %. Angiographic and clinical follow-up were obtained in 33 (61 %) lesions in 32 patients. Recurrent stenosis was seen in one (3 %) lesion. Angioplasty and stenting using a DEB is safe and yields encouragingly low ISR rates. Further technical developments to improve lesion accessibility are, nevertheless, mandatory.

  19. Prevention of Intracranial In-stent Restenoses: Predilatation with a Drug Eluting Balloon, Followed by the Deployment of a Self-Expanding Stent

    International Nuclear Information System (INIS)

    Vajda, Zsolt; Güthe, Thomas; Perez, Marta Aguilar; Kurre, Wiebke; Schmid, Elisabeth; Bäzner, Hansjörg; Henkes, Hans

    2013-01-01

    Stenting in intracranial atherosclerotic disease (ICAD) is increasingly debated, due to issues of procedural safety, technical efficacy, and in-stent recurrent stenoses (ISR). In the present study, feasibility, safety, and efficacy of angioplasty using a drug-eluting balloon (DEB) followed by the implantation of a self-expanding stent (Enterprise) were evaluated for the treatment of ICAD lesions. Fifty-two patients (median age: 71 years; range: 54–86 years; male/female ratio 37:15) underwent stenting of high-grade ICAD lesions between February 2010 and November 2011 in a single center. Angioplasty using a paclitaxel coated SeQuent Please (B. Braun, Germany) or DIOR (Eurocor, Germany) coronary PTCA balloon, followed by the implantation of a self-expanding stent (Enterprise, Codman, USA) was performed in 54 lesions. Angiographic and clinical follow-up was performed at 6 and 12 weeks, 6 and 12 months, and yearly thereafter. Technical success rate, periprocedural complications, occurrence of recurrent ischemic symptoms, and the development of an ISR were analyzed. Angioplasty using a DEB followed by stent implantation was successfully performed in 44 (81 %) cases. DEB insertion failed in 19 % of the cases and angioplasty was finally performed using a conventional PTCA balloon. The combined procedure related permanent neurologic morbidity and mortality rate (stroke, ICH, and subarachnoid hemorrhage) at 30 days and beyond was 5 %. Angiographic and clinical follow-up were obtained in 33 (61 %) lesions in 32 patients. Recurrent stenosis was seen in one (3 %) lesion. Angioplasty and stenting using a DEB is safe and yields encouragingly low ISR rates. Further technical developments to improve lesion accessibility are, nevertheless, mandatory.

  20. Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpañol sobre TROmbosis de stents FArmacoactivos).

    Science.gov (United States)

    de la Torre-Hernández, José M; Alfonso, Fernando; Hernández, Felipe; Elizaga, Jaime; Sanmartin, Marcelo; Pinar, Eduardo; Lozano, Iñigo; Vazquez, Jose M; Botas, Javier; Perez de Prado, Armando; Hernández, Jose M; Sanchis, Juan; Nodar, Juan M Ruiz; Gomez-Jaume, Alfredo; Larman, Mariano; Diarte, Jose A; Rodríguez-Collado, Javier; Rumoroso, Jose R; Lopez-Minguez, Jose R; Mauri, Josepa

    2008-03-11

    This study sought to assess the incidence, predictors, and outcome of drug-eluting stent(DES) thrombosis in real-world clinical practice. The DES thromboses in randomized trials could not be comparable to those observed in clinical practice, frequently including off-label indications. We designed a large-scale, nonindustry-linked multicentered registry, with 20 centers in Spain. The participant centers provided follow-up data for their patients treated with DES, reporting a detailed standardized form in the event of any angiography-documented DES-associated thrombosis occurring. Of 23,500 patients treated with DES, definite stent thrombosis(ST) developed in 301: 24 acute, 125 subacute, and 152 late. Of the late, 62 occurred >1 year(very late ST). The cumulative incidence was 2% at 3 years. Antiplatelet treatment had been discontinued in 95 cases(31.6%). No differences in incidences were found among stent types. Independent predictors for subacute ST analyzed in a subgroup of 14,120 cases were diabetes, renal failure, acute coronary syndrome, ST-segment elevation myocardial infarction, stent length, and left anterior descending artery stenting, and for late ST were ST-segment elevation myocardial infarction, stenting in left anterior descending artery, and stent length. Mortality at 1-year follow-up was 16% and ST recurrence 4.6%. Older age, left ventricular ejection fraction <45%, nonrestoration of Thrombolysis In Myocardial Infarction flow grade 3, and additional stenting were independent predictors for mortality. The cumulative incidence of ST after DES implantation was 2% at 3 years. No differences were found among stent types. Patient profiles differed between early and late ST. Short-term prognosis is poor, especially when restoration of normal flow fails.

  1. Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method

    Science.gov (United States)

    Mueller, Dirk; Breeman, Wouter A P; Klette, Ingo; Gottschaldt, Michael; Odparlik, Andreas; Baehre, Manfred; Tworowska, Izabela; Schultz, Michael K

    2017-01-01

    Gallium-68 (68Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize 68Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system, 68Ga3+ of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3–4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of 68Ga radiopharmaceuticals (12–16 min). PMID:27172166

  2. Isotope generator

    International Nuclear Information System (INIS)

    1979-01-01

    The patent describes an isotope generator incorporating the possibility of stopping elution before the elution vessel is completely full. Sterile ventilation of the whole system can then occur, including of both generator reservoir and elution vessel. A sterile, and therefore pharmaceutically acceptable, elution fluid is thus obtained and the interior of the generator is not polluted with non-sterile air. (T.P.)

  3. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis.

    Science.gov (United States)

    Jang, Ji-Yong; Kim, Jung-Sun; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2015-10-01

    Serial follow-up optical coherence tomography (OCT) was used to evaluate the effect of optimal lipid-lowering therapy on qualitative changes in neointimal tissue characteristics after drug-eluting stent (DES) implantation. DES-treated patients (n = 218) who received statin therapy were examined with serial follow-up OCT. First and second follow-up OCT evaluations were performed approximately 6 and 18 months after the index procedure, respectively. Patients were divided into two groups, based on the level of low-density lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The optimal lipid-lowering group (n = 121) had an LDL-C reduction of ≥50% or an LDL-C level ≤70 mg/dL, and the conventional group (n = 97). Neointimal characteristics were qualitatively categorized as homogeneous or non-homogeneous patterns using OCT. The non-homogeneous group included heterogeneous, layered, or neoatherosclerosis patterns. Qualitative changes in neointimal tissue characteristics between the first and second follow-up OCT examinations were assessed. Between the first and second follow-up OCT procedures, the neointimal cross-sectional area increased more substantially in the conventional group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01). The neointimal pattern changed from homogeneous to non-homogeneous less often in the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent predictor for the prevention of neointimal pattern change from homogeneous to non-homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01∼0.46, p = 0.008). Our findings suggest that an intensive reduction in LDL-C levels can prevent non-homogeneous changes in the neointima and increases in neointimal cross-sectional area compared with conventional LDL-C controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Comparison of outcome in 1809 patients treated with drug-eluting stents or bare-metal stents in a real-world setting

    Directory of Open Access Journals (Sweden)

    Vogt A

    2011-11-01

    Full Text Available Alexander Vogt1, Anke Schoelmerich1, Franziska Pollner1, Manuela Schlitt1, Uwe Raaz1, Lars Maegdefessel2, Iris Reindl1, Michael Buerke1, Karl Werdan1, Axel Schlitt11Department of Medicine III, Martin Luther-University, Halle, Germany; 2Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USAPurpose: The aim of this study was to determine the long-term safety of drug-eluting stent (DES versus bare metal stent (BMS implantation in a “real-world” setting.Patients and methods: A total of 1809 patients who were treated with implantation of either BMS or DES were assessed. Kaplan-Meier and multivariate Cox regression analyses concerning primary endpoint of cardiac mortality were performed.Results: A total of 609 patients received DES. Mean age was 66.2 ± 11.3 years, 69.4% were male, and 1517 (83.8% were treated for acute coronary syndrome (unstable angina 510 [28.2%], non-ST-elevation myocardial infarction [NSTEMI] 506 [28.0%], and ST-elevation myocardial infarction [STEMI] 501 [27.7%]. Mean follow-up was 34 ± 15 months. During follow-up, 268 patients died of cardiac causes (DES 42 [7.3%]; BMS 226 [19.6%]; P < 0.001. Univariate Kaplan-Meier analysis showed an advantage of DES over BMS concerning the primary endpoint (P < 0.001. When adjusting for classic risk factors and additional factors that affect the progression of coronary heart disease (CHD, DES was not found to be superior to BMS (hazard ratio 0.996, 95% confidence interval 0.455–2.182, P = 0.993. Severely impaired renal function was an independent predictor for cardiac mortality after stent implantation.Conclusion: Treatment with DES is safe in the long term, also in patients presenting with STEMI. However, in multivariate analyses it is not superior to BMS treatment.Keywords: coronary stent, outcome, renal insufficiency, myocardial infarction, STEMI

  5. Fast Gradient Elution Reversed-Phase HPLC with Diode-Array Detection as a High Throughput Screening Method for Drugs of Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Peter W. Carr; K.M. Fuller; D.R. Stoll; L.D. Steinkraus; M.S. Pasha; Glenn G. Hardin

    2005-12-30

    A new approach has been developed by modifying a conventional gradient elution liquid chromatograph for the high throughput screening of biological samples to detect the presence of regulated intoxicants. The goal of this work was to improve the speed of a gradient elution screening method over current approaches by optimizing the operational parameters of both the column and the instrument without compromising the reproducibility of the retention times, which are the basis for the identification. Most importantly, the novel instrument configuration substantially reduces the time needed to re-equilibrate the column between gradient runs, thereby reducing the total time for each analysis. The total analysis time for each gradient elution run is only 2.8 minutes, including 0.3 minutes for column reequilibration between analyses. Retention times standard calibration solutes are reproducible to better than 0.002 minutes in consecutive runs. A corrected retention index was adopted to account for day-to-day and column-to-column variations in retention time. The discriminating power and mean list length were calculated for a library of 47 intoxicants and compared with previous work from other laboratories to evaluate fast gradient elution HPLC as a screening tool.

  6. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: the PLUS-ONE first-in-man study.

    Science.gov (United States)

    Calderas, Carlos; Condado, Jose Francisco; Condado, Jose Antonio; Flores, Alejandra; Mueller, Amy; Thomas, Jack; Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa; Fitzgerald, Peter

    2014-01-01

    The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18mm, n=30) or group B (8 μg/18mm, n=30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30mm and 0.34 ± 0.20mm P=.773). In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year. © 2014.

  7. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: The PLUS-ONE first-in-man study

    Energy Technology Data Exchange (ETDEWEB)

    Calderas, Carlos [Instituto de Clinicas Urologia Tamanaco, Caracas (Venezuela, Bolivarian Republic of); Condado, Jose Francisco; Condado, Jose Antonio [Hospital Centro Medico de Caracas y Hospital Miguel Perez Carreno, Caracas (Venezuela, Bolivarian Republic of); Flores, Alejandra [Instituto de Clinicas Urologia Tamanaco, Caracas (Venezuela, Bolivarian Republic of); Mueller, Amy; Thomas, Jack [Medlogics Device Corporation, Santa Rosa, CA (United States); Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa [Stanford University, Stanford, CA (United States); Fitzgerald, Peter, E-mail: crci-cvmed@stanford.edu [Stanford University, Stanford, CA (United States)

    2014-01-15

    Background: The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol–gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. Methods: A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18 mm, n = 30) or group B (8 μg/18 mm, n = 30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Results: Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P = 1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30 mm and 0.34 ± 0.20 mm P = .773). Conclusions: In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol–gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year.

  8. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: The PLUS-ONE first-in-man study

    International Nuclear Information System (INIS)

    Calderas, Carlos; Condado, Jose Francisco; Condado, Jose Antonio; Flores, Alejandra; Mueller, Amy; Thomas, Jack; Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa; Fitzgerald, Peter

    2014-01-01

    Background: The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol–gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. Methods: A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18 mm, n = 30) or group B (8 μg/18 mm, n = 30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Results: Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P = 1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30 mm and 0.34 ± 0.20 mm P = .773). Conclusions: In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol–gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year

  9. Clinical outcomes in low risk coronary artery disease patients treated with different limus-based drug-eluting stents--a nationwide retrospective cohort study using insurance claims database.

    Directory of Open Access Journals (Sweden)

    Chao-Lun Lai

    Full Text Available The clinical outcomes of different limus-based drug-eluting stents (DES in a real-world setting have not been well defined. The aim of this study was to investigate the clinical outcomes of three different limus-based DES, namely sirolimus-eluting stent (SES, Endeavor zotarolimus-eluting stent (E-ZES and everolimus-eluting stent (EES, using a national insurance claims database. We identified all patients who received implantation of single SES, E-ZES or EES between January 1, 2007 and December 31, 2009 from the National Health Insurance claims database, Taiwan. Follow-up was through December 31, 2011 for all selected clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. Cox regression model adjusting for baseline characteristics was used to compare the relative risks of different outcomes among the three different limus-based DES. Totally, 6584 patients were evaluated (n=2142 for SES, n=3445 for E-ZES, and n=997 for EES. After adjusting for baseline characteristics, we found no statistically significant difference in the risk of all-cause mortality in three DES groups (adjusted hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 0.94-1.38, p=0.20 in E-ZES group compared with SES group; adjusted HR: 0.77, 95% CI: 0.54-1.10, p=0.15 in EES group compared with SES group. Similarly, we found no difference in the three stent groups in risks of acute coronary events, heart failure needing hospitalization, and cerebrovascular disease. In conclusion, we observed no difference in all-cause mortality, acute coronary events, heart failure needing hospitalization, and cerebrovascular disease in patients treated with SES, E-ZES, and EES in a real-world population-based setting in Taiwan.

  10. The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.

    Science.gov (United States)

    Suh, Jung-Won; Lee, Seung-Pyo; Park, KyungWoo; Kang, Hyun-Jae; Koo, Bon-Kwon; Cho, Young-Seok; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju; Rha, Seung-Woon; Bae, Jang-Ho; Kwon, Taek-Geun; Bae, Jang-Whan; Cho, Myeong-Chan; Kim, Hyo-Soo

    2017-12-12

    It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

  11. Randomized comparison of a sirolimus-eluting Orsiro stent with a biolimus-eluting Nobori stent in patients treated with percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Maeng, Michael

    2015-01-01

    BACKGROUND: Third-generation coronary drug-eluting stents (DES) with biodegradable polymers have been designed to improve safety and efficacy. We designed a large scale registry-based randomized clinical trial to compare 2 third-generation DES: a thin strut, cobalt-chromium DES with silicon carbide......-coating releasing sirolimus from a biodegradable polymer (O-SES, Orsiro; Biotronik, Bülach, Switzerland) with the stainless steel biodegradable polymer biolimus-eluting Nobori stents (N-BES, Nobori; Terumo, Tokyo, Japan) in an all-comer patient population. DESIGN: The multicenter SORT OUT VII trial (NCT01879358...... will be used. An event rate of 6.5% is assumed in each stent group. With a sample size of 1,157 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the O-SES compared with the N...

  12. Application of Snyder-Dolan Classification Scheme to the Selection of “Orthogonal” Columns for Fast Screening for Illicit Drugs and Impurity Profiling of Pharmaceuticals - I. Isocratic Elution

    Science.gov (United States)

    Fan, Wenzhe; Zhang, Yu; Carr, Peter W.; Rutan, Sarah C.; Dumarey, Melanie; Schellinger, Adam P.; Pritts, Wayne

    2011-01-01

    Fourteen judiciously selected reversed-phase columns were tested with 18 cationic drug solutes under the isocratic elution conditions advised in the Snyder-Dolan (S-D) hydrophobic subtraction method of column classification. The standard errors (S.E.) of the least squares regressions of log k′ vs. log k′REF were obtained for a given column against a reference column and used to compare and classify columns based on their selectivity. The results are consistent with those obtained with a study of the 16 test solutes recommended by Snyder and Dolan. To the extent that these drugs are representative these results show that the S-D classification scheme is also generally applicable to pharmaceuticals under isocratic conditions. That is, those columns judged to be similar based on the S-D 16 solutes were similar based on the 18 drugs; furthermore those columns judged to have significantly different selectivities based on the 16 S-D probes appeared to be quite different for the drugs as well. Given that the S-D method has been used to classify more than 400 different types of reversed phases the extension to cationic drugs is a significant finding. PMID:19698948

  13. Nanosized Minicells Generated by Lactic Acid Bacteria for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huu Ngoc Nguyen

    2017-01-01

    Full Text Available Nanotechnology has the ability to target specific areas of the body, controlling the drug release and significantly increasing the bioavailability of active compounds. Organic and inorganic nanoparticles have been developed for drug delivery systems. Many delivery systems are through clinical stages for development and market. Minicell, a nanosized cell generated by bacteria, is a potential particle for drug delivery because of its size, safety, and biodegradability. Minicells produced by bacteria could drive therapeutic agents against cancer, microbial infection, and other diseases by targeting. In addition, minicells generated by lactic acid bacteria being probiotics are more interesting than others because of their benefits like safety, immunological improvement, and biodegradation. This review aims to highlight the stages of development of nanoparticle for drug delivery and discuss their advantages and limitations to clarify minicells as a new opportunity for the development of potential nanoparticle for drug delivery.

  14. Country report: Vietnam. Setting Up of a {sup 90}Sr/{sup 90}Y Generator System Based on Supported Liquid Membrane (SLM) Technique and Radiolabeling of Eluted {sup 90}Y with Biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Thu, Nguyen Thi; Dong, Duong Van; Cuong, Bui Van; Khoa, Chu Van [Vietnam Atomic Energy Commission (VAEC), Nuclear Research Institute, Dalat (Viet Nam)

    2010-07-01

    In the course of participating in the IAEA-CRP during the last two years, Vietnam has achieved the goal of setting up a {sup 90}Sr/{sup 90}Y generator system based on Supported Liquid Membrane (SLM) technique and also radiolabeling of the eluted {sup 90}Y with antibody, peptides and albumin. A two stage SLM based {sup 90}Sr-{sup 90}Y generator was set up in-house to generate carrier-free {sup 90}Y at different activity levels viz. 5, 20, 50 mCi. The generator system was operated in sequential mode in which 2-ethylhexyl 2-ethylhexyl phosphonic acid (PC88A) based SLM was used in the first stage for the transport {sup 90}Y in 4.0 M nitric acid from source phase where {sup 90}Sr-{sup 90}Y equilibrium mixture is placed in nitric acid medium at pH to 1-2. In the second stage, octyl (phenyl)-N,N-diisobutylcarbamoylmethyl phosphine oxide (CMPO) based SLM was used for the transport of {sup 90}Y selectively to 1.0 M acetic acid which is the best medium for radiolebeling. The eluted {sup 90}Y from the generator was tested for the presence of any traces of {sup 90}Sr using the Extraction Paper Chromatography (EPC) and was found suitable for radiolabeling. The generator system could be upgraded to 100 mCi level successfully due to an expert mission from India through IAEA. The {sup 90}Y product obtained from the generator system was used for radiolabeling of antibody and peptides viz. Rituximab, DOTATATE and albumin particles under different experimental conditions. A new chromatography system could be developed for analyzing {sup 90}Y labeled albumin using the TAE buffer as mobile phase in PC and ITLC.

  15. Red blood cell distribution width and long-term outcome in patients undergoing percutaneous coronary intervention in the drug-eluting stenting era: a two-year cohort study.

    Science.gov (United States)

    Yao, Hai-Mu; Sun, Tong-Wen; Zhang, Xiao-Juan; Shen, De-Liang; Du, You-You; Wan, You-Dong; Zhang, Jin-Ying; Li, Ling; Zhao, Luo-Sha

    2014-01-01

    Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. In total of 2169 non-anemic patients (1468 men, mean age 60.2 ± 10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27% ≤ RDW <13%), Quartile 3 (13% ≤ RDW<13.5%), and Quartile 4 (RDW ≥ 13.5). The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15-1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05). High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.

  16. Red blood cell distribution width and long-term outcome in patients undergoing percutaneous coronary intervention in the drug-eluting stenting era: a two-year cohort study.

    Directory of Open Access Journals (Sweden)

    Hai-Mu Yao

    Full Text Available BACKGROUND: Previous studies suggest the higher the red blood cell distribution width (RDW the greater the risk of mortality in patients with coronary artery disease (CAD. However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI with a drug-eluting stent (DES remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD. METHODS: In total of 2169 non-anemic patients (1468 men, mean age 60.2 ± 10.9 years with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%, Quartile 2 (12.27% ≤ RDW <13%, Quartile 3 (13% ≤ RDW<13.5%, and Quartile 4 (RDW ≥ 13.5. RESULTS: The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05. After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05. The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05. Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR = 1.37, 95% confidence interval (CI = 1.15-1.62, P<0.001 and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04-1.39, P = 0.013. The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05. CONCLUSION: High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.

  17. A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial

    NARCIS (Netherlands)

    de Winter, Robbert J.; Katagiri, Yuki; Asano, Taku; Milewski, Krzysztof P.; Lurz, Philipp; Buszman, Pawel; Jessurun, Gillian A. J.; Koch, Karel T.; Troquay, Roland P. T.; Hamer, Bas J. B.; Ophuis, Ton Oude; Wöhrle, Jochen; Wyderka, Rafał; Cayla, Guillaume; Hofma, Sjoerd H.; Levesque, Sébastien; Żurakowski, Aleksander; Fischer, Dieter; Kośmider, Maciej; Goube, Pascal; Arkenbout, E. Karin; Noutsias, Michel; Ferrari, Markus W.; Onuma, Yoshinobu; Wijns, William; Serruys, Patrick W.

    2018-01-01

    Background MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical

  18. Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe

    2015-01-01

    The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11......,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST......-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p clinical...

  19. Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

    Energy Technology Data Exchange (ETDEWEB)

    Bhagat, Nikhil, E-mail: nbhagat1@jhmi.edu; Reyes, Diane K., E-mail: dreyes@jhmi.edu [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States); Lin, Mingde, E-mail: ming.lin@philips.com [Philips Research North America, Clinical Informatics, Interventional, and Translational Solutions (CIITS) (United States); Kamel, Ihab [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States); Pawlik, Timothy M. [Johns Hopkins University Medical Center, Department of Surgery (United States); Frangakis, Constantine, E-mail: cfrangak@jhsph.edu [Johns Hopkins University, Department of Biostatistics, Bloomberg School of Public Health (United States); Geschwind, J. F., E-mail: jfg@jhmi.edu [Johns Hopkins University Medical Center, Johns Hopkins Hospital, Division of Vascular and Interventional Radiology, Department of Radiology (United States)

    2013-04-15

    To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4-75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100-300 {mu}m beads loaded with {<=}100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

  20. Phase II Study of Chemoembolization With Drug-Eluting Beads in Patients With Hepatic Neuroendocrine Metastases: High Incidence of Biliary Injury

    International Nuclear Information System (INIS)

    Bhagat, Nikhil; Reyes, Diane K.; Lin, Mingde; Kamel, Ihab; Pawlik, Timothy M.; Frangakis, Constantine; Geschwind, J. F.

    2013-01-01

    To evaluate safety in an interim analysis of transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) in 13 patients with hepatic metastases from neuroendocrine tumors (NETs) as part of a phase II trial. Institutional Review Board approval and informed consent were obtained. Thirteen patients completed preliminary safety analysis. Their mean age was 65 years, Eastern Cooperative Oncology Group status was 0/1, tumor burden range was 4–75 %, and mean targeted tumor size was 5.9 cm. Up to four DEB-TACE sessions (100–300 μm beads loaded with ≤100 mg doxorubicin) within 6 months were allowed. Tumor response was assessed by magnetic resonance imaging 1 month after treatment using contrast-enhancement [European Association for the Study of the Liver (EASL) and size Response Evaluation Criteria in Solid Tumors (RECIST)] criteria. Safety was assessed by National Cancer Institute Common Terminology Criteria. DEB-TACE was successfully performed in all 13 patients. At 1 month follow-up, there was a mean 12 % decrease in tumor size (p < 0.0003) and a 56 % decrease in tumor enhancement (p < 0.0001). By EASL criteria, the targeted lesion objective response rate was 78 %. Grade 3 to 4 toxicities were fatigue (23 %), increased alanine amino transferase (15 %), hyperglycemia (15 %), and abdominal pain (8 %). Seven patients developed bilomas (54 %); all of these patients had multiple small (<4 cm) lesions. Subsequently, four underwent percutaneous drainage, three for abscess formation and one for symptoms related to mass effect. Although biloma and liver abscess are known risks after TACE, the high incidence in our study population was unexpected and forced interruption of the trial. Although this occurred in a small group of patients, we have changed our technique and patient selection as a result of these findings, thus allowing resumption of the trial.

  1. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease: A Meta-Analysis of Individual Patient Data.

    Science.gov (United States)

    Lee, Cheol Whan; Ahn, Jung-Min; Cavalcante, Rafael; Sotomi, Yohei; Onuma, Yoshinobu; Suwannasom, Pannipa; Tenekecioglu, Erhan; Yun, Sung-Cheol; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Serruys, Patrick W; Park, Seung-Jung

    2016-12-26

    The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD). The relative efficacy and safety of CABG versus PCI with DES for left main or multivessel CAD remain controversial. Data were pooled from the BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease), PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery vs. Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trials. The primary outcome was a composite of all-cause death, myocardial infarction, or stroke. The median follow-up was 60 months, and follow-up was completed for 96.2% of patients. The rate of primary outcome was significantly lower with CABG than with PCI (13.0% vs. 16.0%; hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.69 to 1.00; p = 0.046). The difference was mainly driven by reduction in myocardial infarction (HR: 0.46; 95% CI: 0.33 to 0.64; p patients with multivessel CAD (p = 0.001), but no between-group difference in those with left main CAD (p = 0.427). The rates for all-cause death and stroke were similar between the 2 groups. By contrast, the need for repeat revascularization was significantly lower in the CABG group compared with the PCI group. CABG, as compared with PCI with DES, reduced long-term rates of the composite of all-cause death, myocardial infarction, or stroke in patients with left main or multivessel CAD. The advantage of CABG over PCI with DES was particularly pronounced in those with multivessel CAD. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  2. Methods of Increasing the Performance of Radionuclide Generators Used in Nuclear Medicine: Daughter Nuclide Build-Up Optimisation, Elution-Purification-Concentration Integration, and Effective Control of Radionuclidic Purity

    Directory of Open Access Journals (Sweden)

    Van So Le

    2014-06-01

    Full Text Available Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of “early elution schedule” was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement

  3. Drug-Eluting Nitinol Stent Treatment of the Superficial Femoral Artery and Above-the-Knee Popliteal Artery (The Zilver PTX Single-Arm Clinical Study): A Comparison Between Diabetic and Nondiabetic Patients

    Energy Technology Data Exchange (ETDEWEB)

    Fanelli, Fabrizio, E-mail: fabrizio.fanelli@uniroma1.it [Sapienza University of Rome, Vascular and Interventional Radiology Unit, Department of Radiological Sciences (Italy); Primo, Massimiliano Di [Hopital Europeen Georges Pompidou, University Paris Descartes (France); Boatta, Emanuele [Sapienza University of Rome, Vascular and Interventional Radiology Unit, Department of Radiological Sciences (Italy); Johnston, Krystal, E-mail: kjohnston@medinst.com [MED Institute, Inc (United States); Sapoval, Marc, E-mail: marc.sapoval2@egp.aphp.fr [Hopital Europeen Georges Pompidou, University Paris Descartes (France)

    2013-10-15

    Purpose: To describe the 1-year results of drug-eluting nitinol stent placement in the femoropopliteal artery of diabetic and nondiabetic patients. Materials and Methods: All patients enrolled in this prospective, multicenter study underwent paclitaxel-eluting stent placement for de novo or restenotic lesions of the superficial femoral and/or popliteal artery. Baseline and follow-up walking impairment questionnaire (WIQ) scores, Rutherford classifications, and ankle-brachial index (ABI) measurements were obtained. Follow-up was completed at 1, 6, and 12 months. Results: There were 285 diabetic patients and 502 nondiabetic patients treated. There were no significant differences in mean lesion length or lesion calcification between patient groups. Procedural success in both treatment groups was >97 %. There were no significant differences between diabetic and nondiabetic groups in Kaplan-Meier estimates of patency, event-free survival (EFS), or freedom from target lesion revascularization (TLR) at 6 and 12 months. Both groups experienced a significant increase in ABI and WIQ values after treatment, and these improvements were sustained to 12-month follow-up; however, nondiabetic patients had significantly greater 6- and 12-month WIQ scores compared with diabetic patients. Based on covariate analysis, the only factors shown to be significant and to negatively influence patency were longer lesion length (p = 0.009), higher Rutherford classification (p = 0.02), and lack of hypertension (p = 0.02); diabetic status was not found to be a significant factor. Conclusion: Diabetic and nondiabetic patients had similar estimates of primary patency, EFS, and freedom from TLR; however, diabetic patients showed less improvement in WIQ scores compared with nondiabetic patients.

  4. Metallic Limus-Eluting Stents Abluminally Coated with Biodegradable Polymers: Angiographic and Clinical Comparison of a Novel Ultra-Thin Sirolimus Stent Versus Biolimus Stent in the DESTINY Randomized Trial.

    Science.gov (United States)

    Lemos, Pedro A; Abizaid, Alexandre A C; Meireles, George C; Sarmento-Leite, Rogério; Prudente, Mauricio; Cantarelli, Marcelo; Dourado, Adriano D; Mariani, Jose; Perin, Marco A; Costantini, Costantino; Costa, Ricardo A; Costa, José Ribamar; Chamie, Daniel; Campos, Carlos A; Ribeiro, Expedito

    2015-12-01

    To evaluate the outcomes of patients treated with a new drug-eluting stent formulation with low doses of sirolimus, built in an ultra-thin-strut platform coated with biodegradable abluminal coating. This study is a randomized trial that tested the main hypothesis that the angiographic late lumen loss of the novel sirolimus-eluting stent is noninferior compared with commercially available biolimus-eluting stent. A final study population comprising 170 patients with one or two de novo lesions was randomized in the ratio 2:1 for sirolimus-eluting stent or biolimus-eluting stent, respectively. The primary endpoint was 9-month angiographic in-stent late lumen loss. Adverse clinical events were prospectively collected for 1 year. After 9 months, the novel sirolimus-eluting stent was shown noninferior compared with the biolimus stent for the primary endpoint (angiographic in-stent late lumen loss: 0.20 ± 0.29 mm vs. 0.15 ± 0.20 mm, respectively; P value for noninferiority <0.001). The 1-year incidence of death, myocardial infarction, repeat revascularization, and stent thrombosis remained low and not significantly different between the groups. The present randomized trial demonstrates that the tested novel sirolimus-eluting stent was angiographically noninferior in comparison with a last-generation biolimus-eluting stent. © 2015 John Wiley & Sons Ltd.

  5. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Directory of Open Access Journals (Sweden)

    Alessandra Romano

    2014-01-01

    Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

  6. Salvage Therapy of Multiple Myeloma: The New Generation Drugs

    Science.gov (United States)

    Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

    2014-01-01

    During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

  7. Enhancing cognate target elution efficiency in gel-free chemical proteomics

    Directory of Open Access Journals (Sweden)

    Branka Radic-Sarikas

    2015-12-01

    Full Text Available Gel-free liquid chromatography mass spectrometry coupled to chemical proteomics is a powerful approach for characterizing cellular target profiles of small molecules. We have previously described a fast and efficient elution protocol; however, altered target profiles were observed. We hypothesised that elution conditions critically impact the effectiveness of disrupting drug-protein interactions. Thus, a number of elution conditions were systematically assessed with the aim of improving the recovery of all classes of proteins whilst maintaining compatibility with immunoblotting procedures. A double elution with formic acid combined with urea emerged as the most efficient and generically applicable elution method for chemical proteomics

  8. Expert consensus (SBC/SBHCI) on the use of drug-eluting stents: recommendations of the Brazilian society of interventional cardiology/ Brazilian society of cardiology for the Brazilian public single healthcare system.

    Science.gov (United States)

    Lima, Valter C; Mattos, Luiz Alberto P; Caramori, Paulo R A; Perin, Marco A; Mangione, José A; Machado, Bruno M; Coelho, Wilson M C; Bueno, Ronaldo R L

    2006-10-01

    The authors review percutaneous coronary intervention (PCI) evolution and its growing application in myocardial revascularization for patients with coronary heart disease in Brazil and worldwide. PCI was introduced in 1977 using only the catheter balloon. Limitations of this method (acute occlusion and coronary restenosis) led to the adoption of coronary stents and more recently the advent of drug-eluting stents2, which were developed to drastically reduce restenosis rates. These developments allowed the exponential growth of percutaneous coronary intervention (PCI) procedures in Brazil which have replaced many bypass surgery procedures and have become the gold standard for the majority of symptomatic patients suffering from coronary artery disease. The preference for this procedure gained new dimensions in 2000 when the Brazilian Public Healthcare System (SUS) began reimbursing for stent procedures. This measure exemplified the importance of the Public Healthcare System's participation in incorporating medical advances and offering a high standard of cardiovascular treatment to a large portion of the Brazilian population. It is emphasized that prevention of in-stent restenosis is complex due to its unpredictable and ubiquitous occurrence. Control of this condition improves quality of life and reduces the recurrence of angina pectoris, the need to perform new revascularization procedures and hospital readmissions. The overall success of the drug-eluting stents has proven to be reliable and consistent in overcoming restenosis and has some beneficial impact for all clinical and angiographic conditions. This paper discusses the adoption and criteria for the use of drug-eluting stents in other countries as well as the recommendations established by the Brazilian Society of Interventional Cardiology for their reimbursement by SUS. The incorporation of new healthcare technology involves two distinct stages. During the first stage, the product is registered with the

  9. Generative Recurrent Networks for De Novo Drug Design.

    Science.gov (United States)

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  10. Cefoperazone and cefoperazone-sulbactam susceptibility tests with anaerobic bacteria by the thioglycolate disk elution method.

    OpenAIRE

    Barry, A L; Packer, R R; Jones, R N

    1985-01-01

    Tests were performed with 104 anaerobic microorganisms to evaluate the thioglycolate disk elution technique for the detection of resistance to cefoperazone and cefoperazone-sulbactam. An unacceptably high false-resistance rate and a poor reproducibility record make the disk elution procedure unsatisfactory for routine testing of this drug or combination of drugs.

  11. Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China.

    Science.gov (United States)

    Zhong, Zhixiong; Hou, Jingyuan; Zhang, Qifeng; Li, Bin; Li, Cunren; Liu, Zhidong; Yang, Min; Zhong, Wei; He, Xuebo; Wu, Hesen; Zhong, Miaocai; Zhao, Pingsen

    2018-04-01

    The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China. Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90 mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75 mg and the patients were followed-up for at least 12 months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke. The allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12 months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; P = 0.044). Our results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to

  12. Intra-stent tissue evaluation within bare metal and drug-eluting stents > 3 years since implantation in patients with mild to moderate neointimal proliferation using optical coherence tomography and virtual histology intravascular ultrasound.

    Science.gov (United States)

    Kitabata, Hironori; Loh, Joshua P; Pendyala, Lakshmana K; Omar, Alfazir; Ota, Hideaki; Minha, Sa'ar; Magalhaes, Marco A; Torguson, Rebecca; Chen, Fang; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

    2014-04-01

    We aimed to compare neointimal tissue characteristics between bare-metal stents (BMS) and drug-eluting stents (DES) at long-term follow-up using optical coherence tomography (OCT) and virtual histology intravascular ultrasound (VH-IVUS). Neoatherosclerosis in neointima has been reported in BMS and in DES. Thirty patients with 36 stented lesions [BMS (n=17) or DES (n=19)] >3years after implantation were prospectively enrolled. OCT and VH-IVUS were performed and analyzed independently. Stents with ≥70% diameter stenosis were excluded. The median duration from implantation was 126.0months in the BMS group and 60.0months in the DES group (p 3years to stents had evidence of intimal disruption. The percentage volume of necrotic core (16.1% [9.7, 20.3] vs. 9.7% [7.0, 16.5], p=0.062) and dense calcium (9.5% [3.8, 13.6] vs. 2.7% [0.4, 4.9], p=0.080) in neointima tended to be greater in BMS-treated lesions. Intra-stent VH-TCFA (BMS vs. DES 45.5% vs. 18.2%, p=0.361) did not differ significantly. At long-term follow-up beyond 3 years after implantation, the intra-stent neointimal tissue characteristics appeared similar for both BMS and DES. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Drug-Eluting Beads Loaded With Doxorubicin (DEBDOX) Chemoembolisation Before Liver Transplantation for Hepatocellular Carcinoma: An Imaging/Histologic Correlation Study

    Energy Technology Data Exchange (ETDEWEB)

    Pauwels, Xavier, E-mail: xpauwels@hotmail.com; Azahaf, Mustapha, E-mail: mustapha.azahaf@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Diagnostic and Interventional Radiology (France); Lassailly, Guillaume, E-mail: guillaume.lassailly@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Diseases and Nutrition (France); Sergent, Géraldine, E-mail: geraldine.sergent@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Diagnostic and Interventional Radiology (France); Buob, David, E-mail: david.buob@chru-lille.fr [CHRU Lille, Department of Pathology (France); Truant, Stéphanie, E-mail: stephanie.truant@chru-lille.fr; Boleslawski, Emmanuel, E-mail: emmanuel.boleslawski@gmail.com [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Surgery and Transplantation (France); Louvet, Alexandre, E-mail: alexandre.louvet@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Diseases and Nutrition (France); Gnemmi, Vivianne, E-mail: viviane.gnemmi@chru-lille.fr [CHRU Lille, Department of Pathology (France); Canva, Valérie, E-mail: valerie.canva@chru-lille.fr; Mathurin, Philippe, E-mail: philippe.mathurin@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Diseases and Nutrition (France); Pruvot, François-René, E-mail: francois-rene.pruvot@chru-lille.fr [CHRU Lille, Hôpital Claude Huriez, Department of Digestive Surgery and Transplantation (France); Leteurtre, Emmanuelle, E-mail: emmanuelle.leteurtre@chru-lille.fr [CHRU Lille, Department of Pathology (France); and others

    2015-06-15

    Purpose Most transplant centers use chemoembolisation as locoregional bridge therapy for hepatocellular carcinoma (HCC) before liver transplantation (LT). Chemoembolisation using beads loaded with doxorubicin (DEBDOX) is a promising technique that enables delivery of a large quantity of drugs against HCC. We sought to assess the imaging–histologic correlation after DEBDOX chemoembolisation.Materials and Methods All consecutive patients who had undergone DEBDOX chemoembolisation before receiving liver graft for HCC were included. Tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) and modified RECIST (mRECIST) criteria. The result of final imaging made before LT was correlated with histological data to predict tumour necrosis.ResultsTwenty-eight patients underwent 43 DEBDOX procedures for 45 HCC. Therapy had a significant effect as shown by a decrease in the mean size of the largest nodule (p = 0.02) and the sum of viable part of tumour sizes according to mRECIST criteria (p < 0.001). An objective response using mRECIST criteria was significantly correlated with mean tumour necrosis ≥90 % (p = 0.03). A complete response using mRECIST criteria enabled accurate prediction of complete tumour necrosis (p = 0.01). Correlations using RECIST criteria were not significant.ConclusionOur data confirm the potential benefit of DEBDOX chemoembolisation as bridge therapy before LT, and they provide a rational basis for new studies focusing on recurrence-free survival after LT. Radiologic evaluation according to mRECIST criteria enables accurate prediction of tumour necrosis, whereas RECIST criteria do not.

  14. Nickel elution properties of contemporary interatrial shunt closure devices.

    Science.gov (United States)

    Verma, Divya Ratan; Khan, Muhammad F; Tandar, Anwar; Rajasekaran, Namakkal S; Neuharth, Renée; Patel, Amit N; Muhlestein, Joseph B; Badger, Rodney S

    2015-02-01

    We sought to compare nickel elution properties of contemporary interatrial shunt closure devices in vitro. There are two United States Food and Drug Administration (FDA)-approved devices for percutaneous closure of secundum atrial septal defect: the Amplatzer septal occluder (ASO; St Jude Medical Corporation) and Gore Helex septal occluder (HSO; W.L. Gore & Associates). The new Gore septal occluder (GSO) device is in clinical trials. These are also used off-label for patent foramen ovale closure in highly selected patients. These devices have high nickel content. Nickel allergy is the most common reason for surgical device explantation. Nickel elution properties of contemporary devices remain unknown. We compared nickel elution properties of 4 devices - ASO, GSO, HSO, and sternal wire (SW) - while Dulbecco's phosphate-buffered saline (DPBS) served as control. Three samples of each device were submerged in DPBS. Nickel content was measured at 14 intervals over 90 days. Nickel elution at 24 hours, compared to control (0.005 ± 0.0 mg/L), was significantly higher for ASO (2.98 ± 1.65 mg/L; P=.04) and SW (0.03 ± 0.014 mg/L; P=.03). Nickel levels at 90 days, compared to control (0.005 ± 0.0 mg/L) and adjusting for multiple comparisons, were significantly higher for ASO (19.80 ± 2.30 mg/L; P=.01) and similar for HSO (P=.34), GSO (P=.34), and SW (P=.34). ASO had significantly higher nickel elution compared to HSO, GSO, and SW (P=.01). There is substantial variability in nickel elution; devices with less exposed nickel (HSO and GSO) have minimal elution. The safety of low nickel elution devices in patients with nickel allergy needs to be evaluated in prospective trials.

  15. Solving the Issue of Restenosis After Stenting of Intracranial Stenoses: Experience with Two Thin-Strut Drug-Eluting Stents (DES)—Taxus Element™ and Resolute Integrity™

    Energy Technology Data Exchange (ETDEWEB)

    Kurre, Wiebke, E-mail: wiebke.kurre@gmx.de; Aguilar-Pérez, Marta [Klinikum Stuttgart, Klinik für Diagnostische und Interventionelle Neuroradiologie (Germany); Fischer, Sebastian [Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Institut für Diagnostische und Interventionelle Radiologie, Neuroradiologie und Nuklearmedizin (Germany); Arnold, Guy [Klinikverbund Südwest, Klinikum Sindelfingen, Klinik für Neurologie (Germany); Schmid, Elisabeth; Bäzner, Hansjörg [Klinikum Stuttgart, Klinik für Neurologie (Germany); Henkes, Hans [Klinikum Stuttgart, Klinik für Diagnostische und Interventionelle Neuroradiologie (Germany)

    2015-06-15

    PurposeThin-strut, flexible DES are suitable for intracranial stenting and may improve long-term vessel patency. The purpose of this study was to report our experience with two new-generation DES for the treatment of intracranial atherosclerotic disease.Patients and MethodsWe retrospectively reviewed all patients treated with Taxus Element™ or Resolute Integrity™ stent for an intracranial atherosclerotic stenosis between March 2011 and August 2013. Technical success was defined as the ability to deploy the device at the desired location and reduce the degree of stenosis below 50 %. All procedure-related strokes were recorded. Control angiography was scheduled after 6 weeks, 3, 6, and 12 months and yearly thereafter. A luminal narrowing ≥50 % was regarded as a restenosis. Stroke recurrence in the territory of the treated artery was reported.ResultsIn the defined period we treated 101 patients harboring 117 intracranial stenoses. The procedure was successful in 100 (85.5 %) lesions. Procedure-related strokes occurred in 10 (9.9 %) patients with a permanent morbidity in 3 (3.0 %). Follow-up angiography was available for 83 of 100 (83.0 %) successfully treated lesions with an average of 355 days (IQR 153–482 days). Three (3.6 %) asymptomatic restenoses were detected. All occurred after treatment with Resolute Integrity™, none after Taxus Element™ (p = 0.059). New strokes in the territory of the treated artery were encountered in 2 (2.6 %) occasions.ConclusionThin-strut DES improve long-term patency and reduce the risk of subsequent stroke. Differences between devices may exist. Feasibility is comparable to bare-metal balloon-mounted stents and procedure-related strokes occurred within the expected range.

  16. Study design of the influence of SErotonin inhibition on patients with RENAl impairment or diabetes undergoing drug-eluting stent implantation (SERENADE) study: A multicenter, open-label, prospective, randomized study.

    Science.gov (United States)

    Lee, Seung-Ah; Suh, Jung-Won; Park, Jin Joo; Yoon, Chang-Hwan; Cho, Young-Suk; Youn, Tae-Jin; Chae, In-Ho; Kim, Hyo-Soo; Kim, Sang-Hyun; Choi, Dong-Ju

    2015-07-01

    The rates of stent failure after percutaneous coronary intervention have decreased since the introduction of the drug-eluting stent (DES). However, chronic kidney disease (CKD) and diabetes mellitus (DM) remain strong clinical predictors of poor prognosis despite DES implantation. Sarpogrelate, a selective serotonin (5-hydroxytryptamine (HT)2a [5-HT2A]) receptor antagonist, has antiproliferative effects, reducing neointimal hyperplasia and smooth muscle cell proliferation, as well as potent antiplatelet action, inhibiting 5-HT-induced platelet aggregation. However, efficacy and safety data for sarpogrelate in patients with CKD or DM are limited. We aim to determine whether sarpogrelate has beneficial effects in patients with CDK or DM treated with DES implantation. The SERENADE trial is a multicenter, open-label, prospective, randomized study that will test the superiority of triple anti-platelet therapy (TAT; aspirin, clopidogrel, and sarpogrelate) to conventional dual antiplatelet therapy (DAT; aspirin and clopidogrel) in preventing late lumen loss 9 months after the index procedure in patients with CKD or DM. A total of 220 patients diagnosed with coronary artery disease with DM or CKD will be randomized to the TAT or DAT groups (1:1 ratio) after DES implantation. The primary endpoint is late lumen loss at 9 months assessed by quantitative coronary angiography. Secondary efficacy endpoints are composites of major adverse cardiovascular events including cardiac death, nonfatal myocardial infarction, and target lesion revascularization. Secondary safety endpoints are major bleeding events and hepatic or renal impairment. The SERENADE trial will provide insight on the efficacy of adjunctive therapy with sarpogrelate after DES implantation for patients with high-risk profiles such as CKD or DM. National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov NCT02294643). Copyright © 2015. Published by Elsevier Inc.

  17. Long-Term Effectiveness of the Zilver PTX Drug-Eluting Stent for Femoropopliteal Peripheral Artery Disease in Patients with No Patent Tibial Runoff Vessels-Results from the Zilver PTX Japan Post-Market Surveillance Study.

    Science.gov (United States)

    Cipollari, Stefano; Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Saunders, Alan T; Dake, Michael D

    2018-01-01

    To evaluate 2-year results of the Zilver PTX (Cook Medical, Bloomington, Indiana) drug-eluting stent (DES) for femoropopliteal peripheral artery disease (PAD) in patients with no continuous patent infrapopliteal runoff arteries compared with patients with ≥ 1 continuous patent runoff vessels. A retrospective analysis of patients with femoropopliteal PAD enrolled in the Zilver PTX Post-Market Surveillance Study in Japan was performed. There were no exclusion criteria. Outcomes, including freedom from target lesion revascularization (TLR), patency, and clinical benefit, for the no-runoff group (n = 54) were compared with the runoff group (n = 846). The 2 groups were similar in terms of demographics, lesion characteristics, and comorbidities (P > .05). There was a higher incidence of critical limb ischemia in the no-runoff group compared with the runoff group (44.8% vs 19.7%; P < .01). There were 3 amputations (5.6%) in the no-runoff group versus 7 amputations (0.8%) in the runoff group (P = .02). At 2 years, freedom from TLR rates were 81.3% versus 83.8% (P = .87), patency rates were 68.4% versus 70.7% (P = .95), and clinical benefit rates were 73.7% versus 80.0% (P = .16) in the no-runoff versus runoff group, respectively. Results in patients with no continuous patent tibial runoff were favorable through 2 years and similar to results for patients with ≥ 1 continuous patent runoff vessels, indicating that the Zilver PTX DES may be a valid treatment option for patients with these difficult-to-treat lesions. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  18. Intra-arterial therapy of neuroendocrine tumour liver metastases: comparing conventional TACE, drug-eluting beads TACE and yttrium-90 radioembolisation as treatment options using a propensity score analysis model

    Energy Technology Data Exchange (ETDEWEB)

    Minh, Duc Do; Gorodetski, Boris; Smolka, Susanne; Savic, Lynn Jeanette; Wainstejn, David [Charite Universitaetsmedizin, Campus Virchow Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Chapiro, Julius; Schlachter, Todd [Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Huang, Qiang [Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Capital Medical University, Department of Interventional Radiology, Beijing Chaoyang Hospital, Beijing (China); Liu, Cuihong [Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Shandong Provincial Hospital Affiliated to Shandong University, The Ultrasound Department, Jinan (China); Lin, MingDe [Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Philips Research North America, U/S Imaging and Interventions (UII), Cambridge, MA (United States); Gebauer, Bernhard [Charite Universitaetsmedizin, Campus Virchow Klinikum, Department of Diagnostic and Interventional Radiology, Berlin (Germany); Geschwind, Jean-Francois [Yale University School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States)

    2017-12-15

    To compare efficacy, survival outcome and prognostic factors of conventional transarterial chemoembolisation (cTACE), drug-eluting beads TACE (DEB-TACE) and yttrium-90 radioembolisation (Y90) for the treatment of liver metastases from gastroenteropancreatic (GEP) neuroendocrine tumours (NELM). This retrospective analysis included 192 patients (58.6 years mean age, 56% men) with NELM treated with cTACE (N = 122), DEB-TACE (N = 26) or Y90 (N = 44) between 2000 and 2014. Radiologic response to therapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) and World Health Organization (WHO) criteria using periprocedural MR imaging. Survival analysis included propensity score analysis (PSA), median overall survival (MOS), hepatic progression-free survival, Kaplan-Meier using log-rank test and the uni- and multivariate Cox proportional hazards model (MVA). MOS of the entire study population was 28.8 months. As for cTACE, DEB-TACE and Y90, MOS was 33.8 months, 21.7 months and 23.6 months, respectively. According to the MVA, cTACE demonstrated a significantly longer MOS as compared to DEB-TACE (p <.01) or Y90 (p =.02). The 5-year survival rate after initial cTACE, DEB-TACE and Y90 was 28.2%, 10.3% and 18.5%, respectively. Upon PSA, our study suggests significant survival benefits for patients treated with cTACE as compared to DEB-TACE and Y90. This data supports the therapeutic decision for cTACE as the primary intra-arterial therapy option in patients with unresectable NELM until proven otherwise. (orig.)

  19. The short- and long-term outcomes of percutaneous intervention with drug-eluting stent vs bare-metal stent in saphenous vein graft disease: An updated meta-analysis of all randomized clinical trials.

    Science.gov (United States)

    Kheiri, Babikir; Osman, Mohammed; Abdalla, Ahmed; Ahmed, Sahar; Bachuwa, Ghassan; Hassan, Mustafa

    2018-05-11

    The use of drug-eluting stents (DES) vs bare-metal stents (BMS) in saphenous vein graft (SVG) lesions remains controversial. We conducted a meta-analysis of all randomized clinical trials comparing the outcomes of DES with BMS in SVG percutaneous coronary interventions. A search of PubMed, Embase, the Cochrane Register of Controlled Trials, and Clinicaltrials.gov was performed for all randomized clinical trials. We evaluated the short- and long-term clinical outcomes of the following: all-cause mortality, major adverse cardiovascular events (MACE), definite/probable stent thrombosis, target lesion revascularization (TLR), and target-vessel revascularization (TVR). From a total of 1582 patients in 6 randomized clinical trials, 797 had DES and 785 had BMS. Patients with DES had lower short-term MACE, TLR, and TVR in comparison with BMS (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.35-0.91, P = 0.02; OR: 0.43, 95% CI: 0.19-0.99, P = 0.05; and OR: 0.45, 95% CI: 0.22-0.95, P = 0.04, respectively). However, there were no different outcomes for all-cause mortality (P = 0.63) or stent thrombosis (P = 0.21). With long-term follow-up, there were no significant reductions of MACE (P = 0.20), TLR (P = 0.57), TVR (P = 0.07), all-cause mortality (P = 0.29), and stent thrombosis (P = 0.76). The use of DES in SVG lesions was associated with lower short-term MACE, TLR, and TVR in comparison with BMS. However, there were no significant differences with long-term follow-up. © 2018 Wiley Periodicals, Inc.

  20. Incidence and Clinical Outcomes of Stent Fractures on the Basis of 6,555 Patients and 16,482 Drug-Eluting Stents From 4 Centers.

    Science.gov (United States)

    Kan, Jing; Ge, Zhen; Zhang, Jun-Jie; Liu, Zhi-Zhong; Tian, Nai-Liang; Ye, Fei; Li, Sui-Ji; Qian, Xue-Song; Yang, Song; Chen, Meng-Xuan; Rab, Tanveer; Chen, Shao-Liang

    2016-06-13

    The present study aimed to analyze the incidence of SF and its correlation with clinical events after DES implantation and the outcome of re-intervention for symptomatic in-stent restenosis (ISR) induced by stent fracture (SF). SF is associated with a high rate of clinical events after the implantation of drug-eluting stents (DES). However, the chronological rate of SF and the effect of SF on clinical outcomes from a large patient population remain underreported. A total of 6,555 patients with 16482 DES in 10751 diseased vessels and surveillance angiography between November 2003 and January 2014 were prospectively studied. The primary endpoints included the incidence of SF, in-stent restenosis (ISR), target lesion revascularization (TLR), and definite stent thrombosis (ST) at the end of follow-up before and after propensity score matching. Clinical outcomes after TLR were also followed up. The SF rate was detected in 803 (12.3%) patients, 3,630 (22.0%) stents, and 1,852 (17.2%) diseased vessels. SF increased over time. SF was associated with higher unadjusted rates of ISR (42.1%), TLR (24.8%, n = 379), and definite ST (4.6%) compared with stents without fracture (10.7%, 6.6%, and 1.03%, all p stents after reintervention, and 6 (7.5%) stents required repeat TLR. SF is more frequently observed after DES implantation. TLR was required in almost one-fourth of fractured stents. Increased events in the SF group did not translate into a difference in mortality compared with the non-SF group. Reintervention was associated with acceptable clinical results. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Five-year outcome after implantation of zotarolimus- and everolimus-eluting stents in randomized trial participants and nonenrolled eligible patients : A secondary analysis of a randomized clinical trial

    NARCIS (Netherlands)

    Von Birgelen, Clemens; Van Der Heijden, Liefke C.; Basalus, Mounir Welson Zakhary; Kok, Marlies M.; Sen, Hanim; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Linssen, Gerard C.M.; Tandjung, Kenneth; Doggen, Carine J.M.; Van Der Palen, Job; Löwik, Marije M.

    2017-01-01

    IMPORTANCE: Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported. OBJECTIVE: To assess 5-year safety and efficacy

  2. Percutaneous Coronary Intervention of Left Main Disease: Pre- and Post-EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) Era.

    Science.gov (United States)

    Park, Duk-Woo; Park, Seung-Jung

    2017-06-01

    For nearly half a century, coronary artery bypass grafting has been the standard treatment for patients with obstructive left main coronary artery (LMCA) disease. However, there has been considerable evolution in the field of percutaneous coronary intervention, and especially, percutaneous coronary intervention for LMCA disease has been rapidly expanded with adoption of drug-eluting stents. Some, but not all randomized trials, have shown that percutaneous coronary intervention with drug-eluting stents might be a suitable alternative for selected patients with LMCA disease instead of bypass surgery. However, none of previous trials involving early-generation drug-eluting stents was sufficiently powered and comparative trials using contemporary drug-eluting stents were limited. Recently, primary results of 2 new trials of EXCEL (Evaluation of XIENCE Everolimus Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) and NOBLE (Nordic-Baltic-British Left Main Revascularization Study) were reported. However, these trials showed conflicting results, which might pose uncertainty on the optimal revascularization strategy for LMCA disease. In this article, with the incorporation of a key review on evolution of LMCA treatment, we summarize the similarity or disparity of the EXCEL and NOBLE trials, focus on how they relate to previous trials in the field, and finally speculate on how the treatment strategy may be changed or recommended for LMCA treatment. © 2017 American Heart Association, Inc.

  3. Size distribution of DNA molecules recovered from non-denaturing filter elution

    International Nuclear Information System (INIS)

    Bloecher, D.; Iliakis, G.

    1991-01-01

    DNA fragments removed from the filter during non-denaturing filter elution were collected and loaded on top of neutral sucrose gradients. Their size distribution was determined by low-speed centrifugation in neutral sucrose gradients. The average size of eluted DNA was found to be approximately 110 S; the average size of DNA collected after short elution times was found to be slightly larger than after long elution times. It is concluded that the size of eluted DNA fragments is not correlated with elution rate, and it is proposed that shear forces generated at the filter pores cause degradation of the DNA. Comparison of sedimentation profiles of carefully prepared cellular DNA before and after elution revealed that generated shear forces during elution break down DNA to an extent equivalent to around 20 000 DNA double-strand breaks (dsb) per G 1 cell. The size of DNA fragments decreased with increasing radiation dose; five times more dsb were found than expected after exposure to radiation alone. It is proposed that excess of dsb may derive from the transformation of other radiation-induced lesions to dsb under the action of shear forces generated during elution. (author)

  4. Exploiting Specific Interactions toward Next-Generation Polymeric Drug Transporters

    NARCIS (Netherlands)

    Wieczorek, Sebastian; Krause, Eberhard; Hackbarth, Steffen; Roeder, Beate; Hirsch, Anna K. H.; Boerner, Hans G.

    2013-01-01

    A generic method describes advanced tailoring of polymer drug carriers based on polymer-block-peptides. Combinatorial means are used to select suitable peptide segments to specifically complex small-molecule drugs. The resulting specific drug formulation agents render insoluble drugs water-soluble

  5. Radio-isotope generator

    International Nuclear Information System (INIS)

    Benjamins, H.M.

    1983-01-01

    A device is claimed for interrupting an elution process in a radioisotope generator before an elution vial is entirely filled. The generator is simultaneously exposed to sterile air both in the direction of the generator column and of the elution vial

  6. Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial

    DEFF Research Database (Denmark)

    Galløe, Anders M; Thuesen, Leif; Kelbaek, Henning

    2008-01-01

    Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients.......Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients....

  7. Short-versus long-term Dual Antiplatelet therapy after drug-eluting stent implantation in women versus men: A sex-specific patient-level pooled-analysis of six randomized trials.

    Science.gov (United States)

    Sawaya, Fadi J; Morice, Marie-Claude; Spaziano, Marco; Mehran, Roxana; Didier, Romain; Roy, Andrew; Valgimigli, Marco; Kim, Hyo-Soo; Woo Park, Kyung; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Feres, Fausto; Abizaid, Alexandre; Costa, Ricardo A; Colombo, Antonio; Chieffo, Alaide; Giustino, Gennaro; Stone, Gregg W; Bhatt, Deepak L; Palmerini, Tullio; Gilard, Martine

    2017-02-01

    Whether the efficacy and safety of dual antiplatelet therapy (DAPT) are uniform between sexes is unclear. We sought to compare clinical outcomes between short- (≤6 months) versus long-term (≥1 year) DAPT after drug-eluting stent (DES) placement in women and men. We pooled individual patient data from 6 randomized trials of DAPT (EXCELLENT, OPTIMIZE, PRODIGY, RESET, SECURITY, ITALIC PLUS). The primary outcome was 1-year risk of major adverse cardiac events (MACE). The main secondary outcome was 1-year risk of any bleeding. Out of the 11,473 randomized patients included in the pooled dataset, 3,454 (30%) were females. At 1-year follow-up, women had higher risk of MACE (3.6% vs. 2.8%; P = 0.01) but similar risk of bleeding (1.9% vs. 1.6%; P = 0.16) as compared with men. Compared with long-term DAPT, short-term DAPT was associated with similar rates of MACE in both women (HR 0.88; 95% CI 0.62-1.25) and men (HR 1.25; 95% CI 0.95-1.6; P interaction = 0.08)]. At 1-year follow-up, short-term DAPT was associated with lower rates of bleeding as compared with long-term DAPT in both women (HR 0.84; 95% CI 0.51-1.37) and men (HR 0.58; 95% CI 0.40-0.84; P-interaction = 0.25). The presence of MVD was associated with higher MACE rates in the short-term DAPT group in women (HR: 1.16; CI 0.60-2.23) and men (HR: 2.29; CI 1.22-4.29; P interaction = 0.25). Short-term DAPT is associated with similar rates of MACE but lower risk of bleeding when as compared with prolonged DAPT. There was no significant difference between sexes in the population studied. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Heparin monotherapy or bivalirudin during percutaneous coronary intervention in patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease: results from the Evaluation of Drug-Eluting Stents and Ischemic Events registry.

    Science.gov (United States)

    Bangalore, Sripal; Pencina, Michael J; Kleiman, Neal S; Cohen, David J

    2014-06-01

    The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use

  9. Drug-eluting versus plain balloon angioplasty for the treatment of failing dialysis access: Final results and cost-effectiveness analysis from a prospective randomized controlled trial (NCT01174472)

    Energy Technology Data Exchange (ETDEWEB)

    Kitrou, Panagiotis M., E-mail: panoskitrou@gmail.com [Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion 26504 (Greece); Katsanos, Konstantinos [Department of Interventional Radiology, Guy' s and St. Thomas’ Hospitals, NHS Foundation Trust, King' s Health Partners, London SE1 7EH (United Kingdom); Spiliopoulos, Stavros; Karnabatidis, Dimitris; Siablis, Dimitris [Department of Interventional Radiology, Patras University Hospital, School of Medicine, Rion 26504 (Greece)

    2015-03-15

    Highlights: •1-Year target lesion primary patency significantly higher after PCB application compared to plain balloon angioplasty in the failing dialysis access. •Significant difference in favor of PCB in cumulative primary patency of AVGs at 1 year. •No significant difference in cumulative primary patency of AVFs treated with PCB at 1 year. •Cost effectiveness analysis performed. •Paclitaxel-coated balloon angioplasty proves to be a cost-effective option for treating dialysis access. -- Abstract: Objective: To report the final results and cost-effectiveness analysis of a prospective randomized controlled trial investigating drug-eluting balloon (DEB) versus plain balloon angioplasty (BA) for the treatment of failing dialysis access ( (NCT01174472)). Methods: 40 patients were randomized to angioplasty with either DEB (n = 20) or BA (n = 20) for treatment of significant venous stenosis causing a failing dialysis access. Both arteriovenous fistulas (AVF) and synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was scheduled every two months. Primary endpoints were technical success and target lesion primary patency at 1 year. Cumulative and survival analysis was performed. Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER) were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn. Results: Baseline variables were equally distributed between the two groups. At 1 year, cumulative target lesion primary patency was significantly higher after DEB application (35% vs. 5% after BA, p < 0.001). Overall, median primary patency was 0.64 years in case of DEB vs. 0.36 years in case of BA (p = 0.0007; unadjusted HR = 0.27 [95%CI: 0.13–0.58]; Cox adjusted HR = 0.23 [95%CI: 0.10–0.50]). ICER was 2198 Euros (€) per primary patency year of dialysis access gained. INB was 1068€ (95%CI: 31–2105€) for a willingness-to-pay (WTP) threshold of 5000€ (corresponding acceptability probability >97

  10. The Indicating FTA Elute Cartridge

    Science.gov (United States)

    de Bie, Roosmarie P.; Schmeink, Channa E.; Bakkers, Judith M.J.E.; Snijders, Peter J.F.; Quint, Wim G.V.; Massuger, Leon F.A.G.; Bekkers, Ruud L.M.; Melchers, Willem J.G.

    2011-01-01

    The clinically validated high-risk human papillomavirus (hrHPV) Hybrid Capture 2 (HC2) and GP5+/6+-PCR assays were analyzed on an Indicating FTA Elute cartridge (FTA cartridge). The FTA cartridge is a solid dry carrier that allows safe transport of cervical samples. FTA cartridge samples were compared with liquid-based samples for hrHPV and high-grade cervical intraepithelial neoplasia (CIN) detection. One cervical sample was collected in a liquid-based medium, and one was applied to the FTA cartridge. DNA was eluted directly from the FTA cartridge by a simple elution step. HC2 and GP5+/6+-PCR assays were performed on both the liquid-based and the FTA-eluted DNA of 88 women. Overall agreement between FTA and liquid-based samples for the presence of hrHPV was 90.9% with GP5+/6+-PCR and 77.3% with HC2. The sensitivity for high-grade CIN of hrHPV testing on the FTA cartridges was 84.6% with GP5+/6+-PCR and only 53.8% with HC2. By comparison, these sensitivities on liquid-based samples were 92.3% and 100% for GP5+/6+-PCR and HC2, respectively. Therefore, the FTA cartridge shows reasonably good overall agreement for hrHPV detection with liquid-based media when using GP5+/6+-PCR but not HC2 testing. Even with GP5+/6+-PCR, the FTA cartridge is not yet capable of detecting all high-grade CIN lesions. PMID:21704269

  11. 2-year clinical outcomes after implantation of sirolimus-eluting, paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart Registry)

    DEFF Research Database (Denmark)

    Kaltoft, Anne; Jensen, Lisette Okkels; Maeng, Michael

    2009-01-01

    OBJECTIVES: This registry study assessed the safety and efficacy of the 2 types of drug-eluting stents (DES), sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), compared with bare-metal stents (BMS). BACKGROUND: Drug-eluting stents may increase the risk of stent thrombosis (ST...... databases. We used Cox regression analysis to control for confounding. RESULTS: The 2-year incidence of definite ST was 0.64% in BMS patients, 0.79% in DES patients (adjusted relative risk [RR]: 1.09; 95% confidence interval [CI]: 0.72 to 1.65), 0.50% in SES patients (adjusted RR: 0.63, 95% CI: 0.35 to 1...

  12. Bioabsorbable polymer-coated sirolimus-eluting stent implantation preserves coronary vasomotion: A DESSOLVE II trial sub-study.

    Science.gov (United States)

    Rusinaru, Dan; Vrolix, Mathias; Verheye, Stefan; Chowdhary, Saqib; Schoors, Danny; Di Mario, Carlo; Desmet, Walter; Donohoe, Dennis J; Ormiston, John A; Knape, Charlene; Bezerra, Hiram; Lansky, Alexandra; Wijns, William

    2015-12-01

    We studied coronary vasomotion in patients treated with the Mistent(®) absorbable polymer sirolimus-eluting stent (APSES) and in patients implanted with the Endeavor(®) zotarolimus-eluting stent (ZES). First generation (1st-gen) drug-eluting stents (DES) induce persistent vasomotor dysfunction in the treated coronary artery. It is unknown whether and to what extent the implantation of an absorbable polymer DES impairs coronary vasomotion. This sub-study of the DESSOLVE II trial included 19 APSES Mistent(®) and 10 ZES Endeavor(®) patients. Incremental atrial pacing and quantitative coronary angiography were used to assess vasomotion proximal and distal to the stent and in a reference segment at 9 months after implantation. Percent changes in vessel diameter with pacing versus baseline were calculated and compared. Vasomotor response of the APSES group was also compared with changes observed in a historical group of 17 patients implanted with a 1st-gen sirolimus-eluting stent (SES). Normal vasomotion (vasodilatation) was preserved and of comparable magnitude in the APSES and in the ZES group both proximally (P = 0.34) and distally (P = 0.38) to the stent. This finding was not observed in the 1st-gen SES group showing marked pacing-induced vasoconstriction at both stent edges (P absorbable polymer sirolimus-eluting stent is associated with preserved coronary vasomotion, comparable to that observed after implantation of the Endeavor(®) ZES, and distinct from 1st-gen SES which induce coronary vasomotor dysfunction. © 2015 Wiley Periodicals, Inc.

  13. Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits.

    Directory of Open Access Journals (Sweden)

    Matthijs S Ruiter

    Full Text Available The introduction of drug-eluting stents (DES has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC, endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface.Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions.Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation.We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.

  14. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study

    Directory of Open Access Journals (Sweden)

    Teeuwen Koen

    2012-12-01

    Full Text Available Abstract Background Percutaneous recanalization of total coronary occlusion (TCO was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST with drug-eluting stents (DES for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO. Methods/Design The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence

  15. The new generation of antiepileptic drugs: advantages and disadvantages.

    Science.gov (United States)

    Perucca, E

    1996-11-01

    1. After a hiatus of over 20 years, several new antiepileptic drugs (vigabatrin, lamotrigine, gabapentin, oxcarbazepine, topiramate, felbamate, zonisamide and tiagabine) have reached or approached the registration phase. 2. Compared with older agents, many new drugs exhibit simpler pharmacokinetics. This is especially true for vigabatrin and gabapentin, which are renally eliminated and have a low interaction potential. 3. Unlike most of the older agents, vigabatrin, lamotrigine, gabapentin and tiagabine are devoid of significant enzyme inducing or inhibiting properties. Topiramate, oxcarbazepine and felbamate may induce the metabolism of steroid oral contraceptives. In addition, felbamate also acts as a metabolic inhibitor. 4. To date, the efficacy of new drugs has been evaluated extensively only under add-on conditions in patients with partial seizures (with or without secondary generalization) refractory to conventional treatment. However, there is evidence that lamotrigine, zonisamide, felbamate and, possibly, topiramate may also be effective in generalized epilepsies. 5. In placebo-controlled studies, typically between 15 and 40% of patients with difficult-to-treat partial epilepsy have shown an improvement (defined as a 50% or greater decrease in seizure frequency) after addition of a new drug. Only a small minority of these patients achieved complete seizure control. 6. Compared with older agents, some of the new drugs may have a better tolerability profile. Felbamate, however, has been associated with a high risk of aplastic anaemia and hepatotoxicity. 7. At present, the main use of the new agents is in patients refractory to first-line drugs such as carbamazepine or valproate, and further studies are required to characterize their activity spectrum as well as their potential value in monotherapy. In most patients, new drugs cannot be recommended for first-line use until evidence is obtained that potential advantages in tolerability or ease of use outweigh

  16. 生物可吸收支架与药物洗脱支架治疗冠心病Meta分析%Biore sorbable stents and drug-eluting stents in treatment of coronary heart disease:a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    朱永翔; 蔡金赞; 朱灏; 庞思; 何光朝; 张瑶俊

    2017-01-01

    Objective To system evaluate the safety and efficacy of absorb bioresorbable vascular scaffold (BVS) and drug-eluting stents(DES) for coronary heart disease.Methods Using computer to retrieve PubMed,EMBASE,the Cochrane Library,EBSCO,Scopus and CBMdisc;at the same time,manually retrieved relevant cardiovascular meeting records internal and international,clinical studys which had 2 years of follow-up results about Absorb BVS and new generation DES for treatment of coronary heart disease(CHD) from January 2010 to April 2017 were selected.Using RevMan 5.3 software to perform meta analysis,to compare the safety and efficacy of Absorb BVS and new generation DES for CHD.Results There were finally 9 clinical studies been selected,including 7 randomized control trials with 6 673 patients(3 766 in Absorb BVS group and 2 907 in DES group).There was no statistically significant difference between the two groups in all-cause death,cardiac death and the incidence of patient-oriented composite endpoints(P>0.05).In Absorb BVS group,the incidence of primary clinical endpoints target lesion failure rate(OR=1.38,95%CI:1.14~1.67,P0.05);Absorb BVS组患者主要临床终点靶病变失败[比值比(OR)=1.38,95%可信区间(95%CI)为1.14~1.67,P<0.05]发生率显著高于DES组;Absorb BVS组患者次要临床终点所有心肌梗死(OR=1.63,95%CI为1.27~2.08,P<0.05),明确/极可能的支架内血栓(OR=3.06,95%CI为1.96~4.78,P<0.05),极晚期支架内血栓(OR=4.36,95%CI为1.72~11.07,P<0.05),靶病变再次血运重建(OR=1.41,95%CI为1.11~1.79,P<0.05)发生率显著高于DES组.结论 Absorb BVS治疗冠心病的长期安全性与有效性可能劣于新一代DES.

  17. Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

    Science.gov (United States)

    Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

    2011-01-01

    Background Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. Methods The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Results Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Conclusion Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development. PMID:22267921

  18. Fourth Generation Warfare in Chile: Illicit Drug Trafficking Threats

    Science.gov (United States)

    2011-03-21

    effective tools, such as global marketing and communications beyond the borders, allow states and non-state actors to build a gigantic net of contacts...agencies57 to coordinate, articulate and promote public policies in drugs and implement programs of prevention, control, treatment and rehabilitation

  19. Beyond THC: the new generation of cannabinoid designer drugs

    Directory of Open Access Journals (Sweden)

    Liana eFattore

    2011-09-01

    Full Text Available Synthetic cannabinoids are functionally similar to delta9-tetrahydrocannabinol (THC, the psychoactive principle of cannabis, and bind to the same cannabinoid receptors in the brain and peripheral organs. From 2008, synthetic cannabinoids were detected in herbal smoking mixtures sold on websites and in head shops under the brand name of Spice Gold, Yucatan Fire, Aroma, and others. Although these products (also known as Spice drugs or legal highs do not contain tobacco or cannabis, when smoked they produce effects similar to THC. Intoxication, withdrawal, psychosis and death have been recently reported after consumption, posing difficult social, political and health challenges. More than 140 different Spice products have been identified to date. The ability to induce strong cannabis-like psychoactive effects, along with the fact that they are readily available on the Internet, still legal in many countries, marketed as natural safe substances, and undetectable by conventional drug screening tests, has rendered these drugs very popular and particularly appealing to young and drug-naïve individuals seeking new experiences. An escalating number of compounds with cannabinoid receptor activity are currently being found as ingredients of Spice, of which almost nothing is known in terms of pharmacology, toxicology and safety. Since legislation started to control the synthetic cannabinoids identified in these herbal mixtures, many new analogs have appeared on the market. New cannabimimetic compounds are likely to be synthesized in the near future to replace banned synthetic cannabinoids, leading to a dog chasing its tail situation. Spice smokers are exposed to drugs that are extremely variable in composition and potency, and are at risk of serious, if not lethal, outcomes. Social and health professionals should maintain a high degree of alertness for Spice use and its possible psychiatric effects in vulnerable people.

  20. Elution behaviors of elements from the hair

    International Nuclear Information System (INIS)

    Akashi, Junko; Fukushima, Ichiro; Imahori, Akira

    1981-01-01

    The elution of the neutron activated elements out of hair soaked in some organic solvents and EDTA solution was studied. Soakage of the hair sample, which was washed with water and acetone in advance as IAEA's proposal, in ether and acetone for 30 minutes each resulted in no elution of Hg, Zn, Co and Se. Elution of Zn and Co from the powdered hair sample soaked in 0.1 M EDTA solution was rapid, while Zn did not elute out from the cut hair (2 -- 3 mm length) on the same condition. Hg, Se and Au were not eluted out by 0.1 M EDTA solution in the both case of cut hair and of powdered hair. Br was removed by 0.1 M EDTA solution from the cut hair and from the powdered hair with equal ease. (author)

  1. Increasing flexibility in two-dimensional liquid chromatography by pulsed elution of the first dimension

    DEFF Research Database (Denmark)

    Jakobsen, Simon S.; Christensen, Jan H.; Verdier, Sylvain

    2017-01-01

    This work demonstrates the development of an online two-dimensional liquid chromatography (2D-LC) method where the first dimension column is eluted by a sequence of pulses of increasing eluotropic strength generated by the LC pumps (pulsed-elution 2D-LC). Between the pulses, the first dimension...... online comprehensive 2D-LC: undersampling, difficulties in refocusing, and lack of flexibility in the selection of column dimensions and flow rates because the two dimensions constrain each other. The pulsed-elution 2D-LC was applied for the analysis of a basic fraction of vacuum gas oil. Peak capacity...

  2. NanoCrySP technology for generation of drug nanocrystals: translational aspects and business potential.

    Science.gov (United States)

    Shete, Ganesh; Bansal, Arvind Kumar

    2016-08-01

    Drug nanocrystals have rapidly evolved into a mature drug delivery strategy in the last decade, with almost 16 products currently on the market. Several "top-down" technologies are available in the market for generation of nanocrystals. Despite several advantages, very few bottom-up technologies have been explored for commercial purpose. This short communication highlights a novel, bottom-up, spray drying based technology-NanoCrySP-to generate drug nanocrystals. Nanocrystals are generated in the presence of non-polymeric excipients that act as crystallization inducer for the drug. Excipients encourage crystallization of drug by plasticization, primary heterogeneous nucleation, and imparting physical barrier to crystal growth. Nanocrystals have shown significant improvement in dissolution and thereby oral bioavailability. NanoCrySP technology is protected through patents in India, the USA, and the European Union. NanoCrySP can be utilized for (i) pharmaceutical development of new chemical entities, (ii) differentiated products of existing molecules, and (iii) generic drug products. The aggregation of drug nanocrystals generated using NanoCrySP poses significant challenges in the nanocrystal-based product development. Addition of stabilizers either during spray drying or during dissolution has shown beneficial effects.

  3. Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent : 4-year results of the PROTECT randomized trial

    NARCIS (Netherlands)

    Wijns, William; Steg, Ph. Gabriel; Mauri, Laura; Kurowski, Volkhard; Parikh, Keyur; Gao, Runlin; Bode, Christoph; Greenwood, John P.; Lipsic, Erik; Alamgir, Farqad; Rademaker-Havinga, Tessa; Boersma, Eric; Radke, Peter; van Leeuwen, Frank; Camenzind, Edoardo

    2014-01-01

    Aims To compare the long-term clinical safety between two drug-eluting stents with different healing characteristics in the Patient Related Outcomes with Endeavour (E-ZES) vs. Cypher (C-SES) Stenting Trial (PROTECT). At 3 years, there was no difference in the primary outcome of definite or probable

  4. Molecular dynamics in drug design: new generations of compstatin analogs.

    Science.gov (United States)

    Tamamis, Phanourios; López de Victoria, Aliana; Gorham, Ronald D; Bellows-Peterson, Meghan L; Pierou, Panayiota; Floudas, Christodoulos A; Morikis, Dimitrios; Archontis, Georgios

    2012-05-01

    We report the computational and rational design of new generations of potential peptide-based inhibitors of the complement protein C3 from the compstatin family. The binding efficacy of the peptides is tested by extensive molecular dynamics-based structural and physicochemical analysis, using 32 atomic detail trajectories in explicit water for 22 peptides bound to human, rat or mouse target protein C3, with a total of 257 ns. The criteria for the new design are: (i) optimization for C3 affinity and for the balance between hydrophobicity and polarity to improve solubility compared to known compstatin analogs; and (ii) development of dual specificity, human-rat/mouse C3 inhibitors, which could be used in animal disease models. Three of the new analogs are analyzed in more detail as they possess strong and novel binding characteristics and are promising candidates for further optimization. This work paves the way for the development of an improved therapeutic for age-related macular degeneration, and other complement system-mediated diseases, compared to known compstatin variants. © 2012 John Wiley & Sons A/S.

  5. Neointimal Healing Evaluated by Optical Coherence Tomography after Drug-Eluting Absorbable Metal Scaffold Implantation in de novo Native Coronary Lesions: Rationale and Design of the Magmaris-OCT Study.

    Science.gov (United States)

    Karjalainen, Pasi; Paana, Tuomas; Sia, Jussi; Nammas, Wail

    We sought to explore neointimal healing assessed by optical coherence tomography (OCT) following implantation of the Magmaris sirolimus-eluting absorbable metal scaffold. The Magmaris-OCT is a prospective, multicenter, single-arm observational clinical study, intended to enrol 60 consecutive patients with up to 2 de novo native coronary lesions, each located in different major epicardial vessels, with a reference vessel diameter of 2.5-3.5 mm, and a maximum lesion length of 20 mm. Patients will undergo Magmaris scaffold implantation in the target lesion, according to the standard practice. Clinical follow-up will take place at 30 days, and at 3, 6, 9, and 12 months. For invasive-imaging follow-up, patients will be classified into 3 groups: cohort A will be scheduled for follow-up at 3 months, cohort B at 6 months, and cohort C at 12 months. Invasive imaging will include quantitative coronary angiography, OCT evaluation, and coronary flow reserve measurement. The primary end point will be the percentage of uncovered scaffold struts assessed by OCT at the prespecified follow-up. This study will provide insight into the short- and mid-term healing properties following Magmaris scaffold implantation, with special emphasis on the neointimal coverage of scaffold struts. © 2017 S. Karger AG, Basel.

  6. Nonmedical prescription opioids and pathways of drug involvement in the US: Generational differences.

    Science.gov (United States)

    Wall, Melanie; Cheslack-Postava, Keely; Hu, Mei-Chen; Feng, Tianshu; Griesler, Pamela; Kandel, Denise B

    2018-01-01

    This study sought to specify (1) the position of nonmedical prescription opioids (NMPO) in drug initiation sequences among Millennials (1979-96), Generation X (1964-79), and Baby Boomers (1949-64) and (2) gender and racial/ethnic differences in sequences among Millennials. Data are from the 2013-2014 National Surveys on Drug Use and Health (n = 73,026). We identified statistically significant drug initiation sequences involving alcohol/cigarettes, marijuana, NMPO, cocaine, and heroin using a novel method distinguishing significant sequences from patterns expected only due to correlations induced by common liability among drugs. Alcohol/cigarettes followed by marijuana was the most common sequence. NMPO or cocaine use after marijuana, and heroin use after NMPO or cocaine, differed by generation. Among successively younger generations, NMPO after marijuana and heroin after NMPO increased. Millennials were more likely to initiate NMPO than cocaine after marijuana; Generation X and Baby Boomers were less likely (odds ratios = 1.4;0.3;0.2). Millennials were more likely than Generation X and Baby Boomers to use heroin after NMPO (hazards ratios = 7.1;3.4;2.5). In each generation, heroin users were far more likely to start heroin after both NMPO and cocaine than either alone. Sequences were similar by gender. Fewer paths were significant among African-Americans. NMPOs play a more prominent role in drug initiation sequences among Millennials than prior generations. Among Millennials, NMPO use is more likely than cocaine to follow marijuana use. In all generations, transition to heroin from NMPO significantly occurs only when both NMPO and cocaine have been used. Delineation of drug sequences suggests optimal points in development for prevention and treatment efforts. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Ultrasound-mediated drug delivery by gas bubbles generated from a chemical reaction.

    Science.gov (United States)

    Lee, Sungmun; Al-Kaabi, Leena; Mawart, Aurélie; Khandoker, Ahsan; Alsafar, Habiba; Jelinek, Herbert F; Khalaf, Kinda; Park, Ji-Ho; Kim, Yeu-Chun

    2018-02-01

    Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N 2 ) by chemical reaction when it reacts with hydrogen peroxide (H 2 O 2 ), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N 2 microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of H 2 O 2 . HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.

  8. Evaluation of electrochemical ion exchange for cesium elution

    International Nuclear Information System (INIS)

    Bontha, J.D.; Kurath, D.E.; Surma, J.E.; Buehler, M.F.

    1996-04-01

    Electrochemical elution was investigated as an alternative method to acid elution for the desorption of cesium from loaded ion exchange resins. The approach was found to have several potential advantages over existing technologies, in particular, electrochemical elution eliminates the need for addition of chemicals to elute cesium from the ion exchange resin. Also, since, in the electrochemical elution process the eluting solution is not in direct contact with the ion exchange material, very small volumes of the eluting solution can be used in a complete recycle mode in order to minimize the total volume of the cesium elute. In addition, the cesium is eluted as an alkaline solution that does not require neutralization with caustic to meet the tank farm specifications. Other advantages include easy incorporation of the electrochemical elution process into the present cesium recovery schemes

  9. Zotarolimus-eluting vs. sirolimus-eluting coronary stents in patients with and without acute coronary syndromes

    DEFF Research Database (Denmark)

    Thim, Troels; Maeng, Michael; Kaltoft, Anne Kjer

    2012-01-01

    To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial.......To compare clinical outcomes among patients with acute coronary syndrome treated with zotarolimus-eluting and sirolimus-eluting stents in the SORT OUT III trial....

  10. Titania nanotubes with adjustable dimensions for drug reservoir sites and enhanced cell adhesion

    International Nuclear Information System (INIS)

    Çalışkan, Nazlı; Bayram, Cem; Erdal, Ebru; Karahaliloğlu, Zeynep; Denkbaş, Emir Baki

    2014-01-01

    This study aims to generate a bactericidal agent releasing surface via nanotube layer on titanium metal and to investigate how aspect ratio of nanotubes affects drug elution time and cell proliferation. Titania nanotube layers were generated on metal surfaces by anodic oxidation at various voltage and time parameters. Gentamicin loading was carried out via simple pipetting and the samples were tested against S. aureus for the efficacy of the applied modification. Drug releasing time and cell proliferation were also tested in vitro. Titania nanotube layers with varying diameters and lengths were prepared after anodization and anodizing duration was found as the most effective parameter for amount of loaded drug and drug releasing time. Drug elution lasted up to 4 days after anodizing for 80 min of the samples, whereas release completed in 24 h when the samples were anodized for 20 min. All processed samples had bactericidal properties against S. aureus organism except unmodified titanium, which was also subjected to drug incorporation step. The anodization also enhanced water wettability and cell adhesion results. Anodic oxidation is an effective surface modification to enhance tissue–implant interactions and also resultant titania layer can act as a drug reservoir for the release of bactericidal agents. The use of implants as local drug eluting devices is promising but further in vivo testing is required. - Highlights: • Titanium surfaces were anodized and a nanotubular titania layer was obtained. • Drug eluting time was found to be increasing with anodizaton time. • Varying nanotube diameters has no effect in drug elution time but amount of incorporated drug

  11. Titania nanotubes with adjustable dimensions for drug reservoir sites and enhanced cell adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Çalışkan, Nazlı; Bayram, Cem; Erdal, Ebru; Karahaliloğlu, Zeynep; Denkbaş, Emir Baki, E-mail: denkbas@hacettepe.edu.tr

    2014-02-01

    This study aims to generate a bactericidal agent releasing surface via nanotube layer on titanium metal and to investigate how aspect ratio of nanotubes affects drug elution time and cell proliferation. Titania nanotube layers were generated on metal surfaces by anodic oxidation at various voltage and time parameters. Gentamicin loading was carried out via simple pipetting and the samples were tested against S. aureus for the efficacy of the applied modification. Drug releasing time and cell proliferation were also tested in vitro. Titania nanotube layers with varying diameters and lengths were prepared after anodization and anodizing duration was found as the most effective parameter for amount of loaded drug and drug releasing time. Drug elution lasted up to 4 days after anodizing for 80 min of the samples, whereas release completed in 24 h when the samples were anodized for 20 min. All processed samples had bactericidal properties against S. aureus organism except unmodified titanium, which was also subjected to drug incorporation step. The anodization also enhanced water wettability and cell adhesion results. Anodic oxidation is an effective surface modification to enhance tissue–implant interactions and also resultant titania layer can act as a drug reservoir for the release of bactericidal agents. The use of implants as local drug eluting devices is promising but further in vivo testing is required. - Highlights: • Titanium surfaces were anodized and a nanotubular titania layer was obtained. • Drug eluting time was found to be increasing with anodizaton time. • Varying nanotube diameters has no effect in drug elution time but amount of incorporated drug.

  12. Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

    Science.gov (United States)

    Takayama, Kazuo; Mizuguchi, Hiroyuki

    2017-02-01

    Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  13. Differentiated analysis of an everolimus-eluting stent and a paclitaxel-eluting stent among higher risk subgroups for restenosis: results from the SPIRIT II trial.

    Science.gov (United States)

    Khattab, Ahmed A; Richardt, Gert; Verin, Vitali; Kelbaek, Henning; Macaya, Carlos; Berland, Jacques; Miquel-Hebert, Karine; Dorange, Cécile; Serruys, Patrick W

    2008-03-01

    Restenosis is higher among certain subpopulations when subjected to percutaneous coronary interventions even when using drug-eluting stents. The randomised SPIRIT II trial demonstrated the superiority of the XIENCE V Everolimus Eluting Coronary Stent System over the TAXUS Paclitaxel-Eluting Stent System in terms of in-stent late loss at six months among 300 patients treated for de novo native coronary artery lesions. In this post-hoc analysis of SPIRIT II we focused on six-month angiographic outcomes of diabetic patients (n=69), left anterior descending arteries (n=149), long lesions >20 mm (n=43), small vessels B2 and C lesions (n=233). In-stent late loss was consistently less among all subgroups when treated by everolimus-eluting stents compared to paclitaxel-eluting stents: diabetics 0.15+/-0.26 mm versus 0.39+/-0.34 mm, p=0.006; LAD 0.12+/-0.23 mm versus 0.44+/-0.37 mm, pB2/C lesions 0.12+/-0.31 mm versus 0.36+/-0.36 mm, pSPIRIT II trial population.

  14. EVALUATION OF PETROLEUM HYDROCARBONS ELUTION FROM SOIL

    Directory of Open Access Journals (Sweden)

    Janina Piekutin

    2015-06-01

    Full Text Available The paper presents studies on oil removal from soil by means of water elution with a help of shaking out the contaminants from the soil. The tests were performed on simulated soil samples contaminated with a mixture of petroleum hydrocarbons. The study consisted in recording the time influence and the number of elution cycles to remove contaminants from the soil. The samples were then subject to the determination of petroleum hydrocarbons, aliphatic hydrocarbons, and BTEX compounds (benzene, toluene, ethylbenzene, xylene. Due to adding various concentrations of petroleum into particular soil samples and applying different shaking times, it was possible to find out the impact of petroleum content and sample shaking duration on the course and possibility of petroleum substances removal by means of elution process.

  15. Vascular Response of the Segments Adjacent to the Proximal and Distal Edges of the ABSORB Everolimus-Eluting Bioresorbable Vascular Scaffold

    DEFF Research Database (Denmark)

    Gogas, Bill D; Serruys, Patrick W; Diletti, Roberto

    2012-01-01

    This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS).......This study sought to investigate in vivo the vascular response at the proximal and distal edges of the second-generation ABSORB everolimus-eluting bioresorbable vascular scaffold (BVS)....

  16. Nine-month Angiographic and Two-year Clinical Follow-up of Novel Biodegradable-polymer Arsenic Trioxide-eluting Stent Versus Durable-polymer Sirolimus-eluting Stent For Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Li Shen

    2015-01-01

    Full Text Available Background: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES, compared with traditional sirolimus-eluting stent (SES. Methods: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF, and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR by telephone visit and late luminal loss (LLL at 9-month by angiographic follow-up. Results: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980. Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028. There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008. Conclusions: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

  17. Softening and elution of monomers in ethanol

    DEFF Research Database (Denmark)

    Benetti, Ana Raquel; Asmussen, Erik; Munksgaard, E Christian

    2009-01-01

    The purpose of this study was to investigate the effect of light-curing protocol on softening and elution of monomers in ethanol as measured on a model polymer. It was a further aim to correlate the measured values with previously reported data on degree of conversion and glass transition...

  18. Safety and efficacy of limus-eluting stents and balloon angioplasty for sirolimus-eluting in-stent restenosis

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Hideaki [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Mahmoudi, Michael [University of Surrey, Guildford Road, Surrey, GU2-7XH (United Kingdom); Kitabata, Hironori; Torguson, Rebecca; Chen, Fang; Satler, Lowell F.; Suddath, William O.; Pichard, Augusto D. [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Waksman, Ron, E-mail: ron.waksman@medstar.net [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States)

    2015-03-15

    Objectives: The aim of this study was to compare the safety and efficacy of everolimus-eluting stent (EES), sirolimus-eluting stent (SES), and plain old balloon angioplasty (POBA) for the treatment of SES in-stent restenosis (S-ISR). Background: The optimal treatment for drug-eluting in-stent restenosis remains controversial. Methods: The study cohort comprised 310 consecutive patients (444 lesions) who presented with S-ISR to our institution and underwent treatment with EES (43 patients), SES (102), or POBA (165). The analyzed clinical parameters were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac event (MACE) defined as the composite of death, MI, or TLR at 1-year. Results: The three groups were well matched for the conventional risk factors for coronary artery disease except for smoking. The 1-year analyzed clinical parameters were similar in the three groups: MACE (EES = 14%, SES = 18%, POBA = 20%; p = 0.65), death (EES = 2.3%, SES = 6.2%, POBA = 6.1%; p = 0.61), MI (EES = 4.8%, SES = 2.1%, POBA = 2.5%; p = 0.69), TLR (EES = 11.9%, SES = 12.1%, POBA = 24%; p = 0.78), and TVR (EES = 11.9%, SES = 24.8%, POBA = 22.2%; p = 0.23). There were no cases of definite ST. MACE-free rate was significantly lower in patients with recurrent in-stent restenosis (log-rank p = 0.006). Presentation with acute MI, number of treated lesions and a previous history of MI were found to be independent predictors of MACE. Conclusions: In patients presenting with S-ISR, treatment with implantation of an EES, SES, or POBA is associated with similar clinical outcomes. Patients presenting with recurrent ISR may have a poorer clinical outcome.

  19. Aluminum elution and precipitation in glass vials: effect of pH and buffer species.

    Science.gov (United States)

    Ogawa, Toru; Miyajima, Makoto; Wakiyama, Naoki; Terada, Katsuhide

    2015-02-01

    Inorganic extractables from glass vials may cause particle formation in the drug solution. In this study, the ability of eluting Al ion from borosilicate glass vials, and tendencies of precipitation containing Al were investigated using various pHs of phosphate, citrate, acetate and histidine buffer. Through heating, all of the buffers showed that Si and Al were eluted from glass vials in ratios almost the same as the composition of borosilicate glass, and the amounts of Al and Si from various buffer solutions at pH 7 were in the following order: citrate > phosphate > acetate > histidine. In addition, during storage after heating, the Al concentration at certain pHs of phosphate and acetate buffer solution decreased, suggesting the formation of particles containing Al. In citrate buffer, Al did not decrease in spite of the high elution amount. Considering that the solubility profile of aluminum oxide and the Al eluting profile of borosilicate glass were different, it is speculated that Al ion may be forced to leach into the buffer solution according to Si elution on the surface of glass vials. When Al ions were added to the buffer solutions, phosphate, acetate and histidine buffer showed a decrease of Al concentration during storage at a neutral range of pHs, indicating the formation of particles containing Al. In conclusion, it is suggested that phosphate buffer solution has higher possibility of forming particles containing Al than other buffer solutions.

  20. Effect of trimetazidine on recurrent angina pectoris and left ventricular structure in elderly multivessel coronary heart disease patients with diabetes mellitus after drug-eluting stent implantation: a single-centre, prospective, randomized, double-blind study at 2-year follow-up.

    Science.gov (United States)

    Xu, Xiaohan; Zhang, Weijun; Zhou, Yujie; Zhao, Yingxin; Liu, Yuyang; Shi, Dongmei; Zhou, Zhiming; Ma, Hanying; Wang, Zhijian; Yu, Miao; Ma, Qian; Gao, Fei; Shen, Hua; Zhang, Jianwei

    2014-04-01

    Trimetazidine has been shown to improve angina pectoris and left ventricular (LV) function in diabetic patients with ischaemic cardiomyopathy. The objective of this study was to evaluate the effects of trimetazidine on recurrent angina pectoris and LV structure after drug-eluting stent (DES) implantation in elderly multivessel coronary heart disease (CHD) patients with diabetes mellitus (DM) and a left ventricular ejection fraction (LVEF) of ≥ 50 %. This was a single-centre, prospective, randomized, double-blind evaluation study. Between January 2010 and September 2010, 700 CHD patients with DM who were aged ≥ 65 years and undergoing coronary angiography at An Zhen Hospital (Beijing, China) were recruited and prospectively randomized to receive trimetazidine (20 mg three times daily) or placebo after DES implantation as an addition to conventional CHD treatment. The primary end points were the incidence of recurrent angina pectoris and measures of various echocardiographic parameters, which included LVEF. At 2-year follow-up, patients in the trimetazidine group (n = 255) showed significant improvements in the incidence (P = 0.024) and severity of angina pectoris, compared with the control group, as well as silent myocardial ischaemia (P = 0.009) and angina pectoris-free survival (P = 0.011). LV function and structure in trimetazidine-treated patients were relatively stable at 2-year follow-up, while they deteriorated in the control group (n = 255) with a significant difference between groups (all P angina pectoris as well as LV function and structure in elderly multivessel CHD patients with DM.

  1. Characterization of SNARE Cleavage Products Generated by Formulated Botulinum Neurotoxin Type-A Drug Products

    Directory of Open Access Journals (Sweden)

    Jack Xie

    2010-08-01

    Full Text Available The study evaluated substrate cleavage product(s generated by three botulinum neurotoxin serotype A (BoNT/A medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198–Ala199 (normal BoNT/A cleavage is Gln197–Arg198. Arg198–Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.

  2. A proposal for a drug information database and text templates for generating package inserts

    Directory of Open Access Journals (Sweden)

    Okuya R

    2013-07-01

    Full Text Available Ryo Okuya,1 Masaomi Kimura,2 Michiko Ohkura,2 Fumito Tsuchiya3 1Graduate School of Engineering and Science, 2Faculty of Engineering, Shibaura Institute of Technology, Tokyo, 3School of Pharmacy, International University of Health and Welfare, Tokyo, Japan Abstract: To prevent prescription errors caused by information systems, a database to store complete and accurate drug information in a user-friendly format is needed. In previous studies, the primary method for obtaining data stored in a database is to extract drug information from package inserts by employing pattern matching or more sophisticated methods such as text mining. However, it is difficult to obtain a complete database because there is no strict rule concerning expressions used to describe drug information in package inserts. The authors' strategy was to first build a database and then automatically generate package inserts by embedding data in the database using templates. To create this database, the support of pharmaceutical companies to input accurate data is required. It is expected that this system will work, because these companies can earn merit for newly developed drugs to decrease the effort to create package inserts from scratch. This study designed the table schemata for the database and text templates to generate the package inserts. To handle the variety of drug-specific information in the package inserts, this information in drug composition descriptions was replaced with labels and the replacement descriptions utilizing cluster analysis were analyzed. To improve the method by which frequently repeated ingredient information and/or supplementary information are stored, the method was modified by introducing repeat tags in the templates to indicate repetition and improving the insertion of data into the database. The validity of this method was confirmed by inputting the drug information described in existing package inserts and checking that the method could

  3. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  4. Sentiment Analysis of User-Generated Content on Drug Review Websites

    Directory of Open Access Journals (Sweden)

    Na, Jin-Cheon

    2015-03-01

    Full Text Available This study develops an effective method for sentiment analysis of user-generated content on drug review websites, which has not been investigated extensively compared to other general domains, such as product reviews. A clause-level sentiment analysis algorithm is developed since each sentence can contain multiple clauses discussing multiple aspects of a drug. The method adopts a pure linguistic approach of computing the sentiment orientation (positive, negative, or neutral of a clause from the prior sentiment scores assigned to words, taking into consideration the grammatical relations and semantic annotation (such as disorder terms of words in the clause. Experiment results with 2,700 clauses show the effectiveness of the proposed approach, and it performed significantly better than the baseline approaches using a machine learning approach. Various challenging issues were identified and discussed through error analysis. The application of the proposed sentiment analysis approach will be useful not only for patients, but also for drug makers and clinicians to obtain valuable summaries of public opinion. Since sentiment analysis is domain specific, domain knowledge in drug reviews is incorporated into the sentiment analysis algorithm to provide more accurate analysis. In particular, MetaMap is used to map various health and medical terms (such as disease and drug names to semantic types in the Unified Medical Language System (UMLS Semantic Network.

  5. Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Liu R

    2012-10-01

    Full Text Available Rong Liu,1,2,* Yusi Lai,1,* Bin He,1 Yuan Li,1 Gang Wang,1 Shuang Chang,1 Zhongwei Gu1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China; 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China*These authors contributed equally to this paperAbstract: A new approach of fabricating supramolecular nanoparticles generated by self-assembly polyrotaxanes for antitumor drug delivery has been reported. Cinnamic-acid-modified poly(ethylene glycol chains were threaded in a-cyclodextrins to form polyrotaxanes. The polyrotaxanes self-assembled supramolecular nanoparticles. The morphology of the nanoparticles was changed from nanovesicle to micelle after the antitumor drug, doxorubicin, was loaded. The release profile of the drug-loaded nanoparticles was investigated, and it was found that the sustaining release time could last for 32 hours. The drug-loaded nanoparticles were co-cultured with mouse 4T1 breast cancer cells with a drug concentration of 10 µg/mL; the cell survival rate was 3.3% after a 72-hour incubation. In an in vivo study of breast cancer in a mouse model, the drug-loaded nanoparticles were injected in the tail veins of mice with a dose of 5 mg/kg body weight. The tumor inhibition rate of drug-loaded nanoparticles was 53%, which was better than that of doxorubicin hydrochloride. The cardiac toxicity of doxorubicin was decreased greatly after the encapsulation into supramolecular polyrotaxane nanoparticles.Keywords: polyrotaxane, self-assembly, nanoparticle, doxorubicin, supermolecular

  6. Elution of Monomers from Provisional Composite Materials

    Directory of Open Access Journals (Sweden)

    Simon Daniel Schulz

    2015-01-01

    Full Text Available The aim of this study was to evaluate the elution of substances from different materials used for the manufacturing of temporary indirect restorations, after storage in saliva and ethanol 75%. 10 samples of three chemically cured materials (Protemp 3 Garant, Systemp.c&b, and Trim and one light-cured material (Clip F were stored in saliva and ethanol 75% for 24 h, 7, and days 28 days. From the storage media at each time period, samples were prepared and analysed by LC-MS/MS, in order to access the elution of monomers. The results differed among the materials (P ≤ 0.05. No monomers were detected in the samples of Protemp 3 Garant and Clip F. Substances were detected only in ethanol samples of Systemp.c&b and Trim. The amount of BisGMA, TEGDMA, and UDMA 2 released from Systemp.c&b was higher compared to Trim. Storage time affected the release of substances (P ≤ 0.05. The highest release was observed within the first 24 h. It can be concluded that provisional resin composite materials do not show high release of monomers and this release is material dependent. However, the detection of additional peaks during the analysis, suggesting the formation of by-products of the eluted substances, may not be in favour of these materials with respect to their toxicity.

  7. Next generation human skin constructs as advanced tools for drug development.

    Science.gov (United States)

    Abaci, H E; Guo, Zongyou; Doucet, Yanne; Jacków, Joanna; Christiano, Angela

    2017-11-01

    Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation. Development of biomimetic in vitro human skin models with these physiological functions provides a new tool for drug discovery, disease modeling, regenerative medicine and basic research for skin biology. This goal, however, has long been delayed by the limited availability of different cell types, the challenges in establishing co-culture conditions, and the ability to recapitulate the 3D anatomy of the skin. Recent breakthroughs in induced pluripotent stem cell (iPSC) technology and microfabrication techniques such as 3D-printing have allowed for building more reliable and complex in vitro skin models for pharmaceutical screening. In this review, we focus on the current developments and prevailing challenges in generating skin constructs with vasculature, skin appendages such as hair follicles, pigmentation, immune response, innervation, and hypodermis. Furthermore, we discuss the promising advances that iPSC technology offers in order to generate in vitro models of genetic skin diseases, such as epidermolysis bullosa and psoriasis. We also discuss how future integration of the next generation human skin constructs onto microfluidic platforms along with other tissues could revolutionize the early stages of drug development by creating reliable evaluation of patient-specific effects of pharmaceutical agents. Impact statement Skin is a complex tissue that hosts various

  8. Effect of biolimus-eluting stents with biodegradable polymer vs bare-metal stents on cardiovascular events among patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Räber, Lorenz; Kelbæk, Henning; Ostojic, Miodrag

    2012-01-01

    The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).......The efficacy and safety of drug-eluting stents compared with bare-metal stents remains controversial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI)....

  9. Titania nanotubes with adjustable dimensions for drug reservoir sites and enhanced cell adhesion.

    Science.gov (United States)

    Çalışkan, Nazlı; Bayram, Cem; Erdal, Ebru; Karahaliloğlu, Zeynep; Denkbaş, Emir Baki

    2014-02-01

    This study aims to generate a bactericidal agent releasing surface via nanotube layer on titanium metal and to investigate how aspect ratio of nanotubes affects drug elution time and cell proliferation. Titania nanotube layers were generated on metal surfaces by anodic oxidation at various voltage and time parameters. Gentamicin loading was carried out via simple pipetting and the samples were tested against S. aureus for the efficacy of the applied modification. Drug releasing time and cell proliferation were also tested in vitro. Titania nanotube layers with varying diameters and lengths were prepared after anodization and anodizing duration was found as the most effective parameter for amount of loaded drug and drug releasing time. Drug elution lasted up to 4 days after anodizing for 80 min of the samples, whereas release completed in 24 h when the samples were anodized for 20 min. All processed samples had bactericidal properties against S. aureus organism except unmodified titanium, which was also subjected to drug incorporation step. The anodization also enhanced water wettability and cell adhesion results. Anodic oxidation is an effective surface modification to enhance tissue-implant interactions and also resultant titania layer can act as a drug reservoir for the release of bactericidal agents. The use of implants as local drug eluting devices is promising but further in vivo testing is required. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Innovative Elution Processes for Recovering Uranium from Seawater

    International Nuclear Information System (INIS)

    Wai, Chien; Tian, Guoxin; Janke, Christopher

    2014-01-01

    Utilizing amidoxime-based polymer sorbents for extraction of uranium from seawater has attracted considerable interest in recent years. Uranium collected in the sorbent is recovered typically by elution with an acid. One drawback of acid elution is deterioration of the sorbent which is a significant factor that limits the economic competitiveness of the amidoxime-based sorbent systems for sequestering uranium from seawater. Developing innovative elution processes to improve efficiency and to minimize loss of sorbent capacity become essential in order to make this technology economically feasible for large-scale industrial applications. This project has evaluated several elution processes including acid elution, carbonate elution, and supercritical fluid elution for recovering uranium from amidoxime-based polymer sorbents. The elution efficiency, durability and sorbent regeneration for repeated uranium adsorption- desorption cycles in simulated seawater have been studied. Spectroscopic techniques are used to evaluate chemical nature of the sorbent before and after elution. A sodium carbonate-hydrogen peroxide elution process for effective removal of uranium from amidoxime-based sorbent is developed. The cause of this sodium carbonate and hydrogen peroxide synergistic leaching of uranium from amidoxime-based sorbent is attributed to the formation of an extremely stable uranyl peroxo-carbonato complex. The efficiency of uranium elution by the carbonate-hydrogen peroxide method is comparable to that of the hydrochloric acid elution but damage to the sorbent material is much less for the former. The carbonate- hydrogen peroxide elution also does not need any elaborate step to regenerate the sorbent as those required for hydrochloric acid leaching. Several CO2-soluble ligands have been tested for extraction of uranium from the sorbent in supercritical fluid carbon dioxide. A mixture of hexafluoroacetylacetone and tri-n-butylphosphate shows the best result but uranium

  11. Innovative Elution Processes for Recovering Uranium from Seawater

    Energy Technology Data Exchange (ETDEWEB)

    Wai, Chien [Univ. of Idaho, Moscow, ID (United States); Tian, Guoxin [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Janke, Christopher [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-05-29

    Utilizing amidoxime-based polymer sorbents for extraction of uranium from seawater has attracted considerable interest in recent years. Uranium collected in the sorbent is recovered typically by elution with an acid. One drawback of acid elution is deterioration of the sorbent which is a significant factor that limits the economic competitiveness of the amidoxime-based sorbent systems for sequestering uranium from seawater. Developing innovative elution processes to improve efficiency and to minimize loss of sorbent capacity become essential in order to make this technology economically feasible for large-scale industrial applications. This project has evaluated several elution processes including acid elution, carbonate elution, and supercritical fluid elution for recovering uranium from amidoxime-based polymer sorbents. The elution efficiency, durability and sorbent regeneration for repeated uranium adsorption- desorption cycles in simulated seawater have been studied. Spectroscopic techniques are used to evaluate chemical nature of the sorbent before and after elution. A sodium carbonate-hydrogen peroxide elution process for effective removal of uranium from amidoxime-based sorbent is developed. The cause of this sodium carbonate and hydrogen peroxide synergistic leaching of uranium from amidoxime-based sorbent is attributed to the formation of an extremely stable uranyl peroxo-carbonato complex. The efficiency of uranium elution by the carbonate-hydrogen peroxide method is comparable to that of the hydrochloric acid elution but damage to the sorbent material is much less for the former. The carbonate- hydrogen peroxide elution also does not need any elaborate step to regenerate the sorbent as those required for hydrochloric acid leaching. Several CO2-soluble ligands have been tested for extraction of uranium from the sorbent in supercritical fluid carbon dioxide. A mixture of hexafluoroacetylacetone and tri-n-butylphosphate shows the best result but uranium

  12. Cross-generational effects on gender differences in psychoactive drug abuse and dependence.

    Science.gov (United States)

    Holdcraft, Laura C; Iacono, William G

    2004-05-10

    Studies of patients with cocaine and heroin use disorders have shown gender differences in prevalence, course, and outcome. These differences may be decreasing in successive generations. Less is known about gender differences in course and symptomatology for other illicit drug use disorders, especially in community samples. Participants (1323 men and 1384 women) who were biological or step-parents of twins and born in the 1940-1960s, from the Minnesota Twin-Family Study (MTFS) were divided into two cohorts based on the median birth year. A structured interview was used to assess DSM-III-R cannabis, amphetamine, cocaine and hallucinogen use disorders. There was a higher prevalence of each of these drug disorders and earlier onset of cannabis and amphetamine use disorders in later-born participants. For most drug use disorder categories, men and women were similar with respect to age of onset and severity of disorder but women had a shorter course of drug use disorders. Women with amphetamine disorders were atypical with respect to having a higher frequency of use but similar number of lifetime uses compared to men, and more emotional effects of amphetamine intoxication than men. In addition, women with amphetamine disorders were more likely to have anorexia nervosa than those without amphetamine disorders. These results have several implications for prevention, etiology and treatment.

  13. Drug utilisation review (DUR) of the third generation cephalosporins. Focus on ceftriaxone, ceftazidime and cefotaxime.

    Science.gov (United States)

    Adu, A; Armour, C L

    1995-09-01

    Six parenteral third generation cephalosporins have been introduced into clinical use in the past 10 years. The 3 most frequently available agents are cefotaxime, ceftriaxone and ceftazidime. These 3 third generation cephalosporins are characterised by a broad spectrum of activity and increased stability to beta-lactamases compared with the first and second generation cephalosporins. However, there are growing numbers of reports of resistance to these agents with increasing use. The major differences in the properties of the 3 agents are the long half-life of ceftriaxone and its dual route of elimination. Ceftazidime is best restricted to Pseudomonas aeruginosa infections where other agents are contraindicated or ineffective. Cefotaxime and ceftriaxone can be used in nosocomial Gram-negative infections where P. aeruginosa can be ruled out. The types and incidences of adverse drug reactions are not different for the 3 agents. A number of drug utilisation review (DUR) studies of these agents in the hospital setting have reported a considerable incidence of inappropriate use and substantial avoidable costs. There are methodological problems with most of the DUR studies, especially the criteria and the methods of cost estimation. The use of pharmacoeconomic methodology could ensure more realistic cost estimation; however, outcome data are, in most cases, not available.

  14. Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns.

    Science.gov (United States)

    Luise, Nicola; Wyatt, Paul

    2018-05-07

    Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. This communication highlights the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The impact of engagement in street-based income generation activities on stimulant drug use cessation among people who inject drugs.

    Science.gov (United States)

    Ti, Lianping; Richardson, Lindsey; DeBeck, Kora; Nguyen, Paul; Montaner, Julio; Wood, Evan; Kerr, Thomas

    2014-08-01

    Despite the growing prevalence of illicit stimulant drug use internationally, and the widespread involvement of people who inject drugs (IDU) within street-based drug markets, little is known about the impact of different types of street-based income generation activities on the cessation of stimulant use among IDU. Data were derived from an open prospective cohort of IDU in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards regression to examine the effect of different types of street-based income generation activities (e.g., sex work, drug dealing, and scavenging) on time to cessation of stimulant use. Between December, 2005 and November, 2012, 887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal methamphetamine) were prospectively followed-up for a median duration of 47 months. In Kaplan-Meier analyses, compared to those who did not engage in street-based income generation activities, participants who reported sex work, drug dealing, scavenging, or more than one of these activities were significantly less likely to report stimulant drug use cessation (all pstreet-based income generation activity remained significantly associated with a slower time to stimulant drug cessation (all p<0.005). Our findings highlight the urgent need for strategies to address stimulant dependence, including novel pharmacotherapies. Also important, structural interventions, such as low-threshold employment opportunities, availability of supportive housing, legal reforms regarding drug use, and evidence-based approaches that reduce harm among IDU are urgently required. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Toxic vessel reaction to an absorbable polymer-based paclitaxel-eluting stent in pig coronary arteries.

    Science.gov (United States)

    Jabara, Refat; Chronos, Nicolas; Tondato, Fernando; Conway, Damian; Molema, Warner; Park, Kenneth; Mabin, Tom; King, Spencer; Robinson, Keith

    2006-08-01

    The goal of this study was to evaluate a new drug-eluting stent (DES) comprising a bioabsorbable polymer eluting a moderate dose of paclitaxel in a clinically relevant animal model. Although DES limit restenosis, adverse vascular pathologies and toxicities continue to be of major concern. Optimization of DES components, especially completely absorbable polymers, may reduce these toxicities. Bare-metal (BM), absorbable polymer coating only (POLY), and polymer-based paclitaxel-eluting (PACL) stents were implanted in porcine coronary arteries using intravascular ultrasound (IVUS) to optimize stent apposition. The dose density of paclitaxel was 0.30-0.35 mcg/mm2, with in vitro elution studies demonstrating a gradual elution over 6-8 weeks. The animals were terminated at 1 week, 1 month and 3 months. Histopathologic and histomorphometric analyses were perform. The arteries with PACL showed extensive smooth muscle cell necrosis at 1 week and poor apposition of stent struts at 1 month (malapposition measured as gap width between strut and internal elastic lamina), with greater gap width compared to the BM and POLY groups (0.22 mm +/- 0.02 vs. 0.03 mm +/- 0.02 and 0.02 mm +/- 0.01, respectively; p stent malapposition and late neointimal thickening. Since the therapeutic window for paclitaxel may be narrower than currently inferred, thorough preclinical testing coupled with the polymer development process for stents eluting paclitaxel is needed.

  17. Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice.

    Science.gov (United States)

    Sato, Taiki; Kishimoto, Yu; Asakawa, Sanki; Mizuno, Natsumi; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2016-07-01

    Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24h. NiCl2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl2 and further potentiated by PGE2. Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be

  18. Paclitaxel-eluting versus sirolimus-eluting stents in diabetes mellitus: a report from the National Heart, Lung, and Blood Institute Dynamic Registry.

    Science.gov (United States)

    Wolf, William M; Vlachos, Helen A; Marroquin, Oscar C; Lee, Joon S; Smith, Conrad; Anderson, William D; Schindler, John T; Holper, Elizabeth M; Abbott, J Dawn; Williams, David O; Laskey, Warren K; Kip, Kevin E; Kelsey, Sheryl F; Mulukutla, Suresh R

    2010-02-01

    Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry. Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed. PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

  19. Treatments that generate higher number of adverse drug reactions and their symptoms

    Directory of Open Access Journals (Sweden)

    Lucía Fernández-López

    2015-12-01

    Full Text Available Objectives: Adverse drug reactions (ADRs are an important cause of morbidity and mortality worldwide and generate high health costs. Therefore, the aims of this study were to determine the treatments which produce more ADRs in general population and the main symptoms they generate. Methods: An observational, cross-sectional study consisting in performing a self-rated questionnaire was carried out. 510 patients were asked about the treatments, illnesses and ADRs, they had suffered from. Results: 26.7% of patients had suffered from some ADR. Classifying patients according to the type of prescribed treatment and studying the number of ADR that they had, we obtained significant differences (p ≤ 0.05 for treatments against arthrosis, anemia and nervous disorders (anxiety, depression, insomnia. Moreover, determining absolute frequencies of these ADRs appearance in each treatment, higher frequencies were again for drugs against arthrosis (22.6% of patients treated for arthrosis suffered some ADR, anemia (14.28%, nerve disorders (13.44% and also asthma (16%. Regarding the symptoms produced by ADRs, the most frequent were gastrointestinal (60% of patients who suffered an ADR, had gastrointestinal symptoms and nervous alterations (dizziness, headache, sleep disturbances etc (24.6%. Conclusion: Therapeutic groups which produce more commonly ADRs are those for arthrosis, anemia, nervous disorders and asthma. In addition, symptoms which are generated more frequently are gastrointestinal and nervous problems. This is in accordance with the usual side effects of mentioned treatments. Health professionals should be informed about it, so that they would be more alert about a possible emergence of an ADR in these treatments. They also could provide enough information to empower patients and thus, they probably could detect ADR events. This would facilitate ADR detection and would avoid serious consequences generated to both patients' health and health economics.

  20. The Road from Host-Defense Peptides to a New Generation of Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Alicia Boto

    2018-02-01

    Full Text Available Host-defense peptides, also called antimicrobial peptides (AMPs, whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1 broad spectrum of activity; (2 unlike classic antibiotics, they induce very little resistance; (3 they act synergically with conventional antibiotics; (4 they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.

  1. Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery.

    Science.gov (United States)

    Young, Paul M; Traini, Daniela; Ong, Hui Xin; Granieri, Angelo; Zhu, Bing; Scalia, Santo; Song, Jie; Spicer, Patrick T

    2017-10-01

    Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips. Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive's potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient. The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray. Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.

  2. Overtime evaluation of the vascular HEALing process after everolimus-eluting stent implantation by optical coherence tomography. The HEAL-EES study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuki, Shuji; Brugaletta, Salvatore, E-mail: sabrugal@clinic.ub.es; Sabaté, Manel; Shiratori, Yoshitaka; Gomez-Monterrosas, Omar; Scalone, Giancarla; Romero-Villafañe, Sebastian; Hernández-Enríquez, Marco; Freixa, Xavier; Martín-Yuste, Victoria; Masotti, Mónica

    2016-06-15

    Purpose: Second-generation drug-eluting stent (DES) have shown a better safety and efficacy as compared to first generation DES due to an improved vascular healing process. This process has not been so far evaluated in vivo in an overtime fashion by optical coherent tomography (OCT). We sought to evaluate the vascular healing process after everolimus-eluting stent (EES) implantation at 6, 9 and 12 months, by OCT. Methods: Consecutive 36 patients undergoing percutaneous coronary intervention with EES were randomized 1:1:1 to receive OCT imaging at 6 (group A), 9 (group B) or 12-month follow-up (group C). One patient from group C was excluded because of target lesion revascularization at 1-month, whereas 5 patients withdraw the informed consent. Finally, 30 patients were analyzed. Results: Neointimal thickness was not different between 3 groups (group A: 99.50 [94.06–127.79] μm, group B: 107.26 [83.48–133.59] μm, group C: 127.67 [102.51–138.49] μm; p = 0.736). Although the percentage of “uncovered struts” was significantly higher in group A as compared to the other groups (8.0% vs. 4.4% vs. 2.9%, respectively; p = 0.180), the ratio of uncovered to total struts per section < 30% was similar between 3 groups (0.3% vs. 0.3% vs. 0%, respectively; p = 1.000). Conclusion: Healing process following EES implantation seems almost completed at 6-month follow-up. These data, which need to be confirmed in a larger study, may support the decision to shorten dual antiplatelet therapy. - Highlights: • Healing process following everolimus-eluting stent implantation is complete at 6-month • There are no difference in RUTTS > 30% between 6, 9 and 12 months analyses. • This finding may support to shorten dual antiplatelet therapy in this context.

  3. Serial assessment by optical coherence tomography of early and late vascular responses after implantation of an absorbable-coating Sirolimus-Eluting stent (from the first-in-human DESSOLVE I trial).

    Science.gov (United States)

    Attizzani, Guilherme F; Bezerra, Hiram G; Ormiston, John; Wang, Wei; Donohoe, Dennis; Wijns, William; Costa, Marco A

    2013-11-15

    The initial enthusiasm caused by the potent antirestenotic effect of early generation drug-eluting stents was recently plagued by concerns regarding their safety profile. Investigators worldwide were stimulated, therefore, to seek for improvement in drug-eluting stent technology, such as eliminating their permanent polymer blamed for vascular inflammation and delayed healing. Optical coherence tomography (OCT) assessments of stent-vessel interactions are used as a surrogate for vessel healing after DES implantation. Herewith, we report serial OCT assessments of vascular reactions to the implantation of a novel absorbable polymer sirolimus-eluting stent (MiStent). In total, 30 patients were included. At 4-, 6-, and 8-month follow-up, different groups of 10 patients underwent OCT imaging, whereas all the patients had OCT assessments scheduled at 18-month follow-up. A total of 13,569 stent struts were analyzed. Low rates of uncovered (14.34 ± 15.35%, 6.62 ± 10.93%, 3.51 ± 2.87%, and 0.84 ± 1.15%, respectively, p stent struts coupled with thin and increasingly homogenous neointimal proliferation were demonstrated. Neointimal area increased from 4- to 8-month follow-up (0.46 ± 0.29 and 1.12 ± 0.73 mm(2), respectively, p stent struts (8.8%, 3.1%, 0.3%, and 0%, respectively, p absorbable polymer sirolimus-eluting stent-vessel interactions up to 18-month follow-up. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions.

    Science.gov (United States)

    Thongnopkoon, Thanu; Puttipipatkhachorn, Satit

    2017-07-01

    This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15 min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500 nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5 µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.

  5. Insights into Integrated Lead Generation and Target Identification in Malaria and Tuberculosis Drug Discovery.

    Science.gov (United States)

    Okombo, John; Chibale, Kelly

    2017-07-18

    New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery. This Account recaps the existing challenges facing antimalarial and antituberculosis drug discovery, including limitations associated with experimental animal models as well as biological complexities intrinsic to the causative pathogens. We enlist various highlights from a body of work within our research group aimed at identifying and characterizing new chemical leads, and navigating these challenges to contribute toward the global drug discovery and development pipeline in malaria and tuberculosis. We describe a catalogue of in-house efforts toward deriving safe and efficacious preclinical drug development candidates via cell-based medicinal chemistry optimization of phenotypic whole-cell medium and high throughput screening hits sourced from various small molecule chemical libraries. We also provide an appraisal of target-based screening, as invoked in our laboratory for mechanistic evaluation of the hits generated, with particular focus on the enzymes within the de novo pyrimidine biosynthetic and hemoglobin degradation pathways, the latter constituting a heme detoxification process and an associated cysteine

  6. In Vivo and In Vitro Elution of Analgesics from Multilayered Poly(D,L-lactide-co-glycolide Nanofibers Incorporated Ureteral Stents

    Directory of Open Access Journals (Sweden)

    Yi-Chia Lin

    2018-01-01

    Full Text Available We develop novel analgesic-eluting nanofiber-incorporated ureteral stents that offer sustained release of lidocaine and ketorolac for local drug delivery. Lidocaine and poly(D,L-lactide-co-glycolide (PLGA were dissolved in hexafluoroisopropanol and were electrospun into nonwoven nanofibers onto the surface of ureteral stents. This was followed by electrospinning of another layer of PLGA nanofibers containing ketorolac. Electrospun drug-loaded nanofibers were then characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle analysis. In addition, the elution behavior characteristics of the analgesics, both in vivo and in vitro, from the nanofiber-incorporated stents were evaluated. Experimental results indicate that the analgesic-eluting ureteral stents could liberate high strengths of analgesics in vitro and in vivo for at least 50 and 30 days, respectively. The analgesic-eluting nanofiber-incorporated ureteral stents are potentially applicable for alleviating the discomfort associated with stent implant.

  7. Creative Destruction: Next Generation Sequencing in Drug Development, Formulary Evaluations and Pricing

    Directory of Open Access Journals (Sweden)

    Paul C Langley

    2016-11-01

    Full Text Available Next generation sequencing (NGS has the potential to disrupt not only the accepted process of drug development but also the hurdles a drug manufacturer would be expected to face in securing formulary approval and a possible premium price for the new compound. The purpose of this commentary is to consider the role of NGS in this process, one which is characterized as a process of creative destruction, where adoption of NGS in personalized medicine sets in train a mechanism of incessant product and process review. A mechanism driven by continuing modifications and extensions to NGS platforms as our understanding of the role of mutations and mutation load in therapy choice expands. At the same time this mechanism has significant implications for the continued revision of treatment guidelines and their adoption of NGS as integral parts of the treatment pathway. There are, however, a number of unresolved issues which have to be addressed. These include the choice of NGS platform, barriers to integrating evidence to support NGS-based therapy choices in treatment guidelines, the implications of NGS for drug development and the modification or rejection of current trial structures, the integration of comorbid disease states and the standards that formulary committees should adopt to evaluate NGS claims. The overarching theme, however, is the need to invest in a robust and credible evidence base. While we are a long way from achieving this, the focus must be on putting claims for therapy choice forward that are credible, evaluable and replicable.   Type: Commentary

  8. A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore.

    Science.gov (United States)

    López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Pérez-Nieto, Miguel Ángel; Alamo, Cecilio

    2014-01-01

    A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors 'atypic* antipsychotic*', 'second-generation antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone', 'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride', 'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and 'blonanserin' in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal(4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature.

  9. A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial.

    Science.gov (United States)

    de Winter, Robbert J; Katagiri, Yuki; Asano, Taku; Milewski, Krzysztof P; Lurz, Philipp; Buszman, Pawel; Jessurun, Gillian A J; Koch, Karel T; Troquay, Roland P T; Hamer, Bas J B; Ophuis, Ton Oude; Wöhrle, Jochen; Wyderka, Rafał; Cayla, Guillaume; Hofma, Sjoerd H; Levesque, Sébastien; Żurakowski, Aleksander; Fischer, Dieter; Kośmider, Maciej; Goube, Pascal; Arkenbout, E Karin; Noutsias, Michel; Ferrari, Markus W; Onuma, Yoshinobu; Wijns, William; Serruys, Patrick W

    2018-02-03

    MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50-3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45

  10. Hypotonic elution, a new desorption principle in immunoadsorbent chromatography

    DEFF Research Database (Denmark)

    Danielsen, Erik Michael; Sjöström, H; Norén, O

    1982-01-01

    of finding an efficient means of elution which is not denaturing to neither the purified enzyme nor the immunoadsorbent column. Common properties of the microvillar enzymes with regard to amphiphilicity, glycosylation or subunit composition could hypothetically account for the similar elution properties...

  11. Enhanced drug delivery capabilities from stents coated with absorbable polymer and crystalline drug

    OpenAIRE

    Carlyle, Wenda C.; McClain, James B.; Tzafriri, Abraham R.; Bailey, Lynn; Zani, Brett G.; Markham, Peter M.; Stanley, James R.L.; Edelman, Elazer R.

    2012-01-01

    Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-p...

  12. Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

    Science.gov (United States)

    Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

    2017-10-01

    The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

  13. Analyzing user-generated online content for drug discovery: development and use of MedCrawler.

    Science.gov (United States)

    Helfenstein, Andreas; Tammela, Päivi

    2017-04-15

    Ethnopharmacology, or the scientific validation of traditional medicine, is a respected starting point in drug discovery. Home remedies and traditional use of plants are still widespread, also in Western societies. Instead of perusing ancient pharmacopeias, we developed MedCrawler, which we used to analyze blog posts for mentions of home remedies and their applications. This method is free and accessible from the office computer. We developed MedCrawler, a data mining tool for analyzing user-generated blog posts aiming to find modern 'traditional' medicine or home remedies. It searches user-generated blog posts and analyzes them for correlations between medically relevant terms. We also present examples and show that this method is capable of delivering both scientifically validated uses as well as not so well documented applications, which might serve as a starting point for follow-up research. Source code is available on GitHub at {{ https://github.com/a-hel/medcrawler }}. paivi.tammela@helsinki.fi. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  14. Impact of polymer formulations on neointimal proliferation after zotarolimus-eluting stent with different polymers: insights from the RESOLUTE trial.

    Science.gov (United States)

    Waseda, Katsuhisa; Ako, Junya; Yamasaki, Masao; Koizumi, Tomomi; Sakurai, Ryota; Hongo, Yoichiro; Koo, Bon-Kwon; Ormiston, John; Worthley, Stephen G; Whitbourn, Robert J; Walters, Darren L; Meredith, Ian T; Fitzgerald, Peter J; Honda, Yasuhiro

    2011-06-01

    Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; Ppolymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents. The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

  15. Efetividade e segurança dos stents farmacológicos em um serviço de cardiologia em Curitiba-PR Efectividad y seguridad de los Stents farmacológicos en un servicio de cardiología en Curitiba-PR Effectiveness and safety of drug-eluting stents in a cardiology clinic in Curitiba, PR, Brazil

    Directory of Open Access Journals (Sweden)

    Chiu Yun Yu Braga

    2010-07-01

    . De esos pacientes, 85 (41,87% eran asintomáticos, y 146 (71,92%, multiarteriales. En las características de las lesiones, 77,45% fueron B2/C (AHA/ACC. Taxus fue implantado en 73,62% de los pacientes. En 381 (81,96%, se constataron stents con diámetro > 2,5 mm. El largo del stent era de BACKGROUND: The effectiveness and safety of drug-eluting stents (DES have still been questioned. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of these stents, as well as the incidence of target lesion revascularization (TLR, in addition to identifying possible variables influencing the need for TLR. METHODS: A total of 203 patients from Hospital Costantini who were clinically followed up for one to 3 years were selected. RESULTS: The sample characteristics were as follows: 470 lesions; 171 (84.24% male patients; 54 (26.6% had diabetes; 131 (64.35% had hypertension; 127 (62.56%, dyslipidemia; 40 (19.70% were smokers; and 79 (38.92% had a family history of coronary artery disease. Also: 49 (24.14% patients presented with stable angina; 58 (28.57%, unstable angina; and 6 (2.96%, myocardial infarction. Eighty five (41.87% patients were asymptomatic, and 146 (71.92%, had multivessel disease. As for the characteristics of the lesions, 77.45% were B2/C (AHA/ACC. Taxus was implanted in 73.62% of the patients. Stents with diameter > 2.5 mm were used in 381 (81.96% patients. The stent length was < 30 mm in 67.87% of the lesions, with a mean of 2.3 stents per patient. After follow-up, 19 patients (9.3% underwent TLR. Four patients died (1.97%, two of them of MI (0.98%, one of stroke (0.49%, and one of abdominal aneurysm (0.49%. Also, one patient died of late thrombosis (0.49%, and one of reinfarction (0.49%. In the statistical analysis carried out, only the bifurcation lesions variable reached values close to the statistical significance level, with p < 0.06. CONCLUSION: In conclusion, drug-eluting stents have good effectiveness and safety profiles; the

  16. Development of epigallocatechin gallate-eluting polymeric stent and its physicochemical, biomechanical and biological evaluations

    International Nuclear Information System (INIS)

    Han, Dong-Wook; Lee, Jun Jae; Jung, Duk-Young; Park, Jong-Chul; Hyon, Suong-Hyu

    2009-01-01

    Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, hypersensitivity reactions caused by their nonresorbable polymer coatings and bare-metal stents may result in serious clinical sequelae. Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, has been shown to exert anti-thrombotic, anti-inflammatory and anti-proliferative activities. In this study, it was hypothesized that sustainedly released EGCG from biodegradable poly(lactide-co-ε-caprolactone, PLCL) would suppress the proliferation of vascular smooth muscle cells (VSMCs). EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG was uniformly dispersed into E-PLCL and sustainedly released for periods up to 7 days by controlled diffusion rather than PLCL degradation. Moreover, EGCG did not affect tensile strength at break, but significantly increased the elastic modulus of PLCL. The proliferation of VSMCs onto E-PLCL was significantly suppressed although the cell attachment onto E-PLCL had been higher than that onto PLCL. On the other hand, EGCG-eluting polymeric stents were prepared with neither cracks nor webbings between struts, and their structural integrity was maintained without delamination or destruction. These results suggest that E-PLCL can be potentially applied for fabricating an EGCG-eluting vascular stent, namely an EGCG-eluting polymeric stent, or even an EGCG-releasing polymer-coated metal stent, to prevent thrombosis, inflammation and in-stent restenosis.

  17. Development of epigallocatechin gallate-eluting polymeric stent and its physicochemical, biomechanical and biological evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dong-Wook [Department of Nanomedical Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan 609-735 (Korea, Republic of); Lee, Jun Jae [Division of Advanced Fibro-Science, Kyoto Institute of Technology, Kyoto 606-8585 (Japan); Jung, Duk-Young [Senior Products Industrial Center, Busan Techno-Park, Busan-617-030 (Korea, Republic of); Park, Jong-Chul [Cellbiocontrol Laboratory, Department of Medical Engineering, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Hyon, Suong-Hyu, E-mail: nanohan@pusan.ac.k, E-mail: biogen@frontier.kyoto-u.ac.j [Department of Medical Simulation Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507 (Japan)

    2009-08-15

    Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, hypersensitivity reactions caused by their nonresorbable polymer coatings and bare-metal stents may result in serious clinical sequelae. Epigallocatechin-3-O-gallate (EGCG), the predominant catechin from tea, has been shown to exert anti-thrombotic, anti-inflammatory and anti-proliferative activities. In this study, it was hypothesized that sustainedly released EGCG from biodegradable poly(lactide-co-epsilon-caprolactone, PLCL) would suppress the proliferation of vascular smooth muscle cells (VSMCs). EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG was uniformly dispersed into E-PLCL and sustainedly released for periods up to 7 days by controlled diffusion rather than PLCL degradation. Moreover, EGCG did not affect tensile strength at break, but significantly increased the elastic modulus of PLCL. The proliferation of VSMCs onto E-PLCL was significantly suppressed although the cell attachment onto E-PLCL had been higher than that onto PLCL. On the other hand, EGCG-eluting polymeric stents were prepared with neither cracks nor webbings between struts, and their structural integrity was maintained without delamination or destruction. These results suggest that E-PLCL can be potentially applied for fabricating an EGCG-eluting vascular stent, namely an EGCG-eluting polymeric stent, or even an EGCG-releasing polymer-coated metal stent, to prevent thrombosis, inflammation and in-stent restenosis.

  18. Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial.

    Science.gov (United States)

    Serruys, Patrick W; Farooq, Vasim; Kalesan, Bindu; de Vries, Ton; Buszman, Pawel; Linke, Axel; Ischinger, Thomas; Klauss, Volker; Eberli, Franz; Wijns, William; Morice, Marie Claude; Di Mario, Carlo; Corti, Roberto; Antoni, Diethmar; Sohn, Hae Y; Eerdmans, Pedro; Rademaker-Havinga, Tessa; van Es, Gerrit-Anne; Meier, Bernhard; Jüni, Peter; Windecker, Stephan

    2013-08-01

    This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority 1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B

    2017-01-01

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Production and setting of fractional elution facility for recovery of useful rare metals from seawater

    International Nuclear Information System (INIS)

    Seko, Noriaki; Kasai, Noboru; Tamada, Masao; Hasegawa, Shin; Katakai, Akio

    2005-01-01

    In September 1999, we have soaked 200 kg of fibrous amidoxime absorbents, synthesized by radiation-induced graft polymerization, into seawater to evaluate their performance. Fractional elution facility was set effectively to elute the rare metals on adsorbents in Mutsu-Establishment. This facility consists of two parts of pre-washing and elution. The present report dealt with planning, manufacture and setting of fractional facility. Marine organism and slime on adsorbent cassette (290 x 295 x 160 mm) were washed out and every 72 cassettes were set in elution unit (1210 x 1210 x H1460 mm) with nonwoven materials as a packing to avoid elution loss. In the elution process alkaline and alkaline earth metals were eluted with low concentration hydrochloric acid (0.01M) and rare metals were eluted with high concentration (0.5 M) after the packing of elution unit into fractional elution facility. Adsorbent cassettes were regenerated with alkaline solution after elution procedure. (author)

  1. The Promus Premier everolimus-eluting platinum chromium stent with durable polymer evaluated in a real world all-comer population in Rotterdam cardiology hospital (the P-SEARCH registry)

    NARCIS (Netherlands)

    Lemmert, M.E.; Mieghem, N.M. van; Geuns, R.J.M. van; Diletti, R.; Bommel, R.J. van; Domburg, R.T. van; Jaegere, P.P. de; Regar, E.; Zijlstra, F.; Boersma, E.; Daemen, J.

    2017-01-01

    BACKGROUND: A new-generation everolimus eluting platinum-chromium stent (EePCS), offering improved radial strength, radiopacity and conformability compared to everolimus-eluting cobalt-chromium stents (EeCCS), was evaluated with regard to safety and efficacy in an all-comer cohort. METHODS: A total

  2. Evaluation on elution feature of bentonite buffer materials

    Energy Technology Data Exchange (ETDEWEB)

    Ishikawa, Hirohisa; Kanno, Takeshi; Matsumoto, Kazuhiro

    1997-09-01

    In order to evaluate long term physical stability of artificial barrier in land disposal of high level radioactive wastes, it is necessary to know quantitatively elution behavior of buffering materials from disposal road (or cavity) to circumferential rock crack. When elution of the buffer material occurs on large scale, amount of bentonite in the disposal road (or cavity) reduces and reduction of various functions expected to the buffer materials is presumed. According to specification examples of road transverse arrangement and disposal vertical arrangement systems, evaluation on elution amount of the buffer materials at disposal environment was conducted. Opening width of rock crack in the disposal environment was supposed to be 0.5 mm. As a result, obtained mass elution ratios of the buffer materials due to extrusion phenomenon were 0.04 to 0.2% after 10,000 year and 2 to 12% after 1,000,000 years. (G.K.)

  3. Characterization of CRUDE OILS and petroleum products: (i) elution ...

    African Journals Online (AJOL)

    Characterization of CRUDE OILS and petroleum products: (i) elution liquid chromatographic separation and gas chromatographic analysis of crude oils and petroleum products. E.O. Odebunmi, E.A. Ogunsakin, P.E.P. Ilukhor ...

  4. Kuldkaru elutöö eest / Endel Link

    Index Scriptorium Estoniae

    Link, Endel

    2001-01-01

    Ameerika näitleja Kirk Douglas (1916), kellele seekordsel Berlinalel antakse elutöö eest Kuldkaru. Austamisõhtul näidatakse teda Stanley Kubricku kaua keelu all olnud filmis "Tee kuulsusele " ("Paths of Glory") : 1957

  5. The elution of certain protein affinity tags with millimolar concentrations of diclofenac.

    Science.gov (United States)

    Baliova, Martina; Juhasova, Anna; Jursky, Frantisek

    2015-12-01

    Diclofenac (2-[(2, 6-dichlorophenyl)amino] benzeneacetic acid) is a sparingly soluble, nonsteroidal anti-inflammatory drug therapeutically acting at low micromolar concentrations. In pH range from 8 to 11, its aqueous solubility can be increased up to 200 times by the presence of counter ions such as sodium. Our protein interaction studies revealed that a millimolar concentration of sodium diclofenac is able to elute glutathione S-transferase (GST), cellulose binding protein (CBD), and maltose binding protein (MBP) but not histidine-tagged or PDZ-tagged proteins from their affinity resins. The elution efficiency of diclofenac is comparable with the eluting agents normally used at similar concentrations. Native gel electrophoresis of sodium diclofenac-treated proteins showed that the interaction is non-covalent and non-denaturing. These results suggest that sodium diclofenac, in addition to its pharmaceutical applications, can also be exploited as a lead for the development of new proteomics reagents. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  7. Generator for radionuclide

    International Nuclear Information System (INIS)

    Weisner, P.S.; Forrest, T.R.F.

    1985-01-01

    This invention provides a radionuclide generator of the kind in which a parent radionuclide, adsorbed on a column of particulate material, generates a daughter radionuclide which is periodically removed from the column. This invention is particularly concerned with technetium generators using single collection vials. The generator comprises a column, a first reservoir for the eluent, a second reservoir to contain the volume of eluent required for a single elution, and means connecting the first reservoir to the second reservoir and the second reservoir to the column. Such a generator is particularly suitable for operation by vacuum elution

  8. Investigation of the elution by seawater of caesium and strontium from loaded clinoptilolite

    International Nuclear Information System (INIS)

    Harder, B.R.; Mitchell, I.H.; Smyth, M.J.

    1985-07-01

    Simple investigations of the elution of caesium and strontium from loaded clinoptilolite are described. The clinoptilolite was loaded to levels expected in the British Nuclear Fuels plc SIXEP plant and contacted with seawater at approx. 15 C. (The elution time was measured until about 99% of the caesium and strontium had been eluted.) It was found that 99% of the caesium was eluted in 35 hours but the strontium (with more variable results) took at least 400 hours for 99% elution. (author)

  9. A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening.

    Science.gov (United States)

    Neto, A I; Correia, C R; Oliveira, M B; Rial-Hermida, M I; Alvarez-Lorenzo, C; Reis, R L; Mano, J F

    2015-04-01

    We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

  10. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial

    DEFF Research Database (Denmark)

    Rasmussen, Klaus; Maeng, Michael; Kaltoft, Anne

    2010-01-01

    In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery disease who we...

  11. Biodegradable Polymer Biolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents in Patients With Coronary Artery Disease: Final 5-Year Report From the COMPARE II Trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent).

    Science.gov (United States)

    Vlachojannis, Georgios J; Smits, Pieter C; Hofma, Sjoerd H; Togni, Mario; Vázquez, Nicolás; Valdés, Mariano; Voudris, Vassilis; Slagboom, Ton; Goy, Jean-Jaques; den Heijer, Peter; van der Ent, Martin

    2017-06-26

    This analysis investigates the 5-year outcomes of the biodegradable polymer biolimus-eluting stent (BP-BES) and durable polymer everolimus-eluting stent (DP-EES) in an all-comers population undergoing percutaneous coronary intervention. Recent 1- and 3-year results from randomized trials have indicated similar safety and efficacy outcomes of BP-BES and DP-EES. Whether benefits of the biodegradable polymer device arise over longer follow-up is unknown. Moreover, in-depth, prospective, long-term follow-up data on metallic drug-eluting stents with durable or biodegradable polymers are scarce. The COMPARE II trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent) was a prospective, randomized, multicenter, all-comers trial in which 2,707 patients were randomly allocated (2:1) to BP-BES or DP-EES. The pre-specified endpoint at 5 years was major adverse cardiac events, a composite of cardiac death, nonfatal myocardial infarction, or target vessel revascularization. Five-year follow-up was available in 2,657 patients (98%). At 5 years, major adverse cardiac events occurred in 310 patients (17.3%) in the BP-BES group and 142 patients (15.6%) in the DP-EES group (p = 0.26). The rate of the combined safety endpoint all-cause death or myocardial infarction was 15.0% in the BP-BES group versus 14.8% in the DP-EES group (p = 0.90), whereas the efficacy measure target vessel revascularization was 10.6% versus 9.0% (p = 0.18), respectively. Interestingly, definite stent thrombosis rates did not differ between groups (1.5% for BP-BES vs. 0.9% for DP-EES; p = 0.17). The 5-year analysis comparing biodegradable polymer-coated BES and the durable polymer-coated EES confirms the initial early- and mid-term results regarding similar safety and efficacy outcomes in this all-comers percutaneous coronary intervention population. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  12. Generation of Multicellular Tumor Spheroids with Microwell-Based Agarose Scaffolds for Drug Testing.

    Directory of Open Access Journals (Sweden)

    Xue Gong

    Full Text Available Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold prepared with the template containing uniform-sized micro-wells in commercially available cell culture plates. The agarose scaffold allows for good adjustment of MCTS size and large-scale production of MCTS. Transparent agarose scaffold also allows for monitoring of spheroid formation under an optical microscopy. The formation of MCTS from MCF-7 cells was prepared using different-size-well templates and systematically investigated in terms of spheroid growth curve, circularity, and cell viability. The doxorubicin cytotoxicity against MCF-7 spheroid and MCF-7 monolayer cells was compared. The drug penetration behavior, cell cycle distribution, cell apoptosis, and gene expression were also evaluated in MCF-7 spheroid. The findings of this study indicate that, compared with cellular monolayer, MCTS provides a valuable platform for the assessment of therapeutic candidates in an in vivo-mimic microenvironment, and thus has great potential for use in drug discovery and tumor biology research.

  13. Generation of drugs coated iron nanoparticles through high energy ball milling

    Energy Technology Data Exchange (ETDEWEB)

    Radhika Devi, A.; Murty, B. S. [Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600036 (India); Chelvane, J. A. [Defence Metallurgical Research Laboratory, Hyderabad 500058 (India); Prabhakar, P. K.; Padma Priya, P. V.; Doble, Mukesh [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036 (India)

    2014-03-28

    The iron nanoparticles coated with oleic acid and drugs such as folic acid/Amoxicillin were synthesized by high energy ball milling and characterized by X-ray diffraction, Transmission electron microscope, zeta potential, dynamic light scattering, Fourier Transform Infra red (FT-IR) measurements, and thermo gravimetric analysis (TGA). FT-IR and TGA measurements show good adsorption of drugs on oleic acid coated nanoparticles. Magnetic measurements indicate that saturation magnetization is larger for amoxicillin coated particles compared to folic acid coated particles. The biocompatibility of the magnetic nanoparticles prepared was evaluated by in vitro cytotoxicity assay using L929 cells as model cells.

  14. Comparing Stent Thrombosis associated with Zotarolimus Eluting Stents versus Everolimus Eluting Stents at 1 year follow up: a systematic review and meta-analysis of 6 randomized controlled trials.

    Science.gov (United States)

    Bundhun, Pravesh Kumar; Yanamala, Chandra Mouli; Huang, Wei-Qiang

    2017-03-16

    Two thousand fifteen has been a winning year for Drug Eluting Stents (DES). Increase in the number of patients with cardiovascular diseases treated by Percutaneous Coronary Intervention (PCI) has resulted to a high demand for second generation DES. This current analysis aimed to compare the different types of Stent Thrombosis (ST) associated with Zotarolimus Eluting Stents (ZES) versus Everolimus Eluting Stents (EES) at 1 year follow up. Electronic databases were searched for studies comparing ZES with EES. Different types of ST reported at 1 year follow up were considered as the primary endpoints in this analysis. Odds Ratios (OR) with 95% Confidence Intervals (CIs) were used as the statistical parameters and the pooled analyses were carried out by the RevMan 5 · 3 software. A total number of 10,512 patients were included in this analysis. No significant difference in any definite ST, acute definite ST, subacute definite ST, and late definite ST were observed between ZES and EES, at 1 year follow up with OR: 1.70, 95% CI: 0.92 - 3.16; P = 0.09, OR: 3.44, 95% CI: 0.82 - 14.43; P = 0.09, OR: 1.13, 95% CI: 0.43 - 2.95; P = 0.80 and OR: 2.39, 95% CI: 0.83 - 6.85; P = 0.11 respectively. Moreover, any definite or probable ST and definite/probable/possible ST were also not significantly different with OR: 1.39, 95% CI: 0.89 - 2.17; P = 0.15 and OR: 1.19, 95% CI: 0.84 - 1.70; P = 0.33 respectively. In addition, any probable ST, acute probable ST, late probable ST and possible ST were also not significantly different at 1 year follow up with OR: 1.11, 95% CI: 0.60 - 2.05; P = 0.75, OR: 0.53, 95% CI: 0.12 - 2.40; P = 0.41, OR: 1.67, 95% CI: 0.35 - 7.86; P = 0.52 and OR: 1.08, 95% CI: 0.64 - 1.82; P = 0.78 respectively. At 1 year follow up, ZES were not associated with significantly lower or higher definite and probable ST compared to EES. In addition, no significant difference was observed in acute, subacute and late

  15. Generation of pharmacophores and classification of drugs using protein-ligand complexes

    Directory of Open Access Journals (Sweden)

    Eliana Velasquez

    2014-04-01

    Full Text Available Pharmacophore identification is a veryimportant step in de novo design, leadoptimization, chemogenomics, and virtualscreening of drugs. Unfortunately,the high cost of comercial software forpharmacophore detection is a commonlimiting factor for researchers with limitedfunding. This paper presents a set offreely available perl routines that weredesigned to help in the process of 3Dpharmacophore identification and QSARstudies. These routines also allowed theclassification of ligands based on theirtridimensional similarity and bindingmechanism. The family of phosphodiesterasesand their inhibitors were used astest model.

  16. Comparative analysis of tumor spheroid generation techniques for differential in vitro drug toxicity

    Science.gov (United States)

    Raghavan, Shreya; Rowley, Katelyn R.; Mehta, Geeta

    2016-01-01

    Multicellular tumor spheroids are powerful in vitro models to perform preclinical chemosensitivity assays. We compare different methodologies to generate tumor spheroids in terms of resultant spheroid morphology, cellular arrangement and chemosensitivity. We used two cancer cell lines (MCF7 and OVCAR8) to generate spheroids using i) hanging drop array plates; ii) liquid overlay on ultra-low attachment plates; iii) liquid overlay on ultra-low attachment plates with rotating mixing (nutator plates). Analysis of spheroid morphometry indicated that cellular compaction was increased in spheroids generated on nutator and hanging drop array plates. Collagen staining also indicated higher compaction and remodeling in tumor spheroids on nutator and hanging drop arrays compared to conventional liquid overlay. Consequently, spheroids generated on nutator or hanging drop plates had increased chemoresistance to cisplatin treatment (20-60% viability) compared to spheroids on ultra low attachment plates (10-20% viability). Lastly, we used a mathematical model to demonstrate minimal changes in oxygen and cisplatin diffusion within experimentally generated spheroids. Our results demonstrate that in vitro methods of tumor spheroid generation result in varied cellular arrangement and chemosensitivity. PMID:26918944

  17. Development of a pheromone elution rate physical model

    Science.gov (United States)

    M.E. Teske; H.W. Thistle; B.L. Strom; H. Zhu

    2015-01-01

    A first principle modeling approach has been applied to available data describing the elution of semiochemicals from pheromone dispensers. These data included field data for 27 products developed by several manufacturers, including homemade devices, as well as environmental chamber data collected on three semiochemical products. The goal of this effort was to...

  18. Disease-responsive drug delivery: the next generation of smart delivery devices.

    Science.gov (United States)

    Wanakule, Prinda; Roy, Krishnendu

    2012-01-01

    With the advent of highly potent and cytotoxic drugs, it is increasingly critical that they be targeted and released only in cells of diseased tissues, while sparing physiologically normal neighbors. Simple ligand-based targeting of drug carriers, although promising, cannot always provide the required specificity to achieve this since often normal cells also express significant levels of the targeted receptors. Therefore, stimuli-responsive delivery systems are being explored to allow drug release from nano- and microcarriers and implantable devices, primarily in the presence of physiological or disease-specific pathophysiological signals. Designing smart biomaterials that respond to temperature or pH changes, protein and ligand binding, disease-specific degradation, e.g. enzymatic cleavage, has become an integral part of this approach. These strategies are used in combination with nano- and microparticle systems to improve delivery efficiency through several routes of administration, and with injectable or implantable systems for long term controlled release. This review focuses on recent developments in stimuli-responsive systems, their physicochemical properties, release profiles, efficacy, safety and biocompatibility, as well as future perspectives.

  19. HIV drug resistance patterns in pregnant women using next generation sequence in Mozambique.

    Science.gov (United States)

    Rupérez, María; Noguera-Julian, Marc; González, Raquel; Maculuve, Sonia; Bellido, Rocío; Vala, Anifa; Rodríguez, Cristina; Sevene, Esperança; Paredes, Roger; Menéndez, Clara

    2018-01-01

    Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care. To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART). Samples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery. Ninety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts HIV-1 genotyping, less than 20% of women with detectable viremia at delivery had HIVDRM before initiating pMTCT or ART. This suggests that factors other than pre-existing resistance, such as lack of adherence or interruptions of the ANC chain, are also relevant to explain lack of virological suppression at the time of delivery in women receiving antiretrovirals drugs during pregnancy.

  20. Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Jakobsen, Lars; Christiansen, Evald H; Maeng, Michael

    2018-01-01

    Background: The Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have...... designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. Methods: The SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro...... stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. The primary end point target lesion...

  1. Comparison of in vivo acute stent recoil between the bioabsorbable everolimus-eluting coronary stent and the everolimus-eluting cobalt chromium coronary stent: insights from the ABSORB and SPIRIT trials

    DEFF Research Database (Denmark)

    Tanimoto, Shuzou; Serruys, Patrick W; Thuesen, Leif

    2007-01-01

    OBJECTIVES: This study sought to evaluate and compare in vivo acute stent recoil of a novel bioabsorbable stent and a metallic stent. BACKGROUND: The bioabsorbable everolimus-eluting coronary stent (BVS) is composed of a poly-L-lactic acid backbone, coated with a bioabsorbable polymer containing...... the antiproliferative drug, everolimus, and expected to be totally metabolized and absorbed in the human body. Because the BVS is made from polymer, it may have more acute recoil than metallic stents in vivo. METHODS: A total of 54 patients, who underwent elective stent implantation for single de novo native coronary...... artery lesions, were enrolled: 27 patients treated with the BVS and 27 patients treated with the everolimus-eluting cobalt chromium stent (EES). Acute absolute recoil, assessed by quantitative coronary angiography, was defined as the difference between mean diameter of the last inflated balloon...

  2. Development of a sirolimus-eluting poly (L-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention.

    Science.gov (United States)

    Grabow, Niels; Bünger, Carsten M; Kischkel, Sabine; Timmermann, J Hinrich; Reske, Thomas; Martin, David P; Williams, Simon F; Schareck, Wolfgang; Sternberg, Katrin; Schmitz, Klaus-Peter

    2013-10-01

    Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0 × 20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50 ± 25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.

  3. Consenso de especialistas (SBC/SBHCI sobre o uso de stents farmacológicos: recomendações da sociedade brasileira de cardiologia/sociedade brasileira de hemodinâmica e cardiologia intervencionista ao sistema único de saúde Expert consensus (SBC/SBHCI on the use of drug-eluting stents: recommendations of the Brazilian society of interventional cardiology/ Brazilian society of cardiology for the Brazilian public single healthcare system

    Directory of Open Access Journals (Sweden)

    Valter C. Lima

    2006-10-01

    de organizações que os representam, às vezes com ações judiciais, ou por pressão política dos médicos e de suas respectivas sociedades científicas. Nosso objetivo é revisar a evolução da intervenção coronariana percutânea (ICP no Brasil, sua situação atual com o advento dos stents farmacológicos, e a crescente participação destes como modalidade de revascularização miocárdica de pacientes portadores de doença arterial coronariana, assim como comparar as normas regulatórias brasileiras e de outros paises, em relação à incorporação desta nova tecnologia, e as recomendações para sua utilização.The authors review percutaneous coronary intervention (PCI evolution and its growing application in myocardial revascularization for patients with coronary heart disease in Brazil and worldwide. PCI was introduced in 1977 using only the catheter balloon. Limitations of this method (acute occlusion and coronary restenosis led to the adoption of coronary stents and more recently the advent of drug-eluting stents², which were developed to drastically reduce restenosis rates. These developments allowed the exponential growth of percutaneous coronary intervention (PCI procedures in Brazil which have replaced many bypass surgery procedures and have become the gold standard for the majority of symptomatic patients suffering from coronary artery disease. The preference for this procedure gained new dimensions in 2000 when the Brazilian Public Healthcare System (SUS began reimbursing for stent procedures. This measure exemplified the importance of the Public Healthcare System's participation in incorporating medical advances and offering a high standard of cardiovascular treatment to a large portion of the Brazilian population. It is emphasized that prevention of in-stent restenosis is complex due to its unpredictable and ubiquitous occurrence. Control of this condition improves quality of life and reduces the recurrence of angina pectoris, the need to

  4. Sirolimus-eluting versus bare-metal stent implantation in patients with ostial lesions

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Kelbæk, Henning; Kløvgaard, Lene

    2010-01-01

    To investigate the efficacy of implantation of sirolimus-eluting stents (SES) in the ostium of coronary arteries.......To investigate the efficacy of implantation of sirolimus-eluting stents (SES) in the ostium of coronary arteries....

  5. In vitro bactericidal activity of aminoglycosides, including the next-generation drug plazomicin, against Brucella spp.

    Science.gov (United States)

    Plazomicin is a next-generation aminoglycoside with a potentially improved safety profile compared to other aminoglycosides. This study assessed plazomicin MICs and MBCs in four Brucella spp. reference strains. Like other aminoglycosides and aminocyclitols, plazomicin MBC values equaled MIC values ...

  6. In Vivo and In Vitro Elution of Analgesics from Multilayered Poly(D,L)-lactide-co-glycolide Nanofibers Incorporated Ureteral Stents

    OpenAIRE

    Lin, Yi-Chia; Liu, Kuo-Sheng; Lee, Demei; Li, Min-Jhan; Liu, Shih-Jung; Ito, Hiroshi

    2018-01-01

    We develop novel analgesic-eluting nanofiber-incorporated ureteral stents that offer sustained release of lidocaine and ketorolac for local drug delivery. Lidocaine and poly(D,L)-lactide-co-glycolide (PLGA) were dissolved in hexafluoroisopropanol and were electrospun into nonwoven nanofibers onto the surface of ureteral stents. This was followed by electrospinning of another layer of PLGA nanofibers containing ketorolac. Electrospun drug-loaded nanofibers were then characterized using scannin...

  7. Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold

    Science.gov (United States)

    Kumar, Sachin; Chatterjee, Kaushik

    2015-01-01

    The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium particles. Thermal gravimetric analysis further confirmed the composition of the hybrid particles as 22 wt% of strontium. Macroporous tissue scaffolds were prepared by incorporating RGO_Sr particles in poly(ε-caprolactone) (PCL). The PCL/RGO_Sr scaffolds were found to elute strontium ions in aqueous medium. Osteoblast proliferation and differentiation was significantly higher in the PCL scaffolds containing the RGO_Sr particles in contrast to neat PCL and PCL/RGO scaffolds. The increased biological activity can be attributed to the release of strontium ions from the hybrid nanoparticles. This study demonstrates that composites prepared using hybrid nanoparticles that elute strontium ions can be used to prepare multifunctional scaffolds with good mechanical and osteoinductive properties. These findings have important implications for designing the next generation of biomaterials for use in tissue regeneration.The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium

  8. A prospective, randomized evaluation of a novel everolimus-eluting coronary stent

    DEFF Research Database (Denmark)

    Stone, Gregg W; Teirstein, Paul S; Meredith, Ian T

    2011-01-01

    We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI).......We sought to evaluate the clinical outcomes with a novel platinum chromium everolimus-eluting stent (PtCr-EES) compared with a predicate cobalt chromium everolimus-eluting stent (CoCr-EES) in patients undergoing percutaneous coronary intervention (PCI)....

  9. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

    Science.gov (United States)

    Carrascosa, J M; Del-Alcazar, E

    2018-04-01

    Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

  10. Outcome of Sirolimus-Eluting Versus Zotarolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus (a SORT OUT III Substudy)

    DEFF Research Database (Denmark)

    Maeng, Michael; Jensen, Lisette O; Tilsted, Hans-Henrik

    2011-01-01

    Diabetes is associated with an increased risk of major adverse cardiac events after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus treated with the second-generation Endeavor zotarolimus-eluting stent (ZES) or the first...... cardiac events defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Secondary end points included these individual end points plus all-cause mortality and target lesion revascularization. In diabetic patients, use of ZES compared to SES was associated.......90 to 13.1), and target lesion revascularization (12.4% vs 1.2%, hazard ratio 11.0, 95% confidence interval 2.59 to 47.1). In patients without diabetes differences in absolute risk decrease were smaller but similarly favored SES. In conclusion, implantation of ZESs compared to SESs is associated...

  11. Quorum sensing inhibitory drugs as next generation antimicrobials: worth the effort?

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Givskov, M.

    2008-01-01

    as biofilms are more tolerant to antibiotics than their planktonic counterparts. Therefore, research should identify new antimicrobial agents and their corresponding targets to decrease the biofilm-forming capability or persistence of the infectious bacteria. Here, we review one such drug target: bacterial......Bacterial resistance poses a major challenge to the development of new antimicrobial agents. Conventional antibiotics have an inherent obsolescence because they select for development of resistance. Bacterial infections have again become a serious threat in developed countries. Particularly......, elderly, immunocompromised, and hospitalized patients are susceptible to infections caused by bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. These bacteria form chronic, biofilm-based infections, which are challenging because bacterial cells living...

  12. Efficient generation of megakaryocytes from human induced pluripotent stem cells using food and drug administration-approved pharmacological reagents.

    Science.gov (United States)

    Liu, Yanfeng; Wang, Ying; Gao, Yongxing; Forbes, Jessica A; Qayyum, Rehan; Becker, Lewis; Cheng, Linzhao; Wang, Zack Z

    2015-04-01

    Megakaryocytes (MKs) are rare hematopoietic cells in the adult bone marrow and produce platelets that are critical to vascular hemostasis and wound healing. Ex vivo generation of MKs from human induced pluripotent stem cells (hiPSCs) provides a renewable cell source of platelets for treating thrombocytopenic patients and allows a better understanding of MK/platelet biology. The key requirements in this approach include developing a robust and consistent method to produce functional progeny cells, such as MKs from hiPSCs, and minimizing the risk and variation from the animal-derived products in cell cultures. In this study, we developed an efficient system to generate MKs from hiPSCs under a feeder-free and xeno-free condition, in which all animal-derived products were eliminated. Several crucial reagents were evaluated and replaced with Food and Drug Administration-approved pharmacological reagents, including romiplostim (Nplate, a thrombopoietin analog), oprelvekin (recombinant interleukin-11), and Plasbumin (human albumin). We used this method to induce MK generation from hiPSCs derived from 23 individuals in two steps: generation of CD34(+)CD45(+) hematopoietic progenitor cells (HPCs) for 14 days; and generation and expansion of CD41(+)CD42a(+) MKs from HPCs for an additional 5 days. After 19 days, we observed abundant CD41(+)CD42a(+) MKs that also expressed the MK markers CD42b and CD61 and displayed polyploidy (≥16% of derived cells with DNA contents >4N). Transcriptome analysis by RNA sequencing revealed that megakaryocytic-related genes were highly expressed. Additional maturation and investigation of hiPSC-derived MKs should provide insights into MK biology and lead to the generation of large numbers of platelets ex vivo. ©AlphaMed Press.

  13. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants

    International Nuclear Information System (INIS)

    Cox, Sophie C.; Jamshidi, Parastoo; Eisenstein, Neil M.; Webber, Mark A.; Hassanin, Hany; Attallah, Moataz M.; Shepherd, Duncan E.T.; Addison, Owen; Grover, Liam M.

    2016-01-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p = 0.01) improved the compressive strength (5.8 ± 0.7 MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6 hour period (< 28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16 μg/mL) and Staphylococcus epidermidis (1 μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. - Highlights: • Titanium implants were additively manufactured with surface connected reservoirs. • Implants

  14. Unfolding and aggregation of a glycosylated monoclonal antibody on a cation exchange column. Part I. Chromatographic elution and batch adsorption behavior.

    Science.gov (United States)

    Guo, Jing; Zhang, Shaojie; Carta, Giorgio

    2014-08-22

    A glycosylated IgG2 monoclonal antibody exhibits a two-peak elution behavior when loaded on a strong cation exchange column and eluted with either a linear salt gradient or two salt steps at increasing salt concentrations. The two-peak behavior is more pronounced for conditions where the initial antibody binding is stronger, i.e. at lower pH and buffer concentration, where the hold time prior to elution is longer, where the protein mass load is lower, and where the load flow rate is higher. The effect is also dependent on the resin type, being prominent for the polymer-functionalized resin Fractogel EMD SO₃(-) and virtually absent for a macroporous resin with similar backbone but no grafted polymers. Size exclusion chromatography and dynamic light scattering show that the early eluting peak consists exclusively of the native monomeric species while the late eluting peak is a mixture of monomeric and aggregated species. Batch adsorption/desorption experiments show that the bound protein can be desorbed in two steps, with a fraction desorbed in 0.33 M NaCl, corresponding to native monomer, and a second fraction desorbed in 1M NaCl. The latter fraction decreases with protein mass load and becomes almost negligible when the resin is initially completely saturated with protein. Confocal laser scanning microscopy showed that the two-peak elution/desorption behavior is related to the unique kinetics of protein binding in the Fractogel resin. Following partial loading of the resin, the bound protein migrates toward the center of the particles during a hold step and is redistributed across the particle volume attaining low local bound protein concentrations. For these conditions the protein is apparently destabilized forming a strongly-bound unfolded intermediate that, in turn, generates aggregates upon elution in high salt. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants.

    Science.gov (United States)

    Khandelwal, Nitin; Chander, Yogesh; Rawat, Krishan Dutt; Riyesh, Thachamvally; Nishanth, Chikkahonnaiah; Sharma, Shalini; Jindal, Naresh; Tripathi, Bhupendra N; Barua, Sanjay; Kumar, Naveen

    2017-08-01

    At a noncytotoxic concentration, emetine was found to inhibit replication of DNA viruses [buffalopoxvirus (BPXV) and bovine herpesvirus 1 (BHV-1)] as well as RNA viruses [peste des petits ruminants virus (PPRV) and Newcastle disease virus (NDV)]. Using the time-of-addition and virus step-specific assays, we showed that emetine treatment resulted in reduced synthesis of viral RNA (PPRV and NDV) and DNA (BPXV and BHV-1) as well as inhibiting viral entry (NDV and BHV-1). In addition, emetine treatment also resulted in decreased synthesis of viral proteins. In a cell free endogenous viral polymerase assay, emetine was found to significantly inhibit replication of NDV, but not BPXV genome, suggesting that besides directly inhibiting specific viral polymerases, emetine may also target other factors essentially required for efficient replication of the viral genome. Moreover, emetine was found to significantly inhibit BPXV-induced pock lesions on chorioallantoic membrane (CAM) along with associated mortality of embryonated chicken eggs. At a lethal dose 50 (LD 50 ) of 126.49 ng/egg and at an effective concentration 50 (EC 50 ) of 3.03 ng/egg, the therapeutic index of the emetine against BPXV was determined to be 41.74. Emetine was also found to significantly delay NDV-induced mortality in chicken embryos associated with reduced viral titers. Further, emetine-resistant mutants were not observed upon long-term (P = 25) sequential passage of BPXV and NDV in cell culture. Collectively, we have extended the effective antiviral activity of emetine against diverse groups of DNA and RNA viruses and propose that emetine could provide significant therapeutic value against some of these viruses without inducing an antiviral drug-resistant phenotype. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Generating genius: how an Alzheimer's drug became considered a 'cognitive enhancer' for healthy individuals.

    Science.gov (United States)

    Wade, Lucie; Forlini, Cynthia; Racine, Eric

    2014-05-12

    Donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease, has been widely cited in media and bioethics literature on cognitive enhancement (CE) as having the potential to improve the cognitive ability of healthy individuals. In both literatures, this claim has been repeatedly supported by the results of a small study published by Yesavage et al. in 2002 on non-demented pilots (30-70 years old). The factors contributing to this specific interpretation of this study's results are unclear. We examined print media and interdisciplinary bioethics coverage of this small study, aiming to provide insight into how evidence from research may be shaped within different discourses, potentially influencing important policy, ethics, and clinical decisions. Systematic qualitative content analysis was used to examine how this study was reported in 27 media and 22 bioethics articles. Articles were analyzed for content related to: (1) headlines and titles; (2) colloquialisms; and, (3) accuracy of reporting of the characteristics and results of the study. In media and bioethics articles referencing this small study, strong claims were made about donepezil as a CE drug. The majority of headlines, titles, and colloquialisms used enhancement language and the majority of these suggest that donepezil could be used to enhance intellectual ability. Further, both literatures moved between reporting the results of the primary study and magnifying the perceived connection between these results and the CE debate that was alluded to in the primary study. Specific descriptions of the results overwhelmingly reported an improvement in performance on a flight simulator, while more general statements claimed donepezil enhanced cognitive performance. Further, a high level of reporting accuracy was found regarding study characteristics of the original study, but variable levels of accuracy surrounded the presentation of complex characteristics (i.e., methods) or

  17. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

    Science.gov (United States)

    Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

    2016-07-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society?

    Science.gov (United States)

    Khatami, Mahin

    2016-12-01

    Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research ('medical/scientific ponzi schemes') is potent recipe for failed therapeutics that kills patients but generates huge corporate profit. American health status ranks last among other developed nations despite the highest amount that USA invests in healthcare. This is a wake-up call to make sure that the evil part of human being does not prevent the health services that the public deserves. Otherwise, 'it does not matter how many resources you have, if you don't know, or don't want to know, how to use them, they will never be enough'. Answer to cancer and improved public health is possible only by switching the current corruptive and abusive culture of 'who you know' to a culture of 'what you know'. Policy makers and professionals in decision making roles are urged to return to common sense and logics that our Forefathers used to serve the public.

  19. Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-08-01

    Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(ΙΙΙ), Zr(ΙV) and U(VΙ) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

  20. Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

    Directory of Open Access Journals (Sweden)

    Ikeda H

    2015-10-01

    Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

  1. Laser-induced microjet: wavelength and pulse duration effects on bubble and jet generation for drug injection

    Science.gov (United States)

    Jang, Hun-jae; Park, Mi-ae; Sirotkin, Fedir V.; Yoh, Jack J.

    2013-12-01

    The expansion of the laser-induced bubble is the main mechanism in the developed microjet injector. In this study, Nd:YAG and Er:YAG lasers are used as triggers of the bubble formation. The impact of the laser parameters on the bubble dynamics is studied and the performance of the injector is evaluated. We found that the main cause of the differences in the bubble behavior comes from the pulse duration and wavelength. For Nd:YAG laser, the pulse duration is very short relative to the bubble lifetime making the behavior of the bubble close to that of the cavitation bubble, while in Er:YAG case, the high absorption in the water and long pulse duration change the initial behavior of the bubble making it close to a vapor bubble. The contraction and subsequent rebound are typical for cavitation bubbles in both cases. The results show that the laser-induced microjet injector generates velocity which is sufficient for the drug delivery for both laser beams of different pulse duration. We estimate the typical velocity within 30-80 m/s range and the breakup length to be larger than 1 mm suitable for trans-dermal drug injection.

  2. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II)

    DEFF Research Database (Denmark)

    Serruys, Patrick W; Chevalier, Bernard; Sotomi, Yohei

    2016-01-01

    BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a re...

  3. Effect of Post-Dilatation Following Primary PCI With Everolimus-Eluting Bioresorbable Scaffold Versus Everolimus-Eluting Metallic Stent Implantation

    DEFF Research Database (Denmark)

    Yamaji, Kyohei; Brugaletta, Salvatore; Sabaté, Manel

    2017-01-01

    OBJECTIVES: This study sought to investigate the effect of post-dilatation on angiographic and intracoronary imaging parameters in the setting of primary percutaneous coronary intervention comparing the everolimus-eluting bioresorbable scaffold (BRS) with the everolimus-eluting metallic stent (EE...

  4. Toxicity of Irinotecan-Eluting Beads in the Treatment of Hepatic Malignancies: Results of a Multi-Institutional Registry

    International Nuclear Information System (INIS)

    Martin, R. C. G.; Howard, J.; Tomalty, D.; Robbins, K.; Padr, R.; Bosnjakovic, P. M.; Tatum, Cliff

    2010-01-01

    PurposeTo evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies.Materials and MethodsA total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included.ResultsA total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most common histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), ≥3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 μg/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay.ConclusionsDEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.

  5. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents

    DEFF Research Database (Denmark)

    Serruys, Patrick W; Silber, Sigmund; Garg, Scot

    2010-01-01

    New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed...

  6. Biodegradable-Polymer Biolimus-Eluting Stents versus Durable-Polymer Everolimus-Eluting Stents at One-Year Follow-Up: A Registry-Based Cohort Study.

    Science.gov (United States)

    Parsa, Ehsan; Saroukhani, Sepideh; Majlessi, Fereshteh; Poorhosseini, Hamidreza; Lofti-Tokaldany, Masoumeh; Jalali, Arash; Salarifar, Mojtaba; Nematipour, Ebrahim; Alidoosti, Mohammad; Aghajani, Hassan; Amirzadegan, Alireza; Kassaian, Seyed Ebrahim

    2016-04-01

    We compared outcomes of percutaneous coronary intervention patients who received biodegradable-polymer biolimus-eluting stents with those who received durable-polymer everolimus-eluting stents. At Tehran Heart Center, we performed a retrospective analysis of the data from January 2007 through December 2011 on 3,270 consecutive patients with coronary artery disease who underwent percutaneous coronary intervention with the biodegradable-polymer biolimus-eluting stent or the durable-polymer everolimus-eluting stent. We excluded patients with histories of coronary artery bypass grafting or percutaneous coronary intervention, acute ST-segment-elevation myocardial infarction, or the implantation of 2 different stent types. Patients were monitored for 12 months. The primary endpoint was a major adverse cardiac event, defined as a composite of death, nonfatal myocardial infarction, and target-vessel and target-lesion revascularization. Durable-polymer everolimus-eluting stents were implanted in 2,648 (81%) and biodegradable-polymer biolimus-eluting stents in 622 (19%) of the study population. There was no significant difference between the 2 groups (2.7% vs 2.7%; P=0.984) in the incidence of major adverse cardiac events. The cumulative adjusted probability of major adverse cardiac events in the biodegradable-polymer biolimus-eluting stent group did not differ from that of such events in the durable-polymer everolimus-eluting stent group (hazard ratio=0.768; 95% confidence interval, 0.421-1.44; P=0.388). We conclude that in our patients the biodegradable-polymer biolimus-eluting stent was as effective and safe, during the 12-month follow-up period, as was the durable-polymer everolimus-eluting stent.

  7. Second-generation magnesium scaffold Magmaris: device design and preclinical evaluation in a porcine coronary artery model.

    Science.gov (United States)

    Waksman, Ron; Zumstein, Philine; Pritsch, Martin; Wittchow, Eric; Haude, Michael; Lapointe-Corriveau, Capucine; Leclerc, Guy; Joner, Michael

    2017-07-20

    The second-generation drug-eluting absorbable magnesium scaffold Magmaris, recently introduced for the treatment of obstructive coronary atherosclerotic lesions, suggests a good safety profile, but preclinical assessment is important for predicting clinical performance. The aim of the present study was to assess subacute and long-term safety as well as pharmacokinetic properties of the Magmaris compared with a current-generation metallic DES and an approved BRS in porcine and rabbit animal models. Ninety Magmaris scaffolds were implanted into non-diseased porcine and rabbit models. A bioresorbable vascular scaffold (Absorb) and a permanent drug-eluting stent (XIENCE Xpedition) served as controls. Scanning electron microscopy showed increased endothelialisation and decreased thrombus formation at three and 28 days in the Magmaris group compared with the Absorb group. In the XIENCE group, inflammation exceeded the level in the Magmaris group at 365 and 730 days. Neointimal growth was greater in the Magmaris group than in the XIENCE group. Late lumen loss decreased over time in both groups. Optical coherence tomography (OCT) showed stable luminal dimensions in both the Magmaris and XIENCE groups. Pharmacokinetic studies demonstrated a retarded elution profile in the Magmaris group with 69.4% of sirolimus released at 90 days. Preclinical results suggest that the Magmaris has a favourable safety profile with advanced healing relative to benchmark, low acute thrombogenicity, and absence of excessive lumen loss up to two years. These results support clinical application of Magmaris for human use.

  8. Transitions in drug use in a new generation of problem drug users in Amsterdam: a 6-year follow-up study

    NARCIS (Netherlands)

    Buster, Marcel C. A.; Witteveen, Ewald; Prins, Maria; van Ameijden, Erik J. C.; Schippers, Gerard; Krol, Anneke

    2009-01-01

    This study describes the transitions in drug use in Amsterdam among young drug users (YDUs) who are inhaling or injecting cocaine or using illicitly obtained opiates. From 2000 until 2003, 187 YDUs (

  9. Reloadable radioactive generator system

    International Nuclear Information System (INIS)

    Colombetti, L.G.

    1977-01-01

    A generator system that can be reloaded with an elutable radioactive material, such as 99 molybdenum, a multiple number of times is described. The system basically comprises a column filled with alumina, a loading vial containing a predetermined amount of the elutable radioactive material, and a rinsing vial containing a sterile solution. The two vials are connected by a conduit so that when communication is achieved between the column and loading vial and an evacuated vial is placed in communication with the bottom of the column, the predetermined amount of the radioactive material in the loading vial will be transferred to the column. The procedure can be repeated as the elutable material in the column is dissipated

  10. Dynamics of silver elution from functionalised antimicrobial nanofiltration membranes.

    Science.gov (United States)

    Choudhari, S; Habimana, O; Hannon, J; Allen, A; Cummins, E; Casey, E

    2017-07-01

    In an effort to mitigate biofouling on thin film composite membranes such as nanofiltration and reverse osmosis, a myriad of different surface modification strategies has been published. The use of silver nanoparticles (Ag-NPs) has emerged as being particularly promising. Nevertheless, the stability of these surface modifications is still poorly understood, particularly under permeate flux conditions. Leaching or elution of Ag-NPs from the membrane surface can not only affect the antimicrobial characteristics of the membrane, but could also potentially present an environmental liability when applied in industrial-scale systems. This study sought to investigate the dynamics of silver elution and the bactericidal effect of an Ag-NP functionalised NF270 membrane. Inductively coupled plasma-atomic emission spectroscopy was used to show that the bulk of leached silver occurred at the start of experimental runs, and was found to be independent of salt or permeate conditions used. Cumulative amounts of leached silver did, however, stabilise following the initial release, and were shown to have maintained the biocidal characteristics of the modified membrane, as observed by a higher fraction of structurally damaged Pseudomonas fluorescens cells. These results highlight the need to comprehensively assess the time-dependent nature of bactericidal membranes.

  11. Elution of monomer from different bulk fill dental composite resins.

    Science.gov (United States)

    Cebe, Mehmet Ata; Cebe, Fatma; Cengiz, Mehmet Fatih; Cetin, Ali Rıza; Arpag, Osman Fatih; Ozturk, Bora

    2015-07-01

    The purpose of this study was to evaluate the elution of Bis-GMA, TEGDMA, HEMA, and Bis-EMA monomers from six bulk fill composite resins over four different time periods, using HPLC. Six different composite resin materials were used in the present study: Tetric Evo Ceram Bulk Fill (Ivoclar Vivadent, Amherst, NY), X-tra Fill (VOCO, Cuxhaven, Germany), Sonic Fill (Kerr, Orange, CA, USA), Filtek Bulk Fill (3M ESPE Dental Product, St. Paul, MN), SDR (Dentsply, Konstanz, Germany), EQUIA (GC America INC, Alsip, IL). The samples (4mm thickness, 5mm diameter) were prepared and polymerized for 20s with a light emitted diode unit. After fabrication, each sample was immediately immersed in 75wt% ethanol/water solution used as extraction fluid and stored in the amber colored bottles at room temperature. Ethanol/water samples were taken (0.5mL) at predefined time intervals:10m (T1), 1h (T2), 24h (T3) and 30 days (T4). These samples were analyzed by HPLC. The obtained data were analyzed with one-way ANOVA and Tukey HSD at significance level of pcomposites (pcomposite resins in all time periods and the amount of eluted monomers was increased with time. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  12. Drug: D06669 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available f phosphorycholine polymer coated drug-eluting stent currently under evaluation for the prevention of corona...ry restenosis following stent replacement MTOR [HSA:2475] [KO:K07203] ... CAS: 221877-54-9 PubChem: 47208320 NIKKAJI: J2.155.474J ...

  13. Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

    Science.gov (United States)

    Kaiser, Christoph; Galatius, Soeren; Jeger, Raban; Gilgen, Nicole; Skov Jensen, Jan; Naber, Christoph; Alber, Hannes; Wanitschek, Maria; Eberli, Franz; Kurz, David J; Pedrazzini, Giovanni; Moccetti, Tiziano; Rickli, Hans; Weilenmann, Daniel; Vuillomenet, André; Steiner, Martin; Von Felten, Stefanie; Vogt, Deborah R; Wadt Hansen, Kim; Rickenbacher, Peter; Conen, David; Müller, Christian; Buser, Peter; Hoffmann, Andreas; Pfisterer, Matthias

    2015-01-06

    Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. http://www.clinicaltrials.gov. Unique identifier: NCT01166685. © 2014 American Heart Association, Inc.

  14. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    Science.gov (United States)

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-06-01

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  15. A non-commercial approach for the generation of transgenic Leishmania tarentolae and its application in antileishmanial drug discovery.

    Science.gov (United States)

    Pineda, Tatiana; Valencia, Yesenia; Flórez, María F; Pulido, Sergio A; Vélez, Iván D; Robledo, Sara M

    2016-08-01

    Leishmaniasis is a parasitic infection caused by several species of the genus Leishmania that is considered as a neglected disease. Drug development process requires a robust and updated high-throughput technology to the evaluation of candidate compounds that imply the manipulation of the pathogenic species of the parasite in the laboratory. Therefore, it is restricted to trained personal and level II biosafety environments. However, it has been established the utility of Leishmania tarentolae as a model for in vitro screening of antileishmanial agents without the necessity of level II biosafety setups. In parallel the transfection of Leishmania parasites with reporter genes as the eGFP using non-commercial integration vectors like the pIRmcs3(-) has proved to be a powerful tool for the implementation of semi automatized high-throughput platforms for the evaluation of antileishmanial compounds. Here we report the generation of a new L. tarentolae strain overexpressing the eGFP gene harboured by the non-commercial vector pIR3(-). We also demonstrate its utility for the semi-automatized screening of antileshmanial compounds in intracellular forms of the L. tarentolae parasite.

  16. Necessary, sufficient and contributory factors generating illegal economic activity, and specifically drug-related activity, in Colombia

    Directory of Open Access Journals (Sweden)

    Francisco E. Thoumi

    2014-06-01

    Full Text Available The international drug control regime is formulated under a basic paradigm: all drugs included in the convention schedules I, II and IV can only have medical and research uses. The policies derived from these conventions forbid all recreational, ritual, experimental, or self-medicating consumption of coca, cocaine, opium, heroin, marijuana and many other drugs. The conventions allow the production of controlled drugs for medical and research uses and criminalize all other production. Where consumption is concerned they are less rigid, as users of illegal drugs do not have to be arrested or jailed. Anti-drug policies seek to suppress both illicit drug supply and demand but are formulated without clearly spelling out the reasons why there is a demand and a supply for illegal drugs. To understand illegal drug demand and supply it is necessary to have clear answers to fundamental criminological questions such as: Why do people commit crimes? Or why some individuals contravene formal or informal norms while others do not? Policymakers, however, do not hesitate to formulate and implement anti-drug policies without having first considered those questions. They proceed as if their answers were obvious or known. Yet, when asked about the reasons why the illegal drugs industry develops in a location, most answers are highly questionable and at best partially right. The aim of this essay is to show this using Colombia as an example.

  17. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants

    Energy Technology Data Exchange (ETDEWEB)

    Cox, Sophie C. [School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Jamshidi, Parastoo [School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Eisenstein, Neil M. [School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Royal Centre for Defence Medicine, Birmingham Research Park, Vincent Drive, Edgbaston B15 2SQ (United Kingdom); Webber, Mark A. [School of Biosciences, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Hassanin, Hany [School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT (United Kingdom); School of Mechanical and Automotive Engineering, Kingston University, London SW15 3DW (United Kingdom); Attallah, Moataz M. [School of Materials and Metallurgy, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Shepherd, Duncan E.T. [Department of Mechanical Engineering, School of Engineering, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Addison, Owen [School of Dentistry, University of Birmingham, Edgbaston B15 2TT (United Kingdom); Grover, Liam M. [School of Chemical Engineering, University of Birmingham, Edgbaston B15 2TT (United Kingdom)

    2016-07-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p = 0.01) improved the compressive strength (5.8 ± 0.7 MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6 hour period (< 28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16 μg/mL) and Staphylococcus epidermidis (1 μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. - Highlights: • Titanium implants were additively manufactured with surface connected reservoirs. • Implants

  18. Safety and efficacy of everolimus-eluting stents for bare-metal in-stent restenosis

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Hideaki [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Mahmoudi, Michael [University of Surrey, Guildford Road, Surrey, GU2-7XH (United Kingdom); Torguson, Rebecca; Satler, Lowell F.; Suddath, William O.; Pichard, Augusto D. [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States); Waksman, Ron, E-mail: ron.waksman@medstar.net [Division of Interventional Cardiology, MedStar Washington Hospital Center, Washington, DC 20010 (United States)

    2015-04-15

    Objective: The aim of this study was to compare the safety and efficacy of the everolimus-eluting stents (EES) with the paclitaxel-eluting stent (PES) and sirolimus-eluting stent (SES) for the treatment of bare-metal in-stent restenosis. Background: The optimal treatment for bare-metal in-stent restenosis remains controversial. Methods: The study cohort comprised 322 consecutive patients (543 lesions) who presented with bare-metal in-stent restenosis to our institution and underwent coronary artery stent implantation with EES (114 patients; 181 lesions), PES (65 patients; 116 lesions) and SES (143 patients; 246 lesions). The analyzed clinical parameters were the 1-year rates of death, Q-wave myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), definite stent thrombosis (ST) and major adverse cardiac events (MACE) defined as the composite of death, MI, or TLR at 1-year. Results: The three groups were well matched for the conventional risk factors except for age and chronic kidney disease. The 1-year analyzed clinical parameters were similar in the three groups: death (EES = 3.5%, PES = 4.6%, SES = 4.2%; p = 0.94), MI (EES = 3.5%, PES = 6.3%, SES = 2.1%; p = 0.31), TLR (EES = 9.8%, PES = 9.5%, SES = 5.7%; p = 0.42), TVR (EES = 14.3%, PES = 11.1%, SES = 11.3%; p = 0.74), definite ST (EES = 0.9%, PES = 3.1%, SES = 3.5%; p = 0.38) and MACE (EES = 14.0%, PES = 15.4%, SES = 10.5%; p = 0.54). Male gender (hazard ratio = 0.47; 95% confidence interval = 0.25–0.88) and number of treated lesions (hazard ratio = 1.47; 95% confidence interval = 1.06–2.05) were found to be independent predictors of MACE. Conclusion: The results of the present study indicate that EES may provide similar safety and efficacy as first generation DES for the treatment of patients presenting with bare-metal in-stent restenosis.

  19. Parenting Practices and Problem Behavior across Three Generations: Monitoring, Harsh Discipline, and Drug Use in the Intergenerational Transmission of Externalizing Behavior

    Science.gov (United States)

    Bailey, Jennifer A.; Hill, Karl G.; Oesterle, Sabrina; Hawkins, J. David

    2009-01-01

    Using data from grandparents (G1), parents (G2), and children (G3), this study examined continuity in parental monitoring, harsh discipline, and child externalizing behavior across generations, and the contribution of parenting practices and parental drug use to intergenerational continuity in child externalizing behavior. Structural equation and…

  20. Determinants of protein elution rates from preparative ion-exchange adsorbents.

    Science.gov (United States)

    Angelo, James M; Lenhoff, Abraham M

    2016-04-01

    The rate processes involved in elution in preparative chromatography can affect both peak resolution and hence selectivity as well as practical factors such as facility fit. These processes depend on the physical structure of the adsorbent particles, the amount of bound solute, the solution conditions for operation or some combination of these factors. Ion-exchange adsorbents modified with covalently attached or grafted polymer layers have become widely used in preparative chromatography. Their often easily accessible microstructures offer substantial binding capacities for biomolecules, but elution has sometimes been observed to be undesirably slow. In order to determine which physicochemical phenomena control elution behavior, commercially available cellulosic, dextran-grafted and unmodified agarose materials were characterized here by their elution profiles at various conditions, including different degrees of loading. Elution data were analyzed under the assumption of purely diffusion-limited control, including the role of pore structure properties such as porosity and tortuosity. In general, effective elution rates decreased with the reduction of accessible pore volume, but differences among different proteins indicated the roles of additional factors. Additional measurements and analysis, including the use of confocal laser scanning microscopy to observe elution within single chromatographic particles, indicated the importance of protein association within the particle during elution. The use of protein stabilizing agents was explored in systems presenting atypical elution behavior, and l-arginine and disaccharide excipients were shown to alleviate the effects for one protein, lysozyme, in the presence of sodium chloride. Incorporation of these excipients into eluent buffer gave rise to faster elution and significantly lower pool volumes in elution from polymer-modified adsorbents. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Development of DNA elution method to detect irradiated foodstuff

    International Nuclear Information System (INIS)

    Copin, M.P.; Bourgeois, C.M.

    1991-01-01

    The aim of the work is to develop a reliable method to detect whether a fresh and frozen foodstuff has been irradiated. The molecule of DNA is one of the targets of ionizing radiation. The induction of three major classes of lesion have been shown. Double strand breaks, single strand breaks and base damage. Among the different techniques used to observe and quantify the strand breaks, techniques of elution are very interesting. The method proposed consisted of a filtration of the DNA at the atmospheric pressure and in non denaturing conditions. The amount of DNA retained on the filter is measured after being suitably labelled by microfluorometry. A difference in the amount of DNA retained on a filter of 2 μm from a lysed muscular tissue sample between a frozen Norway lobster which has been irradiated and one which has not, is observed. 7 refs

  2. Alkaline elution of uranium and molybdenum and their recovery

    International Nuclear Information System (INIS)

    Song Wenlan; Wu Peisheng; Zhao Pinzhi; Tao Dening; Xie Chaoyan

    1987-01-01

    The uranium and molybdenum can be simultaneously eluted by using eluant (NH 4 ) 2 CO 3 + (NH 4 ) 2 SO 4 from resin loaded uranium and molybdenum. The ADU is precipitated from eluant by volatilization of ammonia. The molybdenum is extracted by TFA-TBP-kerosene from the filtrate at pH 3.0-3.2 with molybdenum extraction > 98%. Uranium is nearly not extracted. The precipitation of Mo is reached by sulphuric acid after stripping and the ammonium multimolybdate is obtained. This process can give the total recovery more than 99% for U and 90% for Mo. Because of the use of sulphate salt system, the hazard of NO 3 - can be avoided

  3. Quantitation of radiolabeled compounds eluting from the HPLC system

    International Nuclear Information System (INIS)

    Kessler, M.J.

    1982-01-01

    Three techniques are compared for the quantitation of various radiolabeled compounds eluting in the high performance liquid chromatography system. The first technique requires fraction-collecting the effluent from the HPLC, removing an aliquot to scintillation vials, and counting each fraction in a liquid scintillation counter. The second uses direct interface of the HPLC effluent to a flow-through radioactivity detector. The third involves quantitation of various radiolabeled compounds (proteins, steroids, and nucleotides) by splitting the effluent from the HPLC with an electronic steam splitter, thus diverting a present portion to the fraction collector for further chemical characterization and the remainder to the radioactivity flow detector for direct quantitation. A direct comparison of the chromatograms and the radioactivity counting efficiencies of these three techniques is presented

  4. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  5. Intravascular imaging comparison of two metallic limus-eluting stents abluminally coated with biodegradable polymers: IVUS and OCT results of the DESTINY trial.

    Science.gov (United States)

    Costa, J Ribamar; Chamié, Daniel; Abizaid, Alexandre A C; Ribeiro, Expedito; Meireles, George C; Prudente, Maurício; Campos, Carlos A; Castro, Juliana P; Costa, Ricardo; Lemos, Pedro A

    2017-02-01

    We sought to compare, by means of IVUS and OCT imaging, the performance of a novel sirolimus-eluting drug-eluting stent (DES) with biodegradable polymer (Inspiron™) to the Biomatrix™ DES. From the DESTINY trial, a total of 70 randomized patients (2:1) were enrolled in the IVUS substudy (Inspiron™, n = 46; Biomatrix™: n = 20) while 25 patients were evaluated with OCT (Inspiron™, n = 19; Biomatrix™: n = 06) at 9-month follow-up. The main endpoints were % of neointimal tissue obstruction (IVUS) and neointimal stut coverage (OCT) at 9 months. Patients treated with both DES had very little NIH formation at 9 months either by IVUS (% of NIH obstruction of 4.9 ± 4.1 % with Inspiron™ vs. 2.7 ± 2.9 % with Biomatrix™, p = 0.03) or by OCT (neointimal thickness of 144.2 ± 72.5 µm Inspiron™ vs. 115.0 ± 53.9 µm with Biomatrix™, p = 0.45). Regarding OCT strut-level assessment, again both devices showed excellent 9-month performance, with high rates of strut coverage (99.49 ± 1.01 % with Inspiron™ vs. 97.62 ± 2.21 % with Biomatrix™, p < 0.001) and very rare malapposition (0.29 ± 1.06 % with Inspiron™ vs. 0.53 ± 0.82 % with Biomatrix™, p = 0.44). Patients with any uncovered struts were more frequently identified in the Biomatrix™ group (9.78 ± 7.13 vs. 2.29 ± 3.91 %, p < 0.001). In the present study, midterm IVUS and OCT evaluations showed that both new generation DES with biodegradable polymer were effective in terms of suppressing excessive neointimal response, with very high rates of apposed and covered struts, suggesting a consistent and benign healing pattern.

  6. Possibility of obtaining enriched americium-242g by the elution of recoil atoms from zeolite

    Energy Technology Data Exchange (ETDEWEB)

    Shafiev, A I; Vityutnev, V M; Ivanov, V M; Yakovlev, G N

    1974-12-31

    On the example of production the possibility of obtaining enriched actinide isotopes by the elution of recotl atoms with the use of a zeolite- americium-241 target was shown. The enrichment factor and the recoil atoms of / sup 242g/Am yield depend on preliminary target treatment and solution composition used for elution. (auth)

  7. Elution behavior of heavy metals from cement solidified products of incinerated ash waste - 59102

    International Nuclear Information System (INIS)

    Meguro, Yoshihiro; Kawato, Yoshimi; Nakayama, Takuya; Tomioka, Osamu; Mitsuda, Motoyuki

    2012-01-01

    A method, in which incinerated ash is solidified with a cement material, has been developed to dispose radioactive incinerated ash waste. In order to bury the solidified product, it is required that elution of hazardous heavy metals included in the ash from the solidified products is inhibited. In this study, the elution behavior of the heavy metals from the synthetic solidified products, which included Pb(II), Cd(II), and Cr(VI) and were prepared using ordinary portland cement (OPC), blast furnace slag cement (BFS), or a cement material that showed low alkalinity (LA-Cement), was investigated. Several chemicals and materials were added as additive agents to prevent the elution of the heavy metals. When OPC was used, Cd elution was inhibited, but Pb and Cr were not enough even using the additive agent examined. FeSO 4 and Na 2 S additive agents worked effective to inhibit elution of Cr. When BFS was used, the elution of Pb, Cd and Cr was inhibited for the all products prepared. In the case of LA-Cement, the elution of Pb and Cd was inhibited for the all products, but only the product that was added FeSO 4 showed good result of the elution of Cr. (authors)

  8. Alternative sample-introduction technique to avoid breakthrough in gradient-elution liquid chromatography of polymers

    NARCIS (Netherlands)

    Reingruber, E.; Bedani, F.; Buchberger, W.; Schoenmakers, P.

    2010-01-01

    Gradient-elution liquid chromatography (GELC) is a powerful tool for the characterization of synthetic polymers. However, gradient-elution chromatograms often suffer from breakthrough phenomena. Breakthrough can be averted by using a sample solvent as weak as the mobile phase. However, this approach

  9. Evaluation of the short- and long-term safety and therapy outcomes of the everolimus-eluting bioresorbable vascular scaffold system in patients with coronary artery stenosis: Rationale and design of the German–Austrian ABSORB RegIstRy (GABI-R)

    Energy Technology Data Exchange (ETDEWEB)

    Nef, Holger, E-mail: holger.nef@innere.med.uni-giessen.de [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Wiebe, Jens [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Achenbach, Stefan [University of Erlangen, Medizinische Klinik II, Department of Cardiology, Erlangen (Germany); Münzel, Thomas [Department of Medicine II, University Medical Center, Johannes Gutenberg University Mainz, Mainz (Germany); Naber, Christoph [Klinik für Kardiologie und Angiologie, Elisabeth-Krankenhaus, Essen (Germany); Richardt, Gert [Herzzentrum, Segeberger Kliniken GmbH, Bad Segeberg (Germany); Mehilli, Julinda [Department of Cardiology, Klinikum Großhadern, Ludwig- Maximilian Universität, Munich (Germany); Wöhrle, Jochen [Department of Internal Medicine II, University of Ulm, Ulm (Germany); Neumann, Till; Biermann, Janine [University of Essen, Department of Cardiology, Essen (Germany); Zahn, Ralf [Abteilung für Kardiologie, Herzzentrum Ludwigshafen, Ludwigshafen (Germany); Kastner, Johannes [Department of Cardiology, University of Vienna Medical School, Vienna (Austria); Schmermund, Axel [CCB, Cardioangiologisches Centrum Bethanien, Frankfurt (Germany); Pfannebecker, Thomas [Abbott Vascular Deutschland GmbH, Wetzlar (Germany); Schneider, Steffen; Limbourg, Tobias [Institut für Herzinfarktforschung, Ludwigshafen (Germany); Hamm, Christian W. [University of Giessen, Medizinische Klinik I, Department of Cardiology, Giessen (Germany); Kerckhoff Heart and Thorax Center, Department of Cardiology, Bad Nauheim (Germany)

    2016-01-15

    Background: Third-generation drug-eluting metal stents are the gold standard for treatment of coronary artery disease. The permanent metallic caging of the vessel, however, can result in limited vasomotion, chronic inflammation, and late expansive remodeling, conditions that can lead to late and very late stent thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages over metal stents due to complete biodegradation within 2–4 years. Theoretically, since vessel scaffolding is temporary and no permanent implant remains in the vessel, BRSs, as opposed to metal stents, once degraded would no longer be potential triggers for stent-related adverse events or side effects. Methods/design: The short- and long-term outcome after implantation of an everolimus-eluting, poly-L-lactic acid-based bioresorbable scaffold system (ABSORB, Abbott Vascular, Santa Clara, CA, USA) in the world-wide greatest all-comers cohort will be evaluated in the prospective, non-interventional, multicenter German–Austrian ABSORB RegIstRy (GABI-R). GABI-R will include over 5000 patients from about 100 study sites in Austria and Germany. Safety endpoints such as cardiac death, myocardial infarction, and clinically driven percutaneous or surgical target lesion and vessel revascularization will be evaluated during hospitalization and in the follow-up period (minimum of 5 years). Conclusion: Although two randomized controlled trials and several registries have documented safety and efficacy as well as non-inferiority of this everolimus-eluting ABSORB device compared with drug-eluting metal stents, the current knowledge regarding clinical application, treatment success, and long-term safety of using this BRS in daily routine is limited. Thus, the goal of GABI-R is to address this lack of information. - Highlights: • The GABI-R addresses a lack of data about bioresorbable scaffolds in daily practice. • 5000 patients with minimal in- and exclusion criteria at 100 sites will

  10. Evaluation of the short- and long-term safety and therapy outcomes of the everolimus-eluting bioresorbable vascular scaffold system in patients with coronary artery stenosis: Rationale and design of the German–Austrian ABSORB RegIstRy (GABI-R)

    International Nuclear Information System (INIS)

    Nef, Holger; Wiebe, Jens; Achenbach, Stefan; Münzel, Thomas; Naber, Christoph; Richardt, Gert; Mehilli, Julinda; Wöhrle, Jochen; Neumann, Till; Biermann, Janine; Zahn, Ralf; Kastner, Johannes; Schmermund, Axel; Pfannebecker, Thomas; Schneider, Steffen; Limbourg, Tobias; Hamm, Christian W.

    2016-01-01

    Background: Third-generation drug-eluting metal stents are the gold standard for treatment of coronary artery disease. The permanent metallic caging of the vessel, however, can result in limited vasomotion, chronic inflammation, and late expansive remodeling, conditions that can lead to late and very late stent thrombosis. The development of bioresorbable scaffolds (BRSs) promises advantages over metal stents due to complete biodegradation within 2–4 years. Theoretically, since vessel scaffolding is temporary and no permanent implant remains in the vessel, BRSs, as opposed to metal stents, once degraded would no longer be potential triggers for stent-related adverse events or side effects. Methods/design: The short- and long-term outcome after implantation of an everolimus-eluting, poly-L-lactic acid-based bioresorbable scaffold system (ABSORB, Abbott Vascular, Santa Clara, CA, USA) in the world-wide greatest all-comers cohort will be evaluated in the prospective, non-interventional, multicenter German–Austrian ABSORB RegIstRy (GABI-R). GABI-R will include over 5000 patients from about 100 study sites in Austria and Germany. Safety endpoints such as cardiac death, myocardial infarction, and clinically driven percutaneous or surgical target lesion and vessel revascularization will be evaluated during hospitalization and in the follow-up period (minimum of 5 years). Conclusion: Although two randomized controlled trials and several registries have documented safety and efficacy as well as non-inferiority of this everolimus-eluting ABSORB device compared with drug-eluting metal stents, the current knowledge regarding clinical application, treatment success, and long-term safety of using this BRS in daily routine is limited. Thus, the goal of GABI-R is to address this lack of information. - Highlights: • The GABI-R addresses a lack of data about bioresorbable scaffolds in daily practice. • 5000 patients with minimal in- and exclusion criteria at 100 sites will

  11. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    International Nuclear Information System (INIS)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young; Yuk, Soon Hong; Lee, Yong Seok

    2005-01-01

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models

  12. Influence of paclitaxel-eluting expandable metallic stent on tissue hyperplasia: an experimental study in a canine tracheal model

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ji Hoon; Kim, Jung Sun; Kim, Tae Hyung; Kim, Eun Young; Choi, Won Chan; Woo, Chul Woong; Di, Zhenhai; Song, Ho Young [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yuk, Soon Hong [Hannam University, College of Engineering, Daejeon (Korea, Republic of); Lee, Yong Seok [Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2005-07-15

    To evaluate the efficacy of a paclitaxel-eluting expandable metallic stent in reducing tissue hyperplasia following stent placement in a canine tracheal model. Nine paclitaxel-eluting stents (drug stent, DS) consisting of a proximal bare part and a distal polyurethane-covered part were placed in the trachea of nine dogs and nine control stents (control stent, CS) were placed in the other nine dogs. The dogs were scheduled to be sacrificed 12 weeks after stent placement. Gross and histological factors, such as epithelial erosion/ulcer, granulation tissue thickness and inflammatory cell infiltration were evaluated after each dog was sacrificed. There were no procedure-related complications or malpositioning of any of the stents. One CS migrated less than eight weeks following stent placement. Four dogs (one DS and three CS dogs) died between three and five weeks following stent placement. Therefore, pathologic specimens were obtained from eight DS and five CS dogs. Epithelial erosion/ulcer or inflammatory cell infiltration was slightly more prominent in the DS cases than in the CS cases, in both the bare part and the covered part. However, the data was not statistically significant. Granulation tissue thickness was lower in the DS cases than in the CS cases in both the bare part (mean, 3.63-mm vs. 4.37-mm) and the covered part (mean, 1.75-mm vs. 2,78 mm), but the data was also statistically insignificant. Although the data was not statistically significant, placement of paclitaxel-eluting expandable metallic stent demonstrates a tendency toward a decrease in granulation tissue thickness in canine tracheal models.

  13. Selective elution of HLA antigens and beta 2-microglobulin from human platelets by chloroquine diphosphate

    International Nuclear Information System (INIS)

    Kao, K.J.

    1988-01-01

    To determine whether chloroquine can specifically elute HLA antigens and beta 2-microglobulin (beta 2-M) from the platelet surface, quantitative immunofluorescence flow cytometry and monoclonal antibodies were used to show that HLA antigens and beta 2-M were proportionally eluted from the platelet surface without affecting the membrane glycoproteins IIb and IIIa. Second, an autoradiogram of electrophoresed I-125-labeled platelets showed that only beta 2-M but not other I-125-labeled membrane proteins could be eluted. Although HLA antigens were poorly labeled by I-125 and could not be detected on the autoradiogram, the eluted HLA antigens could be detected by anti-HLA monoclonal antibody and immunoblotting techniques. No loss of plasma membrane integrity was observed by transmission electron microscopy after chloroquine treatment of platelets. The results indicate that chloroquine selectively elutes HLA antigens and their noncovalently associated beta 2-M without affecting other integral platelet membrane proteins

  14. Vorinostat-eluting poly(DL-lactide-co-glycolide nanofiber-coated stent for inhibition of cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Kwak TW

    2017-10-01

    activity against CCA cells in vitro and in vivo. We suggest the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment. Keywords: vorinostat, nanofiber, GI stent, cholangiocarcinoma, drug eluting

  15. Analysis of Biological Samples Using Paper Spray Mass Spectrometry: An Investigation of Impacts by the Substrates, Solvents and Elution Methods.

    Science.gov (United States)

    Ren, Yue; Wang, He; Liu, Jiangjiang; Zhang, Zhiping; McLuckey, Morgan N; Ouyang, Zheng

    2013-10-01

    Paper spray has been developed as a fast sampling ionization method for direct analysis of raw biological and chemical samples using mass spectrometry (MS). Quantitation of therapeutic drugs in blood samples at high accuracy has also been achieved using paper spray MS without traditional sample preparation or chromatographic separation. The paper spray ionization is a process integrated with a fast extraction of the analyte from the raw sample by a solvent, the transport of the extracted analytes on the paper, and a spray ionization at the tip of the paper substrate with a high voltage applied. In this study, the influence on the analytical performance by the solvent-substrate systems and the selection of the elution methods was investigated. The protein hemoglobin could be observed from fresh blood samples on silanized paper or from dried blood spots on silica-coated paper. The on-paper separation of the chemicals during the paper spray was characterized through the analysis of a mixture of the methyl violet 2B and methylene blue. The mode of applying the spray solvent was found to have a significant impact on the separation. The results in this study led to a better understanding of the analyte elution, on-paper separation, as well as the ionization processes of the paper spray. This study also help to establish a guideline for optimizing the analytical performance of paper spray for direct analysis of target analytes using mass spectrometry.

  16. Parenting practices and problem behavior across three generations: Monitoring, harsh discipline, and drug use in the intergenerational transmission of externalizing behavior

    OpenAIRE

    Bailey, Jennifer A.; Hill, Karl G.; Oesterle, Sabrina; Hawkins, J. David

    2009-01-01

    Using data from grandparents (G1), parents (G2), and children (G3), this study examined continuity in parental monitoring, harsh discipline, and child externalizing behavior across generations, and the contribution of parenting practices and parental drug use to intergenerational continuity in child externalizing behavior. Structural equation and path modeling of prospective, longitudinal data from 808 G2 participants, their G1 parents, and their school-aged G3 children (n = 136) showed that ...

  17. Towards enhanced automated elution systems for waterborne protozoa using megasonic energy.

    Science.gov (United States)

    Horton, B; Katzer, F; Desmulliez, M P Y; Bridle, H L

    2018-02-01

    Continuous and reliable monitoring of water sources for human consumption is imperative for public health. For protozoa, which cannot be multiplied efficiently in laboratory settings, concentration and recovery steps are key to a successful detection procedure. Recently, the use of megasonic energy was demonstrated to recover Cryptosporidium from commonly used water industry filtration procedures, forming thereby a basis for a simplified and cost effective method of elution of pathogens. In this article, we report the benefits of incorporating megasonic sonication into the current methodologies of Giardia duodenalis elution from an internationally approved filtration and elution system used within the water industry, the Filta-Max®. Megasonic energy assisted elution has many benefits over current methods since a smaller final volume of eluent allows removal of time-consuming centrifugation steps and reduces manual involvement resulting in a potentially more consistent and more cost-effective method. We also show that megasonic sonication of G. duodenalis cysts provides the option of a less damaging elution method compared to the standard Filta-Max® operation, although the elution from filter matrices is not currently fully optimised. A notable decrease in recovery of damaged cysts was observed in megasonic processed samples, potentially increasing the abilities of further genetic identification options upon isolation of the parasite from a filter sample. This work paves the way for the development of a fully automated and more cost-effective elution method of Giardia from water samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. An optimized method for elution of enteroviral RNA from a cellulose-based substrate.

    Science.gov (United States)

    Li, Yan; Yoshida, Hiromu; Wang, Lu; Tao, Zexin; Wang, Haiyan; Lin, Xiaojuan; Xu, Aiqiang

    2012-12-01

    The Flinders Technology Australia (FTA) Elute Card is a commercial product that facilitates the collection, transport, archiving and processing of nucleic acids from a wide variety of biological samples at room temperature. While the cards have been designed so that sterile/deionized water can elute DNA easily, they are not suitable for some less stable RNAs. This study was undertaken to determine the optimal conditions such as the buffer type, buffer pH and incubation temperature for the elution of enteroviral RNA from FTA Elute Cards prior to quantitative analysis using real-time PCR (qPCR) or consensus degenerate hybrid oligonucleotide primer VP1 RT-semi nested PCR (CODEHOP VP1 RT-snPCR). TE-1 (pH 8.0), rather than sterile water, was the best buffer for high efficiency elution of enteroviral RNA at 95°C. However, as the estimated recovery rate of viral RNA eluted from the cards averaged to be only 6.1%, enterovirus assays using FTA elution should be considered qualitative, especially at low virus titers, and therefore the results of the assay should be interpreted carefully. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Alkaline elution of DNA from mammalian cells on cellulose triacetate filters

    International Nuclear Information System (INIS)

    Moss, A.J. Jr.; Nagle, W.A.; Henle, K.J.; Prior, R.M.

    1984-01-01

    The alkaline elution technique is widely used for the estimation of cellular DNA damage because of its sensitivity in the biologically relevant dose range. The authors have extended the original studies and provide additional characterization of the cellulose triacetate alkaline elution method. This filter material permits the elution of approximately 80 percent of cellular DNA from untreated V79 cells. the total radioactivity in the system was compartmentalized with respect to 1) lysing solution, 2) washing solution, 3) elution fractions, and 4) membrane retained activity. In these studies [/sup 3/H]-thymidine labeled untreated internal control cells were co-eluted with X-irradiated [/sup 14/C]-thymidine labeled cells. For the estimation of DNA damage, elution profiles for treated cells were directly compared with untreated internal control cells. The quantity of DNA eluting in excess of the labeled internal control per fraction is directly proportional to the extent of DNA damage in the treated sample. Using the technique the necessity of an irradiated internal control is eliminated

  20. Description of the Retention and Peak Profile for Chromolith Columns in Isocratic and Gradient Elution Using Mobile Phase Composition and Flow Rate as Factors

    Directory of Open Access Journals (Sweden)

    Elsa Cabo-Calvet

    2014-11-01

    Full Text Available The effect of the modifier concentration and flow rate on the chromatographic performance of a second generation Chromolith® RP-18e column, under isocratic and gradient elution with acetonitrile-water mixtures, was examined using four sulphonamides as probe compounds. The acetonitrile concentration was varied between 5 and 55% (v/v, and the flow rate between 0.1 and 5.0 mL/min, keeping the other factors constant. The changes in both retention and peak profile were modelled, and used to build simple plots, where the logarithm of the retention factor was represented against the modifier concentration (in gradient elution, against the initial modifier concentration, and the half-widths or widths against the retention time (in gradient elution, against the time at the column outlet. A particular plot was needed for describing the retention of each sulphonamide, but due to the similar interaction kinetics, a unique plot described the changes in the half-widths for all four sulphonamides. The changes in retention with the flow showed that allegedly in the second generation Chromolith, the column deformation observed for the first generation Chromolith, with the applied pressure at increasing flow, is decreased.

  1. Electrospun 4th-Generation Solid Dispersions of Poorly Water-Soluble Drug Utilizing Two Different Processes

    Directory of Open Access Journals (Sweden)

    Zhu Zhang

    2018-01-01

    Full Text Available Different from traditional solid dispersion (SD for improving the dissolution rates of poorly water-soluble drugs, the upgraded 4th SD was developed to furnish a drug sustained-release profile. In this work, two different kinds of 4th SDs were fabricated using two electrospinning processes. One is a ternary SD (nanofibers F2 that consisted of ethyl cellulose (EC, polyethylene glycol 1000 (PEG, and tamoxifen citrate (TAM from a modified coaxial process, and the other is a binary SD (nanofibers F1 which is comprised of EC and TAM from a single-fluid blending process. Scanning electronic microscopic observations demonstrated that F2 (330±50 nm showed a better quality than F1 (870±230 nm in terms of size and size distribution although both of them had a smooth surface morphology and a cross section. X-ray diffraction patterns verified that both SDs were amorphous nanocomposites owing to the favorable secondary interactions among these components, as suggested from the results of FTIR. In vitro dissolution experiments indicated that F2 could furnish an improved drug sustained-release characteristics compared to F1, exhausting all the contained TAM and having weaker leveling-off late release. The molecular behaviors of drug sustained-release from the binary 4th SD were suggested. The protocols reported here paved an alternative way for developing novel functional nanomaterials for effective delivery of poorly water-soluble drugs.

  2. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial

    DEFF Research Database (Denmark)

    Rasmussen, Klaus; Maeng, Michael; Kaltoft, Anne

    2010-01-01

    BACKGROUND: In low-risk patients, the zotarolimus-eluting stent has been shown to reduce rates of restenosis without increasing the risk of stent thrombosis. We compared the efficacy and safety of the zotarolimus-eluting stent versus the sirolimus-eluting stent in patients with coronary artery...... disease who were receiving routine clinical care with no direct follow-up. METHODS: We did a single-blind, all-comer superiority trial in adult patients with chronic stable coronary artery disease or acute coronary syndromes, and at least one target lesion. Patients were treated at one of five...... Danish administrative and health-care registries. The primary endpoint was a composite of major adverse cardiac events within 9 months: cardiac death, myocardial infarction, and target vessel revascularisation. Intention-to-treat analyses were done at 9-month and 18-month follow-up. This trial...

  3. Randomised comparison of a bioresorbable everolimus-eluting scaffold with a metallic everolimus-eluting stent for ischaemic heart disease caused by de novo native coronary artery lesions

    DEFF Research Database (Denmark)

    Chevalier, Bernard; Onuma, Yoshinobu; van Boven, Ad J

    2016-01-01

    AIMS: The one-year randomised data of the ABSORB II trial showed that the everolimus-eluting bioresorbable scaffold and the everolimus-eluting metallic stent were comparable for the composite secondary clinical outcomes of patient-oriented composite endpoint (PoCE) and device-oriented composite...... Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (XIENCE; Abbott Vascular). The trial enrolled 501 patients. Clinical follow-up at two years was available in 320 patients in the Absorb BVS arm and 160 patients in the XIENCE arm. At two years, the PoCE for the Absorb and XIENCE arms......-six percent and 34% of patients remained on DAPT at two years, respectively. Ninety-two percent of patients in both arms remained on aspirin. CONCLUSIONS: Two-year clinical results demonstrate sustained low rates of PoCE, MACE, DoCE and TVF with the Absorb BVS as compared to the XIENCE stent....

  4. Stent coverage and neointimal proliferation in bare metal stents postdilated with a Paclitaxel-eluting balloon versus everolimus-eluting stents: prospective randomized study using optical coherence tomography at 6-month follow-up.

    Science.gov (United States)

    Poerner, Tudor C; Otto, Sylvia; Gassdorf, Johannes; Nitsche, Kristina; Janiak, Florian; Scheller, Bruno; Goebel, Björn; Jung, Christian; Figulla, Hans R

    2014-12-01

    In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up. http://www.clinicaltrials.gov. Unique identifier: NCT01056744. © 2014 American Heart Association, Inc.

  5. Optimization of elution salt concentration in stepwise elution of protein chromatography using linear gradient elution data. Reducing residual protein A by cation-exchange chromatography in monoclonal antibody purification.

    Science.gov (United States)

    Ishihara, Takashi; Kadoya, Toshihiko; Endo, Naomi; Yamamoto, Shuichi

    2006-05-05

    Our simple method for optimization of the elution salt concentration in stepwise elution was applied to the actual protein separation system, which involves several difficulties such as detection of the target. As a model separation system, reducing residual protein A by cation-exchange chromatography in human monoclonal antibody (hMab) purification was chosen. We carried out linear gradient elution experiments and obtained the data for the peak salt concentration of hMab and residual protein A, respectively. An enzyme-linked immunosorbent assay was applied to the measurement of the residual protein A. From these data, we calculated the distribution coefficient of the hMab and the residual protein A as a function of salt concentration. The optimal salt concentration of stepwise elution to reduce the residual protein A from the hMab was determined based on the relationship between the distribution coefficient and the salt concentration. Using the optimized condition, we successfully performed the separation, resulting in high recovery of hMab and the elimination of residual protein A.

  6. Support housing for radioisotope generation

    International Nuclear Information System (INIS)

    Fries, B.A.

    1976-01-01

    A support housing for on-site radioisotope generation is disclosed in which the formation of a short-lived daughter radioisotope from its longer-lived parent features countercurrent batch flow of the eluting reagent interior of the housing. 6 claims, 4 drawing figures

  7. Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.

    Science.gov (United States)

    Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

    2010-02-02

    Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.

  8. Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey.

    Science.gov (United States)

    Tagliani, Elisa; Hassan, Mohamed Osman; Waberi, Yacine; De Filippo, Maria Rosaria; Falzon, Dennis; Dean, Anna; Zignol, Matteo; Supply, Philip; Abdoulkader, Mohamed Ali; Hassangue, Hawa; Cirillo, Daniela Maria

    2017-12-15

    Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.

  9. Bicarbonate Elution of Uranium from Amidoxime-Based Polymer Adsorbents for Sequestering Uranium from Seawater

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Horng-Bin [Department of Chemistry, University of Idaho, Moscow, Idaho 83844 USA; Wai, Chien M. [Department of Chemistry, University of Idaho, Moscow, Idaho 83844 USA; Kuo, Li-Jung [Pacific Northwest National Laboratory, Marine Sciences Laboratory, Sequim, Washington 98382 USA; Gill, Gary [Pacific Northwest National Laboratory, Marine Sciences Laboratory, Sequim, Washington 98382 USA; Tian, Guoxin [Lawrence Berkeley National Laboratory, Berkeley, California 94720 USA; Rao, Linfeng [Lawrence Berkeley National Laboratory, Berkeley, California 94720 USA; Das, Sadananda [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 USA; Mayes, Richard T. [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 USA; Janke, Christopher J. [Materials Science and Technology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 USA

    2017-05-02

    Uranium adsorbed on amidoxime-based polyethylene fibers in simulated seawater can be quantitatively eluted using 3 M KHCO3 at 40°C. Thermodynamic calculations are in agreement with the experimental observation that at high bicarbonate concentrations (3 M) uranyl ions bound to amidoxime molecules are converted to uranyl tris-carbonato complex in the aqueous solution. The elution process is basically the reverse reaction of the uranium adsorption process which occurs at a very low bicarbonate concentration (~10-3 M) in seawater. In real seawater experiments, the bicarbonate elution is followed by a NaOH treatment to remove natural organic matter adsorbed on the polymer adsorbent. Using the sequential bicarbonate and NaOH elution, the adsorbent is reusable after rinsing with deionized water and the recycled adsorbent shows no loss of uranium loading capacity based on real seawater experiments.

  10. The application of PLC automatic control system for resin transfer in pulsed elution

    International Nuclear Information System (INIS)

    Long Maoxiong

    2001-01-01

    An application of Programmable Logic Controller (PLC) in automatic control system for resin transfer in pulsed elution column is described. The design principle as well as hardware and software are also described in detail

  11. Alendronate-Eluting Biphasic Calcium Phosphate (BCP Scaffolds Stimulate Osteogenic Differentiation

    Directory of Open Access Journals (Sweden)

    Sung Eun Kim

    2015-01-01

    Full Text Available Biphasic calcium phosphate (BCP scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN- eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM, energy-dispersive X-ray spectroscopy (EDS, and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR. An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation.

  12. Boron removal from aqueous solutions by ion-exchange resin: Column sorption-elution studies

    International Nuclear Information System (INIS)

    Koese, T. Ennil; Oztuerk, Nese

    2008-01-01

    A column sorption-elution study was carried out by using a strong base anion-exchange resin (Dowex 2 x 8) for the removal of boron from aqueous solutions. The breakthrough curve was obtained as a function of feed flow rate and the total and breakthrough capacity values of the resin were calculated. The boron on the resin was quantitatively eluted with 0.5 M HCl solution at different flow rates. Three consecutive sorption-elution-washing-regeneration-washing cycles were applied to the resin in order to investigate the reusability of the ion-exchange resin. Total capacity values remained almost the same after three sorption-elution-regeneration cycles. The Thomas and the Yoon-Nelson models were applied to experimental data to predict the breakthrough curves and to determine the characteristic column parameters required for process design. The results proved that the models would describe the breakthrough curves well

  13. Preparation and characterization of iron(III) {sup 99}Mo-molybdate(VI) gels for the assessment of {sup 99m}Tc elution performance

    Energy Technology Data Exchange (ETDEWEB)

    Amin, Mahmoud; Fasih, Tharwat W.; El-Absy, Mohamed A. [Egyptian Atomic Energy Authority, Cairo (Egypt)

    2018-04-01

    New iron(III) {sup 99}Mo-molybdate(VI) gels (Fe{sup 99}Mo) of high Mo content were prepared by the precipitation/filtration method. {sup 99}Mo-MoO{sub 3} dissolved in NaOH was added to aqueous solutions of Fe(NO{sub 3}){sub 3} at Mo/Fe mole fractions ∝2.21 and 1.99 with continuous stirring at ambient room temperature. Two different Fe{sup 99}Mo were precipitated from the mixed solutions adjusted at pH 2 and 4.7. The amount of water of hydration increased with the increasing the gel settling time and pH of the mixed solution. The matrices were characterized by radiometric, XRD, SEM, XRF, FT-IR, TGA, and DTA measurements. Small chromatographic columns of 2.0 g Fe{sup 99}Mo containing ≥800 mg Mo tagged with 740 MBq {sup 99}Mo were eluted with 5 mL saline solution. Highly reproducible {sup 99m}Tc elution indices suitable for preparation of {sup 99}Mo/{sup 99m}Tc generators were achieved from generator supported with 0.5 g Al{sub 2}O{sub 3} filter. Elution performance of {sup 99m}Tc radionuclide was highly dependent on the gel structural properties.

  14. Preparation and characterization of iron(III) 99Mo-molybdate(VI) gels for the assessment of 99mTc elution performance

    International Nuclear Information System (INIS)

    Amin, Mahmoud; Fasih, Tharwat W.; El-Absy, Mohamed A.

    2018-01-01

    New iron(III) 99 Mo-molybdate(VI) gels (Fe 99 Mo) of high Mo content were prepared by the precipitation/filtration method. 99 Mo-MoO 3 dissolved in NaOH was added to aqueous solutions of Fe(NO 3 ) 3 at Mo/Fe mole fractions ∝2.21 and 1.99 with continuous stirring at ambient room temperature. Two different Fe 99 Mo were precipitated from the mixed solutions adjusted at pH 2 and 4.7. The amount of water of hydration increased with the increasing the gel settling time and pH of the mixed solution. The matrices were characterized by radiometric, XRD, SEM, XRF, FT-IR, TGA, and DTA measurements. Small chromatographic columns of 2.0 g Fe 99 Mo containing ≥800 mg Mo tagged with 740 MBq 99 Mo were eluted with 5 mL saline solution. Highly reproducible 99m Tc elution indices suitable for preparation of 99 Mo/ 99m Tc generators were achieved from generator supported with 0.5 g Al 2 O 3 filter. Elution performance of 99m Tc radionuclide was highly dependent on the gel structural properties.

  15. EW-7197 eluting nano-fiber covered self-expandable metallic stent to prevent granulation tissue formation in a canine urethral model.

    Directory of Open Access Journals (Sweden)

    Kichang Han

    Full Text Available To evaluate an EW-7197-eluting nanofiber-covered stent (NFCS for suppressing granulation tissue formation after stent placement in a canine urethral model.All experiments were approved by the committee of animal research. A total of 12 NFCSs were placed in the proximal and distal urethras of six dogs. Dogs were divided into two groups with 3 dogs each. The control stent (CS group received NFCSs and the drug stent (DS group received EW-7197 (1000 μg-eluting NFCSs. All dogs were sacrificed 8 weeks after stent placement Histologic findings of the stented urethra were compared using the Mann-Whitney U test.Stent placement was technically successful in all dogs without procedure-related complications. On urethrographic analysis, the mean luminal diameter was significantly larger in the DS group than in the CS group at 4 and 8 weeks after stent placement (all p 0.05.The EW-7197-eluting NFCS is effective and safe for suppressing granulation tissue formation after stent placement in a canine urethral model.

  16. Direct elution of sup(99m)Tc complexes from neutron irradiation produced 99Mo incorporated in a MoCl2-MoBr2 mixture

    International Nuclear Information System (INIS)

    Ganzerli Valentini, M.T.; Stella, R.; Genova, N.

    1987-01-01

    A novel type of sup(99m)Tc generator, enabling radiopharmaceutical preparation without reductant addition, was prepared and tested. Neutron activated product 99 Mo, in the form of dichloride cluster, was incorporated into inactive molybdenum dichloride-dibromide mixture (MCB) that was left to settle over an activated alumina layer. Direct elution with aqueous ligands such as salicylate or iminodiacetate derivatives in the pH range 6.5-7.5 yielded chemically stable sup(99m)Tc complexes accompanied by small amounts of secondary products (mostly sup(99m)TcO - 4 ). Pentavalent oxidation state in the salicylate complex and tervalent in the iminodiacetate (IDA) and in the N-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetate (HIDA) complexes were assigned to the element after comparison with reference complexes. The anion exchange version of reverse-phase HPLC was used to resolve the eluted product mixture. (author)

  17. Development of an elution device for ViroCap virus filters.

    Science.gov (United States)

    Fagnant, Christine Susan; Toles, Matthew; Zhou, Nicolette Angela; Powell, Jacob; Adolphsen, John; Guan, Yifei; Ockerman, Byron; Shirai, Jeffry Hiroshi; Boyle, David S; Novosselov, Igor; Meschke, John Scott

    2017-10-19

    Environmental surveillance of waterborne pathogens is vital for monitoring the spread of diseases, and electropositive filters are frequently used for sampling wastewater and wastewater-impacted surface water. Viruses adsorbed to electropositive filters require elution prior to detection or quantification. Elution is typically facilitated by a peristaltic pump, although this requires a significant startup cost and does not include biosafety or cross-contamination considerations. These factors may pose a barrier for low-resource laboratories that aim to conduct environmental surveillance of viruses. The objective of this study was to develop a biologically enclosed, manually powered, low-cost device for effectively eluting from electropositive ViroCap™ virus filters. The elution device described here utilizes a non-electric bilge pump, instead of an electric peristaltic pump or a positive pressure vessel. The elution device also fully encloses liquids and aerosols that could contain biological organisms, thereby increasing biosafety. Moreover, all elution device components that are used in the biosafety cabinet are autoclavable, reducing cross-contamination potential. This device reduces costs of materials while maintaining convenience in terms of size and weight. With this new device, there is little sample volume loss due to device inefficiency, similar virus yields were demonstrated during seeded studies with poliovirus type 1, and the time to elute filters is similar to that required with the peristaltic pump. The efforts described here resulted in a novel, low-cost, manually powered elution device that can facilitate environmental surveillance of pathogens through effective virus recovery from ViroCap filters while maintaining the potential for adaptability to other cartridge filters.

  18. PeptideNavigator: An interactive tool for exploring large and complex data sets generated during peptide-based drug design projects.

    Science.gov (United States)

    Diller, Kyle I; Bayden, Alexander S; Audie, Joseph; Diller, David J

    2018-01-01

    There is growing interest in peptide-based drug design and discovery. Due to their relatively large size, polymeric nature, and chemical complexity, the design of peptide-based drugs presents an interesting "big data" challenge. Here, we describe an interactive computational environment, PeptideNavigator, for naturally exploring the tremendous amount of information generated during a peptide drug design project. The purpose of PeptideNavigator is the presentation of large and complex experimental and computational data sets, particularly 3D data, so as to enable multidisciplinary scientists to make optimal decisions during a peptide drug discovery project. PeptideNavigator provides users with numerous viewing options, such as scatter plots, sequence views, and sequence frequency diagrams. These views allow for the collective visualization and exploration of many peptides and their properties, ultimately enabling the user to focus on a small number of peptides of interest. To drill down into the details of individual peptides, PeptideNavigator provides users with a Ramachandran plot viewer and a fully featured 3D visualization tool. Each view is linked, allowing the user to seamlessly navigate from collective views of large peptide data sets to the details of individual peptides with promising property profiles. Two case studies, based on MHC-1A activating peptides and MDM2 scaffold design, are presented to demonstrate the utility of PeptideNavigator in the context of disparate peptide-design projects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Elution of lead from lead zirconate titanate ceramics to acid rain

    Science.gov (United States)

    Tsurumi, Takaaki; Takezawa, Shuhei; Hoshina, Takuya; Takeda, Hiroaki

    2017-10-01

    The amount of lead that eluted from lead zirconate titanate (PZT) ceramics to artificial acid rain was evaluated. Four kinds of PZT ceramics, namely, pure PZT at MPB composition, CuO-added PZT, PZT with 10 mol % substitution of Ba for Pb, and CuO-added PZT with 10 mol % substitution of Ba for Pb, were used as samples of the elution test. These PZT ceramics of 8 mm2 and 1.1-1.2 mm thickness were suspended in 300 ml of H2SO4 solution of pH 4.0. The concentration of lead eluted from PZT was in the range from 0.2 to 0.8 ppm. It was found that both liquid phase formation by the addition of CuO and the substitution of Ba for Pb were effective to reduce the amount of lead that eluted. By fitting the leaching out curve with a classical equation, a master curve assuming no sampling effect was obtained. The lead concentration evaluated from the amount of lead that eluted from a commercial PZT plate to H2SO4 solution of pH 5.3 was almost the same as the limit in city water. It is concluded that PZT is not harmful to health and the environment and the amount of lead that eluted from PZT can be controlled by modifying PZT composition.

  20. Radioactive cesium elution speed in dried wild Mushrooms collected in 2015

    International Nuclear Information System (INIS)

    Yamaguchi, Toshiro; Arai, Hirotsugu; Ohnuma, Tohru; Arai, Hiromu; Takyu, Sodai; Matsuyama, Tetsuo; Ishii, Keizo

    2016-01-01

    Dried wild mushrooms (12 species, 13 samples) collected in Nagano, Fukushima, and Miyagi Prefectures, Japan, in 2015 were immersed in water for 1,440 min. The elution rate of radioactive cesium (Cs) was calculated based on its radioactivity, which was measured with a high-purity germanium semiconductor detector (GX2018; CANBERRA Industries, Meriden, CT, USA) before and after immersion for each mushroom. Immersion fluid was sampled after 10, 30, 60, 180, 360, and 1,440 min of immersion and dried on aluminum foil. Then, imaging plates (BAS-III, Fujifilm, Tokyo, Japan) exposed to the dried immersion fluid were measured with a Bio-imaging Analyzer System-1800 II (Fujifilm). The 50% elution time of each wild mushroom was calculated based on the photo stimulated luminescence density of the autoradiographs. The radioactive Cs elution rate was > 80% for 11 samples (84% of total) comprising 11 mushroom species. Moreover, the 50% elution time was < 30 min for 9 samples (69% of total) comprising 9 species. This shows that the radioactive Cs elution rate and elution speed were not constant among mushroom species. Based on these results, immersing the mushrooms, which were dried, in water for at least 120 min is an effective method for removing radioactive Cs from wild mushrooms. (author)

  1. Randomized comparison between intracoronary β-radiation brachytherapy and implantation of paclitaxel-eluting stents for the treatment of diffuse in-stent restenosis

    International Nuclear Information System (INIS)

    Schukro, Christoph; Syeda, Bonni; Kirisits, Christian; Schmid, Rainer; Pichler, Philipp; Pokrajac, Boris; Lang, Irene; Poetter, Richard; Glogar, Dietmar

    2007-01-01

    Background and purpose: Intracoronary brachytherapy was the primary therapeutic option for the treatment of in-stent restenosis (ISR) during the last years. Especially for the treatment of diffuse ISR (lesions >10 mm), β-source brachytherapy was significantly superior to singular balloon angioplasty. Despite lacking clinical database, the implantation of drug eluting stents recently became a common procedure for the treatment of ISR. This randomized trial aimed to compare the efficacy of β-brachytherapy with β-radioisotopes 90 Sr/ 90 Y and paclitaxel-eluting stent implantation for the treatment of diffuse ISR. Material and methods: Thirty-seven patients with diffuse ISR were randomly assigned to β-brachytherapy after balloon angioplasty (Beta-Cath TM in 17 patients) or paclitaxel-eluting stent implantation (Taxus-Express2 TM in 20 patients). Six-month clinical follow-up was obtained for all patients, while angiographic follow-up was available for 30 patients. Results: Binary ISR (restenosis >50%) within target segment was observed in three patients treated with Beta-Cath TM , of which one needed target segment revascularisation for recurrent ISR, whereas no significant restenosis occurred in the patients treated with Taxus-Express2 TM (P = 0.037). No further major adverse cardiac (target segment revascularisation, myocardial infarction, death) was found in either group (P = NS). Stent implantation was the more time-saving (31 ± 11 min versus 60 ± 23 min, P TM arm, we found no difference in clinical outcome after implantation of paclitaxel-eluting stents for the treatment of diffuse ISR when compared to β-brachytherapy

  2. Composite outcomes in 2.25-mm drug eluting stents: a systematic review

    International Nuclear Information System (INIS)

    Lee, Justin Z.; Singh, Nirmal; Ortega, Gilbert; Low, See Wei; Kanakadandi, Uday; Fortuin, F. David; Lassar, Tom; Lee, Kwan S.

    2015-01-01

    Background: Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps. Methods: We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics. Results: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up. Conclusions: This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. - Highlights: • Safety and efficacy of 2.25-mm DES have been poorly defined. • We performed a systematic review on all published 2.25 mm data to estimate composite DES-specific performance and highlight current knowledge gaps. • We pooled data from 9 clinical studies and 1,476 patients. • Composite clinical and angiographic data at less than 12 months, 24 months and 60 months were displayed. • Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. • Paucity of outcome data on contemporary 2.25-mm DES was highlighted

  3. Novel insights in reperfusion therapy and stent thrombosis in the drug eluting stent era

    NARCIS (Netherlands)

    Hassan, Ayman Khairy Mohamed

    2009-01-01

    Objective: Early abciximab administration before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is recommended in practice guidelines. However, optimal timing of administration remains unclear. Our aim was to evaluate the effects of early

  4. [Fully absorbable drug eluting coronary stent: where do we stand in 2014?].

    Science.gov (United States)

    Kočka, Viktor; Toušek, Petr; Lisa, Libor; Buděšínský, Tomáš

    2014-04-01

    Coronary stent is routinely used in majority percutaneous coronary interventions for a long time. They have an important role, especially, in the first months after intervention. We can consider as a breakthrough point the development of stent which has ability to absorb in intervened artery after a few years. The review presents current techniques of fully absorbable coronary stents and also provides clinical trials and experiences available in 2014. The article continues with discussion between supporters and opponents of this new technique, but definitive conclusion can't be done yet. The authors conclude the review with their own opinion. There are many encouraging data in patients with good clinical outcome after implantation of absorbable stents in more than 10 years follow-up.

  5. Composite outcomes in 2.25-mm drug eluting stents: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Justin Z. [Department of Medicine, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ, 85724 (United States); Singh, Nirmal [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Ortega, Gilbert [College of Medicine, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Low, See Wei; Kanakadandi, Uday [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Fortuin, F. David [Department of Cardiovascular Diseases, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ, 85054 (United States); Lassar, Tom [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States); Lee, Kwan S., E-mail: klee@shc.arizona.edu [Department of Cardiovascular Diseases, University of Arizona, 1501 N Campbell Ave, Tucson, AZ, 85724 (United States)

    2015-06-15

    Background: Coronary atherosclerosis often involves small-caliber coronaries, yet the safety and efficacy of 2.25-mm DES have been poorly defined, with a general lack of separation of 2.25 with 2.5-mm performance. No randomized head-to-head 2.25 mm DES studies have been reported. There are several single-arm prospective studies, and we aim to systematically review all published specific 2.25-mm data to estimate composite DES-specific performance and highlight current knowledge gaps. Methods: We performed a systematic literature search of PubMed, EMBASE, Web of Science and Cochrane database for clinical trials of 2.25-mm DES. Angiographic and composite clinical outcomes were compared with descriptive statistics. Results: 2.25 mm-Paclitaxel (PES), sirolimus (SES), everolimus (EES) and platinum chromium EES DES-specific outcomes have been reported. Death at 12 months for SES, PES, EES and platinum chromium EES was 1.3%, 3.0%, 1.5%, and 4.4%. Rates of target vessel revascularization at 12 months for SES, PES, EES and platinum chromium EES were 5.7%, 13.3%, 8.8%, and 3.3%. Angiographic outcomes at 9 months to one year were as follows: mean late lumen loss (LLL) for SES, PES, and EES was 0.15 ± 0.11-mm, 0.28 ± 0.11-mm, and 0.16 ± 0.41-mm and mean diameter restenosis for SES, PES, and EES were 29.5 ± 6.2%, 34.7 ± 4.2%, and 20.9 ± 22.5%. Reported stent thrombosis rates for 2.25-mm DES were low ranging from 0% to 2.2% in up to 24-months of follow-up. Conclusions: This systematic review summarizes and tabulates all available specific data on 2.25-mm DES. Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. - Highlights: • Safety and efficacy of 2.25-mm DES have been poorly defined. • We performed a systematic review on all published 2.25 mm data to estimate composite DES-specific performance and highlight current knowledge gaps. • We pooled data from 9 clinical studies and 1,476 patients. • Composite clinical and angiographic data at less than 12 months, 24 months and 60 months were displayed. • Based on our descriptive analysis, 2.25-mm DESs have a favorable safety and efficacy profile for the treatment of very small coronary lesions. • Paucity of outcome data on contemporary 2.25-mm DES was highlighted.

  6. Dexamethasone Drug Eluting Nanowafers Control Inflammation in Alkali-Burned Corneas Associated With Dry Eye

    Science.gov (United States)

    Bian, Fang; Shin, Crystal S.; Wang, Changjun; Pflugfelder, Stephen C.; Acharya, Ghanashyam; De Paiva, Cintia S.

    2016-01-01

    Purpose To evaluate the efficacy of a controlled release dexamethasone delivery system for suppressing inflammation in an ocular burn + desiccating stress (OB+DS) model. Methods Nanowafers (NW) loaded with Dexamethasone (Dex, 10 μg) or vehicles (2.5% Methylcellulose; MC) were fabricated using hydrogel template strategy. C57BL/6 mice were subjected to unilateral alkali ocular burn with concomitant desiccating stress for 2 or 5 days and topically treated either with 2 μL of 0.1% Dex or vehicle four times per day and compared with mice that had MC-NW or Dex-NW placed on their corneas. Clinical parameters were evaluated daily. Mice were euthanized after 2 or 5 days. Quantitative PCR evaluated the expression of inflammatory cytokines IL-1β and IL-6 and matrix metalloproteinases (MMP) in whole cornea lysates. Myeloperoxidase activity (MPO) was measured using a commercial kit in cornea lysates. Results Both Dex drop and Dex-NW groups had significantly lower corneal opacity scores compared with their vehicles. Both Dex drops and Dex-NW significantly decreased expression of IL-1β, IL-6, and MMP-9 RNA transcripts compared with vehicle drops or wafers 2 and 5 days after the initial lesion. A significant lower number of neutrophils was found in both Dex treatment groups and this was accompanied by decreased MPO activity compared with vehicle controls. Conclusions Dex-NW has efficacy equal to Dex drops in preserving corneal clarity and decreasing expression of MMPs and inflammatory cytokines of the corneas of mice subjected to an OB+DS model. PMID:27327581

  7. Preparation of an sup(113m) indium generator

    International Nuclear Information System (INIS)

    Ling, H.W.

    1979-01-01

    This paper describes the features related to the preparation of sup(113m) In from a generator for nuclear medicine application. 113 Sn radioisotope is adsorbed on a hidrated zirconium oxide column and sup(113m) In generated from the decay of 113 Sn is eluted with diluted hydrochloric acid. This procedure is simple and appropriate for the separation of the desired radionuclide. Parameters which may affect the adsorption of 113 Sn like tin and hydrochloric acid concentration and temperature are studied. The influence of eluent concentration and temperature and flow rate of elution on sup(113m) In separation yields are observed. The purity of eluted sup(113m) In is analysed and variation of elution yield in a generator prepared with enriched tin is studied. (Author) [pt

  8. Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results.

    Science.gov (United States)

    Lammer, Johannes; Bosiers, Marc; Deloose, Koen; Schmidt, Andrej; Zeller, Thomas; Wolf, Florian; Lansink, Wouter; Sauguet, Antoine; Vermassen, Frank; Lauwers, Geert; Scheinert, Dierk; Popma, Jeffrey J; McGreevy, Robert; Rapoza, Richard; Schwartz, Lewis B; Jaff, Michael R

    2016-06-13

    This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). Drug-eluting BVS has shown promise in coronary arteries. The ESPRIT BVS system is a device-drug combination consisting of an everolimus-eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 ± 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure-related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 ± 0.14 improved from pre-procedure to 0.96 ± 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent:the SPIRIT II trial

    NARCIS (Netherlands)

    Serruys, Patrick W.; Ruygrok, Peter; Neuzner, Jörg; Piek, Jan J.; Seth, Ashok; Schofer, Joachim J.; Richardt, Gert; Wiemer, Marcus; Carrié, Didier; Thuesen, Leif; Boone, Els; Miquel-Herbert, Karine; Daemen, Joost

    2006-01-01

    Background: Everolimus has been successfully tested in humans using both an erodable and a durable polymer in small previous studies.Methods: This single blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated the safety and performance of the XIENCE V Everolimus Eluting

  10. High-throughput expression of animal venom toxins in Escherichia coli to generate a large library of oxidized disulphide-reticulated peptides for drug discovery.

    Science.gov (United States)

    Turchetto, Jeremy; Sequeira, Ana Filipa; Ramond, Laurie; Peysson, Fanny; Brás, Joana L A; Saez, Natalie J; Duhoo, Yoan; Blémont, Marilyne; Guerreiro, Catarina I P D; Quinton, Loic; De Pauw, Edwin; Gilles, Nicolas; Darbon, Hervé; Fontes, Carlos M G A; Vincentelli, Renaud

    2017-01-17

    Animal venoms are complex molecular cocktails containing a wide range of biologically active disulphide-reticulated peptides that target, with high selectivity and efficacy, a variety of membrane receptors. Disulphide-reticulated peptides have evolved to display improved specificity, low immunogenicity and to show much higher resistance to degradation than linear peptides. These properties make venom peptides attractive candidates for drug development. However, recombinant expression of reticulated peptides containing disulphide bonds is challenging, especially when associated with the production of large libraries of bioactive molecules for drug screening. To date, as an alternative to artificial synthetic chemical libraries, no comprehensive recombinant libraries of natural venom peptides are accessible for high-throughput screening to identify novel therapeutics. In the accompanying paper an efficient system for the expression and purification of oxidized disulphide-reticulated venom peptides in Escherichia coli is described. Here we report the development of a high-throughput automated platform, that could be adapted to the production of other families, to generate the largest ever library of recombinant venom peptides. The peptides were produced in the periplasm of E. coli using redox-active DsbC as a fusion tag, thus allowing the efficient formation of correctly folded disulphide bridges. TEV protease was used to remove fusion tags and recover the animal venom peptides in the native state. Globally, within nine months, out of a total of 4992 synthetic genes encoding a representative diversity of venom peptides, a library containing 2736 recombinant disulphide-reticulated peptides was generated. The data revealed that the animal venom peptides produced in the bacterial host were natively folded and, thus, are putatively biologically active. Overall this study reveals that high-throughput expression of animal venom peptides in E. coli can generate large

  11. High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next-generation antiviral drug discovery.

    Directory of Open Access Journals (Sweden)

    Dhara A Patel

    Full Text Available Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE activity in a fully automated and robust format (Z'>0.7. Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV. The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify

  12. Evaluation of fresh and old eluate of 99Mo/99mTc generators used for labeling of different pharmaceutical kits

    International Nuclear Information System (INIS)

    Urbano, N.; Chinol, M.; Modoni, S.; Guerra, M.

    2005-01-01

    Sixty 99 Mo/ 99m Tc wet column generators, loaded with two different 99 Mo activities, were analyzed in order to assess the quality of their eluates. Each elution was used for labeling of different radiopharmaceuticals, in order to evaluate whether 'risky' elutions, namely those performed just after generator delivery and at 72 hours or more from the last elution, could be conveniently employed when fresh available radioactivity is not enough for the planned labeling or when shipping problems arise, or delay in delivery of a new generator occurs. Radiochemical quality control of all radiopharmaceuticals labeled with these elutions was performed. The elutions differed mainly in 99 Tc ground state ( 99g Tc) and amounts of oxidizing impurities. Radiolabeling procedures, however, were not affected, suggesting that these 'risky' elutions might be appropriately used, in 'emergency' conditions, for labeling radiopharmaceuticals although their radiochemical purity control is recommended prior to patient administration. (author)

  13. Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

    DEFF Research Database (Denmark)

    Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

    2017-01-01

    if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG......), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS: The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p 

  14. The prognostic utility of the SYNTAX score on 1-year outcomes after revascularization with zotarolimus- and everolimus-eluting stents: a substudy of the RESOLUTE All Comers Trial

    DEFF Research Database (Denmark)

    Garg, Scot; Serruys, Patrick W; Silber, Sigmund

    2011-01-01

    This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents.......This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents....

  15. The effect of modulators of radiat