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Sample records for multicenter intracoronary stem

  1. Design and rationale for the Myocardial Stem Cell Administration After Acute Myocardial Infarction (MYSTAR) Study: a multicenter, prospective, randomized, single-blind trial comparing early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of nonselected autologous bone marrow cells to patients after acute myocardial infarction.

    PubMed

    Nyolczas, Noémi; Gyöngyösi, Mariann; Beran, Gilbert; Dettke, Markus; Graf, Senta; Sochor, Heinz; Christ, Günther; Edes, István; Balogh, László; Krause, Korff T; Jaquet, Kai; Kuck, Karl-Heinz; Benedek, Imre; Hintea, Theodora; Kiss, Róbert; Préda, István; Kotevski, Vladimir; Pejkov, Hristo; Dudek, Darius; Heba, Grzegorz; Sylven, Christer; Charwat, Silvia; Jacob, Ronaldo; Maurer, Gerald; Lang, Irene; Glogar, Dietmar

    2007-02-01

    Previous data suggest that bone marrow-derived stem cells (BM-SCs) decrease the infarct size and beneficially affect the postinfarction remodeling. The Myocardial Stem Cell Administration After Acute Myocardial Infarction Study is a multicenter, prospective, randomized, single-blind clinical trial designed to compare the early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of BM-SCs to patients after acute myocardial infarction (AMI) with reopened infarct-related artery. The primary end points are the changes in resting myocardial perfusion defect size and left ventricular ejection fraction (gated single photon emission computed tomography [SPECT] scintigraphy) 3 months after BM-SCs therapy. The secondary end points relate to evaluation of (1) the safety and feasibility of the application modes, (2) the changes in left ventricular wall motion score index (transthoracic echocardiography), (3) myocardial voltage and segmental wall motion (NOGA mapping), (4) left ventricular end-diastolic and end-systolic volumes (contrast ventriculography), and (5) the clinical symptoms (Canadian Cardiovascular Society [CCS] anina score and New York Heart Association [NYHA] functional class) at follow-up. Three hundred sixty patients are randomly assigned into 1 of 4 groups: group A, early treatment (21-42 days after AMI) with intracoronary injection; group B, early treatment with combined application; group C, late treatment (3 months after AMI) with intracoronary delivery; and group D, late treatment with combined administration of BM-SCs. Besides the BM-SCs therapy, the standardized treatment of AMI is applied in all patients. The Myocardial Stem Cell Administration After Acute Myocardial Infarction Trial is the first randomized trial to investigate the effects of the combined (intramyocardial and intracoronary) and the intracoronary mode of delivery of BM-SCs therapy in the early and late periods after AMI.

  2. Ventricular arrhythmias following intracoronary bone marrow stem cell transplantation.

    PubMed

    Villa, Adolfo; Sanchez, Pedro L; Fernandez-Aviles, Francisco

    2007-12-01

    We describe the appearance of delayed episodes of ventricular arrhythmias in 4 patients out of 72 undergoing intracoronary transplantation of autologous bone marrow mononuclear cells (BMMC) following ST elevated myocardial infarction (STEMI). Two cases with severely depressed systolic function presented electrical storms with monomorphic sustained ventricular tachycardia (SVT) within 2 to 3 days following cell transplantation, even though there were no periprocedural complications. Both patients were implanted with an internal defibrillator (ICD) after ruling out coronary re-occlusion. The remaining 2 patients presented several asymptomatic episodes of non-sustained ventricular tachycardia within one month following cell transfer. Only one of the latter presented syncopal SVT through programmed ventricular stimulation, undergoing ICD implantation afterwards. Neither new arrhythmic episodes nor ICD interventions have occurred during later follow-up of the three ICD patients (639+/-59 days). Information from large multicenter databases and our historical cohort of STEMI patients indicates that the rate of VT occurring within the first weeks after the initial 48 hours of infarction is significantly lower than that observed in our cell-therapy experience. The lack of information regarding the appearance of malignant arrhythmias in patients with severe systolic dysfunction following this type of therapy after STEMI requires us to be extremely cautious. However, any claim of a mechanism related to cell transfer would be completely speculative with the available data. Therefore, our only aim when reporting our findings is to recommend a short but longer stay (2-3 days) following cell transplantation, particularly in patients with a natural tendency to develop arrhythmic events.

  3. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models.

    PubMed

    Li, Qianhong; Guo, Yiru; Ou, Qinghui; Chen, Ning; Wu, Wen-Jian; Yuan, Fangping; O'Brien, Erin; Wang, Tao; Luo, Li; Hunt, Gregory N; Zhu, Xiaoping; Bolli, Roberto

    2011-09-01

    A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin(-)/c-kit(+)/GFP(+) cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin(-)/c-kit(+)/GFP(+) CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective.

  4. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models

    PubMed Central

    Li, Qianhong; Guo, Yiru; Ou, Qinghui; Chen, Ning; Wu, Wen-Jian; Yuan, Fangping; O’Brien, Erin; Wang, Tao; Luo, Li; Hunt, Gregory N.; Zhu, Xiaoping

    2013-01-01

    A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin−/c-kit+/GFP+ cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin−/c-kit+/GFP+ CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective. PMID:21516491

  5. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial

    PubMed Central

    Roncalli, Jérôme; Mouquet, Frédéric; Piot, Christophe; Trochu, Jean-Noel; Le Corvoisier, Philippe; Neuder, Yannick; Le Tourneau, Thierry; Agostini, Denis; Gaxotte, Virginia; Sportouch, Catherine; Galinier, Michel; Crochet, Dominique P.; Teiger, Emmanuel; Richard, Marie-Jeanne; Polge, Anne-Sophie; Beregi, Jean-Paul; Manrique, Alain; Carrie, Didier; Susen, Sophie; Klein, Bernard; Parini, Angelo; Lamirault, Guillaume; Croisille, Pierre; Rouard, Hélène; Bourin, Philippe; Nguyen, Jean-Michel; Delasalle, Béatrice; Vanzetto, Gérald; Van Belle, Eric; Lemarchand, Patricia F.

    2011-01-01

    Aims Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicenter study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. Methods and Results One-hundred one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n=49) or a BMC group (n=52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. BMC infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared to 7/43 (16%) in the control group (p = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (p = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (p=0.03). Moreover, a significant adverse role for active smoking (p=0.04) and a positive trend for microvascular obstruction (p=0.07) were observed. Conclusions Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate –but not in univariate – analysis. A large multicenter international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. PMID:21127322

  6. 10 years of intracoronary and intramyocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice.

    PubMed

    Strauer, Bodo-Eckehard; Steinhoff, Gustav

    2011-09-06

    Intracoronary and intramyocardial stem cell therapy aim at the repair of compromised myocardium thereby--as a causal treatment--preventing ventricular remodeling and improving overall performance. Since the first-in-human use of bone marrow stem cells (BMCs) after acute myocardial infarction in 2001, a large number of clinical studies have demonstrated their clinical benefit: BMC therapy can be performed with usual cardiac catheterization techniques in the conscious patient as well as also easily during cardiosurgical interventions. New York Heart Association severity degree of patients as well as physical activity improve in addition to ("on top" of) all other therapeutic regimens. Stem cell therapy also represents an ultimate approach in advanced cardiac failure. For acute myocardial infarction and chronic ischemia, long-term mortality after 1 and 5 years, respectively, is significantly reduced. A few studies also indicate beneficial effects for chronic dilated cardiomyopathy. The clinical use of autologous BMC therapy implies no ethical problems, when unmodified primary cells are used. With the use of primary BMCs, there are no major stem cell-related side effects, especially no cardiac arrhythmias and inflammation. Various mechanisms of the stem cell action in the human heart are discussed, for example, cell transdifferentiation, cell fusion, activation of intrinsic cardiac stem cells, and cytokine-mediated effects. New techniques allow point-of-care cell preparations, for example, within the cardiac intervention or operation theater, thereby providing short preparation time, facilitated logistics of cell transport, and reasonable cost effectiveness of the whole procedure. The 3 main indications are acute infarction, chronic ischemic heart failure, and dilated cardiomyopathy. Future studies are desirable to further elucidate the mechanisms of stem cell action and to extend the current use of intracoronary and/or intramyocardial stem cell therapy by larger and

  7. Intracoronary infusion of a combination of bone marrow-derived stem cells in dogs

    PubMed Central

    Minguell, José J; Florenzano, Fernando M; Ramírez, Manuel R; Martínez, Ramón F; Lasala, Gabriel P

    2010-01-01

    BACKGROUND: Infusion of diverse types of bone marrow cells, as a source of endothelial progenitor cells (EPCs), into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators in the present preclinical translation study hypothesized that the infusion of a combination cell product consisting of EPCs and other cell types, such as mesenchymal stem cells, promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes. The safety and feasibility of the intracoronary infusion of such a cell combination was assessed in a canine model. METHODS: A mixture of canine autologous mononuclear cells (as the source of EPCs) and ex vivo-expanded bone marrow-derived mesenchymal stem cells or a placebo solution were intracoronarily infused into healthy dogs. Follow-up after cell/placebo infusion included an electrocardiogram, serum cardiac enzyme testing, a transthoracic echocardiography and a histopathological heart examination. RESULTS: On follow-up at all time points after infusion, no significant changes or abnormalities in vital signs, electrocardiogram, transthoracic echocardiography and heart histology were detected. CONCLUSIONS: From a clinical perspective, the safety and feasibility of the protocol used in the present animal study demonstrated clinical relevance and provided direct evidence supporting the intracoronary infusion of combination stem/progenitor cell products. PMID:20631864

  8. Intracoronary infusion of a combination of bone marrow-derived stem cells in dogs.

    PubMed

    Minguell, José J; Florenzano, Fernando M; Ramírez, Manuel R; Martínez, Ramón F; Lasala, Gabriel P

    2010-01-01

    Infusion of diverse types of bone marrow cells, as a source of endothelial progenitor cells (EPCs), into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators in the present preclinical translation study hypothesized that the infusion of a combination cell product consisting of EPCs and other cell types, such as mesenchymal stem cells, promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes. The safety and feasibility of the intracoronary infusion of such a cell combination was assessed in a canine model. A mixture of canine autologous mononuclear cells (as the source of EPCs) and ex vivo-expanded bone marrow-derived mesenchymal stem cells or a placebo solution were intracoronarily infused into healthy dogs. Follow-up after cell/placebo infusion included an electrocardiogram, serum cardiac enzyme testing, a transthoracic echocardiography and a histopathological heart examination. On follow-up at all time points after infusion, no significant changes or abnormalities in vital signs, electrocardiogram, transthoracic echocardiography and heart histology were detected. From a clinical perspective, the safety and feasibility of the protocol used in the present animal study demonstrated clinical relevance and provided direct evidence supporting the intracoronary infusion of combination stem/progenitor cell products.

  9. Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial.

    PubMed

    Gao, Lian R; Chen, Yu; Zhang, Ning K; Yang, Xi L; Liu, Hui L; Wang, Zhi G; Yan, Xiao Y; Wang, Yu; Zhu, Zhi M; Li, Tian C; Wang, Li H; Chen, Hai Y; Chen, Yun D; Huang, Chao L; Qu, Peng; Yao, Chen; Wang, Bin; Chen, Guang H; Wang, Zhong M; Xu, Zhao Y; Bai, Jing; Lu, Di; Shen, Yan H; Guo, Feng; Liu, Mu Y; Yang, Yong; Ding, Yan C; Yang, Ye; Tian, Hai T; Ding, Qing A; Li, Li N; Yang, Xin C; Hu, Xiang

    2015-07-10

    The use of adult stem cells is limited by the quality and quantity of host stem cells. It has been demonstrated that Wharton's jelly-derived mesenchymal stem cells (WJMSCs), a primitive stromal population, could integrate into ischemic cardiac tissues and significantly improve heart function. In this randomized, controlled trial, our aim was to assess the safety and efficacy of intracoronary WJMSCs in patients with ST-elevation acute myocardial infarction (AMI). In a multicenter trial, 116 patients with acute ST-elevation MI were randomly assigned to receive an intracoronary infusion of WJMSCs or placebo into the infarct artery at five to seven days after successful reperfusion therapy. The primary endpoint of safety: the incidence of adverse events (AEs) within 18 months, was monitored and quantified. The endpoint of efficacy: the absolute changes in myocardial viability and perfusion of the infarcted region from baseline to four months, global left ventricular ejection fraction (LVEF) from baseline to 18 months were measured using F-18-fluorodeoxyglucose positron emission computed tomography (F-18-FDG-PET) and 99mTc-sestamibi single-photon emission computed tomography (99mTc-SPECT), and two-dimensional echocardiography, respectively. During 18 months follow-up, AEs rates and laboratory tests including tumor, immune, and hematologic indexes were not different between the two groups. The absolute increase in the myocardial viability (PET) and perfusion within the infarcted territory (SPECT) was significantly greater in the WJMSC group [6.9 ± 0.6 % (95 %CI, 5.7 to 8.2)] and [7.1 ± 0.8 % (95 %CI, 5.4 to 8.8) than in the placebo group [3.3 ± 0.7 % (95 %CI, 1.8 to 4.7), P <0.0001] and 3.9 ± 0.6(95 %CI, 2.8 to 5.0), P = 0.002] at four months. The absolute increase in the LVEF at 18 months in the WJMSC group was significantly greater than that in the placebo group [7.8 ± 0.9 (6.0 to approximately 9.7) vs. 2.8 ± 1.2 (0.4 to approximately 5.1), P = 0

  10. Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

    PubMed Central

    Fiarresga, António; Mata, Márcia F.; Cavaco-Gonçalves, Sandra; Selas, Mafalda; Simões, Irina N.; Oliveira, Eunice; Carrapiço, Belmira; Cardim, Nuno; Cabral, Joaquim M. S.; Ferreira, Rui Cruz; da Silva, Cláudia L.

    2015-01-01

    Background Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. Objectives To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. Methods Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. Results CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. Conclusion Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy. PMID:26479722

  11. Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction.

    PubMed

    Gyöngyösi, Mariann; Hemetsberger, Rayyan; Posa, Aniko; Charwat, Silvia; Pavo, Noemi; Petnehazy, Ors; Petrasi, Zsolt; Pavo, Imre J; Hemetsberger, Hani; Benedek, Imre; Benedek, Teodora; Benedek, Istvan; Kovacs, Istvan; Kaun, Christoph; Maurer, Gerald

    2010-04-01

    We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1alpha) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8 +/- 1.2 x 10(6)) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22 +/- 4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1alpha was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1alpha expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1alpha increased immediately post-MI (from 278 +/- 127 to 631 +/- 375 pg/ml, p < 0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1alpha significantly (p < 0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1alpha expression in the infarcted area was higher in Group IM than in Group IC or S (1,963 +/- 586 vs. 1,307 +/- 392 vs. 271 +/- 110 activity per square millimeter, respectively, p < 0.05), while the border zone contained similarly lower level of HIF-1alpha, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1alpha was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1alpha. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1alpha more effectively than does intracoronary delivery.

  12. Impact of intracoronary injection of CD133+ bone marrow stem cells on coronary atherosclerotic progression in patients with STEMI: a COMPARE-AMI IVUS substudy.

    PubMed

    Qiu, Fuyu; Maehara, Akiko; El Khoury, Ramez; Généreux, Philippe; LaSalle, Laura; Mintz, Gary S; Noiseux, Nicolas; Roy, Denis-Claude; Gobeil, François; Stevens, Louis-Mathieu; Reeves, François; Leclerc, Guy; Rivard, Alain; Mansour, Samer

    2016-01-01

    Adverse effects of intracoronary injection of stem cells on in-stent restenosis and atherosclerotic progression remain unclear. We sought to evaluate the adverse effects of intracoronary injection of CD133 cells on in-stent restenosis and atherosclerotic progression in the infarct-related and contralateral arteries using serial intravascular ultrasound (IVUS) analysis. Baseline and 4-month follow-up IVUS images were obtained from 17 patients treated with intracoronary stem cell injection and 20 placebo patients after primary percutaneous coronary intervention in the COMPARE-AMI trial. In the infarct-related artery, the stented segment, 5 mm proximal and distal reference segments, and proximal and distal nonstented segments were analyzed every 1 mm; the entire segment of a contralateral artery was also analyzed every 1 mm. In the infarct-related artery analysis, the median percentage of in-stent neointimal hyperplasia (12.1 vs. 7.6%, P=0.95), the reduction in the minimum lumen area (MLA; -1.6 vs. -1.5 mm(2), P=0.97), and the MLA at follow-up (4.3 vs. 5.3 mm(2), P=0.21) were found to be similar between the stem cell and placebo groups. Changes in proximal and distal nonstented segment lumen areas and plaque burden were also similar between the stem cell and placebo groups; however, there was a decrease in the maximum arc of the attenuated plaque behind the stent from baseline to follow-up in the placebo group (P=0.004), but not in the stem cell group. In the contralateral artery, there were no differences in changes in MLA, plaque burden, or attenuated plaque between stem cell and placebo patients. Intracoronary injection of CD133(+) bone marrow stem cells has no IVUS-detectable effect on neointimal hyperplasia or atherosclerosis progression in either infarct-related or contralateral arteries.

  13. Effects of Intracoronary Administration of Autologous Adipose Tissue-Derived Stem Cells on Acute Myocardial Infarction in a Porcine Model

    PubMed Central

    Lee, Hye Won; Park, Jong Ha; Kim, Bo Won; Ahn, Jinhee; Kim, Jin Hee; Park, Jin Sup; Oh, Jun-Hyok; Choi, Jung Hyun; Cha, Kwang Soo; Hong, Taek Jong; Park, Tae Sik; Kim, Sang-Pil; Song, Seunghwan; Kim, Ji Yeon; Park, Mi Hwa; Jung, Jin Sup

    2015-01-01

    Purpose Adipose-derived stem cells (ADSCs) are known to be potentially effective in regeneration of damaged tissue. We aimed to assess the effectiveness of intracoronary administration of ADSCs in reducing the infarction area and improving function after acute transmural myocardial infarction (MI) in a porcine model. Materials and Methods ADSCs were obtained from each pig's abdominal subcutaneous fat tissue by simple liposuction. After 3 passages of 14-days culture, 2 million ADSCs were injected into the coronary artery 30 min after acute transmural MI. At baseline and 4 weeks after the ADSC injection, 99mTc methoxyisobutylisonitrile-single photon emission computed tomography (MIBI-SPECT) was performed to evaluate the left ventricular volume, left ventricular ejection fraction (LVEF; %), and perfusion defects as well as the myocardial salvage (%) and salvage index. At 4 weeks, each pig was sacrificed, and the heart was extracted and dissected. Gross and microscopic analyses with specific immunohistochemistry staining were then performed. Results Analysis showed improvement in the perfusion defect, but not in the LVEF in the ADSC group (n=14), compared with the control group (n=14) (perfusion defect, -13.0±10.0 vs. -2.6±12.0, p=0.019; LVEF, -8.0±15.4 vs. -15.9±14.8, p=0.181). There was a tendency of reducing left ventricular volume in ADSC group. The ADSCs identified by stromal cell-derived factor-1 (SDF-1) staining were well co-localized by von Willebrand factor and Troponin T staining. Conclusion Intracoronary injection of cultured ADSCs improved myocardial perfusion in this porcine acute transmural MI model. PMID:26446632

  14. Intracoronary thrombus.

    PubMed

    Achenbach, Stephan; Marwan, Mohamed

    2009-01-01

    We present the case of a 62 year old patient admitted with acute chest pain. Coronary CT angiography demonstrated presence of a high grade lesion with pronounced remodeling and the impression of an intracoronary thrombus in the proximal left circumflex coronary artery. Invasive angiography confirmed the presence of a thrombus; thrombus fragments were removed using an extraction device.

  15. A Randomized Comparative Study on the Efficacy of Intracoronary Infusion of Autologous Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells in Patients With Dilated Cardiomyopathy.

    PubMed

    Xiao, Wentao; Guo, Suping; Gao, Chuanyu; Dai, Guoyou; Gao, Yongjv; Li, Muwei; Wang, Xianpei; Hu, Dayi

    2017-02-13

    Stem cell therapy has shown therapeutic benefit in dilated cardiomyopathy (DCM), but doubt remains about the most appropriate stem cell subpopulation. The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells (BMMC) or mesenchymal stem cells (BMSC) in patients with DCM.Fifty-three patients with DCM and reduced (< 40%) left ventricular ejection fraction (LVEF), were randomized to intracoronary infusion of BMMC (BMMC group, n = 16) or BMSC (BMSC group, n = 17) or equal volume normal saline (CTRL group, n = 20). LVEF, New York Heart Association (NYHA) class, left ventricular end-diastolic diameter (LVEDd), and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups. Major adverse cardiovascular events (MACE) were also recorded.At the 3-month follow-up, LVEF, NYHA class, and myocardial perfusion had improved significantly in the BMSC group (P = 0.004, 0.020 and 0.019, respectively) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL (P = 0.042 and 0.047, respectively), however, LVEDd remained unchanged. In comparison with CTRL, LVEF, NYHA class, and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up (P = 0.005, 0.050 and 0.038 respectively), but not in the BMMC group (P > 0.05). There were no significant differences between the transplantation groups during follow-up (P > 0.05). There were no differences in MACE among the 3 groups (P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective, while BMSC and BMMC infusion possess comparable effectiveness.

  16. Effects of Intracoronary Infusion of Escalating Doses of Cardiac Stem Cells in Rats With Acute Myocardial Infarction.

    PubMed

    Tang, Xian-Liang; Rokosh, Gregg; Sanganalmath, Santosh K; Tokita, Yukichi; Keith, Matthew C L; Shirk, Gregg; Stowers, Heather; Hunt, Gregory N; Wu, Wenjian; Dawn, Buddhadeb; Bolli, Roberto

    2015-07-01

    Although c-kit(pos) cardiac stem cells (CSCs) preserve left ventricular (LV) function and structure after myocardial infarction, CSC doses have been chosen arbitrarily, and the dose-effect relationship is unknown. Rats underwent a 90-minute coronary occlusion followed by 35 days of reperfusion. Vehicle or CSCs at 5 escalating doses (0.3×10(6), 0.75×10(6), 1.5×10(6), 3.0×10(6), and 6.0×10(6) cells/heart) were given intracoronarily 4 h after reperfusion. The lowest dose (0.3×10(6)) had no effect on LV function and morphology, whereas 0.75, 1.5, and 3.0×10(6) significantly improved regional and global LV function (echocardiography and hemodynamic studies). These 3 doses had similar effects on echocardiographic parameters (infarct wall thickening fraction, LV end-systolic and end-diastolic volumes, LV ejection fraction) and hemodynamic variables (LV end-diastolic pressure, LV dP/dtmax, preload adjusted maximal power, end-systolic elastance, preload recruitable stroke work) and produced similar reductions in apoptosis, scar size, infarct wall thinning, and LV expansion index and similar increases in viable myocardium in the risk region (morphometry). Infusion of 6.0×10(6) CSCs markedly increased postprocedural mortality. Green fluorescent protein and 5-bromo-2'-deoxyuridine staining indicated that persistence of donor cells and formation of new myocytes were negligible with all doses. Surprisingly, in this rat model of acute myocardial infarction, the dose-response relationship for intracoronary CSCs is flat. A minimal dose between 0.3 and 0.75×10(6) is necessary for efficacy; above this threshold, a 4-fold increase in cell number does not produce greater improvement in LV function or structure. Further increases in cell dose are harmful. © 2015 American Heart Association, Inc.

  17. Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium

    PubMed Central

    Weil, Brian R.; Suzuki, Gen; Leiker, Merced M.; Fallavollita, James A.; Canty, John M.

    2015-01-01

    Rationale Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. Objective Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs, ~35×106) and CDCs (icCDCs, ~35×106) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). Methods and Results Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean ± SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 μm, icCDCs: 16.8±1.2 μm, vehicle: 20.2±3.7 μm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. Conclusions Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. PMID:26271689

  18. Dual isotope simultaneous imaging to evaluate the effects of intracoronary bone marrow-derived mesenchymal stem cells on perfusion and metabolism in canines with acute myocardial infarction.

    PubMed

    Hao, Linjun; Hao, Jin; Fang, Wei; Han, Chunlei; Zhang, Kaixiu; Wang, Xuemei

    2015-07-01

    Stem cell therapy on acute myocardial infarction (AMI) has been performed for over a decade. In the present study, cardiac perfusion, metabolism and function in dogs with AMI treated by intracoronary injection of bone marrow-derived mesenchymal stem cells (MSCs) were evaluated by dual isotope simultaneous acquisition (DISA) of single positron emission computed tomography (SPECT). Dogs (n=12, 20-30 kg) were randomly assigned to two groups: A graft study (n=6) and control group (n=6). Bone marrow mesenchymal aspirate was collected 3 weeks before surgical procedure. Stem cells were induced by 5-azacytidine for differentiation into myocytes. The dog AMI model was produced by blocking the blood stream at 1/3 of the distinct left anterior descending coronary artery for 90 min. For dogs in the grafting group, MSCs were transplanted by intracoronary injection, and for the control group, 0.9% NaCl was injected instead. At 1 and 10 weeks after MSCs were grafted, respectively, SPECT DISA was performed for each dog in the two groups with (99m)Tc-SPECT MIBI (925 MBq) and (18)F-FDG (222 MBq) for evaluation of myocardial perfusion and metabolism. After the dogs were sacrificed, heart tissue was stained by myocyte-specific antibodies for newborn vessels, troponin T and bromodeoxyuridine (BrdU). Following induction by 5-azacytidine, the morphological features with colony formation, microfilament, as well as atrial granules and positive stainings of α-actinin, myosin and troponin I demonstrated strongly that the MSCs differentiated into myocytes. The number of viable myocardial segments was 10 in the grafting group, which was significantly greater compared with the control group. The ejection fraction of the infarcted left ventricle (LVEF,%) increased from 53.80±9.58 to 70.00±7.52 (change, 16.20±2.93) at 1 and 10 weeks after MSCs engraftment, whilst in the control group, LVEF was 50.50±8.02 and 56.50±7.24 (change, 5.50±2.69), respectively. The LVEF difference was

  19. Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution

    PubMed Central

    Hong, Soon Jun; Hou, Dongming; Brinton, Todd J.; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F.; Yock, Paul; March, Keith L.

    2012-01-01

    Objectives To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous or arterial delivery. Background Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. Methods In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either intracoronary (IC) or retrograde coronary venous (RCV) infusion of 107 111Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hours after cell delivery. Results IC delivery of porcine ASCs to normal myocardium was well-tolerated up to a cumulative dose of 14×106 cells (approximately 0.5×106 cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50×106 ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, while at 10×106 ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hour with IC delivery compared to RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, p=0.037) but this initial difference

  20. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology

    PubMed Central

    Tseliou, Eleni; Kanazawa, Hideaki; Dawkins, James; Gallet, Romain; Kreke, Michelle; Smith, Rachel; Middleton, Ryan; Valle, Jackelyn; Marbán, Linda; Kar, Saibal; Makkar, Rajendra; Marbán, Eduardo

    2016-01-01

    Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients. PMID:26784932

  1. Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction – MiHeart/AMI study

    PubMed Central

    Dohmann, Hans FR; Silva, Suzana A; Sousa, André LS; Braga, Alcione MS; Branco, Rodrigo VC; Haddad, Andréa F; Oliveira, Mônica A; Moreira, Rodrigo C; Tuche, Fabio AA; Peixoto, Cíntia M; Tura, Bernardo R; Borojevic, Radovan; Ribeiro, Jorge P; Nicolau, José C; Nóbrega, Antonio C; Carvalho, Antonio CC

    2008-01-01

    Background Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 × 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required. Trial Register This trial is registered at the NIH registry under the number NCT00350766. PMID:18598362

  2. VECTORCARDIOGRAPHIC CHANGES DURING INTRACORONARY INJECTIONS.

    DTIC Science & Technology

    artery blood with the changes in the surface electrocardiogram, simultaneous recordings were made from Frank leads X, Y, and Z during intracoronary ...could be produced by intracoronary injections of saline solutions, but minimal or no changes were observed with injections of hypertonic mannitol

  3. Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy.

    PubMed

    Keith, Matthew C L; Tokita, Yukichi; Tang, Xian-Liang; Ghafghazi, Shahab; Moore, Joseph B; Hong, Kyung U; Elmore, Julius B; Amraotkar, Alok R; Guo, Haixun; Ganzel, Brian L; Grubb, Kendra J; Flaherty, Michael P; Vajravelu, Bathri N; Wysoczynski, Marcin; Bolli, Roberto

    2015-09-01

    It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kit(pos) human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 ± 0.80 % of the injected dose (n = 7), compared with 4.87 ± 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted.

  4. A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction.

    PubMed

    Lee, Jun-Won; Lee, Seung-Hwan; Youn, Young-Jin; Ahn, Min-Soo; Kim, Jang-Young; Yoo, Byung-Su; Yoon, Junghan; Kwon, Woocheol; Hong, In-Soo; Lee, Kyounghoon; Kwan, Jun; Park, Keum Soo; Choi, Donghoon; Jang, Yang Soo; Hong, Mun K

    2014-01-01

    Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9% ± 8.5% vs 1.6% ± 7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105).

  5. Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).

    PubMed

    Malliaras, Konstantinos; Makkar, Raj R; Smith, Rachel R; Cheng, Ke; Wu, Edwin; Bonow, Robert O; Marbán, Linda; Mendizabal, Adam; Cingolani, Eugenio; Johnston, Peter V; Gerstenblith, Gary; Schuleri, Karl H; Lardo, Albert C; Marbán, Eduardo

    2014-01-21

    This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. Autologous CDCs (12.5 to 25 × 10(6)) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration, merit further investigation in future trials

  6. The intracoronary electrocardiogram in percutaneous coronary intervention.

    PubMed

    Yong, Andy S C; Lowe, Harry C; Ng, Martin K C; Kritharides, Leonard

    2009-02-01

    The technique of obtaining an epicardial electrocardiogram trace by connecting the guidewire during coronary angioplasty to an electrocardiogram lead has been used since 1985. The intracoronary electrocardiogram appears to be more sensitive than the surface electrocardiogram in detecting transient ischemia, particularly in the territory of the left anterior descending and left circumflex coronary arteries. Importantly, recent studies have shown the intracoronary electrocardiogram to be particularly useful in demonstrating pre- and postconditioning during interventional procedures, predicting periprocedural myocardial damage, and in the determination of regional viability in the catheterization laboratory. Barriers to the use of the intracoronary electrocardiogram in the clinical setting include the lack of standardized methods for acquiring and analyzing the intracoronary electrocardiogram, and the lack of commercially available continuous intracoronary monitoring systems to permit analysis while performing coronary interventions. Facilitating these relatively simple technical developments may permit optimal integration of the intracoronary electrocardiogram into the catheterization laboratory.

  7. [Intracoronary thrombolysis. A case report].

    PubMed

    Bennett, J M; Kleynhans, P H; Meyer, J M; Geyser, P G

    1982-04-03

    Restoration of blood flow in an occluded right coronary artery of a patient with an acute myocardial infarction was achieved with intracoronary administration of streptokinase. Patency of the vessel was restored within 15 minutes after starting the infusion. The dose of streptokinase used was 3000 U/min. The patient's pain was relieved and the raised ST segments returned to normal after patency was achieved. Cardiac output and stroke volume increased fro 3,6 to 6,3 1/min and from 61 to 70 ml respectively. No complications occurred during the infusion of streptokinase. Intracoronary thrombolysis might well establish itself as the treatment of choice for acute myocardial infarction in selected patients.

  8. Non-invasive in vivo imaging of cardiac stem/progenitor cell biodistribution and retention after intracoronary and intramyocardial delivery in a swine model of chronic ischemia reperfusion injury.

    PubMed

    Collantes, María; Pelacho, Beatriz; García-Velloso, María José; Gavira, Juán José; Abizanda, Gloria; Palacios, Itziar; Rodriguez-Borlado, Luis; Álvarez, Virginia; Prieto, Elena; Ecay, Margarita; Larequi, Eduardo; Peñuelas, Iván; Prósper, Felipe

    2017-03-13

    The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia-reperfusion. Ischemia-reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA(®)-guided IM injection (n = 3) of 50 million of (18)F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP(+) cells three days post-injection. Biodistribution of (18)F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA(®)-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection. PET/CT imaging of (18)F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection.

  9. A prospective, single-blind, multicenter, dose escalation study of intracoronary iNOS lipoplex (CAR-MP583) gene therapy for the prevention of restenosis in patients with de novo or restenotic coronary artery lesion (REGENT I extension).

    PubMed

    von der Leyen, Heiko E; Mügge, Andreas; Hanefeld, Christoph; Hamm, Christian W; Rau, Mathias; Rupprecht, Hans J; Zeiher, Andreas M; Fichtlscherer, Stephan

    2011-08-01

    Neointimal hyperplasia causing recurrent stenosis is a limitation of the clinical utility of percutaneous transluminal coronary interventions (PCI). Nitric oxide (NO) inhibits smooth muscle cell proliferation, platelet activation, and inflammatory responses, all of which have been implicated in the pathogenesis of restenosis. In animals, neointimal proliferation after balloon injury has been shown to be effectively reduced by gene transfer of the inducible NO synthase (iNOS). The primary objective of this first multicenter, prospective, single-blind, dose escalation study was to obtain safety and tolerability information of the iNOS lipoplex (CAR-MP583) gene therapy for reducing restenosis following PCI. Local coronary intramural CAR-MP583 delivery was achieved using the Infiltrator balloon catheter. A total of 30 patients were treated in the study (six patients, 0.5 μg; six patients, 2.0 μg; six patients, 5.0 μg; and 12 patients, 10 μg). There were no complications related to local application of CAR-MP583. In one patient, PCI procedure-related transient vessel occlusion occurred with consecutive troponin elevation. There were no signs of inflammatory responses or hepatic or renal toxicity. No dose relationship was seen with regard to adverse events across the dose groups. Thus, coronary intramural lipoplex-enhanced iNOS gene therapy during PCI is feasible and appears to be safe. These initial clinical results are encouraging to support further clinical research, in particular in conjunction with new local drug delivery technologies.

  10. Intracoronary bone marrow cell application for terminal heart failure in children.

    PubMed

    Rupp, Stefan; Jux, Christian; Bönig, Halvard; Bauer, Jürgen; Tonn, Torsten; Seifried, Erhard; Dimmeler, Stefanie; Zeiher, Andreas M; Schranz, Dietmar

    2012-10-01

    In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports. Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction. Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.

  11. [Effect of intracoronary and intravenous administration of tirofiban loading dose in patients underwent percutaneous coronary interventions because of acute coronary syndrome].

    PubMed

    Turkmen, S; Fettser, D V; Kagliian, K É; Serchelik, A; Arystanova, A Zh; Tekin, K; Balli, M; Batyraliev, T A; Samko, A N; Sidorenko, B A

    2013-01-01

    Aim of this multicenter retrospective study was assessment of effect of intracoronary administration of tirofiban loading dose in troponin positive patients with acute coronary syndrome (ACS). We analyzed multicenter data base of patients subjected to percutaneous coronary interventions (PCI) because of ST-elevation or non-ST elevation ACS from October 2010 to October 2011. Patients who received loading doses of aspirin (300 mg) and clopidogrel (600 mg) before PCI and tirofiban (10 mg/kg bolus with subsequent infusion 0.15 mg/kg/min for 24 h) were selected for the study (n=133, 89 with intravenous and 44 - intracoronary administration of tirofiban loading dose). We assessed hospital mortality, myocardial reinfarctions (reMI), necessity of target vessel revascularization (TVR) and pronounced bleedings. There were no significant differences in mortality, reMI, and TVR between two groups. However major adverse cardiac events was significantly less in patients who received intracoronary tirofiban (6.8 vs. 21.3% in i.v. group; p=0.046). Hospital stay was significantly shorter in intracoronary compared with i.v. group (3.84+/-0.96 vs. 4.55+/-1.11 days; p=0.001). Rates of bleedings did not differ significantly between groups. Thus compared with i.v. intracoronary administration of tirofiban loading dose allows lower rate of major adverse cardiac events as well as to shorten length of hospital stay of patients with ACS.

  12. Intracoronary Cardiosphere-Derived Cells After Myocardial Infarction

    PubMed Central

    Malliaras, Konstantinos; Makkar, Raj R.; Smith, Rachel R.; Cheng, Ke; Wu, Edwin; Bonow, Robert O.; Marbán, Linda; Mendizabal, Adam; Cingolani, Eugenio; Johnston, Peter V.; Gerstenblith, Gary; Schuleri, Karl H.; Lardo, Albert C.; Marbán, Eduardo

    2013-01-01

    Objectives This study sought to report full 1-year results, detailed magnetic resonance imaging analysis, and determinants of efficacy in the prospective, randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction) trial. Background Cardiosphere-derived cells (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete results at the final 1-year endpoint are unknown. Methods Autologous CDCs (12.5 to 25 × 106) grown from endomyocardial biopsy specimens were infused via the intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3 months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months post-MI). Eight patients were followed as routine-care control patients. Results In 13.4 months of follow-up, safety endpoints were equivalent between groups. At 1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared with control patients. Scar mass decreased and viable mass increased in CDC-treated patients but not in control patients. The single patient infused 14 months post-MI responded similarly. CDC therapy led to improved regional function of infarcted segments compared with control patients. Scar shrinkage correlated with an increase in viability and with improvement in regional function. Scar reduction correlated with baseline scar size but not with a history of temporally remote MI or time from MI to infusion. The changes in left ventricular ejection fraction in CDC-treated subjects were consistent with the natural relationship between scar size and ejection fraction post-MI. Conclusions Intracoronary administration of autologous CDCs did not raise significant safety concerns. Preliminary indications of bioactivity include decreased scar size, increased viable myocardium, and improved regional function of infarcted myocardium at 1 year post-treatment. These results, which are consistent with therapeutic regeneration

  13. Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis.

    PubMed

    Petrich, Adam M; Gandhi, Mitul; Jovanovic, Borko; Castillo, Jorge J; Rajguru, Saurabh; Yang, David T; Shah, Khushboo A; Whyman, Jeremy D; Lansigan, Frederick; Hernandez-Ilizaliturri, Francisco J; Lee, Lisa X; Barta, Stefan K; Melinamani, Shruthi; Karmali, Reem; Adeimy, Camille; Smith, Scott; Dalal, Neil; Nabhan, Chadi; Peace, David; Vose, Julie; Evens, Andrew M; Shah, Namrata; Fenske, Timothy S; Zelenetz, Andrew D; Landsburg, Daniel J; Howlett, Christina; Mato, Anthony; Jaglal, Michael; Chavez, Julio C; Tsai, Judy P; Reddy, Nishitha; Li, Shaoying; Handler, Caitlin; Flowers, Christopher R; Cohen, Jonathon B; Blum, Kristie A; Song, Kevin; Sun, Haowei Linda; Press, Oliver; Cassaday, Ryan; Jaso, Jesse; Medeiros, L Jeffrey; Sohani, Aliyah R; Abramson, Jeremy S

    2014-10-09

    Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed. © 2014 by The American Society of Hematology.

  14. Clinical outcomes of intracoronary eptifibatide bolus only versus intracoronary bolus and intravenous infusion of eptifibatide in primary percutaneous coronary intervention.

    PubMed

    Soon, Dinna; Ho, Hee Hwa; Loh, Kwok Kong; Ooi, Yau Wei; Foo, David; Jafary, Fahim H; Ong, Paul Jau

    2012-03-01

    Intracoronary bolus of eptifibatide during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to result in higher local platelet glycoprotein IIb/IIIa receptor occupancy with improved microvascular perfusion. It is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes. We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in patients undergoing primary PCI for ST-elevation MI. They were divided into two groups: Group A (n=67) who received fixed-dose intracoronary eptifibatide bolus only and Group B (n=88) who received intracoronary bolus and continuous intravenous infusion of eptifibatide for 18 h. The preliminary findings from our registry showed that both regimens were associated with good angiographic outcomes, few bleeding events and low in-hospital major adverse cardiac events. A large prospective randomized, multi-centre trial is needed to confirm our observation.

  15. Assessment of coronary vasomotion by intracoronary ultrasound

    NASA Astrophysics Data System (ADS)

    Dupouy, Patrick J.; Dubois-Rande, Jean Luc; Pelle, Gabriel; Gallot, Dominique; Geschwind, Herbert J.

    1993-06-01

    Recently, new intravascular ultrasound devices for intracoronary use became available. The aim of the study was to evaluate the accuracy of intravascular ultrasound for the assessment of coronary artery vasomotion and endothelial function in patients with atherosclerosis. Twenty patients with luminal irregularities on coronary angiogram and a high cholesterol level (287 +/- 19 mg/dl) (group 1) and 6 patients with angiographically smooth arteries and a minimally elevated cholesterol level (197 +/- 12 mg/dl) (group 2) were studied. A mechanical intravascular ultrasound probe (4.3 French, 30 MHz, Cardiovascular Imaging Systems) was placed into the proximal segment of the coronary artery. Off-line measurements of the lumen area and calculation of mean intimal thickness indice was performed using digitized ultrasound images. Endothelial function was studied during a sympathetic stimulation by a cold pressor test and after intracoronary administration of papaverine and linsidomine. Mean intimal thickness was higher in group 1 than in group 2 (1.52 +/- 0.64 mm vs. 0.18 +/- 0.08 mm, p < 0.001). Linsidomine infusion induced a significant vasodilating effect in both groups (p < 0.001).

  16. Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study.

    PubMed

    Fassas, A; Passweg, J R; Anagnostopoulos, A; Kazis, A; Kozak, T; Havrdova, E; Carreras, E; Graus, F; Kashyap, A; Openshaw, H; Schipperus, M; Deconinck, E; Mancardi, G; Marmont, A; Hansz, J; Rabusin, M; Zuazu Nagore, F J; Besalduch, J; Dentamaro, T; Fouillard, L; Hertenstein, B; La Nasa, G; Musso, M; Papineschi, F; Rowe, J M; Saccardi, R; Steck, A; Kappos, L; Gratwohl, A; Tyndall, A; Samijn, J; Samign, J

    2002-08-01

    Phase I/II studies of autologous hematopoietic stem cell transplantation (HSCT) for multiple sclerosis ( MS) were initiated, based on results of experimental transplantation in animal models of multiple sclerosis and clinical observations in patients treated concomitantly for malignant disease. Eighty-five patients with progressive MS were treated with autologous HSCT in 20 centers and reported to the autoimmune disease working party of the European Group for Blood and Marrow Transplantation (EBMT). 52 (61 %) were female, median age was 39 [20-58] years. The median interval from diagnosis to transplant was 7 [1-26] years. Patients suffered from severe disease with a median EDSS score of 6.5 [4.5-8.5]. Active disease prior to transplant was documented in 79 of 82 evaluable cases. The stem cell source was bone marrow in 6 and peripheral blood in 79, and stem cells were mobilized into peripheral blood using either cyclophosphamide combined with growth factors or growth factors alone. Three patients experienced transient neurological complications during the mobilization phase. The high dose regimen included combination chemotherapy, with or without anti-lymphocyte antibodies or, with or without, total body irradiation. The stem cell transplants were purged of lymphocytes in 52 patients. Median follow-up was 16 [3-59] months. There were 7 deaths, 5 due to toxicity and infectious complications, 2 with neurological deterioration. The risk of death of any cause at 3 years was 10 (+/-7)% (95 % confidence interval). Neurological deterioration during transplant was observed in 22 patients; this was transient in most but was associated with MS progression in 6 patients. Neurological improvement by > or = 1 point in the EDSS score was seen in 18 (21 %) patients. Confirmed progression-free survival was 74 (+/-12)% at 3 years being 66 (+/-23)% in patients with primary progressive MS but higher in patients with secondary progressive or relapsing-remitting MS, 78 (+/-13)%; p = 0

  17. Call for standards in technical documentation of intracoronary stents.

    PubMed

    Lanzer, Peter; Gijsen, Frank J H; Topoleski, L D Timmie; Holzapfel, Gerhard A

    2010-01-01

    At present, the product information of intracoronary stents provided by the industry contains only limited technical data restricting judgments on the in vivo performance of individual products. Available experimental and clinical evidence suggests that interventional target sites display highly heterogeneous biomechanical behavior needed to be matched by specific stent and stent delivery system characteristics. To allow individualized stent-lesion matching, both, understanding of biomechanical properties of the atherosclerotic coronary artery lesions and expert knowledge of the intracoronary stent systems, are required. Here, the authors review some of the initial data on mechanical properties of coronary artery lesions potentially relevant to stenting and suggest standards for technical documentation of intracoronary stents.

  18. Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: an Italian multicenter experience.

    PubMed

    Faraci, Maura; Zecca, Marco; Pillon, Marta; Rovelli, Attilio; Menconi, Maria Cristina; Ripaldi, Mimmo; Fagioli, Franca; Rabusin, Marco; Ziino, Ottavio; Lanino, Edoardo; Locatelli, Franco; Daikeler, Thomas; Prete, Arcangelo

    2014-02-01

    Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab.

  19. Paroxysmal atrial fibrillation during intracoronary acetylcholine provocation test.

    PubMed

    Saito, Yuichi; Kitahara, Hideki; Shoji, Toshihiro; Tokimasa, Satoshi; Nakayama, Takashi; Sugimoto, Kazumasa; Fujimoto, Yoshihide; Kobayashi, Yoshio

    2016-12-22

    Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48 h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p = 0.01) and body mass index (OR 0.88 CI 0.78-0.99, p = 0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.

  20. Extensive fatal intracoronary thrombosis during percutaneous coronary intervention with bivalirudin.

    PubMed

    Sharma, Sanjiv; Patel, Shirish; Behl, Ashok; Singh, Sarabjeet; Sandhu, Rasham; Bhambi, Neil; Sharma, Rohan; Bhambi, Brijesh

    2014-01-01

    The authors describe 2 cases of extensive intracoronary thrombus formation leading to acute closure of the left main where bivalirudin (Angiomax) was used as the anticoagulant during percutaneous coronary intervention leading to mortality. Both cases had similarity in the cascade of complications of coronary dissection leading to slow flow and prolonged procedure time with compromise of antegrade flow in the coronary artery and a final catastrophic development of extensive intracoronary thrombosis extending into the left main and nonintervened vessel (left anterior descending or circumflex) followed by ventricular fibrillation and death. Bivalirudin has reversible anticoagulant pharmacodynamics because the bivalirudin molecule is cleaved by the thrombin molecule. In situations when the antegrade flow is compromised, delivery of fresh circulating bivalirudin to replenish the catalysis of bivalirudin by thrombin is diminished, allowing thrombin activity to regenerate, thereby creating a prothrombotic milieu in these coronary segments. This can lead to extensive intracoronary thrombus formation in situations of slow flow precipitated by coronary dissection and prolonged dwell time with intracoronary hardware (wires, balloons, and stents). Interventionalists should be aware of the potential risk of this fatal complication and should be proactive in recognizing the scenarios where this is likely to occur. In such anticipated circumstances, the interventionalist may judiciously switch the anticoagulant to heparin and/or use additional glycoprotein IIb/IIIa inhibitor because freshly formed intracoronary thrombus is susceptible to lysis by glycoprotein IIb/IIIa inhibitors.

  1. The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133(+) stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy.

    PubMed

    Noiseux, Nicolas; Mansour, Samer; Weisel, Richard; Stevens, Louis-Mathieu; Der Sarkissian, Shant; Tsang, Katherine; Crean, Andrew M; Larose, Eric; Li, Shu-Hong; Wintersperger, Bernd; Vu, Minh Quan; Prieto, Ignacio; Li, Ren-Ke; Roy, Denis Claude; Yau, Terrence M

    2016-12-01

    The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133(+) stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133(+), CD34(+), CD45(+) triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133(+) cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. Intracoronary ghrelin infusion decreases coronary blood flow in anesthetized pigs.

    PubMed

    Grossini, Elena; Molinari, Claudio; Mary, David A S G; Ghigo, Ezio; Bona, Gianni; Vacca, Giovanni

    2007-02-01

    The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.

  3. Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials

    PubMed Central

    Piñana, José Luis; Martino, Rodrigo; Gayoso, Jorge; Sureda, Anna; de la Serna, Javier; Díez-Martín, Jose Luis; Vazquez, Lourdes; Arranz, Reyes; Tomás, José Francisco; Sampol, Antonia; Solano, Carlos; Delgado, Julio; Sierra, Jorge; Caballero, Dolores

    2010-01-01

    Background Allogeneic hematopoietic stem cell transplantation is an effective treatment for patients with poor risk lymphoma, at least in part because of the graft-versus-lymphoma effect. Over the past decade, reduced intensity conditioning regimens have been shown to offer results similar to those of conventional high-dose conditioning regimens but with lower toxicity early after transplantation, especially in patients with chemosensitive disease at transplant. Design and Methods The aim of this study was to analyze the long-term outcome of patients with follicular lymphoma who received an HLA identical sibling allogeneic stem cell transplant with a reduced intensity conditioning regimen within prospective trials. The prospective multicenter studies considered included 37 patients with follicular lymphoma who underwent allogeneic stem cell transplantation between 1998 and 2007 with a fludarabine plus melphalan-based reduced intensity conditioning regimen. Results The median age of the patients was 50 years (range, 34–62 years) and the median follow-up was 52 months (range, 0.6 to 113 months). Most patients (77%) had stage III-IV at diagnosis, and patients had received a median of three lines of therapy before the reduced intensity conditioning allogeneic stem cell transplantation. At the time of transplantation, 14 patients were in complete remission, 16 in partial remission and 7 had refractory or progressive disease after salvage chemotherapy. The 4-year overall survival rates for patients in complete remission, partial remission, or with refractory or progressive disease were 71%, 48% and 29%, respectively (P=0.09), whereas the 4-year cumulative incidences of non-relapse mortality were 26% (95% CI, 11–61), 33% (95% CI, 16–68) and 71% (95% CI, 44–100), respectively. The incidence of relapse for the whole group was only 8% (95% CI, 2–23). Conclusions We conclude that this strategy of reduced intensity conditioning allogeneic stem cell transplantation

  4. Intracoronary Imaging in the Detection of Vulnerable Plaques.

    PubMed

    Batty, Jonathan A; Subba, Shristy; Luke, Peter; Gigi, Li Wing Chi; Sinclair, Hannah; Kunadian, Vijay

    2016-03-01

    Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging.

  5. Single cardiac cycle three-dimensional intracoronary optical coherence tomography.

    PubMed

    Kim, Tae Shik; Park, Hyun-Sang; Jang, Sun-Joo; Song, Joon Woo; Cho, Han Saem; Kim, Sunwon; Bouma, Brett E; Kim, Jin Won; Oh, Wang-Yuhl

    2016-12-01

    While high-speed intracoronary optical coherence tomography (OCT) provides three-dimensional (3D) visualization of coronary arteries in vivo, imaging speeds remain insufficient to avoid motion artifacts induced by heartbeat, limiting the clinical utility of OCT. In this paper, we demonstrate development of a high-speed intracoronary OCT system (frame rate: 500 frames/s, pullback speed: 100 mm/s) along with prospective electrocardiogram (ECG) triggering technology, which enabled volumetric imaging of long coronary segments within a single cardiac cycle (70 mm pullback in 0.7 s) with minimal cardiac motion artifact. This technology permitted detailed visualization of 3D architecture of the coronary arterial wall of a swine in vivo and fine structure of the implanted stent.

  6. Single cardiac cycle three-dimensional intracoronary optical coherence tomography

    PubMed Central

    Kim, Tae Shik; Park, Hyun-Sang; Jang, Sun-Joo; Song, Joon Woo; Cho, Han Saem; Kim, Sunwon; Bouma, Brett E.; Kim, Jin Won; Oh, Wang-Yuhl

    2016-01-01

    While high-speed intracoronary optical coherence tomography (OCT) provides three-dimensional (3D) visualization of coronary arteries in vivo, imaging speeds remain insufficient to avoid motion artifacts induced by heartbeat, limiting the clinical utility of OCT. In this paper, we demonstrate development of a high-speed intracoronary OCT system (frame rate: 500 frames/s, pullback speed: 100 mm/s) along with prospective electrocardiogram (ECG) triggering technology, which enabled volumetric imaging of long coronary segments within a single cardiac cycle (70 mm pullback in 0.7 s) with minimal cardiac motion artifact. This technology permitted detailed visualization of 3D architecture of the coronary arterial wall of a swine in vivo and fine structure of the implanted stent. PMID:28018710

  7. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

    PubMed

    Fermand, J P; Ravaud, P; Chevret, S; Divine, M; Leblond, V; Belanger, C; Macro, M; Pertuiset, E; Dreyfus, F; Mariette, X; Boccacio, C; Brouet, J C

    1998-11-01

    Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

  8. The need for stent-lesion matching to optimize outcomes of intracoronary stent implantation.

    PubMed

    Lanzer, Peter; Strupp, Gerhard; Schmidt, Wolfram; Topoleski, L D Timmie

    2013-11-01

    Intracoronary stents have markedly improved the outcomes of catheter-based coronary interventions. Intracoronary stent implantation rates of over 90% during coronary angioplasty are common. Stent implantations are associated with a small but statistically significant number of adverse outcomes including restenosis, thrombosis, strut malapposition, incomplete strut endothelialization, and various types of stenting failure. Better matching of biomechanical properties of stents and lesions could further improve the clinical outcome of intracoronary stenting. Thus, in this article, we assess the need for advanced intracoronary stent-lesion matching. We reviewed the data on biomechanics of coronary stents and lesions to develop knowledge-based rationale for optimum intracoronary stent selection. The available technical information on marketed intracoronary stents and the current understanding of the biomechanical properties of coronary lesions at rest and under stress are limited, preventing the development of knowledge-based rationale for optimum intracoronary stent selection at present. Development of knowledge-based selection of intracoronary stents requires standardization of mechanical stent testing, communication of the nonproprietary technical data on stents by the industry and dedicated research into procedural stent-lesion interactions.

  9. Computational simulation of intracoronary flow based on real coronary geometry.

    PubMed

    Boutsianis, Evangelos; Dave, Hitendu; Frauenfelder, Thomas; Poulikakos, Dimos; Wildermuth, Simon; Turina, Marko; Ventikos, Yiannis; Zund, Gregor

    2004-08-01

    To assess the feasibility of computationally simulating intracoronary blood flow based on real coronary artery geometry and to graphically depict various mechanical characteristics of this flow. Explanted fresh pig hearts were fixed using a continuous perfusion of 4% formaldehyde at physiological pressures. Omnipaque dye added to lead rubber solution was titrated to an optimum proportion of 1:25, to cast the coronary arterial tree. The heart was stabilized in a phantom model so as to suspend the base and the apex without causing external deformation. High resolution computerized tomography scans of this model were utilized to reconstruct the three-dimensional coronary artery geometry, which in turn was used to generate several volumetric tetrahedral meshes of sufficient density needed for numerical accuracy. The transient equations of momentum and mass conservation were numerically solved by employing methods of computational fluid dynamics under realistic pulsatile inflow boundary conditions. The simulations have yielded graphic distributions of intracoronary flow stream lines, static pressure drop, wall shear stress, bifurcation mass flow ratios and velocity profiles. The variability of these quantities within the cardiac cycle has been investigated at a temporal resolution of 1/100th of a second and a spatial resolution of about 10 microm. The areas of amplified variations in wall shear stress, mostly evident in the neighborhoods of arterial branching, seem to correlate well with clinically observed increased atherogenesis. The intracoronary flow lines showed stasis and extreme vorticity during the phase of minimum coronary flow in contrast to streamlined undisturbed flow during the phase of maximum flow. Computational tools of this kind along with a state-of-the-art multislice computerized tomography or magnetic resonance-based non-invasive coronary imaging, could enable realistic, repetitive, non-invasive and multidimensional quantifications of the effects of

  10. Pandemic 2009 Influenza A (H1N1) virus infection in cancer and hematopoietic stem cell transplant recipients; a multicenter observational study.

    PubMed Central

    Dignani, Maria Cecilia; Costantini, Patricia; Salgueira, Claudia; Jordán, Rosana; Guerrini, Graciela; Valledor, Alejandra; Herrera, Fabián; Nenna, Andrea; Mora, Claudia; Roccia-Rossi, Inés; Stecher, Daniel; Carbone, Edith; Laborde, Ana; Efron, Ernesto; Altclas, Javier; Calmaggi, Aníbal; Cozzi, José

    2015-01-01

    Background: During March 2009 a novel Influenza A virus emerged in Mexico. We describe the clinical picture of the pandemic Influenza A (H1N1) Influenza in cancer patients during the 2009 influenza season. Methods: Twelve centers participated in a multicenter retrospective observational study of cancer patients with confirmed infection with the 2009 H1N1 Influenza A virus (influenza-like illness or pneumonia plus positive PCR for the 2009 H1N1 Influenza A virus  in respiratory secretions). Clinical data were obtained by retrospective chart review and analyzed.  Results: From May to August 2009, data of 65 patients were collected. Median age was 51 years, 57 % of the patients were female. Most patients (47) had onco-hematological cancers and 18 had solid tumors. Cancer treatment mainly consisted of chemotherapy (46), or stem cell transplantation (SCT) (16). Only 19 of 64 patients had received the 2009 seasonal Influenza vaccine. Clinical presentation included pneumonia (43) and upper respiratory tract infection (22). Forty five of 58 ambulatory patients were admitted. Mechanical ventilation was required in 12 patients (18%). Treatment included oseltamivir monotherapy or in combination with amantadine for a median of 7 days. The global 30-day mortality rate was 18%. All 12 deaths were among the non-vaccinated patients. No deaths were observed among the 19 vaccinated patients. Oxygen saturation <96% at presentation was a predictor of mortality (OR 19.5; 95%CI: 2.28 to 165.9). Conclusions: In our cancer patient population, the pandemic 2009 Influenza A (H1N1) virus was associated with high incidence of pneumonia (66%), and 30-day mortality (18.5%). Saturation <96% was significantly associated with death. No deaths were observed among vaccinated patients. PMID:25469231

  11. Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT.

    PubMed

    Basak, G W; Wiktor-Jedrzejczak, W; Labopin, M; Schoemans, H; Ljungman, P; Kobbe, G; Beguin, Y; Lang, P; Koenecke, C; Sykora, K W; Te Boome, L; van Biezen, A; van der Werf, S; Mohty, M; de Witte, T; Marsh, J; Dreger, P; Kröger, N; Duarte, R; Ruutu, T

    2015-03-01

    We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.

  12. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multi-center survey

    PubMed Central

    Zeiser, Robert; Burchert, Andreas; Lengerke, Claudia; Verbeek, Mareike; Maas-Bauer, Kristina; Metzelder, Stephan K.; Spoerl, Silvia; Ditschkowski, Markus; Ecsedi, Matyas; Sockel, Katja; Ayuk, Francis; Ajib, Salem; de Fontbrune, Flore Sicre; Na, Il-Kang; Penter, Livius; Holtick, Udo; Wolf, Dominik; Schuler, Esther; Meyer, Everett; Apostolova, Petya; Bertz, Hartmut; Marks, Reinhard; Lübbert, Michael; Wäsch, Ralph; Scheid, Christof; Stölzel, Friedrich; Ordemann, Rainer; Bug, Gesine; Kobbe, Guido; Negrin, Robert; Brune, Mats; Spyridonidis, Alexandros; Schmitt-Gräff, Annette; van der Velden, Walter; Huls, Gerwin; Mielke, Stephan; Grigoleit, Götz Ulrich; Kuball, Jürgen; Flynn, Ryan; Ihorst, Gabriele; Du, Jing; Blazar, Bruce R; Arnold, Renate; Kröger, Nicolaus; Passweg, Jakob; Halter, Jörg; Socié, Gerard; Beelen, Dietrich; Peschel, Christian; Neubauer, Andreas; Finke, Jürgen; Duyster, Justus; von Bubnoff, Nikolas

    2016-01-01

    Despite major improvements in allogeneic hematopoietic cell transplantation over the last decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage-therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grade III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1–7) and SR-cGVHD (1–10). The ORR was 81.5% (44/54) in SR-aGVHD including 25 CRs (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3%–90.7%,95% CI) and 97.4% (92.3%–100%,95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and CMV-reactivation were observed during ruxolitinib-treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial. PMID:26228813

  13. Immediate outcomes of eptifibatide therapy during intracoronary stent implantation

    PubMed Central

    Shariati, Hooman; Sanei, Hamid; Pourmoghadas, Ali; Salehizadeh, Leila; Amirpour, Afshin

    2016-01-01

    Background: The objective of the present study was to assess the major immediate outcomes of eptifibatide therapy during intracoronary stent implantation. Materials and Methods: In an interventional study, patients undergoing percutaneous coronary intervention (PCI) were randomized into either the eptifibatide (n = 100) or the control (n = 107) group. In each group, demographic and clinical characteristics such as cardiac death, stent thrombosis (ST), myocardial infarction (MI), rates of target lesion and vessel revascularization, cerebral vascular accident (CVA), and emergency coronary artery bypass grafting (CABG) were recorded. Results: The overall rates of major adverse events such as mortality, Stent thrombosis (ST), Myocardial Infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), CVA, and emergency CABG within 24 h after stent implantation were low and comparable between the two groups; P > 0.05 considered significant for all comparisons. Conclusion: There were no statistical differences between the clinical outcomes of groups administered with single-dose intracoronary eptifibatide and control groups among patients undergoing PCI during stent implantation. PMID:28217642

  14. Reflex cardiovascular effects of intracoronary acetylstrophanthidin in the conscious dog.

    PubMed

    Barron, K W; Bishop, V S

    1985-06-01

    The present experiments were designed to examine the reflex cardiovascular effects of intracoronary administration of acetylstrophanthidin in the conscious dog. Administration of 4 micrograms/kg of this agent into the left circumflex coronary artery increased left ventricular dP/dtmax but had no effect on mean arterial pressure, heart rate, renal resistance, or iliac resistance. The positive inotropic effects of acetylstrophanthidin were less under control conditions (+599 mmHg/s) than during bilateral cervical vagal cold block (+850 mmHg/s, P less than 0.05); however, interruption of vagal efferent influences (atropine) alone did not alter the contractile effects of acetylstrophanthidin. Interruption of sympathetic efferent influences on the heart with either the nicotinic ganglionic receptor antagonist, hexamethonium, or the beta 1-adrenergic receptor antagonist, metoprolol, also augmented the inotropic effects of acetylstrophanthidin to a degree similar to that observed with vagal cold block. In contrast to the effects observed with acetylstrophanthidin, the inotropic effects of intracoronary administration of calcium gluconate were not altered by vagal cold block or any other conditions examined in this study. We conclude that interruption of vagal afferents results in an augmentation of the positive inotropic actions of acetylstrophanthidin and that this augmented inotropic effect can be accounted for by interruption of cardiac vagal afferent-mediated restraint on sympathetic outflow to the heart.

  15. No-Reflow Phoenomenon by Intracoronary Thrombus in Acute Myocardial Infarction.

    PubMed

    Lim, Sang Yup

    2016-01-01

    Recently, percutaneous coronary intervention has been the treatment of choice in most acute myocardial infarction cases. Although the results of percutaneous coronary interventions have ben good, the no-reflow phenomenon and distal embolization of intracoronary thrombus are still major problems even after successful interventions. In this article, we will briefly review the deleterious effects of no-reflow and distal embolization of intracoronary thrombus during percutaneous coronary interventions. The current trials focused on the prevention and treatment of the no-reflow phenomenon and intracoronary thrombus.

  16. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma.

    PubMed

    Thomas, Alissa A; Abrey, Lauren E; Terziev, Robert; Raizer, Jeffrey; Martinez, Nina L; Forsyth, Peter; Paleologos, Nina; Matasar, Matthew; Sauter, Craig S; Moskowitz, Craig; Nimer, Stephen D; DeAngelis, Lisa M; Kaley, Thomas; Grimm, Sean; Louis, David N; Cairncross, J Gregory; Panageas, Katherine S; Briggs, Samuel; Faivre, Geraldine; Mohile, Nimish A; Mehta, Jayesh; Jonsson, Philip; Chakravarty, Debyani; Gao, Jianjiong; Schultz, Nikolaus; Brennan, Cameron W; Huse, Jason T; Omuro, Antonio

    2017-10-01

    Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3.2 mg/kg/day × 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017. NCT00588523.

  17. Current Developments and Future Applications of Intracoronary Hemodynamics

    PubMed Central

    Coverstone, Edward; Shapiro, Robert; Singh, Jasvindar

    2015-01-01

    Intracoronary hemodynamic assessment of the physiologic significance of coronary lesions improves clinical outcomes in patients with coronary artery disease. Coronary flow velocity reserve (CFVR), fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and index of microcirculatory resistance (IMR) utilize sensor-mounted guidewires to approximate coronary flow. CFVR and FFR rely on pharmacologic administration of adenosine to achieve hyperemia and diagnose epicardial lesion severity. As an adenosine-free index, iFR utilizes a wave-free period in mid-late diastole during which resistance is constant and low to assess lesion significance. IMR combines hyperemic pressure measurements with thermodilution to quantify microvascular resistance. We review the physiology, clinical trials, and clinical applications of these invasive hemodynamic assessments. PMID:25946656

  18. Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

    PubMed Central

    Tura, Bernardo R; Martino, Helena F; Gowdak, Luis H; dos Santos, Ricardo Ribeiro; Dohmann, Hans F; Krieger, José E; Feitosa, Gilson; Vilas-Boas, Fábio; Oliveira, Sérgio A; Silva, Suzana A; Bozza, Augusto Z; Borojevic, Radovan; de Carvalho, Antonio C Campos

    2007-01-01

    Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT

  19. Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

    PubMed

    Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

    2016-04-25

    Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary

  20. Intracoronary Acetylcholine Provocation Testing for Assessment of Coronary Vasomotor Disorders.

    PubMed

    Ong, Peter; Athanasiadis, Anastasios; Sechtem, Udo

    2016-08-18

    Intracoronary acetylcholine provocation testing (ACH-test) is an established method for assessment of epicardial coronary artery spasm in the catheterization laboratory which was introduced more than 30 years ago. Due to the short half-life of acetylcholine it can only be applied directly into the coronary arteries. Several studies have demonstrated the safety and clinical usefulness of this test. However, acetylcholine testing is only rarely applied in the U.S. or Europe. Nevertheless, it has been shown that 62% of Caucasian patients with stable angina and unobstructed coronary arteries on coronary angiography suffer from coronary vasomotor disorders that can be diagnosed with acetylcholine testing. In recent years it has been appreciated that the ACH-test not only assesses the presence of epicardial spasm but that it can also be useful for the detection of coronary microvascular spam. In such cases no epicardial spasm is seen after injection of acetylcholine but ischemic ECG shifts are present together with a reproduction of the patient's symptoms during the test. This article describes the experience with the ACH-test and its implementation in daily clinical routine.

  1. Dynamic single gold nanoparticle visualization by clinical intracoronary optical coherence tomography.

    PubMed

    Hu, Jie; Rivero, Fernando; Torres, Rio Aguilar; Loro Ramírez, Héctor; Rodríguez, Emma Martín; Alfonso, Fernando; García Solé, José; Jaque, Daniel

    2017-05-01

    The potential use of Gold Nanoparticles (GNPs) as contrast agents for clinical intracoronary frequency domain Optical Coherence Tomography (OCT) is here explored. The OCT contrast enhancement caused by GNPs of different sizes and morphologies has been systematically investigated and correlated with their optical properties. Among the different GNPs commercially available with plasmon resonances close to the operating wavelength of intracoronary OCT (1.3 µm), Gold Nanoshells (GNSs) have provided the best OCT contrast due to their largest scattering cross section at this wavelength. Clinical intracoronary OCT catheters are here demonstrated to be capable of three dimensional visualization and real-time tracking of individual GNSs. Results here included open an avenue to novel application of intravascular clinical OCT in combination with GNPs, such as real time evaluation of intravascular obstructions or pressure gradients. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Acute myocardial infarction caused by left atrial myxoma: Role of intracoronary catheter aspiration.

    PubMed

    Al-Fakhouri, Ahmad; Janjua, Muhammad; DeGregori, Michele

    2017-01-01

    Acute ST-segment elevation myocardial infarction (STEMI) caused by left atrial myxoma is very rare. Catheter-based approaches or thrombolytic therapy are mostly the first step in the management of STEMI with less time delay. We report a case of acute anterior/lateral STEMI caused by a left atrial myxoma. The patient was successfully treated by intracoronary aspiration with an Export aspiration catheter, with excellent distal coronary flow. Intracoronary catheter aspiration in acute myocardial infarction caused by a left atrial myxoma may help to salvage the infarcting myocardium with less time delay.

  3. Efficiencies of intracoronary sodium nitroprusside on fractional flow reserve measurement

    PubMed Central

    Li, Shaosheng; Deng, Jie; Wang, Xiaozeng; Zhao, Xin; Han, Yaling

    2015-01-01

    Background: Fractional flow reserve (FFR) has certain advantages of assessing functional severity of coronary stenosis. Adenosine(AD) is the most widely used agents in FFR measurement but has the disadvantages of higher rate of complications. Sodium Nitroprusside (SNP) represents a valuable alternative. Methods and results: In 75 patients with 86 moderate coronary stenosis, FFR values, heart rate and blood pressure were measured at baseline, after 0.6 μg boluses of intracoronary (IC) SNP, and after 140 μg/kg /min of continuous intravenous (IV) AD. FFR values decreased significantly after administering IV AD and IC SNP compared with the baseline Pd/Pa values (P < 0.001). Mean FFR induced by IV AD was not significantly different from that by IC SNP (t = 0.577, P = 0.566). The mean kappa value in the evaluation of two methods was 0.973 for FFR. There was a significant correlation between the FFR values of IV AD and IC SNP (R = 0.911, P < 0.001). Significant decreases in the blood pressures were found after agents were given compared to the baseline. No significant difference was found between AD and SNP. In addition, immediate complications occurred in 60.5% patients of IV AD in contrast to no adverse events after IC SNP. Conclusion: SNP is a safe and effective agent and easy to use for the FFR measurement. Maximal hyperemia by IC SNP is equivalent to that by IV AD. IC SNP could be considered a potential alternative in patients with contraindications to AD administration. PMID:25932219

  4. Automatic atherosclerotic heart disease detection in intracoronary optical coherence tomography images.

    PubMed

    Xu, Mengdi; Cheng, Jun; Wong, Damon Wing Kee; Taruya, Akira; Tanaka, Atsushi; Liu, Jiang

    2014-01-01

    Intracoronary optical coherence tomography (OCT) is a new invasive imaging system which produces high-resolution images of coronary arteries. Preliminary data suggests that the atherosclerotic disease can be detected from the intracoronary OCT images. However, manual assessment of the intracoronary OCT images is time-consuming and subjective. In this work, we present an automatic atherosclerotic disease detection system on intracoronary OCT images. In the system, a preprocessing scheme is first applied to remove speckle noise and artifacts caused by catheter. Intensity, Histograms of Oriented Gradients (HOG), and Local Binary Patterns (LBP) are then extracted to represent the OCT image. Finally a linear SVM classifier is employed to detect the unhealthy subject. Four-fold cross-validation process is conducted to evaluate the proposed system; and a dataset with 200 images from healthy subjects and 200 images from unhealthy subjects is built to evaluate the system. The mean accuracy is 0.90 and standard deviation is 0.0427, which indicates that the proposed system is accurate and stable.

  5. Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study

    PubMed Central

    Suter, Melissa J.; Kashiwagi, Manabu; Gallagher, Kevin A; Nadkarni, Seemantini K.; Asanani, Nayan; Tanaka, Atsushi; Conditt, Gerard B.; Tellez, Armando; Milewski, Krzysztof; Kaluza, Greg L.; Granada, Juan F.; Bouma, Brett E.; Tearney, Guillermo J.

    2015-01-01

    Background and Aims Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. Methods and Results 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in 3 swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23% (<0.0001). This error was eliminated with careful refractive index calibration. Conclusions Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful

  6. Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study.

    PubMed

    Suter, Melissa J; Kashiwagi, Manabu; Gallagher, Kevin A; Nadkarni, Seemantini K; Asanani, Nayan; Tanaka, Atsushi; Conditt, Gerard B; Tellez, Armando; Milewski, Krzysztof; Kaluza, Greg L; Granada, Juan F; Bouma, Brett E; Tearney, Guillermo J

    2015-08-01

    Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23% (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be

  7. Curved versus Straight Stem Uncemented Total Hip Arthroplasty Osteoarthritis Multicenter trial (CUSTOM): design of a prospective blinded randomised controlled multicentre trial

    PubMed Central

    van Beers, Loes W A H; van Oldenrijk, Jakob; Scholtes, Vanessa A B; Geerdink, Carel H; Niers, Bob B A M; Runne, Wouter; Bhandari, Mohit; Poolman, Rudolf W

    2016-01-01

    Introduction Answering the demands of an increasingly young and active patient population, recent developments in total hip arthroplasty (THA) have shifted towards minimising tissue damage. The Collum Femoris Preserving (CFP) stem was developed to preserve the trochanteric region of the femur, which potentially preserves the insertion of the gluteus musculature. This might accelerate early postoperative rehabilitation and improve functional outcome. Currently the functional results of the CFP stem have not been compared with conventional straight stems in a randomised controlled trial (RCT). The primary purpose of this trial is to compare the functional result of CFP stem THA with conventional uncemented straight stem THA, measured by the Dutch Hip disability and Osteoarthritis Outcome Score (HOOS) at 3-month follow-up. Methods A prospective blinded multicentre RCT will be performed. We aim to recruit 150 patients. The patients will be randomly allocated to a THA with a straight or a curved stem. All patients, research assistants, clinical assessors and investigators will be blinded for the type of prosthesis for 5 years. Clinical assessments and roentgenograms will be taken preoperative, at 6 weeks after surgery, at 1, 2, 3, 4 and 5 years after surgery. Patient reported outcome measures (PROMs) will be obtained at the same follow-up moments. In addition, the PROMs will also be sent to the patients at 3 and 6 months after surgery. The HOOS at 3-month follow-up will be our primary outcome. Ethics and dissemination This trial will be performed in accordance with the Declaration of Helsinki. A local ethics committee has approved this trial. Written informed consent will be obtained from all participating patients. All serious adverse events will be reported to the ethics committee. Results Results will be submitted for publication to an orthopaedics related journal. Trial registration number NTR1560. PMID:27009147

  8. STEM?!?!

    ERIC Educational Resources Information Center

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  9. STEM?!?!

    ERIC Educational Resources Information Center

    Merrill, Jen

    2012-01-01

    The author's son has been an engineer since birth. He never asked "why" as a toddler, it was always "how's it work?" So that he wanted a STEM-based home education was no big surprise. In this article, the author considers what kind of curricula would work best for her complex kid.

  10. Local Intracoronary Infusion of Glycoprotein IIb/IIIa Inhibitors via a Perfusion Catheter versus Intracoronary Guiding Catheter Injection during Primary Percutaneous Coronary Intervention: A Pilot Observational Study

    PubMed Central

    Zaki, Tarek; Labib, Salwa; El-Abbady, Maged; El-Kilany, Wael; Mortada, Ayman; Rashid, Tarek; Ragy, Hany; El-Itreby, Adel; Nammas, Wail

    2017-01-01

    Background Glycoprotein IIb IIIa inhibitors improved short- and long-term outcome when added to primary percutaneous coronary intervention (PPCI) in patients with ST-segment-elevation myocardial infarction (STEMI). We hypothesized that intracoronary eptifibatide infusion via a perfusion catheter improves angiographic and clinical outcome of patients with STEMI undergoing PPCI, versus conventional intracoronary bolus injection. Methods Prospectively, we enrolled 80 patients with acute STEMI and thrombolysis in myocardial infarction (TIMI) thrombus grade ≥ 2. Patients were assigned to receive eptifibatide (180 μg) either via a dedicated coronary perfusion catheter (ClearWayTM) during PPCI (group I), or guiding catheter (group II). Assessment of TIMI thrombus grade, TIMI flow grade, and TIMI myocardial perfusion (TMP) grade was performed both at baseline and post- procedurally. The primary ‘angiographic’ endpoint was final TMP grade 0/1. The primary ‘clinical’ endpoint was a composite of cardiac death, non-fatal re-infarction, target vessel revascularization, and recurrent ischemia at 30-day follow-up. Results Mean age was 52.3 ± 8.9 years (17.5% females). Clearance of visible thrombus (TIMI thrombus grade 0) at final angiogram was more frequent in group I. Additionally, both final TIMI flow grade 3 and final TMP grade 3 occurred more frequently in group I. The primary angiographic endpoint was more frequent in group II versus group I (17.5% versus 0%, respectively, p = 0.001). The primary clinical endpoint was more frequent in group II (20% versus 0%, respectively, p = 0.003). Conclusions In patients with STEMI, intracoronary eptifibatide infusion via a perfusion catheter during PPCI improved immediate angiographic outcome, and reduced clinical events at 30-day follow-up, versus bolus injection via the guiding catheter. PMID:28559656

  11. Sustained quality of life improvement after intracoronary injection of autologous bone marrow cells in the setting of acute myocardial infarction: results from the BONAMI trial.

    PubMed

    Lamirault, Guillaume; de Bock, Elodie; Sébille, Véronique; Delasalle, Béatrice; Roncalli, Jérôme; Susen, Sophie; Piot, Christophe; Trochu, Jean-Noël; Teiger, Emmanuel; Neuder, Yannick; Le Tourneau, Thierry; Manrique, Alain; Hardouin, Jean-Benoît; Lemarchand, Patricia

    2017-01-01

    Cardiac cell therapy is a promising treatment for acute myocardial infarction (AMI), leading to cardiac function improvement. However, whether it translates into quality of life (QoL) improvement is unclear. We hypothesized that administration of bone marrow cells (BMC) to patients with AMI improves QoL. In the multicenter BONAMI trial (NCT00200707), patients with reperfused AMI and decreased myocardial viability were randomized to intracoronary autologous BMC infusion (n = 52) or state-of-the-art therapy (n = 49). QoL data, derived from the Minnesota Living with Heart Failure questionnaire (MLHFQ), were obtained 1, 3, and 12 months after AMI and analyzed using a Rasch-family model. Using this model, QoL improved over time in the BMC group (p = 0.025) but not in the control group. Furthermore, the BMC-group patients displayed a better QoL than the control-group patients at 3 and 12 months post-AMI (p = 0.034 and p = 0.003, respectively). These findings were not detected when analyzing MLHFQ data using a standard method. Cardiac function, myocardial viability, mortality, and number of major adverse cardiac events did not differ between treatment groups. Our results suggest that BMC therapy can improve QoL, stressing the need for confirmation trials and for systematic QoL assessment in cardiac cell therapy trials .

  12. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: results of a multicenter prospective phase 2 trial.

    PubMed

    Mohty, Mohamad; Malard, Florent; Blaise, Didier; Milpied, Noel; Furst, Sabine; Tabrizi, Resa; Guillaume, Thierry; Vigouroux, Stéphane; El-Cheikh, Jean; Delaunay, Jacques; Le Gouill, Steven; Moreau, Philippe; Labopin, Myriam; Chevallier, Patrice

    2015-02-15

    The optimal intensity of myeloablation delivered as part of a reduced-intensity/toxicity conditioning (RIC/RTC) regimen to decrease the recurrence rate, without increasing nonrecurrence mortality (NRM), remains to be established. The current phase 2, prospective, multicenter trial aimed to assess the efficacy and safety of an RIC/RTC regimen based on busulfan at a dose of 130 mg/m(2) /day intravenously for 3 days, fludarabine at a dose of 30 mg/m(2) /day for 5 days, and antithymocyte globulins at a dose of 2.5 mg/kg/day for 2 days. A total of 80 patients (median age, 53 years; range, 25-64 years) with hematological malignancies were included. With a median follow-up of 21 months (range, 12-36.5 months), the Kaplan-Meier estimates of overall and disease-free survival at 2 years were 62% (95% confidence interval [95% CI], 51%-73%) and 50% (95% CI, 33%-57%), respectively. The cumulative incidences of grade 2 to 4 acute graft-versus-host disease (GVHD) and chronic GVHD (all grades) were 29% (95% CI, 19%-39%) and 35% (95% CI, 24%-46%), respectively. At 2 years, the cumulative incidence of recurrence/disease progression and NRM were 44% (95% CI, 31%-56%) and 11% (95% CI, 6%-19%), respectively. Patient age, diagnosis, donor type, sex, presence of comorbidities, and the Hematopoietic cell transplantation-specific comorbidities index did not appear to have any statistically significant impact on NRM, recurrence/disease progression, disease-free survival, or overall survival. The RIC/RTC regimen used in the current study appeared to be safe, with a low NRM rate at 2 years noted among high-risk patients, and efficient disease control, warranting prospective phase 3 trials. © 2014 American Cancer Society.

  13. Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

    PubMed

    Kurekci, Emin; Küpesiz, Alphan; Anak, Sema; Öztürk, Gülyüz; Gürsel, Orhan; Aksoylar, Serap; Ileri, Talia; Kuşkonmaz, Barış; Eker, İbrahim; Cetin, Mualla; Tezcan Karasu, Gülsün; Kaya, Zühre; Fışgın, Tunç; Ertem, Mehmet; Kansoy, Savaş; Yeşilipek, Mehmet Akif

    2017-05-01

    Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 10(6) CD 34(+) cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Adjunctive intra-coronary imaging for the assessment of coronary artery disease

    PubMed Central

    Shah, Nikunj; Ussen, Bassey

    2016-01-01

    Atherosclerotic coronary artery disease remains a leading cause of worldwide morbidity and mortality. Invasive angiography currently remains the gold standard method of diagnosing and treating coronary disease; however, more sophisticated adjunctive interventional technologies have been developed to combat the inter and intra-observer variability frequently encountered in the assessment of lesion severity. Intravascular imaging now plays a key role in optimising percutaneous coronary interventions and provides invaluable information as part of the interventional cardiologist’s diagnostic arsenal. The principles, technical aspects and uses of two modalities of intracoronary imaging, intravascular ultrasound and optical coherence tomography, are discussed. We additionally provide examples of cases where the adjunctive intracoronary imaging was superior to angiography alone in successfully identifying and treating acute coronary syndromes. PMID:27540480

  15. Randomised phase 2 trial of intra-coronary nitrite during acute myocardial infarction

    PubMed Central

    Jones, Daniel A; Pellaton, Cyril; Velmurugan, Shanti; Rathod, Krishnaraj Sinha; Andiapen, Mervyn; Antoniou, Sotiris; van Eijl, Sven; Webb, Andrew J; Westwood, Mark A; Parmar, Mahesh K; Mathur, Anthony; Ahluwalia, Amrita

    2015-01-01

    Rationale Pre-clinical evidence demonstrates that inorganic nitrite, following its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury. Objective We investigated whether intra-coronary injection of nitrite during primary percutaneous coronary intervention (PCI) might improve infarct size in ST-elevated myocardial infarction (STEMI). Methods and Results Patients undergoing primary PCI (n=80) were randomised to receive intracoronary (10mL) sodium nitrite (1.8μmol) or NaCl (placebo) before balloon inflation. The primary endpoint was infarct size assessed by measuring creatine kinase (CK) release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac magnetic resonance imaging (CMR) on day 2. Baseline characteristics were similar between the groups. No evidence of differences in CK release (p=0.92), troponin T (p=0.85) or CMR-assessed infarct size (p=0.254) were evident. In contrast there was an improvement in myocardial salvage index (p=0.05) and reduction in MACE at 1 year (2.6% vs 15.8%, p=0.04) in the nitrite group. In a 66-patient sub-group with TIMI≤1 flow there was reduced serum CK (p=0.030) and a 19% reduction in CMR-determined infarct size (p=0.034) with nitrite. No adverse effects of nitrite were detected. Conclusions In this phase II study intra-coronary nitrite infusion did not alter infarct size although a trend to improved myocardial salvage index and a significant reduction in MACE was evident. In a sub-group of patients with TIMI flow≤1 nitrite reduced infarct size and MACE and improved myocardial salvage index indicating that a phase III clinical trial assessing intra-coronary nitrite administration as an adjunct to PCI in STEMI patients is warranted. Clinical Trial Registration URL: http://clinicaltrials.gov NCT01584453. PMID:25512434

  16. Relief of mitral incompetence by selective intracoronary thrombolysis in hyperacute myocardial infarction.

    PubMed

    Keltai, M; Palik, I; Rozsa, Z; Szente, A

    1985-01-01

    Left ventriculography and coronary arteriography were performed in 47 patients with hyperacute myocardial infarction prior to recanalization of the infarct-related vessel. Mitral regurgitation was found in ten patients. After successful recanalization, left ventriculography was repeated in eight of the ten patients with mitral incompetence, and the mitral regurgitation had disappeared in seven. Selective intracoronary thrombolysis resulted in improved left ventricular function and disappearance of mitral incompetence.

  17. Intracoronary hypothermia for acute myocardial infarction in the isolated beating pig heart

    PubMed Central

    Otterspoor, Luuk C; van Nunen, Lokien X; Rosalina, Tilaï T; Veer, Marcel van’t; Tuijl, Sjoerd Van; Stijnen, Marco; Rutten, Marcel CM; van de Vosse, Frans N; Pijls, Nico HJ

    2017-01-01

    Hypothermia may attenuate reperfusion injury and thereby improve acute myocardial infarction therapy. Systemic cooling trials failed to reduce infarct size, perhaps because the target temperature was not reached fast enough. The use of selective intracoronary hypothermia combined with intracoronary temperature monitoring allows for titrating to target temperature and optimizing the cooling rate. We aimed to the test the feasibility of intracoronary cooling for controlled, selective myocardial hypothermia in an isolated beating pig heart. In five porcine hearts the left anterior descending artery (LAD) was occluded by an over-the-wire balloon (OTWB). After occlusion, saline at 22°C was infused through the OTWB lumen for 5 minutes into the infarct area at a rate of 30 ml/min. Thereafter the balloon was deflated but infusion continued with saline at 4°C for 5 minutes. Distal coronary temperature was continuously monitored by a pressure/temperature guidewire. Myocardial temperature at several locations in the infarct and control areas was recorded using needle thermistors. In the occlusion phase, coronary temperature decreased by 11.4°C (range 9.4-12.5°C). Myocardial temperature throughout the infarct area decreased by 5.1°C (range 1.8-8.1°C) within three minutes. During the reperfusion phase, coronary temperature decreased by 6.2°C (range 4.1-10.3°C) and myocardial temperature decreased by 4.5°C (range 1.5-7.4°C). Myocardial temperature outside the infarct area was not affected. In the isolated beating pig heart with acute occlusion of the LAD, we were able to rapidly “induce, maintain, and control” a stable intracoronary and myocardial target temperature of at least 4°C below body temperature without side effects and using standard PCI equipment, justifying further studies of this technique in humans. PMID:28337283

  18. Intracoronary Infusion of Thioflavin-S to Study Microvascular Obstruction in a Model of Myocardial Infarction.

    PubMed

    Hervas, Arantxa; de Dios, Elena; Forteza, Maria J; Miñana, Gema; Nuñez, Julio; Ruiz-Sauri, Amparo; Bonanad, Clara; Perez-Sole, Nerea; Chorro, Francisco J; Bodi, Vicente

    2015-11-01

    Microvascular obstruction exerts deleterious effects after myocardial infarction. To elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction, we performed a preliminary methodological study to accurately define this process in an in vivo model. Myocardial infarction was induced in swine by means of 90-min of occlusion of the mid left anterior descending coronary artery using angioplasty balloons. Intracoronary infusion of thioflavin-S was applied and compared with traditional intra-aortic or intraventricular instillation. The left anterior descending coronary artery perfused area and microvascular obstruction were quantified in groups with no reperfusion (thioflavin-S administered through the lumen of an inflated over-the-wire balloon) and with 1-min, 1-week, and 1-month reperfusion (thioflavin-S administered from the intracoronary catheter after balloon deflation). In comparison with intra-aortic and intraventricular administration, intracoronary infusion of thioflavin-S permitted a much clearer assessment of the left anterior descending coronary artery perfused area and of microvascular obstruction. Ischemia-reperfusion injury exerted a decisive role on the occurrence and dynamics of microvascular obstruction. The no-reperfusion group displayed completely preserved perfusion. With the same duration of coronary occlusion, microvascular obstruction was already detected in the 1-min reperfusion group (14%±7%), peaked in the 1-week reperfusion group (21%±7%), and significantly decreased in the 1-month reperfusion group (4%±3%; P<.001). We present proof-of-concept evidence on the crucial role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction. The described porcine model using intracoronary injection of thioflavin-S permits accurate characterization of microvascular obstruction after myocardial infarction. Copyright © 2015 Sociedad Española de Cardiología. Published by

  19. GPU-accelerated framework for intracoronary optical coherence tomography imaging at the push of a button.

    PubMed

    Han, Myounghee; Kim, Kyunghun; Jang, Sun-Joo; Cho, Han Saem; Bouma, Brett E; Oh, Wang-Yuhl; Ryu, Sukyoung

    2015-01-01

    Frequency domain optical coherence tomography (FD-OCT) has become one of the important clinical tools for intracoronary imaging to diagnose and monitor coronary artery disease, which has been one of the leading causes of death. To help more accurate diagnosis and monitoring of the disease, many researchers have recently worked on visualization of various coronary microscopic features including stent struts by constructing three-dimensional (3D) volumetric rendering from series of cross-sectional intracoronary FD-OCT images. In this paper, we present the first, to our knowledge, "push-of-a-button" graphics processing unit (GPU)-accelerated framework for intracoronary OCT imaging. Our framework visualizes 3D microstructures of the vessel wall with stent struts from raw binary OCT data acquired by the system digitizer as one seamless process. The framework reports the state-of-the-art performance; from raw OCT data, it takes 4.7 seconds to provide 3D visualization of a 5-cm-long coronary artery (of size 1600 samples x 1024 A-lines x 260 frames) with stent struts and detection of malapposition automatically at the single push of a button.

  20. Local Intracoronary Eptifibatide versus Mechanical Aspiration in Patients with Acute ST-Elevation Myocardial Infarction.

    PubMed

    Hamza, Mohamed A; Galal, Ayman; Suweilam, Salwa; Ismail, Mohamed

    2014-01-01

    Objectives. We compared local delivery of intracoronary eptifibatide via perfusion catheter to thrombus aspiration in primary PCI. Background. Perfusion catheter increases local concentration of the drugs at the culprit site and prolongs their residency time. Methods. 75 patients with acute STEMI were randomized to three groups: 25 received local intracoronary eptifibatide and verapamil via perfusion catheter; 25 patients were managed by Diver CE thrombectomy device and 25 patients by primary PCI without thrombus aspiration. Primary end point was assessment of postprocedural TIMI flow, MPG, and corrected TIMI frame count (cTFC) in the culprit vessel. Results. Perfusion catheter was superior to thrombus aspiration and conventional PCI as regards MBG (68% versus 36% in Diver CE and 20% in the control arm; P value = 0.002), with shorter cTFC rates than thrombectomy and control groups (20.76 ± 4.44 versus 26.68 ± 8.40 and 28.16 ± 5.96, resp.; P = 0.001). TIMI flow was not different between the 3 groups. Eptifibatide led to less time to peak CK (13.12 hours versus 16.5 and 19.5 hours, respectively, P value = 0.001). Conclusion. Local intracoronary eptifibatide by perfusion catheter reduces thrombus burden with better results in microvascular perfusion assessed by cTFC and MBG compared to aspiration device or conventional PCI.

  1. GPU-Accelerated Framework for Intracoronary Optical Coherence Tomography Imaging at the Push of a Button

    PubMed Central

    Han, Myounghee; Kim, Kyunghun; Jang, Sun-Joo; Cho, Han Saem; Bouma, Brett E.; Oh, Wang-Yuhl; Ryu, Sukyoung

    2015-01-01

    Frequency domain optical coherence tomography (FD-OCT) has become one of the important clinical tools for intracoronary imaging to diagnose and monitor coronary artery disease, which has been one of the leading causes of death. To help more accurate diagnosis and monitoring of the disease, many researchers have recently worked on visualization of various coronary microscopic features including stent struts by constructing three-dimensional (3D) volumetric rendering from series of cross-sectional intracoronary FD-OCT images. In this paper, we present the first, to our knowledge, "push-of-a-button" graphics processing unit (GPU)-accelerated framework for intracoronary OCT imaging. Our framework visualizes 3D microstructures of the vessel wall with stent struts from raw binary OCT data acquired by the system digitizer as one seamless process. The framework reports the state-of-the-art performance; from raw OCT data, it takes 4.7 seconds to provide 3D visualization of a 5-cm-long coronary artery (of size 1600 samples x 1024 A-lines x 260 frames) with stent struts and detection of malapposition automatically at the single push of a button. PMID:25880375

  2. Absence of accelerated atherosclerotic disease progression after intracoronary infusion of bone marrow derived mononuclear cells in patients with acute myocardial infarction--angiographic and intravascular ultrasound--results from the TErapia Celular Aplicada al Miocardio Pilot study.

    PubMed

    Arnold, Roman; Villa, Adolfo; Gutiérrez, Hipólito; Sánchez, Pedro L; Gimeno, Federico; Fernández, Maria E; Gutiérrez, Oliver; Mota, Pedro; Sánchez, Ana; García-Frade, Javier; Fernández-Avilés, Francisco; San Román, Jose A

    2010-06-01

    We tried to evaluate a putative negative effect on coronary atherosclerosis in patients receiving intracoronary infusion of unfractionated bone marrow mononuclear cells (BMMC) following an acute ST-elevation myocardial infarction. Peripheral blood mononuclear cells or enriched CD133(+) BMMC have been associated with accelerated atherosclerosis of the distal segment of the infarct related artery (IRA). Thirty-seven patients with ST-elevation myocardial infarction from the TECAM pilot study underwent intracoronary infusion of autologous BMMC 9 +/- 3.1 days after onset of symptoms. We compared angiographic changes from baseline to 9 months of follow-up in the distal non-stented segment of the IRA, as well as in the contralateral coronary artery, with a matched control group. A subgroup of 15 treated patients underwent additional IVUS within the distal segment of the IRA. No difference between stem cell and control group were found regarding changes in minimum lumen diameter (0.006 +/- 0.42 vs 0.06 +/- 0.41 mm, P = ns) and the percentage of stenosis (-2.68 +/- 12.33% vs -1.78 +/- 8.75%, P = ns) at follow-up. Likewise, no differences were seen regarding changes in the contralateral artery (minimum lumen diameter -0.004 +/- 0.54 mm vs -0.06 +/- 0.35 mm, P = ns). In the intravascular ultrasound substudy, no changes were demonstrated comparing baseline versus follow-up in maximum area stenosis and plaque volume. In this pilot study, analysis of a subgroup of patients found that intracoronary injection of unfractionated BMMC in patients with acute ST-elevation myocardial infarction was not associated with accelerated atherosclerosis progression at mid term. Prospective, randomised studies in large cohorts with long-term angiographic and intravascular ultrasound follow-up are necessary to determine the safety of this therapy. Copyright 2010 Mosby, Inc. All rights reserved.

  3. Comparison of effectiveness of high-dose intracoronary adenosine versus intravenous administration on the assessment of fractional flow reserve in patients with coronary heart disease.

    PubMed

    López-Palop, Ramón; Carrillo, Pilar; Frutos, Araceli; Cordero, Alberto; Agudo, Pilar; Mashlab, Samer; Bertomeu-Martínez, Vicente

    2013-05-01

    Intravenous adenosine is considered the drug of choice to obtain maximum hyperemia in the measurement of the fractional flow reserve (FFR). However, comparative studies performed between intravenous and intracoronary administration have not used high doses of intracoronary adenosine. The present study compared the efficacy and safety of high doses of intracoronary adenosine to intravenous administration when calculating the FFR. Intracoronary bolus doses of 60, 180, 300, and 600 μg adenosine were compared to an intravenous administration of 140 μg/kg/min, 200 μg/kg/min, and 140 μg/kg/min plus an intracoronary bolus of 120 μg. All the cases were performed using the radial approach. FFR was assessed in 102 patients with 108 intermediate lesions by an intracoronary pressure wire. The intracoronary dose of 60 μg was associated with a significantly greater FFR compared to the intravenous infusion (0.02 ± 0.03, p = 0.001). The intracoronary doses of 300 (-0.01 ± 0.00; p = 0.006) and 600 μg (-0.02 ± 0.00; p <0.0005) were significantly associated with a smaller FFR compared to the intravenous infusion. An intracoronary dose of 600 μg revealed a significantly greater percentage of lesions with an FFR <0.80 compared to intravenous infusion at 140 μg/kg/min (37.6 vs 31.5%; p <0.05) and 200 μg/kg/min (37.6 vs 32.4%; p <0.05) and compared to intracoronary doses of 60 (26.9%) and 180 μg (31.5%). In conclusion, an intracoronary bolus dose >300 μg can be equal to or more effective than an intravenous infusion of adenosine in achieving maximum hyperemia when calculating the FFR. Its use could simplify these procedures without having an effect on safety.

  4. High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial.

    PubMed

    Ferreri, Andrés J M; Donadoni, Giovanni; Cabras, Maria Giuseppina; Patti, Caterina; Mian, Michael; Zambello, Renato; Tarella, Corrado; Di Nicola, Massimo; D'Arco, Alfonso M; Doa, Gianluca; Bruno-Ventre, Marta; Assanelli, Andrea; Foppoli, Marco; Citterio, Giovanni; Fanni, Alessandro; Mulè, Antonino; Caligaris-Cappio, Federico; Ciceri, Fabio

    2015-11-20

    Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma. HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients. Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 10(6)/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome. The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and

  5. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study.

    PubMed

    Sun, Yuqian; Meng, Fanyi; Han, Mingzhe; Zhang, Xi; Yu, Li; Huang, He; Wu, Depei; Ren, Hanyun; Wang, Chun; Shen, Zhixiang; Ji, Yu; Huang, Xiaojun

    2015-06-01

    The China Assessment of Antifungal Therapy in Hematological Disease study, the first large-scale observational study of invasive fungal disease (IFD) in China, enrolled 1401 patients undergoing hematopoietic stem cell transplantation (HSCT) (75.2% allogeneic and 24.8% autologous) at 31 hospitals across China. The overall incidence of proven or probable IFD was 7.7% (108 of 1401); another 266 cases (19.0%) were possible IFD. After allogeneic or autologous HSCT, the incidence of proven/probable IFD was 8.9% (94 of 1053) and 4.0% (14 of 348), respectively. Some cases (14 of 108) developed during conditioning before transplantation. The cumulative incidence of proven/probable IFD increased steeply in the first month after transplantation and after 6 months, the incidence was significantly higher in allogeneic than it was in autologous transplant recipients (9.2% versus 3.5%; P = .001) and when stem cells were derived from cord blood or bone marrow and peripheral blood (P = .02 versus other sources). Independent risk factors for proven/probable IFD in allogeneic HSCT were diabetes, HLA-matched unrelated donor, prolonged severe neutropenia (absolute neutrophil count > 500/mm(3) for >14 days), and immunosuppressants (odds ratio, 2.0 to 3.4 for all). Antifungal prophylaxis was independently protective (P = .01). Previous IFD and prolonged severe neutropenia were significant independent risk factors among autologous transplantation patients (P < .01, P = .04, respectively). In total, 1175 (83.9%) patients received antifungal prophylaxis (91.6% triazoles) and 514 (36.7%) were treated in the hospital with therapeutic antifungals (89.1% triazoles; median 27 days). Empirical, pre-emptive, and targeted antifungals were used in 82.3%, 13.6%, and 4.1% of cases, respectively. Overall mortality (13.4%; 188 deaths) was markedly higher in patients with proven (5 of 16; 31.3%), probable (20 of 92; 21.7%), or possible (61 of 266; 22.9%) IFD; allogeneic (171 of 1053; 16.2%) rather

  6. Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC.

    PubMed

    Sutton, Laurent; Chevret, Sylvie; Tournilhac, Olivier; Diviné, Marine; Leblond, Véronique; Corront, Bernadette; Leprêtre, Stéphane; Eghbali, Houchingue; Van Den Neste, Eric; Michallet, Mauricette; Maloisel, Frédéric; Bouabdallah, Krimo; Decaudin, Didier; Berthou, Christian; Brice, Pauline; Gonzalez, Hugo; Chapiro, Elise; Radford-Weiss, Isabelle; Leporrier, Nathalie; Maloum, Karim; Nguyen-Khac, Florence; Davi, Frédéric; Lejeune, Julie; Merle-Béral, Hélène; Leporrier, Michel

    2011-06-09

    Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL. They received 3 courses of mini-CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone/prednisolone) and then 3 courses of fludarabine. Patients in complete response (CR) were then randomized to ASCT or observation, whereas the other patients were randomized to dexamethasone, high-dose aracytin, cisplatin (DHAP) salvage followed by either ASCT or 3 courses of fludarabine plus cyclophosphamide (FC). The primary end point was event-free survival (EFS). After up-front treatment, 105 patients entered CR and were randomized between ASCT (n = 52) and observation (n = 53); their respective 3-year EFS rates were 79.8% and 35.5%; the adjusted hazard ratio was 0.3 (95% CI: 0.1-0.7; P = .003). Ninety-four patients who did not enter CR were randomized between ASCT (n = 46) and FC (n = 48); their respective 3-year EFS rates were 48.9% and 44.4%, respectively; the adjusted hazard ratio was 1.7 (95% CI: 0.9-3.2; P = .13). No difference in overall survival was found between the 2 response subgroups. In young CLL patients in CR, ASCT consolidation markedly delayed disease progression. No difference was observed between ASCT and FC in patients requiring DHAP salvage.

  7. Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes.

    PubMed

    Brammer, J E; Saliba, R M; Jorgensen, J L; Ledesma, C; Gaballa, S; Poon, M; Maziarz, R T; Champlin, R E; Hosing, C; Kebriaei, P

    2017-01-01

    This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

  8. Incidence, risk factors and outcome of pre engraftment Gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an Italian prospective multicenter survey.

    PubMed

    Girmenia, Corrado; Bertaina, Alice; Piciocchi, Alfonso; Carotti, Alessandra; Algarotti, Alessandra; Busca, Alessandro; Cattaneo, Chiara; Raiola, Anna Maria; Guidi, Stefano; Iori, Anna Paola; Candoni, Anna; Irrera, Giuseppe; Milone, Giuseppe; Marcacci, Giampaolo; Scimè, Rosanna; Musso, Maurizio; Cudillo, Laura; Sica, Simona; Castagna, Luca; Corradini, Paolo; Marchesi, Francesco; Pastore, Domenico; Alessandrino, Emilio Paolo; Annaloro, Claudio; Ciceri, Fabio; Santarone, Stella; Nassi, Luca; Farina, Claudio; Viscoli, Claudio; Rossolini, Gian Maria; Bonifazi, Francesca; Rambaldi, Alessandro; Italiano, Gruppo

    2017-08-03

    Gram-negative bacteremia (GNB) is a major cause of morbidity and mortality in Hematopoietic Stem Cell Transplant (HSCT) and updated epidemiological investigation is advisable. We prospectively evaluated the epidemiology of pre-engraftment GNB in 1,118 allogeneic HSCT (allo-HSCT) and 1,625 autologous HSCT (auto-HSCT) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. SIGNB-GITMO-AMCLI is registered with ClinicalTrials.gov, number NCT02088840. The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis variables associated with GNB were a diagnosis of acute leukemia, a transplant from HLA-mismatched donor and from cord-blood, older age and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age and no antibacterial prophylaxis in auto-HSCT. A pre-transplant infection by a resistant pathogen was significantly associated with an increased risk of post-transplant infection by the same microorganism in allo-HSCT. Colonization by resistant Gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4-months both in allo-HSCT (HR 2.13, 95% CI 1.45-3.13;p=.0001) and auto-HSCT (HR 2.43, 95% CI 1.22-4.84;p=.012). Pre-engraftment GNB is an independent factor associated with increased mortality at four months from auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB.

  9. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions.

    PubMed

    Centeno, Christopher J; Al-Sayegh, Hasan; Freeman, Michael D; Smith, Jay; Murrell, William D; Bubnov, Rostyslav

    2016-08-01

    The purpose of the present investigation is to report on detailed complications among a much larger group of 2372 orthopaedic patients treated with stem cell injections who were followed in a treatment registry for up to nine years. All patients underwent an MSC-based, percutaneous injection treatment of an orthopaedic condition between December 2005 and September 2014 at one of 18 clinical facilities. Treated areas of the body included the knee, hip, ankle/foot, hand/wrist, elbow, shoulder, and spine. The patients were followed prospectively via enrollment in a treatment registry. Patients were followed prospectively at one, three, six and 12 months, and annually thereafter, using an electronic system, ClinCapture software. A total of 3012 procedures were performed on 2372 patients with follow-up period of 2.2 years. A total of 325 adverse events were reported. The majority were pain post-procedure (n = 93, 3.9 % of the study population) and pain due to progressive degenerative joint disease (n = 90, 3.8 % of the study population). Seven cases reported neoplasms, a lower rate than in the general population. The lowest rate of adverse events was observed among patients injected with BMC alone. Lowest rate of adverse events was among those patients receiving BMC injections alone, but the higher rate of AEs for BMC plus adipose and cultured cells was readily explained by the nature of the therapy or the longer follow-up. There was no clinical evidence to suggest that treatment with MSCs of any type in this study increased the risk of neoplasm.

  10. [Peripheral stem cell collection, search for predictive factors: a multicenter study. Working Group on Transfusion and Therapeutic Techniques of the French Blood Transfusion Society ].

    PubMed

    Clément, A; Coffe, C; Adjizian, J C; Villard, F; Jolly, D; Desbois, I; Léon, A

    2000-10-01

    A multicentric study involving 12 centers was made to investigate the results of peripheral stem cell collection carried out between 1996 and 1997 from 655 patients with hemopathic syndromes or malignant tumors, The aim of this investigation was to determine the predictive factors for transplant quality, and to thereby optimize collection procedures. Information sheets were completed for 1,346 cytapheretic sessions, i.e., 655 grafts. The samples were taken after induction chemotherapy and exposure to hematopoeitic colony-stimulating growth factors (except the LMCs). Each graft was defined as being of good or bad quality depending on the number of CD34+ cells that it contained. Based on the data available in the literature, a workgroup consensus was reached that a level of CD34+ cells +/- 2.10(6)/kg recipient body weight constituted a good transplant criterion. The 2 subgroups (good graft versus lower quality graft) were compared by univariate analysis followed by discriminant multivariate analysis. It was established that a number of parameters were significantly linked to the criterion of collection quality; however, 3 predictive factors emerged from the multivariate analysis--the level of circulating CD34+ cells; the number of cytaphereses; the number of blood volumes treated. It was concluded that the level of circulating CD34+ cells seems to be an essential aspect in predicting the quality of the transplant and the number of cytaphereses required to obtain a sufficiently rich collection. Moreover, it also appears that at least 2 blood volumes should be treated to optimize the results.

  11. Acute Effects of Intracoronary Tirofiban on No-Reflow Phenomena in Patients With ST-Segment Elevated Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

    PubMed

    Akpek, Mahmut; Sahin, Omer; Sarli, Bahadir; Baktir, Ahmet Oguz; Saglam, Hayrettin; Urkmez, Serkan; Ergin, Ali; Oguzhan, Abdurrahman; Arinc, Huseyin; Kaya, Mehmet G

    2015-07-01

    We evaluated the acute effect of intracoronary administration of tirofiban on no-reflow phenomenon in patients with ST-segment elevated myocardial infarction undergoing primary percutaneous coronary intervention. Consecutive patients (n = 162) were randomized into 2 groups based on whether intracoronary tirofiban was administered. After the administration of intracoronary tirofiban, thrombolysis in myocardial infarction (TIMI) flow grade significantly increased (P < .001) and successful reperfusion was achieved in 26 (32%) patients. In the placebo group, however, after the administration of intracoronary placebo the TIMI flow grade did not change (P = .070), and successful reperfusion was achieved only in 8 (10%) patients. In-hospital major adverse cardiac events (MACE) were significantly lower in the tirofiban group (36% vs 19%, P = .013). Intracoronary administration of tirofiban significantly improves TIMI flow grade and is associated with a lower in-hospital rate of MACE.

  12. Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

    PubMed

    Hensley, Michael Taylor; Tang, Junnan; Woodruff, Kathleen; Defrancesco, Teresa; Tou, Sandra; Williams, Christina M; Breen, Mathew; Meurs, Kathryn; Keene, Bruce; Cheng, Ke

    2017-03-15

    Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells.

  13. Five-year clinical and angiographic follow-up after intracoronary iridium-192 radiation therapy

    SciTech Connect

    Condado, Jose A.; Waksman, Ron; Saucedo, Jorge F.; Bhargava, Balram; Lansky, Alexandra J.; Calderas, Carlos; Gurdiel, Orlando; Gonzalez, Juan; Fadoul, Merche; Parra, Bogart; Iturria, Isabel; Amezaga, Bingen

    2002-06-01

    Background: Ionizing gamma radiation has been shown to reduce neointimal formation and the incidence of restenosis after balloon angioplasty and stenting in clinical trials. However, the long-term effects of this therapy are unknown. The first cohort of patients to receive intracoronary gamma radiation after balloon angioplasty for the prevention of restenosis have completed a 5-year angiographic and clinical follow-up. The outcome of these patients is presented and discussed. Methods: Twenty-one patients with unstable angina (22 arteries) underwent standard balloon angioplasty. Intracoronary radiation therapy was performed immediately after the intervention using an Iridium-192 source wire hand-delivered to the angioplasty site. All patients were followed clinically and Quantitative Coronary Analysis (QCA) was performed at 6, 24, 36 and 60 months. Results: Target lesion revascularization occurred in six lesions, three of which were total occlusions (two early within 30 days and one occurred at 2 years), and one patient had a myocardial infarction attributable to a nontarget vessel. Serial QCA detected a binary restenosis rate of 28.6% (n=6) at 6 months. The late loss (0.29 mm) and loss index (0.25) remained low at 2, 3 and 5 years. Angiographic complications included four aneurysms (two procedure related and two occurring within 3 months). At 2 years, only one aneurysm increased in size (46 vs. 27 mm{sup 2}); and at 3 and 5 years, all aneurysms remained unchanged. No other angiographic complications were observed. Conclusion: The early clinical and angiographic effects of intracoronary gamma radiation were maintained at 5 years without further increase in the aneurysm formation or apparent new adverse effects related to the radiation therapy between 2 and 5 years.

  14. Angiographic appearance of spontaneous coronary artery dissection with intramural hematoma proven on intracoronary imaging.

    PubMed

    Saw, Jacqueline; Mancini, G B John; Humphries, Karin; Fung, Anthony; Boone, Robert; Starovoytov, Andrew; Aymong, Eve

    2016-02-01

    The pathognomonic appearance of multiple radiolucent lumen on angiography is used to diagnose spontaneous coronary artery dissection (SCAD). However, this finding is absent in >70% of SCAD, in which case optical coherence tomography (OCT) or intravascular ultrasound (IVUS) is useful to assess arterial wall integrity. We report the angiographic appearance of SCAD that were proven on intracoronary imaging with OCT or IVUS. Our angiographic classification and algorithm for SCAD diagnosis was previously reported. Patients with type 1 SCAD (multiple radiolucent lumen) do not require OCT/IVUS, whereas, it was recommended for those with suspected type 2 (diffuse stenosis) or 3 (mimic atherosclerosis) SCAD. Twenty-two consecutive patients with non-type 1 angiographic SCAD in 25 coronary arteries (22 OCT and 4 IVUS) were studied. Mean age was 52.9 ± 9.9 years, 89.5% were women, and 16/22 (72.7%) had underlying fibromuscular dysplasia. Sixteen SCAD arteries were type 2 SCAD, and nine were type 3. All 25 SCAD arteries had intramural hematoma and intimomedial membrane separation with double lumen on OCT or IVUS. The mean visual angiographic stenosis was 74.6 ± 17.5% (range 40-100%). Dissected segments were long with mean qualitative coronary analysis (QCA) length 45.2 ± 29.2 mm, especially in patients with type 2 SCAD (mean QCA length 58.3 ± 29.0 mm). The mean QCA length in type 3 SCAD lesions was 22.1 ± 5.7 mm. Intracoronary imaging confirms that SCAD may appear angiographically without multiple radiolucent lumen. Angiographers should be familiar with angiographic SCAD variants to improve SCAD diagnosis, and utilize intracoronary imaging when the diagnosis is uncertain. © 2015 Wiley Periodicals, Inc.

  15. Impact of the Intracoronary Rendezvous technique on coronary angioplasty for chronic total occlusion.

    PubMed

    Nihei, Taro; Yamamoto, Yoshito; Kudo, Shun; Hanawa, Kenichiro; Hasebe, Yuhi; Takagi, Yusuke; Minatoya, Yutaka; Sugi, Masafumi; Shimokawa, Hiroaki

    2016-08-30

    The Rendezvous technique, which requires bidirectional wiring, is one of the useful methods for improving the success rate of recanalization for chronic total occlusion (CTO) in the field of peripheral intervention. Recently, advanced new devices for percutaneous coronary intervention have enabled us to perform the Rendezvous technique for peripheral as well as for coronary CTO lesions. We used the Intracoronary Rendezvous technique to perform angioplasty for coronary CTO. "Intracoronary Rendezvous" means that Rendezvous was achieved within the CTO lesion. From March 2009 to November 2015, 189 patients underwent CTO angioplasty at our institute, and we treated 10 patients with the Intracoronary Rendezvous technique. This technique involves crossing the Gaia series guidewire to the contralateral Corsair microcatheter located inside the plaque of CTO lesions. The majority of the CTO sites examined were in the proximal RCA (60 %). Lesion length of the occlusion was relatively long (64.4 ± 12.2 mm). Using the biplane imaging system, we were able to control the Gaia guidewires in a specific direction. Furthermore, if the antegrade and retrograde wires can be advanced into contiguous space inside the CTO lesion, we intentionally entered either wire into the contralateral Corsair microcatheter, followed by successful CTO crossing. CTO recanalization was completed for all patients without controlled antegrade retrograde subintimal tracking (CART) or reverse CART. No major complications occurred during hospitalization. These results indicate that the Rendezvous technique, assisted by new devices and a biplane imaging system, represents one of the primary options to achieve successful coronary CTO recanalization. (249/250 words).

  16. High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

    PubMed

    Meyer, Markus; Bell, Stephen P; Chen, Zengyi; Nyotowidjojo, Iwan; Lachapelle, Richard R; Christian, Timothy F; Gibson, Pamela C; Keating, Friederike F; Dauerman, Harold L; LeWinter, Martin M

    2013-11-01

    We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

  17. Five-year clinical and angiographic follow-up after intracoronary iridium-192 radiation therapy.

    PubMed

    Condado, Jose A; Waksman, Ron; Saucedo, Jorge F; Bhargava, Balram; Lansky, Alexandra J; Calderas, Carlos; Gurdiel, Orlando; Gonzalez, Juan; Fadoul, Merche; Parra, Bogart; Iturria, Isabel; Amezaga, Bingen

    2002-01-01

    Ionizing gamma radiation has been shown to reduce neointimal formation and the incidence of restenosis after balloon angioplasty and stenting in clinical trials. However, the long-term effects of this therapy are unknown. The first cohort of patients to receive intracoronary gamma radiation after balloon angioplasty for the prevention of restenosis have completed a 5-year angiographic and clinical follow-up. The outcome of these patients is presented and discussed. Twenty-one patients with unstable angina (22 arteries) underwent standard balloon angioplasty. Intracoronary radiation therapy was performed immediately after the intervention using an Iridium-192 source wire hand-delivered to the angioplasty site. All patients were followed clinically and Quantitative Coronary Analysis (QCA) was performed at 6, 24, 36 and 60 months. Target lesion revascularization occurred in six lesions, three of which were total occlusions (two early within 30 days and one occurred at 2 years), and one patient had a myocardial infarction attributable to a nontarget vessel. Serial QCA detected a binary restenosis rate of 28.6% (n=6) at 6 months. The late loss (0.29 mm) and loss index (0.25) remained low at 2, 3 and 5 years. Angiographic complications included four aneurysms (two procedure related and two occurring within 3 months). At 2 years, only one aneurysm increased in size (46 vs. 27 mm(2)); and at 3 and 5 years, all aneurysms remained unchanged. No other angiographic complications were observed. The early clinical and angiographic effects of intracoronary gamma radiation were maintained at 5 years without further increase in the aneurysm formation or apparent new adverse effects related to the radiation therapy between 2 and 5 years.

  18. Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by thallium-201 scintigraphy

    SciTech Connect

    Schuler, G.; Schwarz, F.; Hofmann, M.; Mehmel, H.; Manthey, J.; Maurer, W.; Rauch, B.; Herrmann, H.; Kubler, W.

    1982-09-01

    Twenty-one patients with acute myocardial infarction, admitted to the hospital within 4 hours after the onset of symptoms, were studied by seven-pinhole thallium-201 scintigraphy before and 1 hour and 24 hours after intracoronary fibrinolysis using streptokinase. The size of the thallium-201 perfusion defect was assessed from myocardial cross sections reconstructed from the riginal seven-pinhole data and expressed as a fraction of left ventricular circumference. Recanalization was achieved in 16 patients within 3.9 +/- 1.6 hours after onset of symptoms (group A). In these patients, the size of the perfusion defect had decreased from 36 +/- 17% to 19 +/- 15%(p<0.001) at 24 hours. No significant change was detected to redistribution at 1 hour after the intervention. In five patients, intracoronary fibrinolysis was unsuccessful, and the vessel remained occluded (group B). The thallium-201 perfusion defect affected 40 +/- 15% of the left ventricular circumference before the intervention; it remained virtually unchanged at 1 hour (37 +/- 16%) and at 24 hours (41 +/- 15%) after fibrinolysis. The perfusion defect was most reduced in patients with extensive collaterals supplying the ischemic area or with subtotal occlusion of the affected coronary artery. It is concluded that successful intracoronary fibrinolysis may reduce the size of the thallium-201 perfusion defect in many patients with acute myocardial infarction. One important factor in the final result may be the presence of residual coronary flow supplied by extensive collaterals or by subtotal occlusion of the affected coronary artery when reperfusion is achieved around 4 hours after the onset of symptoms.

  19. Thrombolysis in acute myocardial infarction using intracoronary streptokinase: assessment by /sup 201/Tl scintigraphy

    SciTech Connect

    Schuler, G.; Schwarz, F.; Hofmann, M.; Mehmel, H.; Manthey, J.; Maeurer, W.; Rauch, B.; Herrmann, H.J.; Kuebler, W.

    1982-09-01

    Twenty-one patients with acute myocardial infarction, admitted to the hospital within 4 hours after the onset of symptoms, were studied by seven-pinhole /sup 201/Tl scintigraphy before and 1 hour and 24 hours after intracoronary fibrinolysis using streptokinase. The size of the /sup 201/Tl perfusion defect was assessed from myocardial cross sections reconstructed from the original seven-pinhole data and expressed as a fraction of left ventricular circumference. Recanalization was achieved in 16 patients within 3.9 +/- 1.6 hours after onset of symptoms (group A). In these patients, the size of the perfusion defect had decreased from 36 +/- 17% to 19% +/- 15% (p less than 0.001) at 24 hours. No significant change was detected by redistribution at 1 hour after the intervention. In five patients, intracoronary fibrinolysis was unsuccessful, and the vessel remained occluded (group B). The /sup 201/Tl perfusion defect affected 40 +/- 15% of the left ventricular circumference before the intervention; it remained virtually unchanged at 1 hour (37 +/- 16%) and at 24 hours (41 +/- 15%) after fibrinolysis. The perfusion defect was most reduced in patients with extensive collaterals supplying the ischemic area or with subtotal occlusion of the affected coronary artery. We conclude that successful intracoronary fibrinolysis may reduce the size of the /sup 201/Tl perfusion defect in many patients with acute myocardial infarction. One important factor in the final result may be the presence of residual coronary flow supplied by extensive collaterals or by subtotal occlusion of the affected coronary artery when reperfusion is achieved around 4 hours after the onset of symptoms.

  20. Effect of intracoronary glyceryl trinitrate on perfusion distribution in the collateralised human myocardium.

    PubMed

    Wald, R W; Sternberg, L; Feiglin, D H; Morch, J E

    1980-08-01

    The effect on myocardial perfusion distribution of intracoronary glyceryl trinitrate in a dose (60 micrograms) insufficient to cause alterations in systemic blood pressure or heart rate was studied in eight patients with angiographically demonstrated collaterals from the left coronary system to the distal right coronary artery. Double isotope imaging using technetium-99m and iodine-131 labelled albumin macroaggregates allowed each patient to serve as his own control. The reproducibility of the imaging and data handling techniques was shown in 12 control patients. Glyceryl trinitrate caused a significant diminution in the collateral-mediated fractional perfusion while increasing that of the native coronary bed.

  1. Effect of intracoronary glyceryl trinitrate on perfusion distribution in the collateralised human myocardium.

    PubMed Central

    Wald, R W; Sternberg, L; Feiglin, D H; Morch, J E

    1980-01-01

    The effect on myocardial perfusion distribution of intracoronary glyceryl trinitrate in a dose (60 micrograms) insufficient to cause alterations in systemic blood pressure or heart rate was studied in eight patients with angiographically demonstrated collaterals from the left coronary system to the distal right coronary artery. Double isotope imaging using technetium-99m and iodine-131 labelled albumin macroaggregates allowed each patient to serve as his own control. The reproducibility of the imaging and data handling techniques was shown in 12 control patients. Glyceryl trinitrate caused a significant diminution in the collateral-mediated fractional perfusion while increasing that of the native coronary bed. PMID:6775646

  2. Mechanism of coronary flow reserve reduction in systemic sclerosis: insight from intracoronary pressure wire studies.

    PubMed

    Pintér, Tünde; Faludi, Réka; Magyari, Balázs; Vorobcsuk, András; Kumánovics, Gábor; Minier, Tünde; Czirják, László; Komócsi, András

    2011-04-01

    Functional impairment of coronary microcirculation is thought to be a major pathway in the development of primary cardiac involvement in SSc; however, the underlying mechanism is not fully understood. We aimed to investigate the mechanisms of coronary flow reserve (CFR) reduction in patients with SSc. Seventeen SSc patients and 17 gender- and age-matched controls were enrolled. Coronary angiography and determination of coronary flow parameters including index of myocardial resistance (IMR) using intracoronary pressure wire at basal conditions and during vasodilator-induced maximal hyperaemia were performed. Transit times of repeated intracoronary saline injection were measured to evaluate the role of cold exposure. SSc patients with decreased CFR had accelerated basal coronary flow velocity (P < 0.05), and their IMR in hyperaemia (IMR(hyp)) did not differ from either SSc patients with normal CFR or from the controls (P = 0.292 and P =  0.308). The coronary flow velocity of SSc patients correlated with the IMR at baseline (IMR(bas)) (r  = 0.56, P  = 0.019). Injection of room temperature saline did not provoke changes in coronary transit times. The lack of decrease in the maximal vasodilatation response indicates that there is no irreversible functional damage at the level of the coronary arterioles. In patients with reduced CFR, the decreased basal IMR and higher velocity reflect compensatory vasodilatory mechanisms probably triggered by ischaemic signals deriving from abnormal myocardial microcirculation.

  3. Incidence and angiographic predictors of side branch occlusion following high-pressure intracoronary stenting.

    PubMed

    Aliabadi, D; Tilli, F V; Bowers, T R; Benzuly, K H; Safian, R D; Goldstein, J A; Grines, C L; O'Neill, W W

    1997-10-15

    We evaluated the incidence, angiographic predictors, and clinical outcome of side branch occlusion (SBO) following high-pressure intracoronary stenting in 175 patients. All stent implants during a 7-month period were reviewed for the incidence of major (>1 mm) SBO. Side branches were further characterized based on side branch and index lesion morphology. Clinical events (death, myocardial infarction, and target vessel revascularization rates) were determined at 9 months. A total of 175 patients (182 lesions) had 224 major side branches covered by intracoronary stents. Of these, 43 (19%) occluded. Most SBOs (29 of 43 [67%]) occurred after poststent dilation using high-pressure inflations (15.3 +/- 3.3 atmospheres). No clinical characteristics correlated with SBO. By multivariate analysis, those side branches with >50% ostial narrowing that arose from within or just beyond the diseased portion of the parent vessel (threatened side branch morphologies) were a powerful angiographic predictor of SBO (odds ratio 40, 95% confidence interval, 14 to 130, p <0.0001). At 9-month follow-up there was no difference in combined clinical events between those patients with and without SBO. These data demonstrate that side branches with ostial stenoses in continuity with diseased parent lesions were at risk of occlusion following stenting. SBO, however, was not associated with adverse clinical outcome. These findings lend support to plaque shift ("snow plow effect") as the mechanism behind SBO following stent placement.

  4. Myocardial protection by intracoronary nicardipine administration during percutaneous transluminal coronary angioplasty.

    PubMed

    Hanet, C; Rousseau, M F; Vincent, M F; Lavenne-Pardonge, E; Pouleur, H

    1987-05-01

    To determine if the calcium antagonist nicardipine protects the myocardium against ischemia, myocardial lactate, hypoxanthine and prostanoid function was studied in 12 patients during percutaneous transluminal coronary angioplasty (PTCA). Values were obtained before balloon inflation and during 4 minutes after deflation. Intracoronary injection of 0.2 mg of nicardipine distal to the stenosis was done randomly before the first or second inflation; the other inflation served as a control. One minute after deflation, coronary sinus flow levels were similar during the nicardipine and control procedure (161 +/- 61 vs 159 +/- 72 ml/min); lactate (-9 +/- 21% vs -17 +/- 21%, p less than 0.025) and hypoxanthine production (-107 +/- 85% vs -218 +/- 153%, p less than 0.05) were less severe after nicardipine pretreatment than after control. All patients reverted to lactate extraction 4 minutes after inflation plus nicardipine infusion, whereas lactate was still produced 4 minutes after control inflation. No significant changes in thromboxane B2 or prostacyclin levels were observed in the coronary sinus 1 minute after inflation, but higher arterial thromboxane B2 values were observed after control inflation than after inflation with nicardipine infusion (median values 169 vs 78 pg/ml, p less than 0.05). In conclusion, intracoronary infusion of nicardipine reduced signs of ischemia and alterations in prostanoid handling after coronary occlusion. The mechanisms of myocardial protection appeared unrelated to coronary sinus blood flow changes or to a systemic effect of nicardipine.

  5. Percutaneous catheter-based intracoronary infusion of insulin--a dose finding study in the porcine model.

    PubMed

    Slettom, Grete; Jonassen, Anne K; Tuseth, Vegard; Pettersen, Reidar J; Larsen, Terje H; Seifert, Reinhard; Nordrehaug, Jan E

    2011-06-01

    Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.

  6. Multipotent Stem Cells in Cardiac Regeneration

    PubMed Central

    Karra, Ravi; Wu, Sean M.

    2008-01-01

    Summary The potential for stem cells to ameliorate or cure heart diseases has galvanized a cadre of cardiovascular translational and clinical scientists to take a “first-in-man” approach using autologous stem cells from a variety of tissues. However, recent clinical trial data show that when these cells are given by intracoronary infusion or direct myocardial injection, limited improvement in heart function occurs with no evidence of cardiomyogenesis. These studies illustrate the great need to understand the logic of cell-lineage commitment and the principles of cardiac differentiation. Recent identification of stem/progenitor cells of embryological origin with intrinsic competence to differentiate into multiple lineages within the heart offers new possibilities for cardiac regeneration. When combined with developments in nuclear reprogramming and provided that tumor risks and other challenges of embryonic cell transplantation can be overcome, the prospect of achieving autologous, cardiomyogenic, stem cell-based therapy may be within reach. PMID:18307403

  7. Safety and feasibility of intramyocardial versus intracoronary delivery of autologous cell therapy in advanced heart failure: the REGENERATE-IHD pilot study.

    PubMed

    Mozid, Abdul; Yeo, Chia; Arnous, Samer; Ako, Emmanuel; Saunders, Natalie; Locca, Didier; Brookman, Pat; Archbold, R Andrew; Rothman, Martin; Mills, Peter; Agrawal, Samir; Martin, John; Mathur, Anthony

    2014-05-01

    This study presents an interim safety and feasibility analysis of the REGENERATE-IHD randomized controlled trial, which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells (BMSCs) in patients with ischemic heart failure. The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis (pilot). Symptomatic patients with ischemic heart failure were randomized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum (control). No significant differences were found in terms of safety and feasibility between the different delivery routes, with no significant difference in procedural complications or major adverse cardiac events. There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs. Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure.

  8. Challenges for heart disease stem cell therapy

    PubMed Central

    Hoover-Plow, Jane; Gong, Yanqing

    2012-01-01

    Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress. PMID:22399855

  9. Magnetic Resonance for Noninvasive Detection of Microcirculatory Disease Associated With Allograft Vasculopathy: Intracoronary Measurement Validation.

    PubMed

    Mirelis, Jesús G; García-Pavía, Pablo; Cavero, Miguel A; González-López, Esther; Echavarria-Pinto, Mauro; Pastrana, Miguel; Segovia, Javier; Oteo, Juan F; Alonso-Pulpón, Luis; Escaned, Javier

    2015-07-01

    Cardiac allograft vasculopathy affects both epicardial and microcirculatory coronary compartments. Magnetic resonance perfusion imaging has been proposed as a useful tool to assess microcirculation mostly outside the heart transplantation setting. Instantaneous hyperemic diastolic flow velocity-pressure slope, an intracoronary physiology index, has demonstrated a better correlation with microcirculatory remodelling in cardiac allograft vasculopathy than other indices such as coronary flow velocity reserve. To investigate the potential of magnetic resonance perfusion imaging to detect the presence of microcirculatory remodeling in cardiac allograft vasculopathy, we compared magnetic resonance perfusion data with invasive intracoronary physiological indices to study microcirculation in a population of heart transplantation recipients with macrovascular nonobstructive disease demonstrated with intravascular ultrasound. We studied 8 heart transplantation recipients (mean age, 61 [12] years, 100% male) with epicardial allograft vasculopathy defined by intravascular ultrasound, nonsignificant coronary stenoses and negative visually-assessed wall-motion/perfusion dobutamine stress magnetic resonance. Quantitative stress and rest magnetic resonance perfusion data to build myocardial perfusion reserve index, noninvasively, and 4 invasive intracoronary physiological indices were determined. Postprocessed data showed a mean (standard deviation) myocardial perfusion reserve index of 1.22 (0.27), while fractional flow reserve, coronary flow velocity reserve, hyperemic microvascular resistance and instantaneous hyperemic diastolic flow velocity-pressure slope were 0.98 (0.02), cm/s/mmHg, 2.34 (0.55) cm/s/mmHg, 2.00 (0.69) cm/s/mmHg and 0.91 (0.65) cm/s/mmHg, respectively. The myocardial perfusion reserve index correlated strongly only with the instantaneous hyperemic diastolic flow velocity-pressure slope (r=0.75; P=.033). Myocardial perfusion reserve index derived from a

  10. Effects of priming with recombinant human granulocyte colony-stimulating factor on conditioning regimen for high-risk acute myeloid leukemia patients undergoing human leukocyte antigen-haploidentical hematopoietic stem cell transplantation: a multicenter randomized controlled study in southwest China.

    PubMed

    Gao, Lei; Wen, Qin; Chen, Xinghua; Liu, Yao; Zhang, Cheng; Gao, Li; Kong, Peiyan; Zhang, Yanqi; Li, Yunlong; Liu, Jia; Wang, Qingyu; Su, Yi; Wang, Chunsen; Wang, Sanbin; Zeng, Yun; Sun, Aihua; Du, Xin; Zeng, Dongfeng; Liu, Hong; Peng, Xiangui; Zhang, Xi

    2014-12-01

    HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective and immediate treatment for high-risk acute myeloid leukemia (HR-AML) patients lacking matched donors. Relapse remains the leading cause of death for HR-AML patients after haplo-HSCT. Accordingly, the prevention of relapse remains a challenge in the treatment of HR-AML. In a multicenter randomized controlled trial in southwestern China, 178 HR-AML patients received haplo-HSCT with conditioning regimens involving recombinant human granulocyte colony-stimulating factor (rhG-CSF) or non-rhG-CSF. The cumulative incidences of relapse and graft-versus-host disease (GVHD), 2-year leukemia-free survival (LFS), and overall survival (OS) were evaluated. HR-AML patients who underwent the priming conditioning regimen with rhG-CSF had a lower relapse rate than those who were treated with non-rhG-CSF (38.2%; 95% confidence interval [CI], 28.1% to 48.3% versus 60.7%, 95% CI, 50.5% to 70.8%; P < .01). The cumulative incidences of acute GVHD, chronic GVHD, transplantation-related toxicity, and infectious complications appeared to be equivalent. In total, 53 patients in the rhG-CSF-priming group and 31 patients in the non-rhG-CSF-priming group were still alive at the median follow-up time of 42 months (range, 24 to 80 months). The 2-year probabilities of LFS and OS in the rhG-CSF-priming and non-rhG-CSF-priming groups were 55.1% (95% CI, 44.7% to 65.4%) versus 32.6% (95% CI, 22.8% to 42.3%) (P < .01) and 59.6% (95% CI, 49.4% to 69.7%) versus 34.8% (95% CI, 24.9% to 44.7%) (P < .01), respectively. Multivariate analyses indicated that the 2-year probability of LFS of patients who achieved complete remission (CR) before transplantation was better than that of patients who did not achieve CR. The 2-year probability of LFS of patients with no M4/M5/M6 subtype was better than that of patients with the M4/M5/M6 subtype in the G-CSF-priming group (67.4%; 95% CI, 53.8% to 80.9% versus 41.9%; 95% CI, 27

  11. Intracoronary optical coherence tomography: Clinical and research applications and intravascular imaging software overview.

    PubMed

    Tenekecioglu, Erhan; Albuquerque, Felipe N; Sotomi, Yohei; Zeng, Yaping; Suwannasom, Pannipa; Tateishi, Hiroki; Cavalcante, Rafael; Ishibashi, Yuki; Nakatani, Shimpei; Abdelghani, Mohammad; Dijkstra, Jouke; Bourantas, Christos; Collet, Carlos; Karanasos, Antonios; Radu, Maria; Wang, Ancong; Muramatsu, Takashi; Landmesser, Ulf; Okamura, Takayuki; Regar, Evelyn; Räber, Lorenz; Guagliumi, Giulio; Pyo, Robert T; Onuma, Yoshinobu; Serruys, Patrick W

    2017-01-21

    By providing valuable information about the coronary artery wall and lumen, intravascular imaging may aid in optimizing interventional procedure results and thereby could improve clinical outcomes following percutaneous coronary intervention (PCI). Intravascular optical coherence tomography (OCT) is a light-based technology with a tissue penetration of approximately 1 to 3 mm and provides near histological resolution. It has emerged as a technological breakthrough in intravascular imaging with multiple clinical and research applications. OCT provides detailed visualization of the vessel following PCI and provides accurate assessment of post-procedural stent performance including detection of edge dissection, stent struts apposition, tissue prolapse, and healing parameters. Additionally, it can provide accurate characterization of plaque morphology and provides key information to optimize post-procedural outcomes. This manuscript aims to review the current clinical and research applications of intracoronary OCT and summarize the analytic OCT imaging software packages currently available. © 2017 Wiley Periodicals, Inc.

  12. Online PC-based integration of digital intracoronary ultrasound images into angiographic images during cardiac catheterization.

    PubMed

    Sievers, Burkhard; Böse, Dirk; Sack, Stefan; Philipp, Sebastian; Wieneke, Heinrich; Erbel, Raimund

    2008-08-18

    In recent years, intravascular ultrasound (IVUS) has evolved as an important adjunct to angiography, providing insights that are significantly altering conventional paradigms in diagnosis and therapy. However, major drawbacks in the use of IVUS relied on the fact that a heavy console had to be moved from lab to lab, and extensive time for set up and image analysis. This additional time and the decrease in patients' through-put has not been applicable in clinical practice for many labs. Our manuscript concerns a novel PC-based platform for IVUS that enables the online intergration of digital intracoronary ultrasound images into angiographic images. This new technique offers remote operation, multiple control devices and custom viewing options. The PC-based platform enables IVUS images to be viewed simultaneously from multiple vantage points in the lab, and allows for multiple user interfaces.

  13. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction.

    PubMed

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E; Zaremba, Tomas; Aarøe, Jens; Kjærgaard, Benedict; Simonsen, Carsten W; Rosenberg, Jacob; Gögenur, Ismail

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

  14. Intracoronary nitrite suppresses the inflammatory response following primary percutaneous coronary intervention.

    PubMed

    Jones, Daniel A; Khambata, Rayomand S; Andiapen, Mervyn; Rathod, Krishnaraj S; Mathur, Anthony; Ahluwalia, Amrita

    2017-04-01

    Recent work suggests that intracoronary nitrite reduces myocardial infarct size following primary percutaneous coronary intervention (PPCI) for acute myocardial infarction (AMI), although the exact mechanisms are unclear. We explored the effects of nitrite on reperfusion-induced inflammation, by assessing the levels of specific pro-inflammatory mediators, chemokines and adhesion molecules in plasma and circulating cell subtypes as exploratory end points in the NITRITE-AMI cohort. Peripheral blood leucocyte subsets, cell adhesion molecules, high-sensitivity C reactive protein (hs-CRP), the monocyte and neutrophil chemoattractants CCL2 and CXCL1, CXCL5, respectively were measured in the blood of patients who received either intracoronary sodium nitrite (N=40) or placebo (N=40) during PPCI for AMI. Major adverse cardiac events were recorded at 3 years post-PPCI. In the placebo-treated patients, total circulating neutrophil numbers and levels of hs-CRP were raised postreperfusion and then decreased over time; in nitrite-treated patients these changes were suppressed compared with placebo up to 6 months post-PPCI (p<0.01). This effect was associated with reduced expression of neutrophil CD11b, plasma CXCL1, CXCL5 and CCL2 levels (p<0.05). There were no differences in the number of other any other leucocyte population measured (monocytes and lymphocytes) or activation markers expressed by these cells between the treatment groups. These effects were associated with a reduction in both microvascular obstruction and infarct size. Important reductions in neutrophil numbers and activation post-PPCI in patients with ST elevated myocardial infarction were associated with nitrite treatment, an effect we propose likely underlies, at least in part, the beneficial effects of nitrite upon infarct size. NCT01584453. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Bolting multicenter solutions

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Bossard, Guillaume; Katmadas, Stefanos; Turton, David

    2017-01-01

    We introduce a solvable system of equations that describes non-extremal multicenter solutions to six-dimensional ungauged supergravity coupled to tensor multiplets. The system involves a set of functions on a three-dimensional base metric. We obtain a family of non-extremal axisymmetric solutions that generalize the known multicenter extremal solutions, using a particular base metric that introduces a bolt. We analyze the conditions for regularity, and in doing so we show that this family does not include solutions that contain an extremal black hole and a smooth bolt. We determine the constraints that are necessary to obtain smooth horizonless solutions involving a bolt and an arbitrary number of Gibbons-Hawking centers.

  16. Multicenter Patient Records Research

    PubMed Central

    Behlen, Fred M.; Johnson, Stephen B.

    1999-01-01

    The expanding health information infrastructure offers the promise of new medical knowledge drawn from patient records. Such promise will never be fulfilled, however, unless researchers first address policy issues regarding the rights and interests of both the patients and the institutions who hold their records. In this article, the authors analyze the interests of patients and institutions in light of public policy and institutional needs. They conclude that the multicenter study, with Institutional Review Board approval of each study at each site, protects the interests of both. “Anonymity” is no panacea, since patient records are so rich in information that they can never be truly anonymous. Researchers must earn and respect the trust of the public, as responsible stewards of facts about patients' lives. The authors find that computer security tools are needed to administer multicenter patient records studies and describe simple approaches that can be implemented using commercial database products. PMID:10579601

  17. Devices for stem cell isolation and delivery: current need for drug discovery and cell therapy.

    PubMed

    Reinhardt, Martin; Bader, Augustinus; Giri, Shibashish

    2015-05-01

    Isolation and purification of stem cells and their delivery into diseased or aged tissues or organs need special devices for proper transplantation of stem cells in order to achieve high cell retention at transplant site for repair or regeneration of tissues and organs. The clinical and preclinical importance of special devices such as Celution System, Isolex cell separation device, magnetic surface-enhanced Raman spectroscopic dots, microfluidic devices, immunomagnetic cell separation for stem cell separation and isolation are the main focus in this paper. Further, devices like trans-coronary delivery, trans-endocardial delivery, intracoronary delivery devices for stem cell application to the heart are described. Devices for stem cell application to the brain, the spinal cord and other tissues are also explained. We highlighted scaffolds with incorporated stem cells and other encapsulation devices used to transplant stem cells. Current needs of devices for stem cells isolation, purification and delivery for drug discovery and cell therapy are discussed.

  18. Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs.

    PubMed

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2011-01-01

    The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co-administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of α-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

  19. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial

    PubMed Central

    Makkar, Raj R; Smith, Rachel R; Cheng, Ke; Malliaras, Konstantinos; Thomson, Louise E J; Berman, Daniel; Czer, Lawrence S C; Marbán, Linda; Mendizabal, Adam; Johnston, Peter V; Russell, Stuart D; Schuleri, Karl H; Lardo, Albert C; Gerstenblith, Gary; Marbán, Eduardo

    2015-01-01

    patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center. PMID:22336189

  20. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial.

    PubMed

    Makkar, Raj R; Smith, Rachel R; Cheng, Ke; Malliaras, Konstantinos; Thomson, Louise E J; Berman, Daniel; Czer, Lawrence S C; Marbán, Linda; Mendizabal, Adam; Johnston, Peter V; Russell, Stuart D; Schuleri, Karl H; Lardo, Albert C; Gerstenblith, Gary; Marbán, Eduardo

    2012-03-10

    adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Efficacy and Safety of Thrombectomy Combined with Intracoronary Administration of Tirofiban in ST-segment Elevation Myocardial Infarction (STEMI).

    PubMed

    Gao, Lu; Cao, Zhenhua; Zhang, Hong

    2016-07-31

    BACKGROUND No/slow reflow gives rise to serious complications in STEMI patients undergoing PCI, and can lead to worse outcomes. Several measures are used to prevent no/slow reflow, including thrombus removal processes and intensive use of anticoagulant agents. Our study was designed to evaluate the efficacy and safety of thrombectomy and intracoronary administration of GPIIb/IIIa inhibitors in STEMI patients undergoing PPCI. MATERIAL AND METHODS We randomly assigned 240 STEMI patients into 3 groups. Before PPCI, patients in group A received thrombectomy and intracoronary administration of tirofiban. Patients in group B received thrombectomy, and patients in group C neither of these 2 treatments. Their demographic data and coronary angiography results were recorded. TIMI grade flow was used to evaluate the effect. After the follow-up, major adverse cardiac events were regarded as study endpoints in evaluating the safety of the combined therapy. RESULTS We found no significant differences among the 3 groups in demographic and clinical characteristics (p>0.05). Patients in group A had better TIMI grade classifications and ST-segment elevation (p=0.005), and lower incidence of no/slow reflow (p=0.031) and MACE. During 6-month follow-up, the MACE rate was lower in group A than in groups B and C (p=0.038). CONCLUSIONS The use of thrombectomy combined with intracoronary administration of tirofiban is relatively effective and safe in STEMI patients undergoing PPCI.

  2. Intracoronary Near-Infrared Spectroscopy (NIRS) Imaging for Detection of Lipid Content of Coronary Plaques: Current Experience and Future Perspectives.

    PubMed

    Jaguszewski, Milosz; Klingenberg, Roland; Landmesser, Ulf

    2013-01-01

    Acute coronary syndromes are frequently caused by "vulnerable" coronary plaques with a lipid-rich core. In 1993 near-infrared spectroscopy (NIRS) was first used to detect the lipid (cholesterol) content of atherosclerotic plaques in an experimental animal study. NIRS was then carefully validated using human atherosclerotic plaques (ex vivo), and has subsequently been developed for intracoronary imaging in humans, for which now an FDA-approved catheter-based NIRS system is available. NIRS provides a "chemogram" of the coronary artery wall and is used to detect lipid-rich plaques. Using this technology, recent studies have shown that lipid-rich plaques are very frequent in the culprit lesion of patients with an acute coronary syndrome, and are also common in non-culprit coronary lesions in these patients as compared to patients with stable coronary disease. First studies are evaluating the impact of statin therapy on coronary NIRS-detected lipid cores. Intracoronary NIRS imaging represents a highly interesting method for coronary plaque characterization in humans and may become a valuable tool for the development of novel therapies aiming to impact on the biology of human coronary artery plaques, likely in combination with other intracoronary imaging techniques, such as optical coherence tomography.

  3. Meta-analysis of randomized controlled trials comparing intracoronary and intravenous administration of glycoprotein IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction.

    PubMed

    Wang, Yongshi; Wu, Boting; Shu, Xianhong

    2012-04-15

    Glycoprotein IIb/IIIa receptor inhibitors (GPIs) have been widely adopted as an adjuvant regimen during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction, but whether intracoronary administration of these potent antiplatelet agents conveys better efficacy and safety over the intravenous route has not been well addressed. A meta-analysis was performed by a systematic search of the published research for randomized controlled trials comparing intracoronary versus intravenous administration of GPIs in patients with ST-segment elevation myocardial infarction. Eight studies involving 686 patients in the intracoronary arm and 660 in the intravenous arm met the inclusion criteria. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.08 to 1.98, p <0.05) and myocardial reperfusion grade 2 or 3 (OR 1.78, 95% CI 1.29 to 2.46, p <0.001) were markedly more often achieved in patients who received intracoronary boluses of GPIs than those receiving the intravenous strategy. Intracoronary administration resulted in a reduced incidence of mortality (OR 0.44, 95% CI 0.21 to 0.92, p <0.05), target vessel revascularization (OR 0.53, 95% CI 0.29 to 0.99, p <0.05), and the composite end point of major adverse cardiac events (OR 0.48, 95% CI 0.31 to 0.76, p <0.005) at 30-day follow-up. No significant difference was found in terms of major or minor bleeding (OR 1.14, p = 0.71, and OR 0.86, p = 0.47 respectively). In conclusion, intracoronary administration of GPIs yielded favorable outcomes in postprocedural blood flow restoration and 30-day clinical prognosis in patients with ST-segment elevation myocardial infarction. The intracoronary use of GPIs can be recommended as a preferred regimen during primary percutaneous coronary intervention.

  4. Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure

    PubMed Central

    Hammond, H. Kirk; Penny, William F.; Traverse, Jay H.; Henry, Timothy D.; Watkins, Matthew W.; Yancy, Clyde W.; Sweis, Ranya N.; Adler, Eric D.; Patel, Amit N.; Murray, David R.; Ross, Robert S.; Bhargava, Valmik; Maisel, Alan; Barnard, Denise D.; Lai, N. Chin; Dalton, Nancy D.; Lee, Martin L.; Narayan, Sanjiv M.; Blanchard, Daniel G.; Gao, Mei Hua

    2017-01-01

    Importance Gene transfer has rarely been tested in randomized clinical trials. Objective To evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure. Design, Setting, and Participants A randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt)and decline (−dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization. Interventions Intracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo. Main Outcomes and Measures Primary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and −dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5). Results Fifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants

  5. Ultrasound-Targeted Microbubble Destruction Enhances Gene Expression of microRNA-21 in Swine Heart via Intracoronary Delivery.

    PubMed

    Liu, Yangchun; Li, Lang; Su, Qiang; Liu, Tao; Ma, Zhiying; Yang, Huafeng

    2015-09-01

    Ultrasound-targeted microbubble destruction (UTMD) has proved to be a promising method for gene delivery. However, the feasibility and efficacy of UTMD-mediated gene delivery to the heart of large animals remain unclear. The present study was to explore the probability of increasing the transfection of microRNA-21 (miR-21) in swine heart by UTMD, and to search for the most suitable transfection conditions. We first optimized ultrasound intensity for successful miR-21 delivery. After intravenous injection of miR-21/microbubble mixture (miR-21/MB), transthoracic ultrasound irradiation (US) was applied from the left anterior chest using different intensities (1, 2, and 3 W/cm(2)). Then the efficacy of UTMD-mediated miR-21 delivery into myocardium via intracoronary injection was explored. Solution of miR-21/MB was infused intravenously or intracoronarily with US over the heart. Swine undergoing phosphate-buffered saline (PBS) injection, miR-21/MB injection via ear vein or coronary artery without US served as the control. The dynamic changes of left ventricular ejection fraction (LVEF) and serum troponin I (cTnI) after UTMD were detected, then the left ventricular myocardium was harvested for hematoxylin and eosin (H&E) staining 4 days later; the expression levels of miR-21 and programmed cell death 4 (PDCD4) were detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Results showed that pulse ultrasound at an intensity of 2 W/cm(2) and a 50% duty ratio for 20 minutes, there was no increase in serum cTnI, no histological sign of myocardial damage, and no noted cardiac dysfunction with relatively higher miR-21 expression (P < 0.05). Compared to miR-21/MB alone, UTMD significantly increased gene expression in myocardium regardless of the delivery routes (P < 0.05). Interestingly, the transfection efficiency was found to be a little bit higher with intracoronary injection than that with intravenous injection, though the dose

  6. Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects on myocardial remodeling and function.

    PubMed

    Barlow, Shayne C; Doviak, Heather; Jacobs, Julia; Freeburg, Lisa A; Perreault, Paige E; Zellars, Kia N; Moreau, Karen; Villacreses, Camila F; Smith, Stephen; Khakoo, Aarif Y; Lee, TaeWeon; Spinale, Francis G

    2017-10-01

    Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descending coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n = 9) or saline was infused in the distal LAD. LV echocardiography was performed at 3-28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR) values (66 ± 1% and 40 ± 1 ml, respectively, means ± standard deviation) in both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group by 40% at 28 days post-IR (P < 0.05) and the fall in LV EF was attenuated. Despite equivalent plasma troponin levels (14 ± 3 ng/ml), computed MI size at 28 days was reduced by over 45% in the rTIMP-3 group (P < 0.05), indicating that rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain natriuretic peptide levels, an index of heart failure progression, were reduced by 25% in the rTIMP-3 group compared with MI saline values (P < 0.05). Although the imbalance between MMPs and TIMPs has been recognized as a contributory factor for post-MI remodeling, therapeutic strategies targeting this imbalance have not been forthcoming. This study is the first to demonstrate that a relevant delivery approach (intracoronary) using rTIMP can alter the course of post-MI remodeling.NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury

  7. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.

    PubMed

    Stone, Gregg W; Maehara, Akiko; Witzenbichler, Bernhard; Godlewski, Jacek; Parise, Helen; Dambrink, Jan-Henk E; Ochala, Andrzej; Carlton, Trevor W; Cristea, Ecaterina; Wolff, Steven D; Brener, Sorin J; Chowdhary, Saqib; El-Omar, Magdi; Neunteufl, Thomas; Metzger, D Christopher; Karwoski, Theodore; Dizon, Jose M; Mehran, Roxana; Gibson, C Michael

    2012-05-02

    Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03

  8. Reliability of physiological assessment of coronary stenosis severity using intracoronary pressure techniques: a comprehensive analysis from a large cohort of consecutive intermediate coronary lesions.

    PubMed

    Rivero, Fernando; Cuesta, Javier; Bastante, Teresa; Benedicto, Amparo; Fernández-Pérez, Cristina; Antuña, Paula; García-Guimaraes, Marcos; Alfonso, Fernando

    2017-06-02

    We sought to assess the reliability of the most frequently used intracoronary physiologic indices (including intravenous adenosine FFR [IV-FFR], intracoronary low-dose adenosine FFR [LD-IC-FFR], intracoronary high-dose adenosine FFR [HD-IC-FFR], Pd/Pa and iFR). We also sought to analyse factors affecting their reproducibility in a real-world patient population. A total of 91 lesions in 86 consecutive patients were included. Measurements of all physiological indices were repeated within a systematic standardised prospective protocol. All measured indices showed excellent test-retest reliability, with intraclass correlation coefficient (ICC) over 0.96. IV-FFR showed the highest coefficient of variation (CV) values among the studied measurements (Pd/Pa: 0.05; iFR: 0.10; LD-IC-FFR: 0.10; HD-IC-FFR: 0.08; IV-FFR: 0.12). Pd/Pa was significantly less variable than the other indices. On multivariate analysis, female gender, distal lesion location, history of hypertension or kidney failure, as well as presentation as an acute coronary syndrome, were associated with more variability in all physiological intracoronary measurements. The reliability of most frequently used intracoronary physiologic indices is high. Clinical and anatomic factors significantly influence the reliability of these physiologic indices.

  9. Intracoronary Bivalirudin Bolus in ST-Elevation Myocardial Infarction Patients Treated with Primary Angioplasty: Theoretical Bases, Clinical Experience, and Future Applications.

    PubMed

    Lupi, Alessandro; Schaffer, Alon; Rognoni, Andrea; Cavallino, Chiara; Bongo, Angelo S; Cortese, Bernardo; Jaffe, Allan S; Angiolillo, Dominick J; Porto, Italo

    2016-12-01

    Intracoronary thrombus is a common finding in acute coronary syndromes and often correlates with adverse prognosis and complications during percutaneous coronary interventions (PCIs). Bivalirudin, a direct thrombin inhibitor, is one of the recommended antithrombotic treatments for PCI in ST-elevation myocardial infarction (STEMI). The intracoronary administration of a bivalirudin loading dose, even if off-label, offers theoretical advantages over the standard intravenous route, providing a very high drug concentration in the infarct-related artery without increasing the total dose of the drug administered. After the description in case reports of such an approach, a larger scale experience was recently reported in a large cohort of patients with STEMI treated during primary PCI with a bivalirudin intracoronary loading dose followed by the standard intravenous maintenance infusion. As a control group, a propensity score-matched cohort of patients undergoing primary PCI treated with intravenous bivalirudin in the same institution was selected. Compared with the intravenous bolus, the intracoronary administration of bivalirudin was associated with improved ST-segment resolution, lower post-procedural peak CK-MB levels, and better Thrombolysis in Myocardial Infarction (TIMI) frame count values, without difference in bleeding rates. Thus, this new promising antithrombotic strategy, based on the intracoronary administration of a bivalirudin loading dose during primary PCI, appeared safe, improved myocardial reperfusion, and mitigated enzymatic myocardial infarct size compared with the standard intravenous protocol. Randomized trials are warranted to confirm these results and evaluate the possible long-term clinical benefits.

  10. Intracoronary adenosine versus intravenous adenosine during primary PCI for ST-elevation myocardial infarction: which one offers better outcomes in terms of microvascular obstruction?

    PubMed

    Doolub, Gemina; Dall'armellina, Erica

    2013-01-01

    Aims. Previous studies have suggested that intravenous administration of adenosine improves myocardial reperfusion and reduces infarct size in ST-elevation myocardial infarction (STEMI) patients. Intracoronary administration of adenosine has shown conflicting results. Methods. In this retrospective, single-centre, blinded clinical study, we assessed whether selective intracoronary administration of adenosine distal to the occlusion site immediately before initial balloon inflation reduces microvascular obstruction (MVO) as assessed with cardiac magnetic resonance imaging (MRI). Using contrast-enhanced sequences, microvascular obstruction (MVO) was calculated. We found 81 patients presenting with STEMI within 12 h from symptom onset who were eligible for the study. In 80/81 (100%) patients receiving the study drug, MRI was performed on Day 1 after primary angioplasty. Results. The prevalence of MVO was reduced in the patients treated with intracoronary adenosine, (45%) compared to 85% of patients who were administered intravenous adenosine (P = 0.0043). We found that the size of MVO in patients receiving intracoronary adenosine was significantly reduced compared to 0.91 g in the intravenous-treated group (P = 0.027). There was no statistically significant difference in TIMI flow and clinical outcomes after primary PCI. Conclusion. We found significant evidence that selective high-dose intracoronary administration of adenosine distal to the occlusion site of the culprit lesion in STEMI patients results in a decrease in microvascular obstruction.

  11. Semiautomatic segmentation and quantification of calcified plaques in intracoronary optical coherence tomography images

    NASA Astrophysics Data System (ADS)

    Wang, Zhao; Kyono, Hiroyuki; Bezerra, Hiram G.; Wang, Hui; Gargesha, Madhusudhana; Alraies, Chadi; Xu, Chenyang; Schmitt, Joseph M.; Wilson, David L.; Costa, Marco A.; Rollins, Andrew M.

    2010-11-01

    Coronary calcified plaque (CP) is both an important marker of atherosclerosis and major determinant of the success of coronary stenting. Intracoronary optical coherence tomography (OCT) with high spatial resolution can provide detailed volumetric characterization of CP. We present a semiautomatic method for segmentation and quantification of CP in OCT images. Following segmentation of the lumen, guide wire, and arterial wall, the CP was localized by edge detection and traced using a combined intensity and gradient-based level-set model. From the segmentation regions, quantification of the depth, area, angle fill fraction, and thickness of the CP was demonstrated. Validation by comparing the automatic results to expert manual segmentation of 106 in vivo images from eight patients showed an accuracy of 78+/-9%. For a variety of CP measurements, the bias was insignificant (except for depth measurement) and the agreement was adequate when the CP has a clear outer border and no guide-wire overlap. These results suggest that the proposed method can be used for automated CP analysis in OCT, thereby facilitating our understanding of coronary artery calcification in the process of atherosclerosis and helping guide complex interventional strategies in coronary arteries with superficial calcification.

  12. Effects of intracoronary injection of ergonovine on angiographic normal coronary arteries: study of 108 consecutive patients.

    PubMed

    Fournier, J A; Cortacero, J A; Turá, A; Hernández-Aparicio, C; Granado, C; Vallejo, J

    1989-10-01

    To assess the local and systemic intracoronary (IC) ergonovine maleate (EM), single or repeated 25 micrograms bolus injections were administered to 108 consecutive patients with chest pain and normal coronary arteriograms. Coronary artery spasm (CAS) was induced in 17 (15.7%) patients. None of these patients developed ST-segment depression, and ST-segment elevation appeared in only 6 (35.3%). In 59 of the 91 patients without CAS, both the IC and the intravenous (IV) EM arteriographic and hemodynamic effects were compared. The mean diameter of the vessels was reduced by 15% (p less than 0.001) after two single 25 micrograms ICEM injections. Only insignificant changes were induced in the heart rate (baseline 80 +/- 15; after ICEM 79 +/- 15 beats/min; p = NS) and systolic aortic pressure (baseline 147 +/- 27; after ICEM 149 +/- 28 mmHG; p = NS). Following 350 micrograms of cumulative IVEM, the mean coronary diameter decreased by 20% (p less than 0.01 vs. ICEM dose) and the heart rate diminished slightly (76 +/- 12 beats/min, p less than 0.01). However, the systolic aortic pressures did increase by 16% (171 +/- 28 mmHg; p less than 0.001). No major complications were observed. Thus, to induce CAS the IC delivery route appears to be safe, allows for more accurate titration, and adverse systemic effects, such as hypertension, are avoided.

  13. Methodology for fully automated segmentation and plaque characterization in intracoronary optical coherence tomography images.

    PubMed

    Athanasiou, Lambros S; Bourantas, Christos V; Rigas, George; Sakellarios, Antonis I; Exarchos, Themis P; Siogkas, Panagiotis K; Ricciardi, Andrea; Naka, Katerina K; Papafaklis, Michail I; Michalis, Lampros K; Prati, Francesco; Fotiadis, Dimitrios I

    2014-02-01

    Optical coherence tomography (OCT) is a light-based intracoronary imaging modality that provides high-resolution cross-sectional images of the luminal and plaque morphology. Currently, the segmentation of OCT images and identification of the composition of plaque are mainly performed manually by expert observers. However, this process is laborious and time consuming and its accuracy relies on the expertise of the observer. To address these limitations, we present a methodology that is able to process the OCT data in a fully automated fashion. The proposed methodology is able to detect the lumen borders in the OCT frames, identify the plaque region, and detect four tissue types: calcium (CA), lipid tissue (LT), fibrous tissue (FT), and mixed tissue (MT). The efficiency of the developed methodology was evaluated using annotations from 27 OCT pullbacks acquired from 22 patients. High Pearson's correlation coefficients were obtained between the output of the developed methodology and the manual annotations (from 0.96 to 0.99), while no significant bias with good limits of agreement was shown in the Bland-Altman analysis. The overlapping areas ratio between experts' annotations and methodology in detecting CA, LT, FT, and MT was 0.81, 0.71, 0.87, and 0.81, respectively.

  14. Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus Type 5 in Pig Heart In Situ

    PubMed Central

    Schmarkey, L. Susan; Jiang, Rong; Bone, C. Collin; Condit, Marah E.; Dillehay, Dirck L.; Engler, Robert L.; Rubanyi, Gabor M.; Vinten-Johansen, Jakob

    2012-01-01

    Abstract Efficiency of intracoronary (IC) adenoviral vector transfection is impaired by the vascular endothelium. Ischemia and substances that increase vascular permeability (sodium nitroprusside, nitroglycerin) may augment adenoviral vector transfection efficiency (TE). We tested whether TE of adenoviral vector following IC infusion is improved by nitrates or by ischemia. Fluoroscopically guided angioplasty balloon catheters occluded the coronary artery in Yorkshire pigs and delivered adenoviral type 5 vector encoding the luciferase gene (Ad5Luc, 1011 viral particles). TE (luciferase activity) was minimal and was not augmented by IC co-administration of 50 μg/min sodium nitroprusside to nonischemic myocardium. Two (but not one) 3-min episodes of occlusion tended to increase luciferase activity (p=0.06), and luciferase activity was further increased by IC co-administration of nitroglycerin (p<0.001). After 75 min of coronary artery occlusion, luciferase activity was greater than with shorter periods of ischemia, and was significantly greater in the ischemia-reperfused zone compared to the border zone 3 and 14 days after infusion; there was no transfection in nonischemic myocardium. IC delivery of Ad5Luc into post-ischemic myocardium caused no local inflammation or hemodynamic instability. We conclude that the uptake of IC Ad5 to ischemic reperfused myocardium validates use of IC Ad5 delivery protocols in future human gene therapy trials in patients following myocardial ischemia. PMID:22816318

  15. Perioperative management of patient with intracoronary stent presenting for noncardiac surgery

    PubMed Central

    Gurajala, Indira; Gopinath, Ramachandran

    2016-01-01

    As the number of percutaneous coronary interventions increase annually, patients with intracoronary stents (ICS) who present for noncardiac surgery (NCS) are also on the rise. ICS is associated with stent thrombosis (STH) and requires mandatory antiplatelet therapy to prevent major adverse cardiac events. The risks of bleeding and ischemia remain significant and the management of these patients, especially in the initial year of ICS is challenging. The American College of Cardiologists guidelines on the management of patients with ICS recommend dual antiplatelet therapy (DAT) for minimal 14 days after balloon angioplasty, 30 days for bare metal stents, and 365 days for drug-eluting stents. Postponement of elective surgery is advocated during this period, but guidelines concerning emergency NCS are ambiguous. The risk of STH and surgical bleeding needs to be assessed carefully and many factors which are implicated in STH, apart from the type of stent and the duration of DAT, need to be considered when decision to discontinue DAT is made. DAT management should be a multidisciplinary exercise and bridging therapy with shorter acting intravenous antiplatelet drugs should be contemplated whenever possible. Well conducted clinical trials are needed to establish guidelines as regards to the appropriate tests for platelet function monitoring in patients undergoing NCS while on DAT. PMID:26750683

  16. Regional myocardial perfusion at rest and during intracoronary papaverine in patients with coronary artery disease

    SciTech Connect

    Goldman, S.; Henry, R.; Ovitt, T.; Friedman, M.J.; Rosenfeld, A.; Daly, M.

    1983-03-01

    Regional myocardial perfusion was measured in 32 patients with the xenon-133 washout technique at rest and after 5 mg of intracoronary papaverine. Areas of decreased perfusion and/or decreased vasodilation were identified visually from computer-generated functional images. The locations of arteries and stenoses, obtained from identically positioned cineangiograms, were overlaid on the functional images. Perfusion rates for 62 myocardial regions were calculated and correlated with the percentage of stenosis. There was no association between degree of stenosis and perfusion at rest. Regional myocardial perfusion increased after papaverine in regions supplied by coronary arteries without stenoses (0% to 25%), 88.6 +/- 4.7 ml/min/100 gm. This increase was significantly greater (p less than 0.001) than the increase in regions supplied by 51% to 75% stenoses (23.7 +/- 6.3 ml/min/100 gm), or 76% to 99% stenoses (12.9 +/- 6.3 ml/min/100 gm), or 100% stenoses (2.5 +/- 3.8 ml/min/100 gm). Thus there was an inverse relationship between the increase in myocardial perfusion stimulated by papaverine and the degree of coronary artery stenosis measured angiographically. In regions supplied by two stenoses in series, vasodilation produced less of an increase than a single stenosis of a similar degree.

  17. Two-year follow-up after intracoronary gamma radiation therapy.

    PubMed

    Condado, J A; Waksman, R; Calderas, C; Saucedo, J; Lansky, A

    1999-01-01

    Neointimal hyperplasia and unfavorable remodeling have been demonstrated to be the major limitation to endovascular revascularization procedures. Intracoronary gamma radiation therapy has been shown to reduce the restenosis index. However, the late effects of these novel procedures are unknown. To evaluate the long-term effects on clinical and angiographic outcome of endovascular gamma radiation therapy following percutaneous transluminal coronary angioplasty (PTCA), serial angiography over a 2-year period was performed in 21 patients (22 lesions) who were treated with 192Ir in doses of 20-25 Gy after PTCA. Angiograms were analyzed using quantitative methods (QCA). The mean late loss between PTCA and 6 months was 0.20 +/- 0.59 and 0.13 +/- 0.84 between 6 months and 2 years. At 6 months, angiographic binary restenosis was present in six arteries (27.2%). At 2 years, binary restenosis was observed in six arteries (27.2%), including one patient who had developed restenosis and excluding one patient with spontaneous regression. Two early pseudoaneurysms and two late aneurysms were observed at 6 months, with little increase at 2 years. No other angiographic complication was observed. None of the patients or medical staff developed complications or illnesses that could be related to the effects of the radiation procedure. Gamma radiation therapy decreases late luminal loss, is safe and free of unexpected complications at 6 months follow-up, with no significant changes or late complications at 2-years' follow-up.

  18. Intracoronary versus intravenous high-dose bolus plus maintenance administration of tirofiban in patients undergoing primary percutaneous coronary intervention for acute ST elevation myocardial infarction.

    PubMed

    Candemir, Basar; Kilickap, Mustafa; Ozcan, Ozgur Ulas; Kaya, Cansin Tulunay; Gerede, Menekse; Ozdemir, Aydan Ongun; Ozdol, Cagdas; Kumbasar, Deniz; Erol, Cetin

    2012-07-01

    We aimed to examine whether intracoronary high-dose bolus of tirofiban plus maintenance would result in improved clinical outcome in STEMI patients undergoing primary PCI in this pilot trial. A total of 56 patients were enrolled to receive either intracoronary high-dose bolus plus maintenance (n = 34) or intravenous high-dose bolus plus maintenance (n = 22) of tirofiban. Pre and post intervention TIMI flow grades, myocardial blush grades, peak CKMB and troponin levels, time to peak CKMB and troponin, time to 50% ST resolution and major composite adverse cardiac event rates at 30 days were recorded. Although incidence of major adverse cardiac events was not different, post intervention TIMI flow and TIMI blush grades, peak CKMB and troponin levels, and time to peak CKMB and time to peak troponin were significantly different, favoring intracoronary strategy. In conclusion, this regimen improved myocardial reperfusion and coronary flow, and reduced myocardial necrosis, but failed to improve clinical outcomes at 30 days.

  19. Functional improvement in patients with dilated cardiomyopathy after the intracoronary infusion of autologous bone marrow mononuclear cells.

    PubMed

    Suárez de Lezo, José; Herrera, Concepción; Romero, Miguel; Pan, Manuel; Suárez de Lezo, Javier; Carmona, María Dolores; Jiménez, Rosario; Segura, José; Nogueras, Sonia; Mesa, Dolores; Pavlovic, Djordje; Ojeda, Soledad; Mazuelos, Francisco; Delgado, Mónica; Ruiz, Martin; Castilla, María Luisa; Torres, Antonio

    2013-06-01

    Different studies have shown improvement in patients with idiopathic nonischemic dilated cardiomyopathy treated with cell-therapy. However, factors influencing responsiveness are not well known. This trial investigates functional changes and factors influencing the 6-month gain in ejection fraction in 27 patients with dilated cardiomiopathy treated with intracoronary cell-therapy. Patients received intracoronary infusion of autologous bone-marrow mononuclear cells (mean infused, 10.2 [2.9]×10(8)). Flow cytometry and functional analyses of the cells were also performed. The 6-month angiographic gain in ejection fraction ranged from -9% to 34% (mean, 9%). These changes were distinguished into 2 groups: 21 patients (78%) with a significant improvement at the 6-month evaluation (mean gain, 14 [7]%), and 6 patients who had no response (mean gain, -5 [3]%). The responders were younger as compared to the nonresponders (50 [12] years vs 62 [9] years; P<.04). There was an inverse correlation (r=-0.41; P<.003) between the gain in ejection fraction and the high density lipoprotein level, suggesting higher functional gain with low high density lipoprotein levels. The 24 h migratory capability of the infused cells was significantly reduced in the responders' group (5.4 [1.7]×10(8) vs 8.1 [2.3]×10(8); P<.009 for vascular endothelial growth factor and 5.8 [1.7]×10(8) vs 8.4 [2.9]×10(8); P<.002 for stromal cell-derived factor-1). Younger patients with dilated cardiomiopathy and lower plasma high density lipoprotein levels gain greater benefit from intracoronary cell-therapy. Functional improvement also seems to be enhanced by a lower migratory capacity of the infused cells. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Intracoronary MR imaging using a 0.014-inch MR imaging-guidewire: toward MRI-guided coronary interventions.

    PubMed

    Qiu, Bensheng; Gao, Fabao; Karmarkar, Parag; Atalar, Ergin; Yang, Xiaoming

    2008-08-01

    To validate the feasibility of using a newly designed MR imaging-guidewire (MRIG) to guide angioplasty balloon placement in coronary arteries. A custom gold/sliver/Nitinol/MP35N-based, 0.014-inch MRIG was manufactured. To test its mechanical performance we used the new MRIG to catheterize the left coronary arteries of three dogs under x-ray fluoroscopy. To further validate the feasibility of using the MRIG to generate intracoronary MR imaging, we positioned the MRIG, along with a dilation-perfusion balloon catheter, into the left coronary arteries of an additional three dogs. Longitudinal and four-chamber views of cine cardiac MR images were obtained using a fast gradient recalled echo (FGRE) sequence (TR/TE/FA = 5.2 msec/1.6 msec/20 degrees , field of view [FOV] = 32 x 32 cm, thickness = 5 mm, space = 2 mm, matrix = 256 x 160, number of excites [NEX] = 0.5, and bandwidth [BW] = 32 kHz). Then three-dimensional (3D) MR coronary angiography of the left coronary arteries was obtained using a fast imaging employing steady-state acquisition (FIESTA) sequence. We subsequently used the MRIG, at a receive-only mode, to generate intracoronary MR images using FGRE (TR/TE/FA = 7.2 msec/3.5 msec/20 degrees , FOV = 18 x 18cm, thickness = 3 mm, space = 0.5 mm, matrix = 256 x 256, NEX = 0.5, and BW = 32 kHz). In all six animals the left main coronary arteries were successfully catheterized. 3D MR imaging displayed left coronary artery branches. Intracoronary MR imaging demonstrated the inflated balloons as a "train track" or a bright, thick ring at different views. This study demonstrates the potential of using this newly designed gold/sliver/Nitinol/MP35N-based, 0.014-inch MRIG to catheterize coronary arteries and, thus, generate intracoronary MR imaging with balloon inflation. (c) 2008 Wiley-Liss, Inc.

  1. Combined use of selective intracoronary thrombolysis and percutaneous transluminal coronary angioplasty for the treatment of coronary obstruction.

    PubMed

    Keltai, M; Kádár, A; Palik, I; Rózsa, Z

    1984-01-01

    The case of a young female patient with inferior infarction is presented. In the fifth hour after the onset of MI coronary angiography revealed complete obstruction of the right coronary artery. This obstruction has been recanalized by selective intracoronary infusion of streptokinase. At the site of occlusion there remained a 90% coronary stenosis, causing anginal attacks. By means of balloon-catheter angioplasty the stenosis was reduced to less than 50%. The coronary angioplasty resulted in an improvement of left ventricular function, physical working capacity and cessation of anginal attacks.

  2. Intracoronary electrocardiogram during alcohol septal ablation for hypertrophic obstructive cardiomyopathy predicts myocardial injury size.

    PubMed

    Meng, Jing; Qu, Xiaolong; Huang, Haiyun; Zhang, Shanwen; Zhao, Weibo; He, Guoxiang; Song, Zhiyuan; Hu, Houyuan

    2016-01-01

    Alcohol septal ablation (ASA) has been used widely to treat patients with hypertrophic obstructive cardiomyopathy (HOCM). During the routine ASA procedure, it is difficult to detect the septal injury in real-time. The aim of the present study is to assess myocardial injury during ASA by recording intracoronary electrocardiogram (IC-ECG). From 2012 to 2015, 31 HOCM patients were treated with ASA, and IC-ECG was recorded in 21 patients successfully before and after ethanol injection. The elevation of ST-segment on IC-ECG after ethanol injection was expressed as its ratio to the level before injection or the absolute increasing value. Blood samples were collected before and after ASA for measuring changes in cardiac biomarkers. The ratio value of ST-segment elevation was positively correlated with both the amount of ethanol injected (r = 0.645, P = 0.001) and the myocardial injury size (creatine kinase-MB area under the curve (AUC) of CK-MB) (r = 0.466, P = 0.017). The absolute increment of ST-segment was also positively associated with both the amount of ethanol (r = 0.665, P = 0.001) and AUC of CK-MB (0.685, P = 0.001). However, there was no statistical correlation between the reduction of left ventricular outflow tract gradient and ST-segment elevation. Additionally no severe ASA procedure-related complications were observed in our patients. In conclusion, myocardial injury induced by ethanol injection can be assessed immediately by ST-segment elevation on IC-ECG. This study is the first to show that IC-ECG is a useful method for predicting myocardial injury during ASA in real-time.

  3. Shear bond strength of an orthodontic self-etching adhesive after intracoronary bleaching.

    PubMed

    Fernandes, H O; Santos, L B; Firoozmand, L M

    2015-05-01

    To evaluate the effects of intracoronary bleaching on the bond strength of orthodontic brackets using self-etching and total-etch adhesive systems. In 60 bovine incisors, a coronal lingual access was made to clean the pulp chamber and standardise the thickness of the dentine. The sample was randomly divided into four groups (each n = 15): (CT), control group, without bleaching and bonded with the total-etch system (Transbond(™) XT-3M); (CTSE), without bleaching treatment and bonded with the self-etching system (Transbond(™) Plus Self-Etching Primer-3M); (BT), treated with 35% hydrogen peroxide for internal bleaching and bonded with the total-etch adhesive system; and (BTSE), treated with 35% hydrogen peroxide and bonded with the self-etching adhesive system. Shear bond strength was measured using a universal testing machine (EMIC). The adhesive remnant index (ARI) score was verified. The data were analysed using a two-way anova and Tukey test (p < 0.05). Significant differences were found, and the self-etching adhesive groups presented the highest bond strength values (CTSE=11.55 ± 2.85 MPa; BTSE=14.14 ± 2.23 MPa). The ARI scores revealed significant differences among the groups; the greater amount of remaining adhesive was observed in the CTSE group, and the lowest scores were observed in the BT group. The use of the self-etching adhesive system, even after intracoronal bleaching, presented satisfactory adhesive strength for the bonding of brackets. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Changes in left ventricular regional asynchrony after intracoronary thrombolysis in patients with impending myocardial infarction.

    PubMed Central

    Gibson, D; Mehmel, H; Schwarz, F; Li, K; Kübler, W

    1986-01-01

    Ventriculograms obtained before and a mean (SD) of 4.3 (2.5) weeks after intracoronary thrombolysis in 23 patients who were treated within 3.5 (3.1) hours of the onset of pain were examined for changes in asynchronous left ventricular wall motion. Lysis was achieved in 19 patients, and in 16 the affected artery was still patent at restudy. Angiograms were digitised frame by frame. Left ventricular volumes, ejection fraction, and peak ejection rate were all unchanged after thrombolysis, whereas peak filling rate fell, whether or not patency was achieved or maintained. Regional wall motion was examined by means of isometric and contour plots. The area supplied by the affected coronary artery showed simple hypokinesis or akinesis in 10 cases, which was unchanged at the second study in nine and improved in one. The commonest manifestation of asynchrony was delayed inward motion during isovolumic relaxation. This was present in 12 cases with or without associated hypokinesis; after thrombolysis wall motion improved significantly in eight and returned to normal in six, significantly more frequently than it did in patients with simple hypokinesis. Dyskinesis (three patients) and hyperkinesis (five patients) resolved in all. Outward wall motion during isovolumic relaxation reverted to normal in four out of five cases, and outward motion during isovolumic contraction reverted to normal in five out of seven. The frequency of improvement was also increased when the circulation to the affected segment was not compromised by an important residual stenosis. Flow in the affected artery was re-established or maintained significantly less frequently when simple hypokinesis or akinesis was present at the first study. These observations provide further evidence that asynchronous wall motion early after acute myocardial infarction represents residual contractile activity, and suggest that knowledge of its presence and distribution may be useful in assessing patients on whom

  5. Determinants of coronary blood flow in humans: quantification by intracoronary Doppler and ultrasound.

    PubMed

    Wieneke, Heinrich; von Birgelen, Clemens; Haude, Michael; Eggebrecht, Holger; Möhlenkamp, Stefan; Schmermund, Axel; Böse, Dirk; Altmann, Christoph; Bartel, Thomas; Erbel, Raimund

    2005-03-01

    The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72 to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product (r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.

  6. Immunohistological Analysis of Intracoronary Thrombus Aspirate in STEMI Patients: Clinical Implications of Pathological Findings.

    PubMed

    Blasco, Ana; Bellas, Carmen; Goicolea, Leyre; Muñiz, Ana; Abraira, Víctor; Royuela, Ana; Mingo, Susana; Oteo, Juan Francisco; García-Touchard, Arturo; Goicolea, Francisco Javier

    2017-03-01

    Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress. This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients' clinical and angiographic features, estimation of survival curves, and logistic regression analysis. Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001). The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Intracoronary administration of streptokinase in a canine model. Disturbance in thromboxane A2-prostacyclin balance.

    PubMed

    Becker, G J; Kreipke, D L; Holden, R W; Dreesen, R G; Ryder, K; Petersen, B; Evan, A P; Bendick, P J; Franklin, T D; Klatte, E C

    1986-03-01

    The potential impact of local intracoronary infusion of streptokinase (SK) on vascular prostaglandin synthetic pathways was studied in a canine model. Control animals (n = 10) underwent left coronary artery (LCA) infusion of 50,000 units SK for 90 minutes; experimental animals (n = 10) underwent LCA infusion of normal saline. Plasma samples for radioimmunoassay (RIA) of prostacyclin (PGI-2) and thromboxane (TXA-2) were obtained from the coronary sinus (CS) as follows: one sample preinfusion, six samples during infusion, and three samples postinfusion in each animal. Comparisons between control and experimental plasma levels of PGI-2 and TXA-2 were made for each sampling time. The PGI-2 levels remained at or below the lower limits of detectability by RIA (the most sensitive assay available) in both control and experimental animals. TXA-2 levels were higher in experimental than in control animals at all sampling times, with the most significant differences occurring in samples 3 (after 30 minutes of infusion, .001 less than P less than .01), 4 (after 45 minutes of infusion, .05 less than P less than .10), and 5 (after 60 minutes of infusion, .02 less than P less than .05). We suggest (1) it is unlikely that any of the beneficial effects of coronary streptokinase infusions are PGI-2-mediated, (2) that the TXA-2 increases in our model may represent a pathophysiologic-biochemical correlate of previously identified morphologic evidence of endothelial damage in animals infused with fibrinolytic agents, and (3) that our findings may indicate that fibrinolytic infusions produce competing effects: lysis of thrombi and endothelial injury with TXA-2 production.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effects of intracoronary sodium nitroprusside compared with adenosine on fractional flow reserve measurement.

    PubMed

    Wang, Xiaozeng; Li, Shaosheng; Zhao, Xin; Deng, Jie; Han, Yaling

    2014-03-01

    The purpose of this study was to compare the efficacy and safety of intracoronary (IC) sodium nitroprusside (SNP) and IC adenosine (AD) for fractional flow reserve (FFR) measurement. We compared the FFR response and side effect profiles of IC AD and IC SNP in 40 patients with a combined total of 53 moderate coronary stenoses. Boluses of AD at doses of 40 μg (A1) and 60 μg (A2), and SNP at doses of 0.3 μg/kg (S1), 0.6 μg/kg (S2), and 0.9 μg/kg (S3) were used to achieve coronary hyperemia. The mean FFR value decreased significantly by 7.96% (A1), 10.51% (A2), 8.74% (S1), 10.58% (S2), and 10.73% (S3) compared with the baseline distal coronary pressure/aortic pressure. IC SNP delayed the mean time to peak value of FFR by 87.5%, 79.0%, and 88.6% in S1, S2, and S3, respectively, compared with A2 (P<.001). The mean duration of the plateau phase was longer in S1 (50.47 ± 14.25 s), S2 (51.33 ± 16.41 s) and S3 (57.60 ± 18.07 s) compared with A2 (27.93 ± 11.90 s; P<.01). IC AD caused shortness of breath in 11 patients (27.5%), flushing in 4 patients (10%), headache in 8 patients (20%), and transient second-degree atrioventricular block (AVB) in 6 patients (15%). IC SNP may be used as a hyperemic agent in FFR measurements. It may be preferable to IC AD as a routine clinical stimulus and has the additional advantage of showing a longer plateau phase.

  9. Patient doses in {gamma}-intracoronary radiotherapy: The Radiation Burden Assessment Study

    SciTech Connect

    Thierens, Hubert . E-mail: hubert.thierens@Ughent.be; Reynaert, Nick; Bacher, Klaus; Eijkeren, Marc van; Taeymans, Yves

    2004-10-01

    Purpose: To determine accurately the radiation burden of both patients and staff from intracoronary radiotherapy (IRT) with {sup 192}Ir and to investigate the importance of IRT in the patient dose compared with interventional X-rays. Methods and materials: The Radiation Burden Assessment Study (RABAS) population consisted of 9 patients undergoing {gamma}-IRT after percutaneous transluminal coronary angioplasty and 14 patients undergoing percutaneous transluminal coronary angioplasty only as the control group. For each patient, the dose to the organs and tissues from the internal and external exposure was determined in detail by Monte Carlo N-particle simulations. Patient skin dose measurements with thermoluminescence dosimeters served as verification. Staff dosimetry was performed with electronic dosimeters, thermoluminescence dosimeters, and double film badge dosimetry. Results: With respect to the patient dose from IRT, the critical organs are the thymus (58 mGy), lungs (31 mGy), and esophagus (27 mGy). The mean effective dose from IRT was 8 mSv. The effective dose values from interventional X-rays showed a broad range (2-28 mSv), with mean values of 8 mSv for the IRT patients and 13 mSv for the control group. The mean dose received by the radiotherapist from IRT was 4 {mu}Sv/treatment. The doses to the other staff members were completely negligible. Conclusion: Our results have shown that the patient and personnel doses in {gamma}-IRT remain at an acceptable level. The patient dose from IRT was within the variations in dose from the accompanying interventional X-rays.

  10. Effect of intracoronary tirofiban on platelet alpha-granule membrane protein and myocardial perfusion level during emergency percutaneous coronary intervention.

    PubMed

    Xu, H P; Liu, C M; Zhang, W W

    2014-11-14

    This study aimed to investigate the effect of intracoronary application of tirofiban on platelet alpha-granule membrane protein (GMP-140) and myocardial perfusion levels during emergency percutaneous coronary intervention (PCI). A total of 70 patients who accepted emergency PCI treatment were randomly divided into tirofiban and control groups. We determined GMP-140 and troponin I (cTnI) levels before and 12 h after surgery, as well as N-terminal pro-brain natriuretic peptide levels 1 and 7 days after surgery in the two groups. The results showed that GMP-140 and cTnI levels were significantly (P < 0.01) lower in the tirofiban group than in the control group 12 h after operation (17.99 ± 1.01 vs 24.56 ± 1.96 μg/L and 50.96 ± 2.20 vs 58.69 ± 2.34 ng/mL, respectively). The D-value of the N-terminal pro-brain natriuretic peptide levels between 1 and 7 days after operation was significantly higher in the tirofiban group than in the control group (894.19 ± 90.91 vs 829.50 ± 84.18 pg/mL; P < 0.01). The intracoronary application of tirofiban during emergency PCI clearly reduced the GMP-140 level, inhibited the activation function of platelets, improved myocardial perfusion, and helped recover cardiac function in patients.

  11. Intracoronary versus Intravenous eptifibatide during percutaneous coronary intervention for acute ST-segment elevation myocardial infarction; a randomized controlled trial.

    PubMed

    Sanati, Hamid Reza; Zahedmehr, Ali; Firouzi, Ata; Farrashi, Melody; Amin, Kamyar; Peighambari, Mohammad Mehdi; Shakerian, Farshad; Kiani, Reza

    2016-08-17

    Although aspirin and clopidogrel seem to be quite enough during low risk percutaneous coronary intervention (PCI), the combination may need some reinforcement in complex situations such as primary PCI. By modifying the route and also the duration of administration, glycoprotein IIb/IIIa inhibitors might be a viable option. The aim of this study is to compare the benefits and disadvantages of three different methods of administration of eptifibatide in primary PCI population. Primary PCI candidates were randomized in three groups on which three different methods of administration of eptifibitide were tested: intravenous bolus injection followed by 12-h infusion (IV-IV), intracoronary bolus injection followed by intravenous infusion (IC-IV) and, only intracoronary bolus injection (IC). 99 patients were included in the present study. There was no significant difference among the three groups regarding all cause in hospital and one month mortality (p value = 0.99), re-myocardial infarction (p value = 0.89), post-PCI TIMI flow grade 3 (p value = 0.97), ST segment resolution (p value = 0.77) and peak troponin levels (p value = 0.82). The comparison of vascular access and major bleeding complications were not possible due to low events rate. By modifying the route of administration of eptifibitide, the clinical effect might be preserved without increasing the short-term mortality and procedural failure.

  12. 2D-DIGE-based proteomic analysis of intracoronary versus peripheral arterial blood platelets from acute myocardial infarction patients: Upregulation of platelet activation biomarkers at the culprit site.

    PubMed

    Vélez, Paula; Ocaranza-Sánchez, Raymundo; López-Otero, Diego; Grigorian-Shamagian, Lilian; Rosa, Isaac; Bravo, Susana Belén; González-Juanatey, José Ramón; García, Ángel

    2016-08-01

    Platelets play a fundamental role in the atherothrombotic events that lead to an acute myocardial infarction. In the present study we compared the proteome of intracoronary and peripheral arterial platelets from ST-elevation myocardial infarction (STEMI) patients in the search for potential platelet biomarkers/drug targets related to what is happening at the culprit site. Ten STEMI patients were recruited and blood collected from the occluded coronary artery, at the culprit site, in the moment of reperfusion. Systemic blood obtained from the radial artery of the same patients was used as control. Proteome analysis was based on high-resolution 2D-DIGE and mass spectrometry. Validations were by western blotting in a group of 11 patients. Sixteen differentially regulated protein features were identified, corresponding to 15 ORFs, mostly related to cytoskeletal and signaling proteins. We demonstrate the up-regulation of integrin αIIb (ITA2B), the adapter Src kinase-associated phosphoprotein-2 (SKAP2), and thrombospondin-1 isoforms in intracoronary platelets. This study constitutes the first analyzing in detail the proteome of arterial intracoronary platelets from STEMI patients. We show variations in the platelet proteome when comparing intracoronary and peripheral platelets. Observed differences might be related to platelet activation events at the culprit site. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Ex vivo intracoronary gene transfer of adeno-associated virus 2 leads to superior transduction over serotypes 8 and 9 in rat heart transplants.

    PubMed

    Raissadati, Alireza; Jokinen, Janne J; Syrjälä, Simo O; Keränen, Mikko A I; Krebs, Rainer; Tuuminen, Raimo; Arnaudova, Ralica; Rouvinen, Eeva; Anisimov, Andrey; Soronen, Jarkko; Pajusola, Katri; Alitalo, Kari; Nykänen, Antti I; Lemström, Karl

    2013-11-01

    Heart transplant gene therapy requires vectors with long-lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno-associated virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV2 and AAV8. However, ex vivo analyses revealed that intracoronary perfusion with AAV2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.

  14. Stem-cell transplantation in children with acute lymphoblastic leukemia: A prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial.

    PubMed

    Peters, Christina; Schrappe, Martin; von Stackelberg, Arend; Schrauder, André; Bader, Peter; Ebell, Wolfram; Lang, Peter; Sykora, Karl-Walter; Schrum, Johanna; Kremens, Bernhard; Ehlert, Karoline; Albert, Michael H; Meisel, Roland; Matthes-Martin, Susanne; Gungor, Tayfun; Holter, Wolfgang; Strahm, Brigitte; Gruhn, Bernd; Schulz, Ansgar; Woessmann, Wilhelm; Poetschger, Ulrike; Zimmermann, Martin; Klingebiel, Thomas

    2015-04-10

    Although hematopoietic stem-cell transplantation is widely performed in children with high-risk acute lymphoblastic leukemia (ALL), the influence of donor types is poorly understood. Thus, transplantation outcomes were compared in the prospective multinational Berlin-Frankfurt-Muenster (BFM) study group trial: ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia). After conditioning with total-body irradiation and etoposide, 411 children with high-risk ALL received highly standardized stem-cell transplantations during the first or later remissions. Depending on donor availability, grafts originated from HLA-genoidentical siblings or from HLA-matched unrelated donors who were identified and matched by high-resolution allelic typing and were compatible in at least 9 of 10 HLA loci. Four-year event-free survival (± standard deviation [SD]) did not differ between patients with transplantations from unrelated or sibling donors (0.67 ± 0.03 v 0.71 ± 0.05; P = .405), with cumulative incidences of nonrelapse mortality (± SD) of 0.10 ± 0.02 and 0.03 ± 0.02 (P = .017) and relapse rates (± SD) of 0.22 ± 0.02 and 0.24 ± 0.04 (P = .732), respectively. Among recipients of transplantations from unrelated donors, no significant differences in event-free survival, overall survival, or nonrelapse mortality were observed between 9/10 and 10/10 matched grafts or between peripheral blood stem cells and bone marrow. The absence of chronic graft-versus-host disease had no effect on event-free survival. Engraftment was faster after bone marrow transplantation from siblings and was associated with fewer severe infections and pulmonary complications. Outcome among high-risk pediatric patients with ALL after hematopoietic stem-cell transplantation was not affected by donor type. Standardized myeloablative conditioning produced a low incidence of treatment-related mortality and effective control of leukemia. © 2015 by

  15. Randomized comparison of intracoronary tirofiban versus urokinase as an adjunct to primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: results of the ICTUS-AMI trial.

    PubMed

    Zhu, Tian-qi; Zhang, Qi; Ding, Feng-hua; Qiu, Jian-ping; Jin, Hui-geng; Jiang, Li; Lu, Lin; Zhang, Rui-yan; Hu, Jian; Yang, Zhen-kun; Shen, Ying; Shen, Wei-feng

    2013-08-01

    No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

  16. Current stem cell delivery methods for myocardial repair.

    PubMed

    Sheng, Calvin C; Zhou, Li; Hao, Jijun

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration.

  17. Current Stem Cell Delivery Methods for Myocardial Repair

    PubMed Central

    Sheng, Calvin C.; Zhou, Li; Hao, Jijun

    2013-01-01

    Heart failure commonly results from an irreparable damage due to cardiovascular diseases (CVDs), the leading cause of morbidity and mortality in the United States. In recent years, the rapid advancements in stem cell research have garnered much praise for paving the way to novel therapies in reversing myocardial injuries. Cell types currently investigated for cellular delivery include embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and adult stem cell lineages such as skeletal myoblasts, bone-marrow-derived stem cells (BMSCs), mesenchymal stem cells (MSCs), and cardiac stem cells (CSCs). To engraft these cells into patients' damaged myocardium, a variety of approaches (intramyocardial, transendocardial, transcoronary, venous, intravenous, intracoronary artery and retrograde venous administrations and bioengineered tissue transplantation) have been developed and explored. In this paper, we will discuss the pros and cons of these delivery modalities, the current state of their therapeutic potentials, and a multifaceted evaluation of their reported clinical feasibility, safety, and efficacy. While the issues of optimal delivery approach, the best progenitor stem cell type, the most effective dose, and timing of administration remain to be addressed, we are highly optimistic that stem cell therapy will provide a clinically viable option for myocardial regeneration. PMID:23509740

  18. Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade

    PubMed Central

    Hayase, Motoya; Monte, Federica del; Kawase, Yoshiaki; MacNeill, Briain D.; McGregor, Jennifer; Yoneyama, Ryuichi; Hoshino, Kozo; Tsuji, Tsuyoshi; De Grand, Alec M.; Gwathmey, Judith K.; Frangioni, John V.; Hajjar, Roger J.

    2005-01-01

    Hayase, Motoya, Federica del Monte, Yoshiaki Kawase, Brian D. MacNeill, Jennifer McGregor, Ryuichi Yoneyama, Kozo Hoshino, Tsuyoshi Tsuji, Alec M. De Grand, Judith K. Gwathmey, John V. Frangioni, and Roger J. Hajjar. Catheter-based antegrade intracoronary viral gene delivery with coronary venous blockade. Am J Physiol Heart Circ Physiol 288: H2995–H3000, 2005; doi:10.1152/ajpheart.00703.2004.—The purpose of this study is to evaluate the feasibility of percutaneous antegrade myocardial gene transfer (PAMGT). A consistent and safe technique for in vivo gene transfer is required for clinical application of myocardial gene therapy. PAMGT with concomitant coronary venous blockade was performed in 12 swine. The myocardium was preconditioned with 1 min of occlusion of the left anterior descending and left circumflex arteries. The anterior interventricular vein was occluded during left anterior descending artery delivery, and the great cardiac vein at the entrance of the middle cardiac vein was occluded during left circumflex artery delivery. With arterial and venous balloons inflated (3 min) and after adenosine (25 μg) injection, PAMGT was performed by antegrade injection of an adenoviral solution (1 ml of 1011 plaque-forming units in each coronary artery) carrying β-galactosidase or saline through the center lumen of the angioplasty balloon. In one set of animals, PAMGT was performed with selective coronary vein blockade (n = 9); in another set of animals, PAMGT was performed without coronary vein blockade (n = 5). At 1 wk after gene delivery, the animals were killed. Quantitative β-galactosidase analysis was performed in the left and right ventricular walls. PAMGT was successfully performed in all animals with and without concomitant occlusion of the coronary veins. Quantitative β-galactosidase analysis showed that PAMGT with coronary blockade was superior to PAMGT without coronary blockade. β-Galactosidase activity increased significantly in the

  19. Plasma fibrin clot phenotype independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction.

    PubMed

    Zalewski, Jaroslaw; Bogaert, Jan; Sadowski, Marcin; Woznicka, Olga; Doulaptsis, Konstantinos; Ntoumpanaki, Maria; Ząbczyk, Michal; Nessler, Jadwiga; Undas, Anetta

    2015-06-01

    Determinants of intracoronary thrombus (ICT) composition in patients with ST-elevation myocardial infarction (STEMI) are largely unknown. We sought to investigate whether plasma fibrin phenotype and platelet reactivity affect ICT ultrastructure. We assessed the content of fibrin, platelets and erythrocytes including polyhedrocytes by scanning electron microscopy on the surface and inside ICT aspirated from 80 STEMI patients within 12 hours since chest pain onset. Plasma fibrin clot permeability (Ks), which indicates the average pore size, lysis time (t50 %), platelet reactivity index (PRI) and ADP-induced platelet aggregation (ADP5, 20µM) were evaluated on admission. All patients received aspirin and 45 (56.3 %) 600 mg of clopidogrel, 80 (60-120) min prior to aspiration. Higher content of fibrin (61.6 vs 34.3 %, P< 0.0001) and platelets (8.2 vs 4.8 %, P=0.018) and lower erythrocyte content (15.8 vs 42.9 %, P< 0.0001) were found on ICT surface compared with its inner part. After adjustment for fibrinogen, in both ICT parts fibrin content was correlated with Ks (r≤-0.55, P< 0.0001) and t50 % (r≥ 0.29, P≤ 0.02) but not with PRI and ADP5,20µM. Polyhedrocytes were observed in 16 (20 %) patients and their large amount expressed as ≥ 50 % fields of view covered by polyhedrocytes was associated with the lower PRI values (40 vs 69 %, P=0.015), but not Ks or t50 %. By multivariate regression, Ks (β=-0.62, P< 0.0001), clopidogrel pretreatment (β=-0.36, P< 0.001), ischemia time (β=0.19, P=0.044) and family history (β=0.18, P=0.049) independently predicted fibrin content in the whole ICT (R²=0.65, P< 0.0001). Formation of denser plasma fibrin clots is independently associated with high fibrin content within the ICT in STEMI.

  20. Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention

    PubMed Central

    Li, Yanbing; Li, Qiang; Li, Feiou; Zong, Min; Miao, Guobin; Yang, Xinchun; Tong, Zichuan; Zhang, Jianjun

    2016-01-01

    Background To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. Methods Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. Results Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). Conclusions Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI. PMID:27899850

  1. Direct intramyocardial but not intracoronary injection of bone marrow cells induces ventricular arrhythmias in a rat chronic ischemic heart failure model.

    PubMed

    Fukushima, Satsuki; Varela-Carver, Anabel; Coppen, Steven R; Yamahara, Kenichi; Felkin, Leanne E; Lee, Joon; Barton, Paul J R; Terracciano, Cesare M N; Yacoub, Magdi H; Suzuki, Ken

    2007-05-01

    Therapeutic efficacy of bone marrow (BM) cell injection for treating ischemic chronic heart failure has not been established. In addition, experimental data are lacking on arrhythmia occurrence after BM cell injection. We hypothesized that therapeutic efficacy and arrhythmia occurrence induced by BM cell injection may be affected by the cell delivery route. Three weeks after left coronary artery ligation, wild-type female rats were injected with 1x10(7) mononuclear BM cells derived from green fluorescent protein-transgenic male rats through either a direct intramyocardial or a retrograde intracoronary route. Both intramyocardial and intracoronary injection of BM cells demonstrated similar improvement in left ventricular ejection fraction measured by echocardiography and a similar graft size analyzed by real-time polymerase chain reaction for the Y chromosome-specific Sry gene. Noticeably, intramyocardial injection of BM cells induced frequent ventricular premature contractions (108+/-73 per hour at 7 days after BM cell injection), including multiform, consecutive ventricular premature contractions and ventricular tachycardia for the initial 14 days; intracoronary injection of BM cells and intramyocardial injection of phosphate-buffered saline rarely induced arrhythmias. Immunohistochemistry demonstrated that intramyocardial BM cell injection formed distinct cell clusters containing donor-derived cells and accumulated host-derived inflammatory cells in the infarct border zone, whereas intracoronary BM cell injection provided more homogeneous donor cell dissemination with less inflammation and without disrupting the native myocardial structure. BM cell injection is able to improve cardiac function in ischemic chronic heart failure but has a risk of arrhythmia occurrence when the intramyocardial route is used. Such arrhythmias may be prevented by using the intracoronary route.

  2. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II).

    PubMed

    Lamo-Espinosa, José M; Mora, Gonzalo; Blanco, Juan F; Granero-Moltó, Froilán; Nuñez-Córdoba, Jorge M; Sánchez-Echenique, Carmen; Bondía, José M; Aquerreta, Jesús Dámaso; Andreu, Enrique J; Ornilla, Enrique; Villarón, Eva M; Valentí-Azcárate, Andrés; Sánchez-Guijo, Fermín; Del Cañizo, María Consuelo; Valentí-Nin, Juan Ramón; Prósper, Felipe

    2016-08-26

    Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial. A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 10(6) or 100 × 10(6) cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p < 0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly. The single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a

  3. STEM, STEM Education, STEMmania

    ERIC Educational Resources Information Center

    Sanders, Mark

    2009-01-01

    In this article, the author introduces integrative STEM (science, technology, engineering, and/or mathematics) education and discusses the importance of the program. The notion of integrative STEM education includes approaches that explore teaching and learning between/among any two or more of the STEM subject areas, and/or between a STEM subject…

  4. Successful Treatment of a Left Main Thrombus by Intracoronary Eptifibatide Infusion in a 36-Year-Old Patient

    PubMed Central

    Alipour-Parsa, Saeed; Farahani, Elham

    2016-01-01

    The acute coronary syndrome due to the left main coronary artery (LMCA) thrombosis is a clinically rare and catastrophic event. We describe a young man (smoker, alcoholic, and drug abuser) with a history of recent surgery and typical chest pain who had non-occlusive LMCA thrombosis in coronary angiography. The thrombosis was successfully treated with two 180 µ/kg intracoronary boluses of eptifibatide, which was continued through an intravenous infusion at 2 µ/kg/min for 48 hours postprocedurally. Control angiography, performed 3 days later, revealed that the LMCA was free of thrombosis. The patient had no complaints, including chest pain, and remained completely asymptomatic during the next 30 days' follow-up. PMID:27956914

  5. Distal administration of very high doses of intracoronary adenosine for the treatment of resistant no-reflow

    PubMed Central

    Movahed, Mohammad-Reza; Baweja, Gurpreet

    2008-01-01

    No-reflow is a serious condition, and is associated with substantial morbidity and mortality after percutaneous coronary intervention. The most feared complication of no-reflow is a case of no-reflow that is resistant to multiple drug therapy. This condition usually occurs in patients with distal coronary disease or high thrombus burden. In the present case, a patient with resistant no-reflow that could be reversed by distal intracoronary administration of very high doses of adenosine (1 mg) is described. Administration of very high doses of adenosine via a balloon catheter was safe and did not cause any changes in the heart rate or blood pressure. The present case is the first to be reported in the literature. PMID:19343130

  6. Modulation of protein expression and activity by radiation: Relevance to intracoronary radiation for the prevention of restenosis

    SciTech Connect

    Vodovotz, Yoram; Mitchell, James B.; Lucia, M. Scott; McKinney, Leslie; Kollum, Marc; Cottin, Yves; Chan, Rosanna C.; Barcellos-Hoff, Mary Helen; Waksman, Ron

    2001-08-25

    Restenosis is a common complication of percutaneous transluminal coronary angioplasty. Recent studies have demonstrated a striking reduction in the neointimal hyperplasia characteristic of restenosis following intracoronary radiation (IR), but the mechanisms by which radiation reduces neointima formation following balloon overstretch injury are not elucidated fully. In addition to direct antimitotic effects mediated via oxygen free radicals, ionizing radiation can induce the expression of numerous genes and thereby mediate indirect effects. Additionally, IR prevents restenosis at the cost of decreased healing and increased thrombosis, and we suggest that these adverse reactions can be modulated by adjunct pharmacology or gene-based strategies. This review discusses several genes and proteins modulated by radiation in the context of arterial injury, and their possible therapeutic relevance.

  7. Normal coronary flow reserve after arterial switch operation for transposition of the great arteries: an intracoronary Doppler guidewire study.

    PubMed

    Oskarsson, Gylfi; Pesonen, Erkki; Munkhammar, Peter; Sandström, Staffan; Jögi, Peeter

    2002-09-24

    Recent studies performed with positron emission tomography have suggested that coronary flow reserve (CFR) is moderately to severely reduced after the arterial switch operation (ASO). These findings are of great concern but have not been confirmed by other methods. Eleven symptom-free children were studied between 4 and 11 (median 6.0) years after the ASO. Flow velocity in the left anterior descending (LAD) and right coronary arteries (RCA) was measured with a 0.014-inch Doppler FloWire (Cardiometrics) before and after intracoronary injection of adenosine (0.5 microg/kg) and nitroglycerin (5 microg/kg). CFR was defined as the ratio of hyperemic to basal average peak velocity (APV). The median (range) CFR in the LAD was 3.7 (3.0 to 4.8) and 3.4 (2.9 to 4.8) in the RCA. The increase in APV after intracoronary injection of nitroglycerin was 300% (240% to 420%) in the LAD and 260% (190% to 460%) in the RCA. APV at rest was 15.0 (14.0 to 21.0) cm/s in the LAD and 16.0 (9.6 to 30.0) cm/s in the RCA. A linear relation was found between right ventricular systolic pressure and resting APV in the RCA (r=0.77, P=0.0056), and between resting APV and CFR (r=-0.61, P<0.05) in the RCA. The CFR and coronary vasoreactivity to nitroglycerin in children treated for transposition of the great arteries with the ASO was within normal limits. Increased right ventricular pressure and myocardial hypertrophy can cause increased resting coronary flow velocity in the RCA and affect CFR negatively.

  8. Pooled Analysis Comparing the Efficacy of Intracoronary Versus Intravenous Abciximab in Smokers Versus Nonsmokers Undergoing Primary Percutaneous Coronary Revascularization for Acute ST-Elevation Myocardial Infarction.

    PubMed

    Piccolo, Raffaele; Galasso, Gennaro; Eitel, Ingo; Dominguez-Rodriguez, Alberto; Iversen, Allan Zeeberg; Gu, Youlan L; Abreu-Gonzalez, Pedro; de Smet, Bart J G L; Esposito, Giovanni; Windecker, Stephan; Thiele, Holger; Piscione, Federico

    2016-12-15

    Cigarette smokers with ST-segment elevation myocardial infarction (STEMI) may present different response to potent antithrombotic therapy compared to nonsmokers. We assessed the impact of smoking status and intracoronary abciximab in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). We pooled data from 5 randomized trials comparing intracoronary versus intravenous abciximab bolus in patients undergoing primary PCI. The primary end point was the composite of death or reinfarction at a mean follow-up of 292 ± 138 days. Of 3,158 participants, 1,369 (43.3%) were smokers, and they had a lower risk of the primary end point in crude, but not in adjusted analyses (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.63 to 1.21, p = 0.405). Intracoronary versus intravenous abciximab was associated with a significant reduction in the risk of primary end point among smokers (3.6% vs 8.0%; HR 0.43, 95% CI 0.26 to 0.72, p = 0.001), but not in nonsmokers (10.2% vs 9.9%; HR 0.99, 95% CI 0.72 to 1.36, p = 0.96), with a significant interaction (p = 0.009). Furthermore, intracoronary abciximab decreased the risk of reinfarction in smokers (HR 0.30, 95% CI 0.15 to 0.62, p = 0.001), with no difference in nonsmokers (HR 1.20, 95% CI 0.71 to 2.01, p = 0.50). Stent thrombosis was lowered by intracoronary abciximab in smokers (HR 0.28, 95% CI 0.06 to 0.66, p = 0.009), but was ineffective in nonsmokers (HR 1.04, 95% CI 0.54 to 2.00, p = 0.903). Interaction testing showed heterogeneity in treatment effect for reinfarction (p = 0.002) and stent thrombosis (p = 0.018) according to smoking status. In conclusion, among patients with STEMI undergoing primary PCI, smoking status did not affect the adjusted risk of clinical events. Intracoronary abciximab bolus improved clinical outcomes by reducing the risk of death or reinfarction.

  9. Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

    PubMed

    Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

    2014-01-01

    Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM. © 2014 S. Karger AG, Basel

  10. Stem Cells

    MedlinePlus

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  11. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.

    PubMed

    Schroeder, Thomas; Rachlis, Elena; Bug, Gesine; Stelljes, Matthias; Klein, Stefan; Steckel, Nina Kristin; Wolf, Dominik; Ringhoffer, Mark; Czibere, Akos; Nachtkamp, Kathrin; Dienst, Ariane; Kondakci, Mustafa; Stadler, Michael; Platzbecker, Uwe; Uharek, Lutz; Luft, Thomas; Fenk, Roland; Germing, Ulrich; Bornhäuser, Martin; Kröger, Nicolaus; Beelen, Dietrich W; Haas, Rainer; Kobbe, Guido

    2015-04-01

    To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

  12. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

    PubMed

    Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

    2016-05-01

    Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

  13. Intramyocardial Injection of Stem Cells in Pig Myocardial Infarction Model: The First Trial in Korea.

    PubMed

    Kim, Min Chul; Kim, Yong Sook; Kang, Wan Seok; Lee, Ki Hong; Cho, Meeyoung; Hong, Moon Hwa; Lim, Kyung Seob; Jeong, Myung Ho; Ahn, Youngkeun

    2017-10-01

    Although cell therapy is emerged for cardiac repair, its efficacy is modest by intracoronary infusion. Therefore, we established the intramyocardial delivery technique using a left ventricular (LV) mapping system (NOGA® XP) using 18 pigs. After adipose tissue-derived mesenchymal stem cells (ATSCs) were delivered intramyocardially to porcine infarcted heart, LV ejection fraction (EF) was increased, and LV chamber size was decreased. We proved the therapeutic effect of intramyocardial injection of ATSC through a LV mapping system in the porcine model for the first time in Korea. The adoption of this technique may accelerate the translation into a clinical application in the near future. © 2017 The Korean Academy of Medical Sciences.

  14. Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Prevention and Treatment of Invasive Fungal Disease in Recipients of Allogeneic Stem-Cell Transplantation: A Prospective Multicenter Randomized Phase IV Trial.

    PubMed

    Wan, Liping; Zhang, Yicheng; Lai, Yongrong; Jiang, Ming; Song, Yongping; Zhou, Jianfeng; Zhang, Zhongming; Duan, Xianlin; Fu, Yuewen; Liao, Lianming; Wang, Chun

    2015-12-01

    For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD). We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 μg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 μg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 μg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 10(9)/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment. For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients. For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality. © 2015 by American Society of Clinical Oncology.

  15. The Role of Intracoronary Plaque Imaging with Intravascular Ultrasound, Optical Coherence Tomography, and Near-Infrared Spectroscopy in Patients with Coronary Artery Disease.

    PubMed

    Hoang, Vu; Grounds, Jill; Pham, Don; Virani, Salim; Hamzeh, Ihab; Qureshi, Athar Mahmood; Lakkis, Nasser; Alam, Mahboob

    2016-09-01

    The development of multiple diagnostic intracoronary imaging modalities has increased our understanding of coronary atherosclerotic disease. These imaging modalities, intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), have provided a method to study plaques and introduced the concept of plaque vulnerability. They are being increasingly used for percutaneous coronary intervention (PCI) optimization and are invaluable tools in research studying the pathophysiology of acute coronary syndrome (ACS), in-stent thrombosis and in-stent restenosis. IVUS has the ability to visualize the intracoronary lumen and the vessel wall and can be used to detect early atherosclerotic disease even in the setting of positive arterial remodeling. Studies supporting the use of IVUS to optimize stent deployment and apposition have shown a significant reduction in cardiovascular events. OCT provides even higher resolution imaging and near microscopic detail of plaques, restenoses, and thromboses; thus, it can identify the etiology of ACS. Ongoing trials are evaluating the role of OCT in PCI and using OCT to study stent endothelialization and neointimal proliferation. NIRS is a modality capable of localizing and quantifying lipid core burden. It is usually combined with IVUS and is used to characterize plaque composition. The benefits of NIRS in the setting of ACS have been limited to case reports and series. The utilization of all these intracoronary imaging modalities will continue to expand as their indications for clinical use and research grow. Studies to support their use for PCI optimization resulting in improved outcomes with potential to prevent downstream events are ongoing.

  16. Evaluating the Effect of Intracoronary N-Acetylcysteine on Platelet Activation Markers After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction.

    PubMed

    Eshraghi, Azadeh; Talasaz, Azita Hajhossein; Salamzadeh, Jamshid; Salarifar, Mojtaba; Pourhosseini, Hamidreza; Nozari, Yones; Bahremand, Mostafa; Jalali, Arash; Boroumand, Mohammad Ali

    2016-01-01

    During percutaneous coronary intervention (PCI), trauma occurs in the arterial endothelium, resulting in platelet activation and aggregation. As platelet aggregation may lead to coronary thrombosis, antiplatelet agents are essential adjunctive therapies in patients undergoing PCI. The aim of this study was to determine the effect of the intracoronary administration of high-dose N-acetylcysteine (NAC) for the evaluation of its antiplatelet effects in human subjects. In this triple-blind trial, 147 patients undergoing primary PCI were enrolled. Finally, 100 patients were randomized to receive high-dose intracoronary NAC (100 mg/kg bolus, followed by 10 mg·kg⁻¹·h⁻¹ intracoronary continued intravenously for 12 hours) (n = 50) or dextrose solution (n = 50). Platelet activation biomarkers were measured before and 24 hours after the procedure. Secondary end points, comprising all-cause death, reinfarction, and target-vessel revascularization, were assessed at 30 days and 2 years. In comparison with the placebo, NAC could not reduce the level of platelet activation biomarkers within a 24-hour period after its prescription. Major adverse clinical events at 30 days and 2 years were infrequent and not statistically different between the 2 groups. Our results revealed that NAC, compared with the placebo, did not provide an additional clinical benefit as an effective antiplatelet agent after PCI.

  17. Stem cell therapy for the treatment of myocardial infarction.

    PubMed

    Dauwe, D F; Janssens, S P

    2011-10-01

    Despite timely reperfusion and subsequent optimal postinfarct pharmacotherapy and device-based treatment, the outcome in patients with severe myocardial infarction remains unfavourable. Myocardial salvage is incomplete, resulting in adverse left ventricular remodeling with concomitant morbidity and mortality. The combined risk of recurrent myocardial infarction, death or readmission for heart failure amounts to 25 % within the first year, highlighting the need for additional treatment strategies. Recent and rapidly evolving insights in cardiac biology, recognizing endogenous repair capabilities of the adult human heart, paved the path towards progenitor or stem cell based cardiac protection and repair strategies following ischemic injury. We critically report on the major randomized controlled clinical trials published so far concerning intracoronary transfer of autologous bone marrow cells in the setting of acute myocardial infarction. Moreover, underlying mechanisms, practical aspects, remaining questions and future challenges are highlighted. Taken together, these trials confirm the safety and feasibility of intracoronary progenitor cell transfer in the setting of myocardial infarction. Efficacy data suggests its potential to improve left ventricular function recovery beyond current state of the art therapy, but results are mixed, modest at best and do not support true cardiomyogenesis. Hence, due to its complexity, costs and remaining uncertainties, it is still too early to implement progenitor cell therapy in its current form in standard treatment strategies for ischemic heart disease. Future studies on strategies for cardiomyocyte regeneration in combination with myocardial protection are needed.

  18. Cell Size Critically Determines Initial Retention of Bone Marrow Mononuclear Cells in the Heart after Intracoronary Injection: Evidence from a Rat Model.

    PubMed

    Campbell, Niall G; Kaneko, Masahiro; Shintani, Yasunori; Narita, Takuya; Sawhney, Vinit; Coppen, Steven R; Yashiro, Kenta; Mathur, Anthony; Suzuki, Ken

    2016-01-01

    Intracoronary injection of bone marrow mononuclear cells (BMMNC) is an emerging treatment for heart failure. Initial donor cell retention in the heart is the key to the success of this approach, but this process remains insufficiently characterized. Although it is assumed that cell size of injected cells may influence their initial retention, no scientific evidence has been reported. We developed a unique model utilizing an ex-vivo rat heart perfusion system, enabling quantitative assessment of retention of donor cells after intracoronary injection. The initial (5 minutes after intracoronary injection) retention rate of BMMNC was as low as approximately 20% irrespective of donor cell doses injected (1×106, 8×106, 4×107). Quantitative cell-size assessment revealed a positive relationship between the size of BMMNC and retention ratio; larger subpopulations of BMMNC were more preferentially retained compared to smaller ones. Furthermore, a larger cell type-bone marrow-derived mesenchymal stromal cells (median size = 11.5μm versus 7.0μm for BMMNC)-had a markedly increased retention rate (77.5±1.8%). A positive relationship between the cell size and retention ratio was also seen in mesenchymal stromal cells. Flow-cytometric studies showed expression of cell-surface proteins, including integrins and selectin-ligands, was unchanged between pre-injection BMMNC and those exited from the heart, suggesting that biochemical interaction between donor cells and host coronary endothelium is not critical for BMMNC retention. Histological analyses showed that retained BMMNC and mesenchymal stromal cells were entrapped in the coronary vasculature and did not extravasate by 60 minutes after transplantation. Whilst BMMNC did not change coronary flow after intracoronary injection, mesenchymal stromal cells reduced it, suggesting coronary embolism, which was supported by the histological finding of intravascular cell-clump formation. These data indicate that cell-size dependent

  19. Route of Delivery Modulates the Efficacy of Mesenchymal Stem Cell Therapy for Myocardial Infarction: A Meta-Analysis of Preclinical Studies and Clinical Trials.

    PubMed

    Kanelidis, Anthony J; Premer, Courtney; Lopez, Juan; Balkan, Wayne; Hare, Joshua M

    2017-03-31

    Accumulating data support a therapeutic role for mesenchymal stem cell (MSC) therapy; however, there is no consensus on the optimal route of delivery. We tested the hypothesis that the route of MSC delivery influences the reduction in infarct size and improvement in left ventricular ejection fraction (LVEF). We performed a meta-analysis investigating the effect of MSC therapy in acute myocardial infarction (AMI) and chronic ischemic cardiomyopathy preclinical studies (58 studies; n=1165 mouse, rat, swine) which revealed a reduction in infarct size and improvement of LVEF in all animal models. Route of delivery was analyzed in AMI swine studies and clinical trials (6 clinical trials; n=334 patients). In AMI swine studies, transendocardial stem cell injection reduced infarct size (n=49, 9.4% reduction; 95% confidence interval, -15.9 to -3.0), whereas direct intramyocardial injection, intravenous infusion, and intracoronary infusion indicated no improvement. Similarly, transendocardial stem cell injection improved LVEF (n=65, 9.1% increase; 95% confidence interval, 3.7 to 14.5), as did direct intramyocardial injection and intravenous infusion, whereas intracoronary infusion demonstrated no improvement. In humans, changes of LVEF paralleled these results, with transendocardial stem cell injection improving LVEF (n=46, 7.0% increase; 95% confidence interval, 2.7 to 11.3), as did intravenous infusion, but again intracoronary infusion demonstrating no improvement. MSC therapy improves cardiac function in animal models of both AMI and chronic ischemic cardiomyopathy. The route of delivery seems to play a role in modulating the efficacy of MSC therapy in AMI swine studies and clinical trials, suggesting the superiority of transendocardial stem cell injection because of its reduction in infarct size and improvement of LVEF, which has important implications for the design of future studies. © 2016 American Heart Association, Inc.

  20. Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs.

    PubMed

    Grossini, Elena; Raina, Giulia; Farruggio, Serena; Camillo, Lara; Molinari, Claudio; Mary, David; Walker, Gillian Elisabeth; Bona, Gianni; Vacca, Giovanni; Moia, Stefania; Prodam, Flavia; Surico, Daniela

    2016-06-01

    Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies. In 20 anesthetized pigs, intracoronary 100 pmol/mL DAG infusion with a constant heart rate and aortic blood pressure, increased coronary blood flow and NO release, whereas reducing coronary vascular resistances (P < .05). Dose responses to DAG were evaluated in five pigs. No effects on cardiac contractility/relaxation or myocardial oxygen consumption were observed. Moreover, whereas the blockade of muscarinic cholinoceptors (n = 5) or α- and β-adrenoceptors (n = 5 each) did not abolish the observed responses, NO synthase inhibition (n = 5) prevented the effects of DAG on coronary blood flow and NO release. In coronary artery endothelial cells, DAG dose dependently increased NO release through cAMP signaling and ERK1/2, Akt, and p38 MAPK involvement as well as the phosphorylation of endothelial NO synthase. In conclusion, in anesthetized pigs, DAG primarily increased cardiac perfusion through the involvement of NO release. Moreover, the phosphorylation of ERK1/2 and Akt appears to play roles in eliciting the observed NO production in coronary artery endothelial cells.

  1. Beneficial effects of intracoronary thrombolysis up to eighteen hours after onset of pain in evolving myocardial infarction

    SciTech Connect

    Smalling, R.W.; Fuentes, F.; Freund, G.C.; Reduto, L.A.; Wanta-Matthews, M.; Gaeta, J.M.; Walker, W.; Sterling, R.; Gould, K.L.

    1982-10-01

    Coronary arteriography and intracoronary streptokinase (STK) infusion were performed on 89 patients with evolving acute myocardial infarction (AMI). Ventricular function was followed in these patients during their hospitalization by gated radionuclide ventriculography. In 35 of these patients thallium imaging was performed on admission and 4 hours after reperfusion. An additional 30 patients with AMI who either met exclusion criteria for the STK protocol or refused study served as a control group. In patients admitted 0 to 6, 6 to 12, or 12 to 18 hours after onset of pain, there was no difference in change in left ventricular ejection fraction (LVEF) from admission to discharge, in percent of patients with total occlusion demonstrating reperfusion, or in percent of patients demonstrating a significant increase in LVEF. The average increase in LVEF from admission to discharge in patients reperfused ws 8% (40% +/- 14% to 48% +/- 13%, p less than 0.001). No change in LVEF was demonstrated in the control population or in patients in whom coronary reperfusion was unsuccessful. Reperfusion produced an increase in thallium uptake in the infarct-related myocardium that was accompanied by an improvement in regional function. Failure of reperfusion produced no change in either thallium uptake or regional function.

  2. Recanalization characteristics of intracoronary streptokinase compared to intravenous tissue plasminogen activator following acute myocardial infarction: a community hospital experience.

    PubMed

    Ramos, R S; Salem, B I; Gowda, S; Haikal, M; Coordes, C; Leidenfrost, R

    1995-09-01

    This study compares the recanalization characteristics of intracoronary streptokinase (IC-SK) with those of intravenous tissue plasminogen activator (t-PA) in patients with acute myocardial infarction (AMI) treated in the first 6 hours after onset of symptoms. We studied 263 patients with AMI. Among these, 160 were treated with IC-SK; in 59 the drug was given within the first 3 hours and in 101 from 3 to 6 hours. Another 103 patients were treated with IV t-PA; in 64 the drug was given in the first 3 hours and in 39 within 3 to 6 hours. The recanalization rate in the IC-SK group at 0 to 3 hours was 73% and at 3 to 6 hours was 71%, with an overall recanalization rate of 72% from 0 to 6 hours. In the t-PA group, the recanalization rate at 0 to 3 hours was 72% and at 3 to 6 hours was 46%, with an overall recanalization rate of 62%. We conclude that during the first 6 hours of AMI, IC-SK treatment resulted in a rather steady thrombolysis rate, while t-PA treatment with the standard regimen produced a significant decline in recanalization when administered after 3 hours from the onset of AMI symptoms.

  3. New method for placement of intracoronary stents in order to avoid their embolization in the intravascular space.

    PubMed

    Rokas, S G; Antonellis, I P; Patsilinakos, S P; Agrios, N; Pamboukas, C A; Kranidis, A J; Margaris, N G; Bonou, M; Tsilias, K; Kostopoulos, K G; Tavernarakis, A G; Stamatelopoulos, S F

    1998-10-01

    Stent dislodgment from the delivery catheter is a well-known complication of angioplasty with stent implantation. The aim of our study was to investigate the feasibility, effectiveness, and safety of a new technique of intracoronary stent implantation in order to avoid stent loss in the intravascular space. Fifty consecutive patients were candidates for angioplasty and stent placement. During angioplasty, a technique was followed according to which the guide wire "hindered" the dislodgment of the stent from the balloon catheter. Successful angioplasty and stent placement were performed in 46 out of 50 patients (92% success rate). In three cases of failure of stent implantation, the stent moved onto the balloon catheter; however, this was impeded by the guide wire. One non-Q-wave myocardial infarction occurred. No major complications (Q-wave myocardial infarction, CABG, or death) were observed. In conclusion, the technique applied was feasible enough, safe, and effective. However, the appropriate modification of its "hardware" will render it even more feasible and user-friendly.

  4. Inadvertent intracoronary stent extraction 10 months after implantation complicating cutting balloon angioplasty for in-stent restenosis

    SciTech Connect

    Almeda, Francis Q.; Billhardt, Roger A

    2003-09-01

    We report the case of an unusual complication for Cutting Balloon Angioplasty (CBA) during treatment for instent restenosis (ISR), which resulted in inadvertent intracoronary stent extraction 10 months after implantation. In this case report, CBA was utilized to treat an ISR lesion in the distal right coronary artery (RCA). Due to difficulty in withdrawing the cutting balloon into the guide after treatment of the lesion, the entire system (guide, cutting balloon, and guidewire) was removed as a unit from the body. Upon examination of the system, the previously placed stent in the distal RCA was attached to the microtomes of the cutting balloon. Although the precise mechanisms for stent extraction in this case remain speculative, the initial stent used in the distal RCA may have been undersized, and this may have played a major role in this complication. Although there is limited data regarding the optimal strategy to treat the site of the inadvertent stent extraction, we opted to re-stent the area with a properly-sized coronary stent. Following the intervention, there was no residual stenosis with TIMI 3 flow through the vessel. The patient remained asymptomatic and a serum troponin drawn 18 hours after the procedure was normal, and he was discharged the next day. The interventionist must be vigilant about this rare but serious complication when applying CBA in the treatment of ISR, particularly when an undersized or underdeployed stent is suspected.

  5. Intracoronary brachytherapy following drug-eluting stent failure It's still not time to hang up the spikes{exclamation_point}

    SciTech Connect

    Angiolillo, Dominick J.; Sabate, Manel; Jimenez-Quevedo, Pilar; Alfonso, Fernando; Galvan, Carmen; Fernandez, Jose Miguel; Hernandez-Antolin, Rosana; Escaned, Javier; Banuelos, Camino; Moreno, Raul; Macaya, Carlos

    2003-12-01

    Drug-eluting stents (DES) have significantly reduced the incidence of restenosis. Although the results obtained with these novel antiproliferative devices are encouraging, recent reports have shown that DES are not completely immune from restenosis. Therefore, the broad use of DES has inevitably led to a major issue: treatment of DES failure. Intracoronary brachytherapy (IBT) represents an important advancement for treatment of in-stent restenosis (ISR) and has led to important pathophysiological insight on the restenotic process. To date, IBT, when properly used, still represents the gold standard for treatment of ISR. However, experience with IBT is for treatment of ISR occurring with bare metal stents (BMS). Whether IBT may be used with the same safety and efficacy profile as an adjunctive treatment for ISR following DES implantation is still unknown. In this article, we report the outcome of a series of patients with DES failure treated with IBT. IBT for treatment of DES failure was shown to be both safe and efficient and, therefore, until ISR exists, IBT still remains an important player in this growing and even more challenging setting.

  6. [The effect on myocardial perfusion and clinical outcome of intracoronary nicorandil injection prior to percutaneous coronary intervention in ST-segment elevation myocardial infarction].

    PubMed

    Wang, Z Q; Chen, M X; Liu, D L; Zheng, W X; Cao, X Z; Chen, H; Huang, M F; Luo, Z R

    2017-01-25

    Objective: To investigate the effect of intracoronary administration of nicorandil prior to primary percutaneous coronary intervention (PPCI) on myocardial perfusion and short-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 158 patients with STEMI undergoing PPCI from January 2014 to December 2015 in Fuzhou General Hospital were enrolled consecutively in this prospective controlled randomized trial. Patients were assigned into three groups with random number table: the nicorandil group (patients received intracoronary administration of 6 mg nicorandil after guide wire or balloon successfully crossed the target lesion, n=53), the nitroglycerin group (patients received intracoronary administration of 300 μg nitroglycerin after after guide wire or balloon successfully crossed the target lesion, n=52) and the control group(patients received routine treatment, n=53). The primary outcomes were myocardial perfusion, including the levels of corrected TIMI frame count (cTFC), and the incidence of no reflow or slow flow after PPCI. The secondary outcomes included the incidence of major adverse cardiovascular events (MACE) during hospitalization (all-cause death, reperfusion arrhythmia within 2 hours after PPCI, angina within 24 hours after PPCI, new heart failure or worsening cardiac function, and repeat revascularization) and within 3 months of follow-up (all-cause death, nonfatal myocardial infarction, repeat revascularization, post-infarction angina, and re-hospitalization for congestive heart failure). Results: The age of enrolled patients was (62.9±11.3) years old, and 130 cases (82.3%) of them were male. The median time of symptom-onset to balloon was 4.50 (3.20, 6.43) hours. There were significantly difference in cTFC immediately after PPCI((21.68±7.43)frames, (24.74±8.66)frames, and(27.06±10.40)frames), incidence of no reflow or slow flow after PPCI(5.7%(3/53), 13.5%(7/52), and 22.6%(12/53)), ST

  7. Intracoronary genistein acutely increases coronary blood flow in anesthetized pigs through beta-adrenergic mediated nitric oxide release and estrogenic receptors.

    PubMed

    Grossini, Elena; Molinari, Claudio; Mary, David A S G; Uberti, Francesca; Caimmi, Philippe Primo; Surico, Nicola; Vacca, Giovanni

    2008-05-01

    Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and alpha-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of beta(2)-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary N(omega)-nitro-L-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERalpha/ERbeta; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERalpha/ERbeta and the release of NO through vasodilatory beta(2)-adrenoreceptor effects.

  8. Impact of accuracy of fractional flow reserve to reduction of microvascular resistance after intracoronary adenosine in patients with angina pectoris or non-ST-segment elevation myocardial infarction.

    PubMed

    Niccoli, Giampaolo; Falcioni, Elena; Cosentino, Nicola; Fracassi, Francesco; Roberto, Marco; Fabretti, Alessandro; Panebianco, Mario; Scalone, Giancarla; Burzotta, Francesco; Trani, Carlo; Leone, Antonio Maria; Davies, Justin; Crea, Filippo

    2014-05-01

    Our study aimed to elucidate mechanisms underlying discordance between fractional flow reserve (FFR) and hyperemic stenosis resistance (hSR) in some patient subsets. To do this, we enrolled 30 consecutive patients with stable angina or non-ST elevation myocardial infarction (non-STEMI) and with a nonculprit intermediate coronary lesion (40% to 70%) by coronary angiography. We measured aortic pressure, flow velocity, and pressure distal to lesion simultaneously at basal level and during adenosine-induced (fixed intracoronary dose of 120 μg) hyperemia using a dual-sensor-equipped guidewire. Microvascular resistance (MR; pressure distal to lesion/flow velocity, mm Hg/cm/s) and variation (Δ) in MR levels were calculated both at baseline and after hyperemia, whereas FFR (cutoff <0.80) and hSR [(aortic pressure - pressure distal to lesion)/flow velocity, cutoff >0.80 mm Hg/cm/s] were assessed after intracoronary adenosine. Twenty-three patients (76.7%) showed concordance and 7 patients (23.3%) showed discordance between FFR and hSR (all cases with FFR >0.80 and hSR >0.80). Discordant patients presented more frequently with non-STEMI (85.7% vs 39.1%, p = 0.04), significantly higher C-reactive protein serum levels (median [interquartile range] 5.9 [5.1 to 6.8] vs 4.9 [3.7 to 6.2] mg/L, p = 0.007), and lower ΔMR (p = 0.03) values compared with concordant patients. In conclusion, patients with non-STEMI and those with increased C-reactive protein levels show a lower reduction in MR after intracoronary adenosine-induced hyperemia, leading to FFR underestimation.

  9. Intracoronary autologous bone marrow-derived mononuclear cell transplantation improves coronary collateral vessel formation and recruitment capacity in patients with ischemic cardiomyopathy: a combined hemodynamic and scintigraphic approach.

    PubMed

    Tayyareci, Yelda; Sezer, Murat; Umman, Berrin; Besisik, Sevgi; Mudun, Ayse; Sanli, Yasemin; Oncul, Aytac; Gurses, Nuray; Sargin, Deniz; Meric, Mehmet; Nisanci, Yilmaz

    2008-01-01

    This study investigated the effects of intracoronary autologous bone marrow-derived mononuclear cell (BMC) transplantation on coronary microcirculation. Fifteen patients with ischemic cardiomyopathy were treated by intracoronary infusion of BMCs via the patent infarct-related artery. The thermodilution-derived coronary flow reserve, index of microvascular resistance, pressure-derived collateral flow index, and coronary wedge pressure were measured at baseline and at 6 months. Successive balloon inflations during BMC transplantation were performed to observe the recruitment in pressure-derived collateral flow index and coronary wedge pressure, and the percentage changes between baseline and 6 months were calculated. The mean (SD) coronary flow reserve increased from 1.3 (0.4) to 2.1 (0.5), and the mean (SD) index of microvascular resistance decreased from 44.9 (24.4) to 21.2 (14.1) (P = .001 for both). The mean (SD) improvement in pressure-derived collateral flow index (from 0.14 [0.05] to 0.22 [0.08]) was also statistically significant (P = .001). Similarly, the percentage improvements in pressure-derived collateral flow index and coronary wedge pressure were statistically significant (P = .01 for both). The percentage improvement in perfusion assessed by single-photon emission computed tomography strongly correlated with the percentage changes in pressure-derived collateral flow index (r = 0.88, P = .001) and coronary wedge pressure (r = 0.69, P = .01). These results demonstrate for the first time (to our knowledge) that intracoronary autologous BMC transplantation improves coronary collateral vessel formation and recruitment capacity in human subjects.

  10. Diagnostic accuracy of combined intracoronary pressure and flow velocity information during baseline conditions: adenosine-free assessment of functional coronary lesion severity.

    PubMed

    van de Hoef, Tim P; Nolte, Froukje; Damman, Peter; Delewi, Ronak; Bax, Matthijs; Chamuleau, Steven A J; Voskuil, Michiel; Siebes, Maria; Tijssen, Jan G P; Spaan, Jos A E; Piek, Jan J; Meuwissen, Martijn

    2012-08-01

    The assessment of functional coronary lesion severity using intracoronary physiological parameters such as coronary flow velocity reserve and the more widely used fractional flow reserve relies critically on the establishment of maximal hyperemia. We evaluated the diagnostic accuracy of the stenosis resistance index during nonhyperemic conditions, baseline stenosis resistance index, compared with established hyperemic intracoronary hemodynamic parameters, because achievement of hyperemia can be cumbersome in daily clinical practice. A total of 232 patients, including 299 lesions (mean stenosis diameter 55%±11%), underwent myocardial perfusion scintigraphy for documentation of reversible perfusion defects. Distal coronary pressure and flow velocity were assessed with sensor-equipped guidewires during baseline and maximal hyperemia, induced by an intracoronary bolus of adenosine (20-40 µg). We determined stenosis resistance (SR) during baseline and hyperemic conditions as well as fractional flow reserve and coronary flow velocity reserve. The discriminative value for myocardial ischemia on myocardial perfusion scintigraphy of all parameters was compared using receiver-operating-characteristic curves. Baseline SR showed good agreement with myocardial perfusion scintigraphy. The diagnostic performance of baseline SR (area under the curve, 0.77; 95% CI, 0.71-0.83) was as accurate as fractional flow reserve and coronary flow velocity reserve (area under the curve, 0.77; 95% CI, 0.71-0.83 and area under the curve, 0.75; 95% CI, 0.68-0.81 respectively; P>0.05 compared with baseline SR for both). However, hyperemic SR, combining both pressure and flow velocity information during hyperemia, was superior to all other parameters (area under the curve, 0.81; 95% CI, 0.76-0.87; P<0.05 compared with all other parameters). Combined pressure and flow velocity measurements during baseline conditions may provide a useful tool for functional lesion severity assessment without the

  11. Use of the GuideLiner catheter for aspiration thrombectomy in a patient with ST-elevation myocardial infarction with a large intracoronary thrombus.

    PubMed

    Numasawa, Yohei; Motoda, Hiroyuki; Yamazaki, Hiroyuki; Kuno, Toshiki; Kodaira, Masaki; Fujisawa, Taishi

    2016-04-01

    We report a 67-year-old man with ST-elevation myocardial infarction with a large intracoronary thrombus who was successfully treated with percutaneous thrombectomy using the GuideLiner catheter. This catheter is designed for the "Mother and Child" technique with a rapid exchange system and it has a larger internal diameter than conventional aspiration devices. When aspiration thrombectomy using a conventional aspiration catheter is not feasible or fails, use of the GuideLiner catheter for aspiration of thrombus is a reasonable alternative for primary percutaneous coronary intervention in patients with acute myocardial infarction.

  12. Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial.

    PubMed

    Assmus, Birgit; Walter, Dirk H; Seeger, Florian H; Leistner, David M; Steiner, Julia; Ziegler, Ina; Lutz, Andreas; Khaled, Walaa; Klotsche, Jens; Tonn, Torsten; Dimmeler, Stefanie; Zeiher, Andreas M

    2013-04-17

    The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs. To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure. The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011. Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs. Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events. The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, -0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, -1.2% to 2.1%]) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group

  13. Euclidean supergravity and multi-centered solutions

    NASA Astrophysics Data System (ADS)

    Sabra, W. A.

    2017-04-01

    In ungauged supergravity theories, the no-force condition for BPS states implies the existence of stable static multi-centered solutions. The first solutions to Einstein-Maxwell theory with a positive cosmological constant describing an arbitrary number of charged black holes were found by Kastor and Traschen. Generalisations to five and higher dimensional theories were obtained by London. Multi-centered solutions in gauged supergravity, even with time-dependence allowed, have yet to be constructed. In this letter we construct supersymmetry-preserving multi-centered solutions for the case of D = 5, N = 2 Euclidean gauged supergravity coupled to an arbitrary number of vector multiplets. Higher dimensional Einstein-Maxwell multi-centered solutions are also presented.

  14. Intracoronary secretin increases cardiac perfusion and function in anaesthetized pigs through pathways involving β-adrenoceptors and nitric oxide.

    PubMed

    Grossini, Elena; Molinari, Claudio; Morsanuto, Vera; Mary, David A S G; Vacca, Giovanni

    2013-05-01

    Secretin has been implicated in cardiovascular regulation through its specific receptors, as well as through β-adrenoceptors and nitric oxide, although data on its direct effect on coronary blood flow and cardiac function have remained scarce. The present study aimed to determine the primary in vivo effect of secretin on cardiac function and perfusion and the mechanisms related to the autonomic nervous system, secretin receptors and NO. In addition, in coronary endothelial cells the intracellular pathways involved in the effects of secretin on NO release were also examined. In 30 pigs, intracoronary secretin infusion at 2.97 pg for each millilitre per minute of coronary blood flow at constant heart rate and aortic blood pressure increased coronary blood flow, maximal rate of change of left ventricular pressure, segmental shortening, cardiac output and coronary NO release (P<0.05). These responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoreceptors (n=5) and of α-adrenoceptors (n=5) did not abolish the observed responses to secretin, blockade of β1-adrenoceptors (n=5) prevented the effects of secretin on cardiac function. In addition, blockade of β2-adrenoceptors (n=5) and NO synthase inhibition (n=5) prevented the coronary response and the effect of secretin on NO release. All these effects were abolished by a secretin receptor inhibitor (n=5). In coronary endothelial cells, the increased NO production caused by secretin was found to be related to cAMP/protein kinase A signalling activated as downstream effectors of stimulation of secretin receptors and β2-adrenoceptors. In conclusion, in anaesthetized pigs secretin primarily increased cardiac function and perfusion through the involvement of specific receptors, β-adrenoceptors and NO release.

  15. Transvenous intramyocardial cellular delivery increases retention in comparison to intracoronary delivery in a porcine model of acute myocardial infarction.

    PubMed

    George, Jon C; Goldberg, Jonathan; Joseph, Matthew; Abdulhameed, Nasreen; Crist, Joshua; Das, Hiranmoy; Pompili, Vincent J

    2008-10-01

    Clinical trials using intracoronary (IC) delivery of cells have addressed efficacy but the optimal delivery technique is unknown. Our study aimed to determine whether transvenous intramyocardial (TVIM) approach was advantageous for cellular retention in AMI. Domestic pigs (n = 4) underwent catheterization with coronary angiography and ventriculography prior to infarction and pre- and post-cells. Pigs underwent 90-minute balloon occlusion of the left anterior descending artery (LAD). After one week they were prepared for IC (n = 2) or TVIM (n = 2) delivery of bone marrow mononuclear cells (MNC) labeled with GFP. IC infusion used an over-the-wire catheter to engage the LAD and balloon inflation to prevent retrograde flow. Venography via the coronary sinus was used for TVIM delivery. The anterior interventricular vein was engaged with a guidewire allowing use of the TransAccess catheter that is outfitted with an ultrasound tip for visualization. Animals were sacrificed one hour after delivery and tissue was analyzed. Procedures were performed without complication and monitoring was uneventful. 1 x 10(8) MNC were isolated from each bone marrow (BM) preparation and 1 x 10(7) MNC delivered. Ventriculography at one week revealed wall motion abnormalities consistent with an anterior AMI. TVIM and IC delivery revealed mean 452 cells per section and 235 cells per section on average, respectively, in the infarct zone (P = 0.01). We have demonstrated that TVIM approach for cell delivery is feasible and safe. Moreover, this approach may provide an advantage over IC infusion in retention of the cellular product; however, larger studies will be necessary.

  16. Transvenous Intramyocardial Cellular Delivery Increases Retention in Comparison to Intracoronary Delivery in a Porcine Model of Acute Myocardial Infarction

    PubMed Central

    George, Jon C.; Goldberg, Jonathan; Joseph, Matthew; Abdulhameed, Nasreen; Crist, Joshua; Das, Hiranmoy; Pompili, Vincent J.

    2015-01-01

    Background Clinical trials using intracoronary (IC) delivery of cells have addressed efficacy but the optimal delivery technique is unknown. Our study aimed to determine whether transvenous intramyocardial (TVIM) approach was advantageous for cellular retention in AMI. Methods Domestic pigs (n=4) underwent catheterization with coronary angiography and ventriculography prior to infarction and pre- and post-cells. Pigs underwent 90 minute balloon occlusion of the left anterior descending artery (LAD). After one week they were prepared for IC (n=2) or TVIM (n=2) delivery of bone marrow mononuclear cells (MNC) labeled with GFP. IC infusion used an over-the-wire catheter to engage the LAD and balloon inflation to prevent retrograde flow. Venography via the coronary sinus was used for TVIM delivery. The anterior interventricular vein was engaged with a guide wire allowing use of the TransAccess™ catheter, which is outfitted with an ultrasound tip for visualization. Animals were sacrificed one hour after delivery and tissue was analyzed. Results Procedures were performed without complication and monitoring was uneventful. 1 × 108 MNC’s were isolated from each BM preparation and 1 × 107 MNC delivered. Ventriculography at one week revealed wall motion abnormalities consistent with an anterior AMI. TVIM and IC delivery revealed mean 452 cells/section and 235 cells/section on average, respectively in the infarct zone (p = 0.01). Conclusion We have demonstrated that TVIM approach for cell delivery is feasible and safe. Moreover, this approach may provide an advantage over IC infusion in retention of the cellular product, however, larger studies will be necessary. PMID:19012733

  17. Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.

    PubMed

    Hou, Dongming; Youssef, Eyas Al-Shaykh; Brinton, Todd J; Zhang, Ping; Rogers, Pamela; Price, Erik T; Yeung, Alan C; Johnstone, Brian H; Yock, Paul G; March, Keith L

    2005-08-30

    Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

  18. Near-infrared spectroscopy for intracoronary detection of lipid-rich plaques to understand atherosclerotic plaque biology in man and guide clinical therapy.

    PubMed

    Erlinge, D

    2015-08-01

    Ischaemic heart disease is the leading cause of death worldwide. The common denominator for plaques causing acute coronary syndrome (ACS) is lipid accumulation, either as a lipid core or lipid pools. An intracoronary imaging device to detect lipid-rich plaques (LRPs) could therefore identify most of the plaques causing ACS and sudden death. Near-infrared spectroscopy combined with intravascular ultrasound (NIRS-IVUS) is a promising new intracoronary imaging method that is able to specifically quantify lipid accumulation measured as the lipid core burden index (LCBI). NIRS-IVUS is highly specific for the identification of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) culprit plaques usually in the form of a circular LRP. NIRS-IVUS may assist in defining the aetiology of coronary events. The effect of cholesterol-lowering therapy on the lipid core can be measured in coronary plaques in patients, and NIRS-IVUS may be a useful tool for drug development in phase II studies as a surrogate end-point for future ACS. Plaques with a high LCBI have an increased risk of peri-procedural events. NIRS-IVUS can help to define the diameter and length of stents to avoid procedure-related complications. Increased coronary LCBI predicts a higher risk of future cardiovascular events. Lipid core detection using NIRS may help to identify vulnerable plaques to treat them before they cause ACS or sudden death. © 2015 The Association for the Publication of the Journal of Internal Medicine.

  19. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  20. Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

    PubMed Central

    Kahlert, Philipp; Heiss, Christian; Westenfeld, Ralf; Kelm, Malte; Erbel, Raimund; Heusch, Gerd; Kleinbongard, Petra

    2015-01-01

    Objective Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs. Methods In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41+, endothelium-derived MPs (EMPs) as CD144+, CD62E+ and CD31+/CD41-, leukocyte-derived MPs as CD45+, and erythrocyte-derived MPs as CD235+. Results In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41+: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144+: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E+: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs. Conclusion Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs. Trial Registration ClinicalTrials.gov NCT01430884 PMID:25915510

  1. Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5'-triphosphate infusion.

    PubMed

    Takami, Hironori; Sonoda, Shinjo; Muraoka, Yoshitaka; Sanuki, Yoshinori; Kashiyama, Kuninobu; Fukuda, Shota; Oginosawa, Yasushi; Tsuda, Yuki; Araki, Masaru; Otsuji, Yutaka

    2017-01-01

    Fractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5'-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. Patients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180μg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. In this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). Additional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure. Copyright © 2016

  2. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction.

    PubMed

    Okura, Hanayuki; Saga, Ayami; Soeda, Mayumi; Miyagawa, Shigeru; Sawa, Yoshiki; Daimon, Takashi; Ichinose, Akihiro; Matsuyama, Akifumi

    2012-09-07

    Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p=0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac nuclear factors; nkx2.5 and GATA-4. Our results suggest that intracoronary artery transplantation of hCLCs is a potentially effective therapeutic strategy for future cardiac tissue regeneration.

  3. Types of Stem Cells

    MedlinePlus

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  4. Comparison of neointimal hyperplasia with drug-eluting stents versus bare metal stents in patients undergoing intracoronary bone-marrow mononuclear cell transplantation following acute myocardial infarction.

    PubMed

    Villa, Adolfo; Arnold, Roman; Sánchez, Pedro L; Gimeno, Federico; Ramos, Benigno; Cantero, Teresa; Fernández, Maria Eugenia; Sanz, Ricardo; Gutiérrez, Oliver; Mota, Pedro; García-Frade, Javier; San Román, José Alberto; Fernández-Avilés, Francisco

    2009-06-15

    The aims of this study were to assess the safety of drug-eluting stent (DES) use and to compare the incidence of in-stent restenosis (ISR) and neointimal hyperplasia formation according to the type of stent implanted (DES vs bare-metal stents [BMS]) in patients who underwent intracoronary bone marrow mononuclear cell transplantation after acute ST elevation myocardial infarction. Fifty-nine patients with successfully revascularized ST elevation myocardial infarction (37 using BMS and 22 using DES) underwent paired angiographic examinations at baseline and 6 to 9 months after the intracoronary injection of 91 million +/- 56 million autologous bone marrow mononuclear cells. A subgroup of 30 patients also underwent serial intravascular ultrasound examinations. Off-line angiographic assessment showed 4 cases of binary ISR, primarily in BMS (3 cases), and no major adverse cardiac events were associated with stent type (mean follow-up period 41 +/- 10 months). At follow-up, angiographic late luminal loss was significantly lower in patients with DES than in those patients with BMS (0.35 +/- 0.66 vs 0.71 +/- 0.38 mm, p = 0.011). Multivariate analysis identified the use of DES (beta = -0.32, 95% confidence interval [CI] -0.57 to -0.26, p = 0.03) and a smaller baseline reference vessel diameter (beta = 0.29, 95% CI 0.04 to 0.54, p = 0.02) as independent predictors of lower late loss. Moreover, intravascular ultrasound showed a significant reduction of in-stent neointimal hyperplasia formation related to DES use compared with BMS use (Delta neointimal hyperplasia volume 5.4 mm(3) [95% CI 2.7 to 28.1] vs 35.9 mm(3) [95% CI 22.0 to 43.6], p = 0.035). In conclusion, these findings suggest that the use of DES is safe and may prevent ISR and neointimal hyperplasia formation in patients who undergo intracoronary bone marrow mononuclear cell transplantation after a successfully revascularized ST elevation myocardial infarction.

  5. Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial.

    PubMed

    Ishigami, Shuta; Ohtsuki, Shinichi; Eitoku, Takahiro; Ousaka, Daiki; Kondo, Maiko; Kurita, Yoshihiko; Hirai, Kenta; Fukushima, Yosuke; Baba, Kenji; Goto, Takuya; Horio, Naohiro; Kobayashi, Junko; Kuroko, Yosuke; Kotani, Yasuhiro; Arai, Sadahiko; Iwasaki, Tatsuo; Sato, Shuhei; Kasahara, Shingo; Sano, Shunji; Oh, Hidemasa

    2017-03-31

    Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. We conducted a phase 2 randomized controlled study to assign in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 2 or 3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P=0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 8.2]; P<0.0001) and volumes (P<0.001), somatic growth (P<0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and quality of life, along with a reduced heart failure status (P<0.0001) and cardiac fibrosis (P=0.014) relative to baseline. Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure

  6. Multicenter Guidelines | Division of Cancer Prevention

    Cancer.gov

    A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

  7. Confirmation of the Intracoronary Near-Infrared Spectroscopy Threshold of Lipid-Rich Plaques That Underlie ST-Segment-Elevation Myocardial Infarction.

    PubMed

    Madder, Ryan D; Puri, Rishi; Muller, James E; Harnek, Jan; Götberg, Matthias; VanOosterhout, Stacie; Chi, Margaret; Wohns, David; McNamara, Richard; Wolski, Kathy; Madden, Sean; Sidharta, Samuel; Andrews, Jordan; Nicholls, Stephen J; Erlinge, David

    2016-05-01

    In a previous exploratory analysis, intracoronary near-infrared spectroscopy (NIRS) found the majority of culprit lesions in ST-segment-elevation myocardial infarction (STEMI) to contain a maximum lipid core burden index in 4 mm (maxLCBI4mm) of >400. This initial study was limited by a small sample size, enrollment at a single center, and post hoc selection of the maxLCBI4mm ≥400 threshold. This study was designed a priori to substantiate the ability of NIRS to discriminate STEMI culprit from nonculprit segments and to confirm the performance of the maxLCBI4mm ≥400 threshold. At 2 centers in the United States and Sweden, 75 STEMI patients underwent intracoronary NIRS imaging after establishing thrombolysis in myocardial infarction 3 flow, but before stenting. Blinded core laboratory analysis defined the culprit segment as the 10-mm segment distal to the proximal angiographic culprit margin. The remaining vessel was divided into contiguous 10-mm nonculprit segments. The maxLCBI4mm of culprit segments (median [interquartile range]: 543 [273-756]) was 4.4-fold greater than nonculprit segments (median [interquartile range]: 123 [0-307]; P<0.001). Receiver-operating characteristic analysis demonstrated that maxLCBI4mm differentiated culprit from nonculprit segments with high accuracy (c-statistic=0.83; P<0.001). A threshold maxLCBI4mm ≥400 identified STEMI culprit segments with a sensitivity of 64% and specificity of 85%. This study substantiates the ability of NIRS to accurately differentiate STEMI culprit from nonculprit segments and confirms that a threshold maxLCBI4mm ≥400 is detected by NIRS in the majority of STEMI culprits. © 2016 American Heart Association, Inc.

  8. Intracoronary beta-radiation for the treatment of patients at very high risk for recurrence of in-stent restenosis: a single center experience.

    PubMed

    Parenti, Dennis Zavalloni; Marsico, Federica; Tosi, Giovanni; Catalano, Gianpiero; Maiello, Luigi; Milone, Francesco; Carcagnì, Addolorata; Pron, Paolo Giay; Orecchia, Roberto; Presbitero, Patrizia

    2003-03-01

    Intracoronary brachytherapy has significantly reduced the recurrence of in-stent restenosis. The aim of this study was to evaluate the feasibility, safety and efficacy of intracoronary beta-radiation in patients at very high risk for recurrence of in-stent restenosis. We analyzed 42 patients with 50 lesions submitted to catheter-based beta-radiation (Beta-Cath System, Novoste Corporation, Norcross, GA, USA) for in-stent restenosis. Thirty-eight lesions were at the second restenosis, 8 at the third, and 4 at the fourth; a diffuse pattern was present in 78%. Balloon angioplasty was performed for 30 lesions (60%) and the cutting balloon technique for 20 (40%). In 12 lesions further 14 stents had to be deployed (28%). The delivery catheter was successfully positioned in 96% of the procedures. The mean dwell time was 179 +/- 50 s with a radiation dose ranging from 18.4 to 25.3 Gy, depending on the vessel size. A complete angiographic success without coronary dissection and without any additional stenting after radiation delivery was achieved in 86%. At follow-up (7.2 +/- 2.1 months), the overall restenosis rate was 30.4% (14 lesions). A recurrence was detected in 1/11 lesions with initial focal pattern and in 13/39 lesions with initial diffuse pattern. The restenosis rate was higher in patients in whom a geographic miss had occurred (p < 0.05 vs lesions without geographic miss) and in those in whom a new stent had been deployed (p < 0.05 vs lesions treated without a stent). Brachytherapy reduces the in-stent restenosis rate in patients who are at very high risk of recurrence. The restenosis pattern, geographic miss and new stent deployment seem to be negative prognostic factors for recurrence of restenosis.

  9. Intracoronary Electrocardiogram to guide Percutaneous Interventions in Coronary Bifurcations: A proof of Concept: The FIESTA (Ffr vs. IcEcgSTA) study.

    PubMed

    Vassilev, Dobrin; Dosev, Liubomir; Collet, Carlos; Karamfiloff, Kiril; Stoikova, Jivka; Pancheva, Ralica; Shumkova, Monika; Zlatancheva, Galina; Naunov, Vladimir; Rigatelli, Gianluca; Kassab, Ghassan S; Gil, Robert J; Serruys, Patrick W

    2017-08-22

    The aim of this study was to determine the accuracy of the intracoronary electrocardiogram (icECG) to detect ischemia during bifurcation lesions percutaneous coronary intervention (PCI) with fractional flow reserve (FFR) as a reference. Patients with significant bifurcation lesions defined as FFR≤0.80 were included. FFR and icECG were performed in the main vessel (MV) and side branch (SB) before and after provisional stenting. icECG was recorded with a uninsulated proximal wire end connected to a unipolar lead. The diagnostic accuracy of icECG for the detection of ischemia in the SB after MV stenting was determined with FFR as a reference. Overall, 37 patients were included. Seventeen bifurcations had SB FFR ≤0.80 after MV stenting and 20 patients had ST-segment elevation on the icECG. There was significant correlation between SB FFR and ST-segment elevation on icECG (r=-0.533, p<0.001). The diagnostic accuracy of icECG ST-Elevation to detect functionally significant SB stenosis revealed an AUC of 0.71 (95%CI 0.64- 0.80) with a sensitivity of 88% and specificity of 75% with a positive predictive value of 75% and negative predictive value of 88%. Neither SB FFR nor icECG correlated with SB percent diameter stenosis after MV stenting. Intracoronary ECG has a good ability to predict functionally significant stenosis at the SB after MV stenting during bifurcation PCI. This method provides a novel strategy to assess the significance of a SB lesion without the need of a pressure wire.

  10. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    SciTech Connect

    Okura, Hanayuki; Saga, Ayami; Soeda, Mayumi; Miyagawa, Shigeru; Sawa, Yoshiki; Daimon, Takashi; Ichinose, Akihiro; Matsuyama, Akifumi

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  11. Stem cells.

    PubMed

    Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

    2010-10-01

    Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.

  12. STEM Sell

    ERIC Educational Resources Information Center

    Pantic, Zorica

    2007-01-01

    Between 1994 and 2003, employment in science, technology, engineering and math (STEM) fields grew by a remarkable 23 percent, compared with 17 percent in non-STEM fields, according to federal data. The Bureau of Labor Statistics predicts continued strong growth in STEM job openings through 2014, with emphasis on life sciences, environmental…

  13. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Lorenzo L. Esters, Vice President, APLU (Association of Public and Land-grant Universities), and Project Director, MMSI (Minority Male STEM Initiative) addresses STEM initiative report findings at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  14. Elliptic genera from multi-centers

    NASA Astrophysics Data System (ADS)

    Gaddam, Nava

    2016-05-01

    I show how elliptic genera for various Calabi-Yau threefolds may be understood from supergravity localization using the quantization of the phase space of certain multi-center configurations. I present a simple procedure that allows for the enumeration of all multi-center configurations contributing to the polar sector of the elliptic genera — explicitly verifying this in the cases of the quintic in {P} 4, the sextic in {W}{P} (2,1,1,1,1), the octic in {W}{P} (4,1,1,1,1) and the dectic in {W}{P} (5,2,1,1,1). With an input of the corresponding `single-center' indices (Donaldson-Thomas invariants), the polar terms have been known to determine the elliptic genera completely. I argue that this multi-center approach to the low-lying spectrum of the elliptic genera is a stepping stone towards an understanding of the exact microscopic states that contribute to supersymmetric single center black hole entropy in {N} = 2 supergravity.

  15. Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy

    PubMed Central

    Pinto, Duane S.; Chi, Gerald; Arbetter, Douglas; Yee, Megan; Mehran, Roxana; Bode, Christoph; Halperin, Jonathan; Verheugt, Freek W.A.; Wildgoose, Peter; Burton, Paul; van Eickels, Martin; Korjian, Serge; Daaboul, Yazan; Jain, Purva; Lip, Gregory Y.H.; Cohen, Marc; Peterson, Eric D.; Fox, Keith A.A.

    2017-01-01

    Background: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. Methods: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. Results: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66–0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62–0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. Conclusions: Among patients with

  16. Enhanced mobilization of the bone marrow–derived circulating progenitor cells by intracoronary freshly isolated bone marrow cells transplantation in patients with acute myocardial infarction

    PubMed Central

    Turan, R G; Bozdag-T, I; Turan, C H; Ortak, J; Akin, I; Kische, S; Schneider, H; Rauchhaus, M; Rehders, T C; Kleinfeldt, T; Belu, C; Amen, S; Hermann, T; Yokus, S; Brehm, M; Steiner, S; Chatterjee, T; Sahin, K; Nienaber, C A; Ince, H

    2012-01-01

    Abstract Autologous bone marrow cell transplantation (BMCs-Tx) is a promising novel option for treatment of cardiovascular disease. We analysed in a randomized controlled study the influence of the intracoronary autologous freshly isolated BMCs-Tx on the mobilization of bone marrow–derived circulating progenitor cells (BM-CPCs) in patients with acute myocardial infarction (AMI). Sixty-two patients with AMI were randomized to either freshly isolated BMCs-Tx or to a control group without cell therapy. Peripheral blood (PB) concentrations of CD34/45+- and CD133/45+-circulating progenitor cells were measured by flow cytometry in 42 AMI patients with cell therapy as well as in 20 AMI patients without cell therapy as a control group on days 1, 3, 5, 7, 8 and 3, 6 as well as 12 months after AMI. Global ejection fraction (EF) and the size of infarct area were determined by left ventriculography. We observed in patients with freshly isolated BMCs-Tx at 3 and 12 months follow up a significant reduction of infarct size and increase of global EF as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased with a peak on day 7 as compared to baseline after AMI in both groups (CD34/45+: P < 0.001, CD133/45+: P < 0.001). Moreover, this significant mobilization of BM-CPCs existed 3, 6 and 12 months after cell therapy compared to day 1 after AMI. In control group, there were no significant differences of CD34/45+ and CD133/45+ BM-CPCs mobilization between day 1 and 3, 6 and 12 months after AMI. Intracoronary transplantation of autologous freshly isolated BMCs by use of point of care system in patients with AMI may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in PB and this might increase the regenerative potency after AMI. PMID:21707914

  17. STEM Education.

    PubMed

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-08-01

    Improving science, technology, engineering, and mathematics (STEM) education, especially for traditionally disadvantaged groups, is widely recognized as pivotal to the U.S.'s long-term economic growth and security. In this article, we review and discuss current research on STEM education in the U.S., drawing on recent research in sociology and related fields. The reviewed literature shows that different social factors affect the two major components of STEM education attainment: (1) attainment of education in general, and (2) attainment of STEM education relative to non-STEM education conditional on educational attainment. Cognitive and social psychological characteristics matter for both major components, as do structural influences at the neighborhood, school, and broader cultural levels. However, while commonly used measures of socioeconomic status (SES) predict the attainment of general education, social psychological factors are more important influences on participation and achievement in STEM versus non-STEM education. Domestically, disparities by family SES, race, and gender persist in STEM education. Internationally, American students lag behind those in some countries with less economic resources. Explanations for group disparities within the U.S. and the mediocre international ranking of US student performance require more research, a task that is best accomplished through interdisciplinary approaches.

  18. STEM Education

    PubMed Central

    Xie, Yu; Fang, Michael; Shauman, Kimberlee

    2015-01-01

    Improving science, technology, engineering, and mathematics (STEM) education, especially for traditionally disadvantaged groups, is widely recognized as pivotal to the U.S.’s long-term economic growth and security. In this article, we review and discuss current research on STEM education in the U.S., drawing on recent research in sociology and related fields. The reviewed literature shows that different social factors affect the two major components of STEM education attainment: (1) attainment of education in general, and (2) attainment of STEM education relative to non-STEM education conditional on educational attainment. Cognitive and social psychological characteristics matter for both major components, as do structural influences at the neighborhood, school, and broader cultural levels. However, while commonly used measures of socioeconomic status (SES) predict the attainment of general education, social psychological factors are more important influences on participation and achievement in STEM versus non-STEM education. Domestically, disparities by family SES, race, and gender persist in STEM education. Internationally, American students lag behind those in some countries with less economic resources. Explanations for group disparities within the U.S. and the mediocre international ranking of US student performance require more research, a task that is best accomplished through interdisciplinary approaches. PMID:26778893

  19. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Christine Keller, right, Director of Research, APLU (Association of Public and Land-grant Universities) presents STEM initiative report findings at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  20. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Christine Keller, Director of Research, APLU (Association of Public and Land-grant Universities) presents STEM initiative report findings at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  1. A Bayesian Approach to Multicenter Trials and Metaanalysis.

    ERIC Educational Resources Information Center

    Berry, Donald A.

    The use of a Bayesian approach in evaluating data from clinical trials with many treatment centers and from many studies is discussed. The main distinction between a metaanalysis and an analysis of a multicenter trial is that different studies may have very different designs, while the centers in a multicenter trial usually follow the same…

  2. Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy

    SciTech Connect

    Heller, G.V.; Parker, J.A.; Silverman, K.J.; Royal, H.D.; Kolodny, G.M.; Paulin, S.; Braunwald, E.; Markis, J.E.

    1987-02-01

    Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.

  3. Impact of intraventricular conduction delay on coronary haemodynamics: a study with intracoronary Doppler in patients with bundle branch blocks and normal coronary arteries.

    PubMed

    Wieneke, Heinrich; Sattler, Katherine; von Birgelen, Clemens; Böse, Dirk; Haude, Michael; Rechenberg, Wolfram; Sack, Stefan; Dagres, Nikolaos; Erbel, Raimund

    2006-03-01

    The impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) on myocardial perfusion is not completely understood as data are often blurred by underlying cardiac disease. The present study investigates whether conduction delays per se affect coronary perfusion-an indirect measure of myocardial oxygen demand. Intracoronary Doppler and ultrasound were performed in 8 patients with RBBB, 10 patients with LBBB, and 10 control subjects. All patients had angiographically normal coronary arteries and normal left ventricular function. Baseline (bAPV) and adenosine-induced hyperaemic average flow velocity and coronary flow velocity reserve (CFVR) were measured in left anterior descending arteries. Intravascular ultrasound showed no difference in lumen cross-sectional area and plaque burden between groups. Patients with RBBB and LBBB had higher bAPV values than controls (19.0 +/- 4.9, 21.9 +/- 5.1, and 14.6 +/- 2.4 cm/s, respectively; ANOVA P = 0.003). There was no difference between patients with LBBB and RBBB compared with controls in CFVR (2.8 +/- 0.5, 3.0 +/- 1.0, and 3.4 +/- 0.7, respectively; ANOVA P = 0.21). Bundle branch blocks, in particular LBBB, are associated with an increased coronary flow velocity, which indicates enhanced myocardial oxygen demand on the basis of mechanoenergetic disturbance. This may contribute to the unfavourable outcome of patients with intraventricular conduction delay.

  4. Multicenter neonatal databases: Trends in research uses.

    PubMed

    Creel, Liza M; Gregory, Sean; McNeal, Catherine J; Beeram, Madhava R; Krauss, David R

    2017-01-13

    In the US, approximately 12.7% of all live births are preterm, 8.2% of live births were low birth weight (LBW), and 1.5% are very low birth weight (VLBW). Although technological advances have improved mortality rates among preterm and LBW infants, improving overall rates of prematurity and LBW remains a national priority. Monitoring short- and long-term outcomes is critical for advancing medical treatment and minimizing morbidities associated with prematurity or LBW; however, studying these infants can be challenging. Several large, multi-center neonatal databases have been developed to improve research and quality improvement of treatments for and outcomes of premature and LBW infants. The purpose of this systematic review was to describe three multi-center neonatal databases. We conducted a literature search using PubMed and Google Scholar over the period 1990 to August 2014. Studies were included in our review if one of the databases was used as a primary source of data or comparison. Included studies were categorized by year of publication; study design employed, and research focus. A total of 343 studies published between 1991 and 2014 were included. Studies of premature and LBW infants using these databases have increased over time, and provide evidence for both neonatology and community-based pediatric practice. Research into treatment and outcomes of premature and LBW infants is expanding, partially due to the availability of large, multicenter databases. The consistency of clinical conditions and neonatal outcomes studied since 1990 demonstrates that there are dedicated research agendas and resources that allow for long-term, and potentially replicable, studies within this population.

  5. A PROGNOSTIC SCORE FOR ACUTE GRAFT-VERSUS-HOST DISEASE BASED ON BIOMARKERS: A MULTICENTER STUDY

    PubMed Central

    Levine, John E.; Braun, Thomas M.; Harris, Andrew C.; Holler, Ernst; Taylor, Austin; Miller, Holly; Magenau, John; Weisdorf, Daniel J.; Ho, Vincent T.; Bolaños-Meade, Javier; Alousi, Amin M.; Ferrara, L.M.

    2015-01-01

    SUMMARY Background Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem-cell transplantation (HCT). The severity of symptoms at the onset of GVHD does not accurately define risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to define clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers. Methods We prospectively collected plasma from 492 HCT patients with newly diagnosed acute GVHD and randomly divided them into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and REG3α) to create an algorithm that computed the probability of NRM six months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identified thresholds that created three distinct NRM scores. We evaluated the algorithm in the testset, and again in an independent validation set of 300 additional HCT patients enrolled on multicenter clinical trials of primary therapy for acute GVHD. Findings In all three datasets, the cumulative incidence of twelve month NRM significantly increased as the GVHD score increased (8% [95% confidence interval (CI); 3%, 16%], 27% [95% CI; 20%%, 34%], and 46% [95% CI; 33%, 58%], for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Conversely, the response rates to primary GVHD treatment decreased as the GVHD score increased (86%, 67%, and 46%, for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Interpretation Biomarker-based scores can be used to guide risk-adapted therapy at the onset of acute GVHD. PMID:26687425

  6. Restoring stemness.

    PubMed

    Westphal, Heiner

    2005-12-01

    This essay is focused on a specific line of research toward regenerative therapies that is based on the use of embryonic stem cells but tries to avoid cloning techniques that are the heart of current ethical debates.

  7. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    U.S. Congresswoman Eddie Bernice Johnson (D-TX) addresses the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  8. Allogeneic stem cell transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study.

    PubMed

    Vey, N; Thomas, X; Picard, C; Kovascovicz, T; Charin, C; Cayuela, J M; Dombret, H; Dastugue, N; Huguet, F; Bastard, C; Stamatoulas, A; Giollant, M; Tournilhac, O; Macintyre, E; Buzyn, A; Bories, D; Kuentz, M; Dreyfus, F; Delannoy, A; Raynaud, S; Gratecos, N; Bordessoule, D; de Botton, S; Preudhomme, C; Reman, O; Troussard, X; Pigneux, A; Bilhou, C; Vernant, J P; Boucheix, C; Gabert, J

    2006-12-01

    Adult patients with acute lymphoblastic leukemia (ALL) and t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4 have a poor outcome. We have evaluated the impact of an intensified post-remission therapy using a high-dose chemotherapy course followed by allogeneic or autologous SCT on the outcome of 58 patients with t(1;19)/E2A-PBX1 (E2A group, n=24) or t(4;11)/MLL-AF4 (MLL group, n=34) treated in the LALA-94 multicenter prospective study. Patients in the MLL group had higher WBC counts and more frequent DIC. CR rates achieved by MLL and E2A groups were similar to other B-cell ALL (87, 82 and 86% respectively). While in CR, patients with a donor were assigned to alloSCT (n=22), the remaining patients with were randomized between autoSCT (n=15) or chemotherapy (n=8). Five-year overall survival was 31 and 45% for E2A and MLL groups, respectively. In both groups, DFS was higher in the alloSCT arm as compared to autoSCT and chemotherapy arms. The results of this study show that chemotherapy intensification did not overcome the poor prognosis of adults with t(1;19)/E2A-PBX1. Allogeneic SCT should thus be offered in first CR to patients with t(1;19)/E2A-PBX1 or t(4;11)/MLL-AF4. New therapeutic approaches are needed for patients without donor.

  9. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation.

    PubMed

    Koenecke, Christian; Göhring, Gudrun; de Wreede, Liesbeth C; van Biezen, Anja; Scheid, Christof; Volin, Liisa; Maertens, Johan; Finke, Jürgen; Schaap, Nicolaas; Robin, Marie; Passweg, Jakob; Cornelissen, Jan; Beelen, Dietrich; Heuser, Michael; de Witte, Theo; Kröger, Nicolaus

    2015-03-01

    The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64 and 2.76), compared to patients with very good, good or intermediate risk. When comparing the predictive performance of a series of Cox models both for relapse-free survival and for overall survival, a model with simplified 5-group cytogenetics (merging very good, good and intermediate cytogenetics) performed best. Furthermore, monosomal karyotype is an additional negative predictor for outcome within patients of the poor, but not the very poor risk group of the 5-group classification. The revised International Prognostic Scoring System cytogenetic classification allows patients with myelodysplastic syndromes to be separated into three groups with clearly different outcomes after stem cell transplantation. Poor and very poor risk cytogenetics were strong predictors of poor patient outcome. The new cytogenetic classification added value to prediction of patient outcome compared to prediction models using only traditional risk factors or the 3-group International Prognostic Scoring System cytogenetic classification. Copyright© Ferrata Storti Foundation.

  10. Acute results, complications, and effect of lesion characteristics on outcome with the solid-state, pulsed-wave, mid-infrared laser angioplasty system: final multicenter registry report. Holmium:YAG Laser Multicenter Investigators.

    PubMed

    Topaz, O; McIvor, M; Stone, G W; Krucoff, M W; Perin, E C; Foschi, A E; Sutton, J; Nair, R; deMarchena, E

    1998-01-01

    The solid-state, mid-infrared holmium:YAG laser (2.1 microm wavelength) is a relatively new percutaneous device that has recently been evaluated in a multicenter study. Because of its unique wavelength and photoacoustic effects on atherosclerotic plaques, this laser may be useful in treatment of symptomatic patients with coronary artery disease. This study sought to evaluate the safety and efficacy of mid-infrared laser angioplasty in the treatment of coronary artery lesions. Laser angioplasty was performed on 2,038 atherosclerotic lesions in 1,862 consecutive patients with a mean age of 61 +/- 11 years. Clinical indications included unstable angina (69%), stable angina (20%), acute infarction (6%), and positive exercise test (5%). Complex lesion morphology included eccentricity (62%), thrombus (30%), total occlusion (27%), long lesions (14%), and saphenous vein grafts (11%). This laser catheter alone successfully reduced stenosis (>20%) in 87% of lesions. With adjunct balloon angioplasty, 93% procedural success was achieved. The presence of thrombus within the target lesion was a predictor of procedural success (OR = 2.0 [95% confidence interval 2.0, 4.0], P = .04). Bifurcation lesions (OR = 0.5 [95% confidence interval 0.2, 1.0], P = .05) and severe tortuosity of the treated vessel (OR = 0.4 [95% confidence interval 0.2, 0.9], P = .02) were identified as significant predictors of decreased laser success. Calcium within the lesion was associated with reduced procedural success (OR = 0.57 [95% confidence interval 0.34, 0.97], P = .03), and calcified lesions required significantly more energy pulses than noncalcified lesions (119 +/- 91 pulses vs. 101 +/- 86 pulses, respectively, P = .0002). Complications included in-hospital bypass surgery 2.5%, Q-wave myocardial infarction 1.2%, and death 0.8%. Perforation occurred in 2.2% of patients; major dissection in 5.8% of patients, and spasm in 12% of patients. No predictor of major complications was identified. Six

  11. Measurement of the blood flow rate and velocity in coronary artery stenosis using intracoronary frequency domain optical coherence tomography: Validation against fractional flow reserve.

    PubMed

    Zafar, Haroon; Sharif, Faisal; Leahy, Martin J

    2014-12-01

    The main objective of this study was to assess the blood flow rate and velocity in coronary artery stenosis using intracoronary frequency domain optical coherence tomography (FD-OCT). A correlation between fractional flow reserve (FFR) and FD-OCT derived blood flow velocity is also included in this study. A total of 20 coronary stenoses in 15 patients were assessed consecutively by quantitative coronary angiography (QCA), FFR and FD-OCT. A percutaneous coronary intervention (PCI) optimization system was used in this study which combines wireless FFR measurement and FD-OCT imaging in one platform. Stenoses were labelled severe if FFR ≤ 0.8. Blood flow rate and velocity in each stenosis segment were derived from the volumetric analysis of the FD-OCT pull back images. The FFR value was ≤ 0.80 in 5 stenoses (25%). The mean blood flow rate in severe coronary stenosis (n = 5) was 2.54 ± 0.55 ml/s as compared to 4.81 ± 1.95 ml/s in stenosis with FFR > 0.8 (n = 15). A good and significant correlation between FFR and FD-OCT blood flow velocity in coronary artery stenosis (r = 0.74, p < 0.001) was found. The assessment of stenosis severity using FD-OCT derived blood flow rate and velocity has the ability to overcome many limitations of QCA and intravascular ultrasound (IVUS).

  12. Meta-analysis of prospective randomized controlled trials comparing intracoronary versus intravenous abciximab in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

    PubMed

    Shimada, Yuichi J; Nakra, Navin C; Fox, John T; Kanei, Yumiko

    2012-03-01

    Abciximab is a glycoprotein IIb/IIIa receptor inhibitor that has been shown to improve outcomes in patients with ST-segment elevation myocardial infarction who undergo primary percutaneous coronary intervention (pPCI). An earlier study reported better efficacy with intracoronary (IC) compared to intravenous (IV) administration, but this finding has not been duplicated in other studies, thus leaving a great deal of uncertainty as to the most efficacious route of administration. To investigate if IC abciximab compared to IV administration decreases mortality and major adverse cardiac events in patients with ST-segment elevation myocardial infarction who undergo pPCI, a meta-analysis was performed consisting only of prospective randomized controlled trials. Subgroup analysis was performed to investigate the source of difference in efficacy between the 2 strategies. A meta-analysis of 4 trials including 1,148 subjects revealed that IC abciximab significantly reduced mortality compared to IV administration (1.5% vs 3.6%, odds ratio 0.44, 95% confidence interval 0.20 to 0.95, p = 0.04). Major adverse cardiac events were also reduced in a subgroup in which <30% of patients received aspiration thrombectomy (6.1% vs 16.2%, odds ratio 0.33, 95% confidence interval 0.18 to 0.61, p = 0.0004). In conclusion, the totality of the data available from relatively small but high-quality studies shows a significant mortality reduction associated using IC abciximab for pPCI compared to IV abciximab. IC abciximab in the setting of pPCI for ST-segment elevation myocardial infarction may be beneficial for patients with higher risk profiles.

  13. Meta-Analysis of Randomized Trials of Intracoronary Versus Intravenous Glycoprotein IIb/IIIa Inhibitors in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

    PubMed

    Elbadawi, Ayman; Elgendy, Islam Y; Megaly, Michael; Ha, Le Dung; Mahmoud, Karim; Alotaki, Erfan; Ogunbayo, Gbolahan O; Baig, Basarat; Abuzaid, A S; Saad, Marwan; Depta, Jeremiah P

    2017-10-01

    The efficacy and safety of glycoprotein IIb/IIIa inhibitors via intracoronary (IC) route versus the intravenous (IV) route are not well known. We conducted this meta-analysis of randomized trials evaluating the role of IC versus IV glycoprotein IIb/IIIa in patients undergoing primary percutaneous coronary intervention. The analysis included 14 trials with a total of 3,754 patients. The primary outcome of major adverse cardiac events (MACE) had no statistically significant difference between the IC and the IV groups (relative risk [RR] 0.74, 95% confidence interval [CI] 0.51 to 1.10). Subgroup analysis showed that short-term MACE (i.e., ≤3 months) was reduced in the IC compared with the IV group; however, long-term MACE (>3 months) was not. IC group was superior in achievement of post-procedural Thrombolysis In Myocardial Infarction 3 flow (RR 1.06, 95% CI 1.01 to 1.11), myocardial blush grade II to III (RR 1.15, 95% CI 1.08 to 1.23), ST-segment resolution rates (RR 1.15, 95% CI 1.03 to 1.29; p = 0.01), and improvement of left ventricular ejection fraction (standardized mean difference = 4.32, 95% CI 0.91 to 7.74). There was a trend for lower stent thrombosis with IC route (RR 0.50, 95% CI 0.24 to 1.03). There was no significant difference between the 2 groups in all-cause mortality, re-infarction, and major bleeding. In conclusion, despite lack of significant difference in overall MACE outcome, IC glycoprotein IIb/IIIa inhibitors may improve short -term MACE, Thrombolysis In Myocardial Infarction 3 flow, myocardial blush grade II- to III rates, ST-segment resolution, and left ventricular ejection fraction compared with the IV route. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Global Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells Improves Ventricular Function and Stimulates Endogenous Myocyte Regeneration throughout the Heart in Swine with Hibernating Myocardium

    PubMed Central

    Suzuki, Gen; Weil, Brian R.; Leiker, Merced M.; Ribbeck, Amanda E.; Young, Rebeccah F.; Cimato, Thomas R.; Canty, John M.

    2014-01-01

    Background Cardiosphere-derived cells (CDCs) improve ventricular function and reduce fibrotic volume when administered via an infarct-related artery using the “stop-flow” technique. Unfortunately, myocyte loss and dysfunction occur globally in many patients with ischemic and non-ischemic cardiomyopathy, necessitating an approach to distribute CDCs throughout the entire heart. We therefore determined whether global intracoronary infusion of CDCs under continuous flow improves contractile function and stimulates new myocyte formation. Methods and Results Swine with hibernating myocardium from a chronic LAD occlusion were studied 3-months after instrumentation (n = 25). CDCs isolated from myocardial biopsies were infused into each major coronary artery (∼33×106 icCDCs). Global icCDC infusion was safe and while ∼3% of injected CDCs were retained, they did not affect ventricular function or myocyte proliferation in normal animals. In contrast, four-weeks after icCDCs were administered to animals with hibernating myocardium, %LADWT increased from 23±6 to 51±5% (p<0.01). In diseased hearts, myocyte proliferation (phospho-histone-H3) increased in hibernating and remote regions with a concomitant increase in myocyte nuclear density. These effects were accompanied by reductions in myocyte diameter consistent with new myocyte formation. Only rare myocytes arose from sex-mismatched donor CDCs. Conclusions Global icCDC infusion under continuous flow is feasible and improves contractile function, regresses myocyte cellular hypertrophy and increases myocyte proliferation in diseased but not normal hearts. New myocytes arising via differentiation of injected cells are rare, implicating stimulation of endogenous myocyte regeneration as the primary mechanism of repair. PMID:25402428

  15. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome.

    PubMed

    Ishiguro, Hisaaki; Horiba, Mitsuru; Takenaka, Hiroharu; Sumida, Arihiro; Opthof, Tobias; Ishiguro, Yuko S; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo

    2011-01-01

    Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  16. Morphometric analysis in three-dimensional intracoronary ultrasound: an in vitro and in vivo study performed with a novel system for the contour detection of lumen and plaque.

    PubMed

    von Birgelen, C; Di Mario, C; Li, W; Schuurbiers, J C; Slager, C J; de Feyter, P J; Roelandt, J R; Serruys, P W

    1996-09-01

    Currently, automated systems for quantitative analysis by intracoronary ultrasound (ICUS) are restricted to the detection of the lumen. The aim of this study was to determine the accuracy and reproducibility of a new semiautomated contour detection method, providing off-line identification of the intimal leading edge and external contour of the vessel in three-dimensional ICUS. The system allows cross-sectional and volumetric quantification of lumen and of plaque. It applies a minimum-cost algorithm and the concept that edge points derived from previously detected longitudinal contours guide and facilitate the contour detection in the cross-sectional images. A tubular phantom with segments of various luminal dimensions was examined in vitro during five catheter pull-backs (1 mm/sec), and subsequently 20 diseased human coronary arteries were studied in vivo with 2.9F 30 MHz mechanical ultrasound catheters (200 images per 20 mm segment). The ICUS measurements of phantom lumen area and volume revealed a high correlation with the true phantom areas and volumes (r = 0.99); relative mean differences were -0.65% to 3.86% for the areas and 0.25% to 1.72% for the volumes of the various segments. Intraob-server and interobserver comparisons showed high correlations (r = 0.95 to 0.98 for area and r = 0.99 for volume) and small mean relative differences (-0.87% to 1.08%), with SD of lumen, plaque, and total vessel measurements not exceeding 7.28%, 10.81%, and 4.44% (area) and 2.66%, 2.81%, and 0.67% (volume), respectively. Thus the proposed analysis system provided accurate measurements of phantom dimensions and can be used to perform highly reproducible area and volume measurements in three-dimensional ICUS in vivo.

  17. Multicenter Epidemiological Studies of Atherosclerosis Imaging

    PubMed Central

    Liu, Songtao; Bluemke, David A.

    2011-01-01

    Cardiovascular disease is the leading course of death and disability. Conventional cardiac risk factors do not fully explain the level of cardiovascular risk, incidence of coronary artery disease, and coronary events. Risk stratification and therapy based solely on these conventional risk factors may overlook a population who would benefit from lifestyle and risk factor modification. Thus, research has recently focused on improving risk assessment with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging, both in coronary and extracoronary arterial beds, has proven to be very helpful in this regard. In this article, we review the current literature from multicenter epidemiology studies on the utility of noninvasive imaging modalities for risk stratification in the context of conventional risk factor evaluation. PMID:20805734

  18. A premarketing multicenter trial of lorazepam injection.

    PubMed

    Philbrook, F A; Hatt, D L

    1983-01-01

    Before the introduction of lorazepam injection to the Canadian market, its usefulness and acceptability were assessed in an open multicenter study. Anesthesiologists in teaching hospitals across the country were asked to substitute lorazepam injection for their usual anxiolytic premedicant in ten patients and to complete a brief case report on each patient. The results from 360 patients showed that suitable preoperative sedation, accompanied by anxiolysis but without undue effects on arousability, was obtained in 88% of the patients prior to surgery. The adverse effect most often reported, accounting for 84% of the drug-related adverse reactions, was postoperative drowsiness, which highlighted the need to administer the drug at least two hours before surgery. The anesthesiologists found lorazepam injection to be a satisfactory premedicant, rating it excellent to good in 73% of the patients treated.

  19. Why STEM?

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2016-01-01

    The International Technology and Engineering Educators Association (ITEEA) defines STEM as a new transdisciplinary subject in schools that integrates the disciplines of science, technology, engineering, and mathematics into a single course of study. There are three major problems with this definition: There is no consensus in support of the ITEEA…

  20. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Carl Wieman, Associate Director, Office of Science and Technology Policy, The White House, speaks at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  1. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Woodrow Whitlow, NASA Associate Administrator, Mission Support Directorate, gives opening remarks at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  2. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    J. Keith Motley, Chancellor, University of Massachusetts Boston, and Chair, APLU (Association of Public and Land-grant Universities) Commission on Access, Diversity and Excellence, speaks at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  3. STEM Symposium

    NASA Image and Video Library

    2012-02-28

    Leland Melvin, Associate Administrator, Office of Education and former astronaut, gives opening remarks at the Symposium on Supporting Underrepresented Minority Males in Science, Technology, Engineering and Mathematics (STEM), Tuesday, February 28, 2012 at NASA Headquarters in Washington. Photo Credit: (NASA/Carla Cioffi)

  4. STEM Thinking!

    ERIC Educational Resources Information Center

    Reeve, Edward M.

    2015-01-01

    Science, Technology, Engineering, and Mathematics (STEM) is a term seen almost daily in the news. In 2009, President Obama launched the Educate to Innovate initiative to move American students from the middle to the top of the pack in science and math achievement over the next decade (The White House, n.d.). Learning about the attributes of STEM…

  5. STEM Thinking!

    ERIC Educational Resources Information Center

    Reeve, Edward M.

    2015-01-01

    Science, Technology, Engineering, and Mathematics (STEM) is a term seen almost daily in the news. In 2009, President Obama launched the Educate to Innovate initiative to move American students from the middle to the top of the pack in science and math achievement over the next decade (The White House, n.d.). Learning about the attributes of STEM…

  6. Why STEM?

    ERIC Educational Resources Information Center

    Mitts, Charles R.

    2016-01-01

    The International Technology and Engineering Educators Association (ITEEA) defines STEM as a new transdisciplinary subject in schools that integrates the disciplines of science, technology, engineering, and mathematics into a single course of study. There are three major problems with this definition: There is no consensus in support of the ITEEA…

  7. Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

    PubMed

    Kiefer, T; Hirt, C; Späth, C; Schüler, F; Al-Ali, H K; Wolf, H-H; Herbst, R; Maschmeyer, G; Helke, K; Kessler, C; Niederwieser, D; Busemann, C; Schroeder, H; Vogelgesang, S; Kirsch, M; Montemurro, M; Krüger, W H; Dölken, G

    2012-07-01

    We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

  8. Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study

    PubMed Central

    Syeda, Bonni; Charwat, Silvia; Marzluf, Beatrice; Mascherbauer, Julia; Jakab, Andras; Zimba, Abelina; Sárközy, Márta; Pavo, Noemi; Sochor, Heinz; Graf, Senta; Lang, Irene; Maurer, Gerald; Bergler-Klein, Jutta

    2016-01-01

    Objective The long-term (5-year) outcome of early (3–6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3–4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30–45% post-AMI. Methods Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome. Results Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5–10.1, and 5.7%, 95% CI:1.7–9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0–9.6; and Late group: 8.4%, 95% CI:4.5–12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE. Conclusions Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212). PMID:27764157

  9. Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study.

    PubMed

    Gyöngyösi, Mariann; Giurgea, Georgiana-Aura; Syeda, Bonni; Charwat, Silvia; Marzluf, Beatrice; Mascherbauer, Julia; Jakab, Andras; Zimba, Abelina; Sárközy, Márta; Pavo, Noemi; Sochor, Heinz; Graf, Senta; Lang, Irene; Maurer, Gerald; Bergler-Klein, Jutta

    2016-01-01

    The long-term (5-year) outcome of early (3-6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3-4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30-45% post-AMI. Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome. Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5-10.1, and 5.7%, 95% CI:1.7-9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0-9.6; and Late group: 8.4%, 95% CI:4.5-12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE. Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212).

  10. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

    PubMed

    Montemurro, M; Kiefer, T; Schüler, F; Al-Ali, H K; Wolf, H-H; Herbst, R; Haas, A; Helke, K; Theilig, A; Lotze, C; Hirt, C; Niederwieser, D; Schwenke, M; Krüger, W H; Dölken, G

    2007-04-01

    We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.

  11. Wandering spleen in children: multicenter retrospective study.

    PubMed

    Fiquet-Francois, Caroline; Belouadah, Mohamed; Ludot, Hugues; Defauw, Benoit; Mcheik, Jiad Noel; Bonnet, Jean Paul; Kanmegne, Charly Udozen; Weil, Dominique; Coupry, Lionel; Fremont, Benjamin; Becmeur, Francois; Lacreuse, Isabelle; Montupet, Philippe; Rahal, Eliane; Botto, Nathalie; Cheikhelard, Alaa; Sarnacki, Sabine; Petit, Thierry; Poli Merol, Marie Laurence

    2010-07-01

    Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

  12. Acute necrotizing pancreatitis: a multicenter study.

    PubMed

    Fernández-Cruz, L; Navarro, S; Valderrama, R; Sáenz, A; Guarner, L; Aparisi, L; Espi, A; Jaurietta, E; Marruecos, L; Gener, J

    1994-04-01

    A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

  13. Improved Mobilization of the CD34+ and CD133+ Bone Marrow-Derived Circulating Progenitor Cells by Freshly Isolated Intracoronary Bone Marrow Cell Transplantation in Patients with Ischemic Heart Disease

    PubMed Central

    Bozdag-Turan, Ilkay; Ortak, Jasmin; Akin, Ibrahim; Kische, Stephan; Schneider, Henrik; Turan, Cem Hakan; Rehders, Tim Christopher; Rauchhaus, Mathias; Kleinfeldt, Tilo; Adolph, Ester; Brehm, Micheal; Yokus, Sedat; Steiner, Stephan; Sahin, Kurtulus; Nienaber, Christoph A.; Ince, Hüseyin

    2011-01-01

    Cell therapy is a promising novel option for treatment of cardiovascular disease. Because the role of bone marrow-derived circulating progenitor cells (BM-CPCs) after cell therapy is less clear, we analyzed in this randomized, controlled study the influence of intracoronary autologous freshly isolated bone marrow cell transplantation (BMC-Tx) by using a point-of-care system on cardiac function and on the mobilization of BM-CPCs in patients with ischemic heart disease (IHD). Fifty-six patients with IHD were randomized to either receive freshly isolated BMC-Tx or a control group that did not receive cell therapy. Peripheral blood concentrations of CD34/45+ and CD133/45+ CPCs were measured by flow cytometry pre-, immediately post-, and at 3, 6, and 12 months postprocedure in both groups. Global ejection fraction and the size of infarct area were determined by left ventriculography. We observed in patients with IHD after intracoronary transplantation of autologous freshly isolated BMCs-Tx at 3 and 12 months follow-up a significant reduction of the size of infarct area and increase of global ejection fraction as well as infarct wall movement velocity. The mobilization of CD34/45+ and CD133/45+ BM-CPCs significantly increased at 3, 6, and 12 months after cell therapy when compared with baseline in patients with IHD, although no significant changes were observed between pre- and immediately postintracoronary cell therapy administration. In the control group without cell therapy, there was no significant difference of CD34/45+ and CD133/45+ BM-CPCs mobilization between pre- and at 3, 6, and 12 months postcoronary angiography. Intracoronary transplantation of autologous freshly isolated BMCs by using a point-of-care system in patients with IHD may enhance and prolong the mobilization of CD34/45+ and CD133/45+ BM-CPCs in peripheral blood and this might increase the regenerative potency in IHD. PMID:21190450

  14. Multicenter prospective evaluation of dogs with trauma.

    PubMed

    Hall, Kelly E; Holowaychuk, Marie K; Sharp, Claire R; Reineke, Erica

    2014-02-01

    To determine hospital admission variables for dogs with trauma including values determined with scoring systems (animal trauma triage [ATT], modified Glasgow coma scale [MGCS], and acute patient physiologic and laboratory evaluation [APPLE] scores) and the usefulness of such variables for the prediction of outcome (death vs survival to hospital discharge). Prospective, multicenter, cohort study. 315 client-owned dogs. By use of a Web-based data capture system, trained personnel prospectively recorded admission ATT, MGCS, and APPLE scores; clinical and laboratory data; and outcome (death vs survival to discharge) for dogs with trauma at 4 veterinary teaching hospitals during an 8-week period. Cause of injury was most commonly blunt trauma (173/315 [54.9%]) followed by penetrating trauma (107/315 [34.0%]), or was unknown (35/315 [11.1%]). Of the 315 dogs, 285 (90.5%) survived to hospital discharge. When 16 dogs euthanized because of cost were excluded, dogs with blunt trauma were more likely to survive, compared with dogs with penetrating trauma (OR, 8.5). The ATT (OR, 2.0) and MGCS (OR, 0.47) scores and blood lactate concentration (OR, 1.5) at the time of hospital admission were predictive of outcome. Surgical procedures were performed for 157 (49.8%) dogs; surgery was associated with survival to discharge (OR, 7.1). Results indicated ATT and MGCS scores were useful for prediction of outcome for dogs evaluated because of trauma. Penetrating trauma, low blood lactate concentration, and performance of surgical procedures were predictive of survival to hospital discharge. The methods enabled collection of data for a large number of dogs in a short time.

  15. Canadian multicenter azidothymidine trial: AZT pharmacokinetics.

    PubMed

    Child, S; Montaner, J; Tsoukas, C; Fanning, M; Le, T; Wall, R A; Ruedy, J

    1991-01-01

    The study objective was to describe the pharmacokinetics of azidothymidine (AZT) in a large population of early, asymptomatic human immunodeficiency virus (HIV)-infected individuals. The study design was a multicenter, prospective, descriptive single-dose pharmacokinetic study. Each of 66 fasting, male, HIV-infected homosexuals older than 18 years of age and in CDC classifications II, III, and IVC2 received a single 400-mg oral dose of AZT with subsequent pharmacokinetic measurements performed during an 8-h period for AZT and its major metabolite, glucuronylazidothymidine (GAZT). Results were obtained in 65 patients (36 smokers, 29 nonsmokers), of whom 3 were noted to have hepatic dysfunction. In those with normal hepatic function, the following parameters were described: AZT, area under the curve (AUC) +/- SD, 9.9 +/- 5.7 microM.h, maximum concentration (Cmax) +/- SD, 7.3 +/- 4.7 microM; time to maximum concentration (Tmax) +/- SD, 0.93 +/- 0.42 h, and half-life (t1/2) +/- SD, 1.0 +/- 0.8 h. Corresponding values for GAZT were: AUC +/- SD 35.7 +/- 10.3 microM.h, Cmax +/- SD 21.3 +/- 7.3 microM, Tmax +/- SD 1.2 +/- 0.50 h, t1/2 +/- SD 0.98 +/- 0.62 h, No significant differences were found in comparisons of study site, CDC classification of disease, smokers versus nonsmokers, and in patients with hepatic dysfunction, although a higher AUC and earlier Cmax for AZT was noted in the latter group. It is concluded that AZT pharmacokinetics are similar in patients with early asymptomatic HIV disease when compared with previous reports in patients with later disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. [Inguinofemoral hernia: multicenter study of surgical techniques].

    PubMed

    Porrero, José L; Sánchez-Cabezudo, Carlos; Bonachía, Oscar; López-Buenadicha, Adolfo; Sanjuánbenito, Alfonso; Hidalgo, Manuel

    2005-07-01

    The present study was performed by the Spanish Association of surgeons through its abdominal wall and sutures section. The aim was to determine the current situation of inguinofemoral hernias in Spain and was based on an anonymous multicenter study with the participation of various national hospitals. Fifty general surgery departments in distinct surgical centers throughout Spain responded to an anonymous survey in 2000. The survey gathered data on anesthetic features, surgical techniques and complications in the treatment of inguinofemoral hernias. Sixty-six percent of hospital centers had a specific abdominal wall unit and 24% performed laparoscopic hernia surgery. Prosthetic techniques (especially Lichtenstein) were the most frequently used in the treatment of primary inguinal hernia (72%) and recurrent hernia (100%). The most frequently used prosthetic material was polypropylene mesh (76%). Only 28% of the departments surveyed performed anatomic techniques in the repair of primary inguinal hernia (Shouldice and Bassini). The most frequent treatment for femoral hernia was the Lichtenstein "plug" (78%). Sixty-eight percent of the centers surveyed performed regional anesthesia, 18% used general anesthesia and only 14% used local anesthesia with sedation. Severe complications were found in 20% of departments. Clinical postoperative follow-up was performed in 96% of the centers and telephone follow-up was used in 4%. The recurrence rate was 1.2% for primary inguinal hernia, 2.7% for recurrent inguinal hernia and 0.3% for femoral hernia. In Spain the most commonly used surgical technique in the treatment of inguinal hernia is Lichtenstein hernioplasty under spinal anesthesia and with polypropylene prosthesis. The Lichtenstein plug is the most commonly used technique in the treatment of femoral hernia.

  17. Stem Cell Sciences plc.

    PubMed

    Daniels, Sebnem

    2006-09-01

    Stem Cell Sciences' core objective is to develop safe and effective stem cell-based therapies for currently incurable diseases. In order to achieve this goal, Stem Cell Sciences recognizes the need for multiple technologies and a globally integrated stem cell initiative. The key challenges for the successful application of stem cells in the clinic is the need for a reproducible supply of pure, fully characterized stem cells that have been grown in suitable conditions for use in the clinic.

  18. STEM Girls Night In at Goddard

    NASA Image and Video Library

    2016-11-04

    Girls Night In was held at Goddard on Nov 4-5, 2016. This is a pilot program which reinvigorates, inspires, and engages high school girls who may be struggling or not fully engaged in STEM (Science, Technology Engineering and Math) education. The program allowed NASA women to share and demonstrate the work they do, provide the girls an opportunity to completely immerse themselves in Goddard science, technology, engineering and math as well as provide them activities that will challenge and promote knowledge and discovery. Goddard invites other NASA centers tolearn from this pilot program and work towards a simultaneous multicenter event in the future. Participating schools were: DuVal, Crossland, Flowers, High Point, Northwestern and Oxon Hill

  19. STEM Girls Night In at Goddard

    NASA Image and Video Library

    2016-11-05

    Girls Night In was held at Goddard on Nov 4-5, 2016. This is a pilot program which reinvigorates, inspires, and engages high school girls who may be struggling or not fully engaged in STEM (Science, Technology Engineering and Math) education. The program allowed NASA women to share and demonstrate the work they do, provide the girls an opportunity to completely immerse themselves in Goddard science, technology, engineering and math as well as provide them activities that will challenge and promote knowledge and discovery. Goddard invites other NASA centers tolearn from this pilot program and work towards a simultaneous multicenter event in the future. Participating schools were: DuVal, Crossland, Flowers, High Point, Northwestern and Oxon Hill

  20. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  1. Assessment of a Nuclear Affinity Labeling Method for Tracking Implanted Mesenchymal Stem Cells

    PubMed Central

    Leiker, Merced; Suzuki, Gen; Iyer, Vijay S.; Canty, John M.; Lee, Techung

    2010-01-01

    Therapeutic implantation of mesenchymal stem cells (MSCs) is entering the realm of clinical trials for several human diseases, and yet much remains uncertain regarding their dynamic distribution and cell fate after in vivo application. Discrepancies in the literature can be attributed in part to the use of different cell labeling/tracking methods and cell administration protocols. To identify a stem cell detection method suitable for myocardial implantation in a large animal model, we experimented on three different MSC labeling methods: adenovirus-mediated expression of enhanced green fluorescence protein (EGFP) and β-galactosidase (LacZ), and nuclear staining with DAPI. Intramuscular and intracoronary administrations of labeled porcine MSCs identified the nuclear affinity dye to be a reliable stem cell tracking marker. Stem cell identification is facilitated by an optimized live cell labeling condition generating bright blue fluorescence sharply confined to the nucleus. DAPI-labeled MSCs retained full viability, ceased proliferation, and exhibited an increased differentiation potential. The labeled MSCs remained fully active in expressing key growth factor and cytokine genes, and notably exhibited enhanced expression of the chemokine receptor CXCR4 and its ligand SDF1, indicating their competency in response to tissue injury. Histological analysis revealed that approximately half a million MSCs or ∼2% of the administered MSCs remained localized in the normal pig heart 2 weeks after coronary infusion. That the vast majority of these identified MSCs were interstitial indicated the ability of MSCs to migrate across the coronary endothelium. No evidence was obtained indicating MSC differentiation to cardiomyocyte. PMID:19069634

  2. Multicenter observational prehospital resuscitation on helicopter study.

    PubMed

    Holcomb, John B; Swartz, Michael D; DeSantis, Stacia M; Greene, Thomas J; Fox, Erin E; Stein, Deborah M; Bulger, Eileen M; Kerby, Jeffrey D; Goodman, Michael; Schreiber, Martin A; Zielinski, Martin D; O'Keeffe, Terence; Inaba, Kenji; Tomasek, Jeffrey S; Podbielski, Jeanette M; Appana, Savitri N; Yi, Misung; Wade, Charles E

    2017-07-01

    at any time point, although only 10% of the high-risk sample were able to be matched. Because of the unexpected imbalance in systolic blood pressure, Glasgow Coma Scale, and Injury Severity Score between systems with and without blood products on helicopters, matching was limited, and the results of this study are inconclusive. With few units transfused to each patient and small outcome differences between groups, it is likely large, multicenter, randomized studies will be required to detect survival differences in this important population. Level II.

  3. Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus

    PubMed Central

    Arendrup, M.C.; Warris, A.; Lagrou, K.; Pelloux, H.; Hauser, P.M.; Chryssanthou, E.; Mellado, E.; Kidd, S.E.; Tortorano, A.M.; Dannaoui, E.; Gaustad, P.; Baddley, J.W.; Uekötter, A.; Lass-Flörl, C.; Klimko, N.; Moore, C.B.; Denning, D.W.; Pasqualotto, A.C.; Kibbler, C.; Arikan-Akdagli, S.; Andes, D.; Meletiadis, J.; Naumiuk, L.; Nucci, M.; Melchers, W.J.G.; Verweij, P.E.

    2015-01-01

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. PMID:25988348

  4. Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life.

    PubMed

    Saccardi, Riccardo; Mancardi, Gian Luigi; Solari, Alessandra; Bosi, Alberto; Bruzzi, Paolo; Di Bartolomeo, Paolo; Donelli, Amedea; Filippi, Massimo; Guerrasio, Angelo; Gualandi, Francesca; La Nasa, Giorgio; Murialdo, Alessandra; Pagliai, Francesca; Papineschi, Federico; Scappini, Barbara; Marmont, Alberto M

    2005-03-15

    Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement.

  5. Rotatable stem and lock

    DOEpatents

    Deveney, J.E.; Sanderson, S.N.

    1981-10-27

    A valve stem and lock is disclosed which includes a housing surrounding a valve stem, a solenoid affixed to an interior wall of the housing, an armature affixed to the valve stem and a locking device for coupling the armature to the housing body. When the solenoid is energized, the solenoid moves away from the housing body, permitting rotation of the valve stem.

  6. Rotatable stem and lock

    DOEpatents

    Deveney, Joseph E.; Sanderson, Stephen N.

    1984-01-01

    A valve stem and lock include a housing surrounding a valve stem, a solenoid affixed to an interior wall of the housing, an armature affixed to the valve stem and a locking device for coupling the armature to the housing body. When the solenoid is energized, the solenoid moves away from the housing body, permitting rotation of the valve stem.

  7. Medical students and controversial ethical issues: results from the multicenter study SBRAME.

    PubMed

    Lucchetti, Giancarlo; de Oliveira, Leandro Romani; Leite, José Roberto; Lucchetti, Alessandra Lamas Granero

    2014-12-15

    Medical students(MS) will face ethical issues throughout their lives as doctors. The present study aims to investigate medical students' opinions on controversial ethical issues and factors associated with these opinions. SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study involving 12 Brazilian medical schools with 5950 MS. Participants completed a questionnaire that collected information on socio-demographic data, medical schools characteristics, religious beliefs and opinions on controversial ethical issues. Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women and the mean age was 22.5 years. In general, most MS have no objections to prescription of birth control (90.8%), adult stem cell use (87.5%), embryonic stem cell use (82.0%) and abortion for genetic reasons (51.2%). Approximately half of students have no objections to human cloning (47.3%), 45.7% to withdrawal of artificial life support, 41.4% to euthanasia and 23.3% to abortion for failed contraception. Socio-demographic data such as age, gender and income had little influence on MS opinions. On the other hand, medical schools characteristics (number of medical students in the university, year of medical school foundation, location of the university and type of university) and religious aspects (religious affiliation, religious attendance, non-organizational religiousness and intrinsic religiousness) were highly correlated with their opinions. In general, MS with more supportive opinions on controversial ethical issues were less religious and from non-traditional (newer), urban, public and bigger universities. The current study reveals MS have different opinions regarding controversial ethical issues. Noteworthy, these opinions seem to be shaped more by university characteristics and religious beliefs than socio-demographic data.

  8. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma.

    PubMed

    Fehniger, Todd A; Larson, Sarah; Trinkaus, Kathryn; Siegel, Marilyn J; Cashen, Amanda F; Blum, Kristie A; Fenske, Timothy S; Hurd, David D; Goy, Andre; Schneider, Stephanie E; Keppel, Catherine R; Wagner-Johnston, Nina D; Carson, Kenneth R; Bartlett, Nancy L

    2011-11-10

    Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

  9. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  10. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.

    PubMed

    Bringhen, Sara; Petrucci, Maria Teresa; Larocca, Alessandra; Conticello, Concetta; Rossi, Davide; Magarotto, Valeria; Musto, Pellegrino; Boccadifuoco, Luana; Offidani, Massimo; Omedé, Paola; Gentilini, Fabiana; Ciccone, Giovannino; Benevolo, Giulia; Genuardi, Mariella; Montefusco, Vittorio; Oliva, Stefania; Caravita, Tommaso; Tacchetti, Paola; Boccadoro, Mario; Sonneveld, Pieter; Palumbo, Antonio

    2014-07-03

    This multicenter, open-label phase 2 trial determined the safety and efficacy of carfilzomib, a novel and irreversible proteasome inhibitor, in combination with cyclophosphamide and dexamethasone (CCyd) in patients with newly diagnosed multiple myeloma (NDMM) ≥65 years of age or who were ineligible for autologous stem cell transplantation. Patients (N = 58) received CCyd for up to 9 28-day cycles, followed by maintenance with carfilzomib until progression or intolerance. After a median of 9 CCyd induction cycles (range 1-9), 95% of patients achieved at least a partial response, 71% achieved at least a very good partial response, 49% achieved at least a near complete response, and 20% achieved stringent complete response. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 76% and 87%, respectively. The most frequent grade 3 to 5 toxicities were neutropenia (20%), anemia (11%), and cardiopulmonary adverse events (7%). Peripheral neuropathy was limited to grades 1 and 2 (9%). Fourteen percent of patients discontinued treatment because of adverse events, and 21% of patients required carfilzomib dose reductions. In summary, results showed high complete response rates and a good safety profile. This trial was registered at clinicaltrials.gov as #NCT01346787.

  11. Analysis of different routes of administration of heterologous 5-azacytidine-treated mesenchymal stem cells in a porcine model of myocardial infarction.

    PubMed

    Moscoso, I; Barallobre, J; de Ilarduya, O M; Añón, P; Fraga, M; Calviño, R; Aldama, G; Doménech, N

    2009-01-01

    Stem cell therapy constitutes an exciting, powerful therapy to repair the heart. Nevertheless, there are numerous doubts about the best route of stem cell administration to achieve implantation into the injured myocardium. Development of a preclinical, large animal model may be useful to obtain a better approach to clinical situations. The aim of this work was to study the effectiveness of various routes of heterologous bone marrow mesenchymal stem cell (MSCs) administration in a porcine model of myocardial infarction. MSC treated with 5-azacytidine were stained with a fluorescent compound (DiO) before their administration to previously infarcted pigs via 3 routes: intracoronary (IC), intramyocardial (IM), or endocardial (EC; n = 5 each group). Healthy, noninfarcted animals were used as a control group. At 30 days after delivery, hearts were divided into 12 parts: infarcted zone (1-6), right-left atria, interatrial and interventricular septa, and right-left ventricles. In each zone we looked for and quantified, injected fluorescence-stained cells. In the animals in which presence of DiO-stained cells was detected, cells were located preferentially in the infarcted zone and not in the atria, ventricles, or septa. Comparing various administration routes, the mean number of engrafted cells within the infarct zone was significantly greater after IC infusion than either IM or EC injection. Fluorescent cells were not observed in healthy zones of the myocardium or in healthy animals.

  12. Multicenter patient records research: security policies and tools.

    PubMed

    Behlen, F M; Johnson, S B

    1999-01-01

    The expanding health information infrastructure offers the promise of new medical knowledge drawn from patient records. Such promise will never be fulfilled, however, unless researchers first address policy issues regarding the rights and interests of both the patients and the institutions who hold their records. In this article, the authors analyze the interests of patients and institutions in light of public policy and institutional needs. They conclude that the multicenter study, with Institutional Review Board approval of each study at each site, protects the interests of both. "Anonymity" is no panacea, since patient records are so rich in information that they can never be truly anonymous. Researchers must earn and respect the trust of the public, as responsible stewards of facts about patients' lives. The authors find that computer security tools are needed to administer multicenter patient records studies and describe simple approaches that can be implemented using commercial database products.

  13. Multi-Center Traffic Management Advisor Operational Field Test Results

    NASA Technical Reports Server (NTRS)

    Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

    2005-01-01

    The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

  14. Retrieval of the Leadless Cardiac Pacemaker: A Multicenter Experience.

    PubMed

    Reddy, Vivek Y; Miller, Marc A; Knops, Reinoud E; Neuzil, Petr; Defaye, Pascal; Jung, Werner; Doshi, Rahul; Castellani, Mark; Strickberger, Adam; Mead, R Hardwin; Doppalapudi, Harish; Lakkireddy, Dhanunjaya; Bennett, Matthew; Sperzel, Johannes

    2016-12-01

    Leadless cardiac pacemakers have emerged as a safe and effective alternative to conventional transvenous single-chamber ventricular pacemakers. Herein, we report a multicenter experience on the feasibility and safety of acute retrieval (<6 weeks) and chronic retrieval (>6 weeks) of the leadless cardiac pacemaker in humans. This study included patients enrolled in 3 multicenter trials, who received a leadless cardiac pacemaker implant and who subsequently underwent a device removal attempt. The overall leadless pacemaker retrieval success rate was 94%: for patients whose leadless cardiac pacemaker had been implanted for <6 weeks (acute retrieval cohort), complete retrieval was achieved in 100% (n=5/5); for those implanted for ≥ 6 weeks (chronic retrieval cohort), retrieval was achieved in 91% (n=10/11) of patients. The mean duration of time from implant to retrieval attempt was 346 days (range, 88-1188 days) in the chronic retrieval cohort, and nearly two thirds (n=7; 63%) had been implanted for >6 months before the retrieval attempt. There were no procedure-related adverse events at 30 days post retrieval procedure. This multicenter experience demonstrated the feasibility and safety of retrieving a chronically implanted single-chamber (right ventricle) active fixation leadless pacemaker. URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02051972, NCT02030418, and NCT01700244. © 2016 American Heart Association, Inc.

  15. The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease

    PubMed Central

    Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.

    2017-01-01

    Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. PMID:26196261

  16. Effect of intravenous and intracoronary melatonin as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: Results of the Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty trial.

    PubMed

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; de la Torre-Hernandez, Jose M; Gonzalez-Gonzalez, Julia; Garcia-Camarero, Tamara; Consuegra-Sanchez, Luciano; Garcia-Saiz, Maria Del Mar; Aldea-Perona, Ana; Virgos-Aller, Tirso; Azpeitia, Agueda; Reiter, Russel J

    2017-01-01

    The MARIA randomized trial evaluated the efficacy and safety of melatonin for the reduction of reperfusion injury in patients undergoing revascularization for ST-elevation myocardial infarction (STEMI). This was a prespecified interim analysis. A total of 146 patients presenting with STEMI within 6 hours of chest pain onset were randomized to receive intravenous and intracoronary melatonin (n=73) or placebo (n=73) during primary percutaneous coronary intervention (PPCI). Primary endpoint was myocardial infarct size as assessed by magnetic resonance imaging (MRI) at 6 ± 2 days. Secondary endpoints were changes in left ventricular volumes and ejection fraction (LVEF) at 130 ± 10 days post-PPCI and adverse events during the first year. No significant differences in baseline characteristics were observed between groups. MRI was performed in 108 patients (86.4%). Myocardial infarct size by MRI evaluated 6 ± 2 days post-PPCI, did not differ between melatonin and placebo groups (P=.63). Infarct size assessed by MRI at 130 ± 10 days post-PPCI, performed in 91 patients (72.8%), did not show statistically significant differences between groups (P=.27). The recovery of LVEF from 6 ± 2 to 130 ± 10 days post-PPCI was greater in the placebo group (60.0 ± 10.4% vs 53.1 ± 12.5%, P=.008). Both left ventricular end-diastolic and end-systolic volumes were lower in the placebo group (P=.01). The incidence of adverse events at 1 year was comparable in both groups (P=.150). Thus, in a nonrestricted STEMI population, intravenous and intracoronary melatonin was not associated with a reduction in infarct size and has an unfavourable effect on the ventricular volumes and LVEF evolution. Likewise, there is lack of toxicity of melatonin with the doses used.

  17. Stem Cell Transplant

    MedlinePlus

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  18. Stem Cell Basics

    MedlinePlus

    ... healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of ... as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates ...

  19. STEM Club Participation and STEM Schooling Outcomes

    ERIC Educational Resources Information Center

    Gottfried, Michael A.; Williams, Darryl N.

    2013-01-01

    To develop a more robust understanding of the relationship between non-formal, school-based STEM activities and students' success and persistence in STEM fields, this study evaluates how math club participation influences math GPA and how science club participation influences science GPA. Additionally, this study evaluates how math or science club…

  20. Hypertensive brain stem encephalopathy.

    PubMed

    Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

    2015-01-01

    A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal.

  1. Understanding STEM: Current Perceptions

    ERIC Educational Resources Information Center

    Brown, Ryan; Brown, Joshua; Reardon, Kristin; Merrill, Chris

    2011-01-01

    In many ways, the push for STEM (science, technology, engineering, and mathematics) education appears to have grown from a concern for the low number of future professionals to fill STEM jobs and careers and economic and educational competitiveness. The proponents of STEM education believe that by increasing math and science requirements in…

  2. Prehospital and en route cricothyrotomy performed in the combat setting: a prospective, multicenter, observational study.

    PubMed

    Barnard, Ed B G; Ervin, Alicia T; Mabry, Robert L; Bebarta, Vikhyat S

    2014-01-01

    Airway compromise is the third most common cause of potentially preventable combat death. Surgical cricothyrotomy is an infrequently performed but lifesaving airway intervention. There are limited published data on prehospital cricothyrotomy in civilian or military settings. Our aim was to prospectively describe the survival rate and complications associated with cricothyrotomy performed in the military prehospital and en route setting. The Life-Saving Intervention (LSI) study is a prospective, institutional review board-approved, multicenter trial examining LSIs performed in the prehospital combat setting. We prospectively recorded LSIs performed on patients in theater who were transported to six combat hospitals. Trained site investigators evaluated patients on arrival and recorded demographics, vital signs, and LSIs performed. LSIs were predefined and include cricothyrotomies, chest tubes, intubations, tourniquets, and other procedures. From the large dataset, we analyzed patients who had a cricothyrotomy performed. Hospital outcomes were cross-referenced from the Department of Defense Trauma Registry. Descriptive statistics or Wilcoxon test (nonparametric) were used for data comparisons; statistical significance was set at p<.05. The primary outcome was success of prehospital and en route cricothyrotomy. Of the 1,927 patients enrolled, 34 patients had a cricothyrotomy performed (1.8%). Median age was 24 years (interquartile range [IQR]: 22.5-25 years), 97% were men. Mechanisms of injury were blast (79%), penetrating (18%), and blunt force (3%), and 83% had major head, face, or neck injuries. Median Glasgow Coma Scale score (GCS) was 3 (IQR: 3-7.5) and four patients had GCS higher than 8. Cricothyrotomy was successful in 82% of cases. Reasons for failure included left main stem intubation (n=1), subcutaneous passage (n=1), and unsuccessful attempt (n=4). Five patients had a prehospital basic airway intervention. Unsuccessful endotracheal intubation preceded 15

  3. Nail stem cells.

    PubMed

    Sellheyer, Klaus

    2013-03-01

    Our knowledge on stem cells of the hair follicle has increased exponentially after the bulge was characterized as the stem cell niche two decades ago. In contrast, little is known about stem cells in the nail unit. Whereas hair follicles are plentiful and easy to access, the human body has only twenty nails and they are rarely biopsied. Therefore, examining fetal material offers unique advantages. In the following mini-review, our current knowledge on nail stem cells is summarized and analogies to the hair follicle stem cells are drawn.

  4. Plant stem cell niches.

    PubMed

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  5. Liver cancer stem cells.

    PubMed

    Sell, Stewart; Leffert, Hyam L

    2008-06-10

    In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas (HCC) arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells? For many years the finding of preneoplastic nodules in the liver during experimental induction of HCCs by chemicals was interpreted to support the hypothesis that HCC arose by dedifferentiation of mature liver cells. More recently, recognition of the role of small oval cells in the carcinogenic process led to a new hypothesis that HCC arises by maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties (ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.

  6. Advancing the evidence base in cancer: psychosocial multicenter trials

    PubMed Central

    2012-01-01

    Background The diagnosis and treatment of cancer is associated with significant distress and psychosocial morbidity. Although psychosocial interventions have been developed in an attempt to improve psychosocial outcomes in cancer patients and survivors, there is continued debate about whether there is adequate high-level evidence to establish the effectiveness of these interventions. The evidence base is limited as a result of numerous challenges faced by those attempting to conduct psychosocial intervention trials within the health system. Barriers include insufficient participant recruitment, difficulty generalizing from single-trial studies, difficulty in building and managing research teams with multidisciplinary expertise, lack of research design expertise and a lack of incentives for researchers conducting intervention research. To strengthen the evidence base, more intervention studies employing methodologically rigorous research designs are necessary. Methods In order to advance the evidence base of interventions designed to improve psychosocial outcomes for cancer patients and survivors, we propose the formation of a collaborative trials group that conducts multicenter trials to test the effectiveness of such interventions. Results Establishment of such a group would improve the quality of the evidence base in psychosocial research in cancer patients, by increasing support for conducting intervention research and providing intervention research training opportunities. A multidisciplinary collaborative group conducting multicenter trials would have the capacity to overcome many of the barriers that currently exist. Conclusions A stronger evidence base is necessary to identify effective psychosocial interventions for cancer patients. The proposed formation of a psycho-oncology collaborative trials group that conducts multicenter trials to test the effectiveness of psychosocial interventions would assist in achieving this outcome. PMID:22992443

  7. Investigating Preservice STEM Teacher Conceptions of STEM Education

    ERIC Educational Resources Information Center

    Radloff, Jeff; Guzey, Selcen

    2016-01-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the…

  8. Investigating Preservice STEM Teacher Conceptions of STEM Education

    ERIC Educational Resources Information Center

    Radloff, Jeff; Guzey, Selcen

    2016-01-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the…

  9. Stem cells remember their grade.

    PubMed

    Lo Celso, Cristina; Scadden, David T

    2007-08-16

    The stem cell state is understood based on what cells do in performance assays, crude measures of a highly refined state. In this issue of Cell Stem Cell, Dykstra et al. (2007) reveal stem cell gradation and the extent to which that gradation is retained in stem cell daughters of hematopoietic stem cells.

  10. Global Collaborative STEM Education

    NASA Astrophysics Data System (ADS)

    Meabh Kelly, Susan; Smith, Walter

    2016-04-01

    Global Collaborative STEM Education, as the name suggests, simultaneously supports two sets of knowledge and skills. The first set is STEM -- science, technology, engineering and math. The other set of content knowledge and skills is that of global collaboration. Successful global partnerships require awareness of one's own culture, the biases embedded within that culture, as well as developing awareness of the collaborators' culture. Workforce skills fostered include open-mindedness, perseverance when faced with obstacles, and resourceful use of technological "bridges" to facilitate and sustain communication. In respect for the 2016 GIFT Workshop focus, Global Collaborative STEM Education projects dedicated to astronomy research will be presented. The projects represent different benchmarks within the Global Collaborative STEM Education continuum, culminating in an astronomy research experience that fully reflects how the global STEM workforce collaborates. To facilitate wider engagement in Global Collaborative STEM Education, project summaries, classroom resources and contact information for established international collaborative astronomy research projects will be disseminated.

  11. Electronic medical record integration with a database for adult congenital heart disease: Early experience and progress in automating multicenter data collection.

    PubMed

    Broberg, Craig S; Mitchell, Julie; Rehel, Silven; Grant, Andrew; Gianola, Ann; Beninato, Peter; Winter, Christiane; Verstappen, Amy; Valente, Anne Marie; Weiss, Joseph; Zaidi, Ali; Earing, Michael G; Cook, Stephen; Daniels, Curt; Webb, Gary; Khairy, Paul; Marelli, Ariane; Gurvitz, Michelle Z; Sahn, David J

    2015-10-01

    The adoption of electronic health records (EHR) has created an opportunity for multicenter data collection, yet the feasibility and reliability of this methodology is unknown. The aim of this study was to integrate EHR data into a homogeneous central repository specifically addressing the field of adult congenital heart disease (ACHD). Target data variables were proposed and prioritized by consensus of investigators at five target ACHD programs. Database analysts determined which variables were available within their institutions' EHR and stratified their accessibility, and results were compared between centers. Data for patients seen in a single calendar year were extracted to a uniform database and subsequently consolidated. From 415 proposed target variables, only 28 were available in discrete formats at all centers. For variables of highest priority, 16/28 (57%) were available at all four sites, but only 11% for those of high priority. Integration was neither simple nor straightforward. Coding schemes in use for congenital heart diagnoses varied and would require additional user input for accurate mapping. There was considerable variability in procedure reporting formats and medication schemes, often with center-specific modifications. Despite the challenges, the final acquisition included limited data on 2161 patients, and allowed for population analysis of race/ethnicity, defect complexity, and body morphometrics. Large-scale multicenter automated data acquisition from EHRs is feasible yet challenging. Obstacles stem from variability in data formats, coding schemes, and adoption of non-standard lists within each EHR. The success of large-scale multicenter ACHD research will require institution-specific data integration efforts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration.

    PubMed

    Dolton, Michael J; Ray, John E; Chen, Sharon C-A; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-11-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P < 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P < 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P < 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (P < 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure

  13. Sickness behavior in feverish children is independent of the severity of fever. An observational, multicenter study

    PubMed Central

    Corrard, François; Copin, Christian; Wollner, Alain; Elbez, Annie; Derkx, Véronique; Bechet, Stéphane; Levy, Corinne; Boucherat, Michel; Cohen, Robert

    2017-01-01

    Background. Objectives Behavioral changes in a febrile child are usually considered to stem from the fever. We studied sickness behavior (SB) in terms of its clinical components and its relation to fever. Methods This observational, multicenter study included children aged 6 months to 3 years who were either febrile (fever ≥12 hours, ≥ 39°C and ≥38°C at inclusion) or non-febrile and well. The child had to have been awake for the 2 hours preceding the consultation and cared for by the parent who brought him/her to the doctor. SB was evaluated according to 6 parameters over this 2-hour period: time spent playing, distance covered, time spent seeking comfort, time spent whining or crying, time spent in a state of irritation or of anger, most distorted facial expression. Two parameters were assessed for the 24-hour period preceding the consultation: time spent sleeping and appetite. The parent reported the degree of change in these parameters compared with the usual situation, using rating scales. Results 200 febrile children (most with nonspecific upper respiratory infections) and 200 non-febrile children were included. The mean values of the 8 parameters differed significantly (p<0.001) between the 2 groups and were independent of the height of fever at inclusion in the febrile children. In the study conditions, paracetamol failed to improve SB when the child was still feverish. Conclusion The 8 parameters suggested that SB and fever are two independent manifestations that are activated simultaneously during an infection. This independence is in harmony with recommendations to treat the discomfort of SB and not the fever. PMID:28278190

  14. [Multicenter trial for sudden hearing loss therapy - planning and concept].

    PubMed

    Plontke, S K; Girndt, M; Meisner, C; Probst, R; Oerlecke, I; Richter, M; Steighardt, J; Dreier, G; Weber, A; Baumann, I; Plößl, S; Löhler, J; Laszig, R; Werner, J A; Rahne, T

    2016-04-01

    Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

  15. MAIN ETHICAL BREACHES IN MULTICENTER CLINICAL TRIALS REGULATIONS OF TURKEY

    PubMed Central

    Ekmekci, P. Elif

    2017-01-01

    Turkey has been a growing market for multicenter clinical trials for the last ten years and is considered among the top ten countries in terms of potential study subject populations. The objective of increasing the share of Turkey in multicenter clinical trials is strongly supported. This ambitious goal of Turkey raises the need to have regulations in compliance with other leading countries conducting clinical trials. The latest published Turkish regulations on clinical trials are structured in compliance with the International Conference on Harmonization (ICH) Guidelines and in harmony with the regulations of other leading countries in clinical research, such as the US. There are still flaws in Turkish regulation with the risk of violating human subjects’ rights and issues with responsible conduct of research. The aim of this article is to compare Turkish clinical trials regulations with those of the US, to determine if there exists any incompatibility between the countries’ regulations and, if so, how to ameliorate these. The main flaws in Turkish clinical trials regulations are identified as follows: lack of definition of the term “human subject; absence of explicit referral to the unacceptability of Conflict of Interest (COI) and taking measures to avoid it; exiguity of emphasis on plurality of the IRB members; nonexistence of a clear expression that this is research; and clinical equipoise, regarding the treatment of the existing clinical problem and lack of integration with international accreditation systems for Institutional Review Boards.

  16. Research and operational applications in multi-center ensemble forecasting

    NASA Astrophysics Data System (ADS)

    Zhu, Y.; Toth, Z.

    2009-05-01

    The North American Ensemble Forecast System (NAEFS) was built up in 2004 by the Meteorological Service of Canada (MSC), the National Meteorological Service of Mexico (NMSM), and the US National Weather Service (NWS) as an operational multi-center ensemble forecast system. Currently it combines the 20-member MSC and NWS ensembles to form a joint ensemble of 40 members twice a day. The joint ensemble forecast, after bias correction and statistical downscaling, is used to generate a suite of products for CONUS, North America and for other regions of the globe. The THORPEX Interactive Grand Global Ensemble (TIGGE) project has been established a few years ago to collect operational global ensemble forecasts from world centers, and distribute to the scientific community, to encourage research leading to the acceleration of improvements in the skill and utility of high impact weather forecasts. TIGGE research is expected to advise the development of the operational NAEFS system and eventually the two projects are expected to converge into a single operational system, the Global Interactive Forecast System (GIFS). This presentation will review recent developments, the current status, and plans related to the TIGGE research and NAEFS operational multi-center ensemble projects.

  17. Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter Study.

    PubMed

    Wang, Jeffrey C; Buser, Zorica; Fish, David E; Lord, Elizabeth L; Roe, Allison K; Chatterjee, Dhananjay; Gee, Erica L; Mayer, Erik N; Yanez, Marisa Y; McBride, Owen J; Cha, Peter I; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel

    2017-04-01

    A retrospective multicenter study. Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence. The purpose of this study was to determine the intraoperative mortality rates and associated risk factors in patients undergoing cervical spine surgery. Twenty-one surgical centers from the AOSpine North America Clinical Research Network participated in the study. Medical records of patients who received cervical spine surgery from January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of intraoperative death. A total of 258 patients across 21 centers met the inclusion criteria. Most of the surgeries were done using the anterior approach (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient age was 57.1 ± 13.2 years, and there were more male patients (54.7% male and 45.3% female). There was no case of intraoperative death. Death during cervical spine surgery is a very rare complication. In our multicenter study, there was a 0% mortality rate. Using an adequate surgical approach for patient diagnosis and comorbidities may be the reason how the occurrence of this catastrophic adverse event was prevented in our patient population.

  18. Adjusted regression trend test for a multicenter clinical trial.

    PubMed

    Quan, H; Capizzi, T

    1999-06-01

    Studies using a series of increasing doses of a compound, including a zero dose control, are often conducted to study the effect of the compound on the response of interest. For a one-way design, Tukey et al. (1985, Biometrics 41, 295-301) suggested assessing trend by examining the slopes of regression lines under arithmetic, ordinal, and arithmetic-logarithmic dose scalings. They reported the smallest p-value for the three significance tests on the three slopes for safety assessments. Capizzi et al. (1992, Biometrical Journal 34, 275-289) suggested an adjusted trend test, which adjusts the p-value using a trivariate t-distribution, the joint distribution of the three slope estimators. In this paper, we propose an adjusted regression trend test suitable for two-way designs, particularly for multicenter clinical trials. In a step-down fashion, the proposed trend test can be applied to a multicenter clinical trial to compare each dose with the control. This sequential procedure is a closed testing procedure for a trend alternative. Therefore, it adjusts p-values and maintains experimentwise error rate. Simulation results show that the step-down trend test is overall more powerful than a step-down least significant difference test.

  19. Chest radiographic data acquisition and quality assurance in multicenter studies

    PubMed Central

    Schluchter, Mark; Wood, Beverly P.; Berdon, Walter E.; Boechat, M. Ines; Easley, Kirk A.; Meziane, Moulay; Mellins, Robert B.; Norton, Karen I.; Singleton, Edward; Trautwein, Lynn

    2015-01-01

    Background Multicenter studies rely on data derived from different institutions. Forms can be designed to standardize the reporting process allowing reliable comparison of data. Objective The purpose of the report is to provide a standardized method, developed as a part of a multicenter study of vertically transmitted HIV, for assessing chest radiographic results. Materials and methods Eight hundred and five infants and children were studied at five centers; 3057 chest radiographs were scored. Data were entered using a forced-choice, graded response for 12 findings. Quality assurance measures and inter- rater agreement statistics are reported. Results The form used for reporting chest radiographic results is presented. Inter-rater agreement was moderate to high for most findings, with the best correlation reported for the presence of bronchovascular markings and/or reticular densities addressed as a composite question (kappa = 0.71). The presence of nodular densities (kappa = 0.56) and parenchymal consolidation (kappa = 0.57) had moderate agreement. Agreement for lung volume was low. Conclusion The current tool, developed for use in the pediatric population, is applicable to any study involving the assessment of pediatric chest radiographs for a large population, whether at one or many centers. PMID:9361051

  20. Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

    PubMed Central

    Ugurluer, Gamze; Miller, Robert C.; Li, Yexiong; Thariat, Juliette; Ghadjar, Pirus; Schick, Ulrike; Ozsahin, Mahmut

    2016-01-01

    Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions. Liver function tests were elevated in 56.1% of patients. The most common histopathological diagnosis was diffuse large B-cell lymphoma (65.9%). Most of the patients received Chop-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens; 4 patients received radiotherapy (dose range, 30.6-40.0 Gy). Median survival was 163 months, and 5- and 10-year overall survival rates were 77 and 59%, respectively. The 5- and 10-year disease-free and lymphoma-specific survival rates were 69, 56, 87 and 70%, respectively. Multivariate analysis revealed that fever, weight loss, and normal hemoglobin level were the independent factors influencing the outcome. In this retrospective multicenter RCN study, patients with PHL had a relatively better prognosis than that reported elsewhere. Multicenter prospective studies are still warranted to establish treatment guidelines, outcome, and prognostic factors. PMID:27746888

  1. MAIN ETHICAL BREACHES IN MULTICENTER CLINICAL TRIALS REGULATIONS OF TURKEY.

    PubMed

    Ekmekci, P Elif

    2016-01-01

    Turkey has been a growing market for multicenter clinical trials for the last ten years and is considered among the top ten countries in terms of potential study subject populations. The objective of increasing the share of Turkey in multicenter clinical trials is strongly supported. This ambitious goal of Turkey raises the need to have regulations in compliance with other leading countries conducting clinical trials. The latest published Turkish regulations on clinical trials are structured in compliance with the International Conference on Harmonization (ICH) Guidelines and in harmony with the regulations of other leading countries in clinical research, such as the US. There are still flaws in Turkish regulation with the risk of violating human subjects' rights and issues with responsible conduct of research. The aim of this article is to compare Turkish clinical trials regulations with those of the US, to determine if there exists any incompatibility between the countries' regulations and, if so, how to ameliorate these. The main flaws in Turkish clinical trials regulations are identified as follows: lack of definition of the term "human subject; absence of explicit referral to the unacceptability of Conflict of Interest (COI) and taking measures to avoid it; exiguity of emphasis on plurality of the IRB members; nonexistence of a clear expression that this is research; and clinical equipoise, regarding the treatment of the existing clinical problem and lack of integration with international accreditation systems for Institutional Review Boards.

  2. Computational method for general multicenter electronic structure calculations.

    PubMed

    Batcho, P F

    2000-06-01

    Here a three-dimensional fully numerical (i.e., chemical basis-set free) method [P. F. Batcho, Phys. Rev. A 57, 6 (1998)], is formulated and applied to the calculation of the electronic structure of general multicenter Hamiltonian systems. The numerical method is presented and applied to the solution of Schrödinger-type operators, where a given number of nuclei point singularities is present in the potential field. The numerical method combines the rapid "exponential" convergence rates of modern spectral methods with the multiresolution flexibility of finite element methods, and can be viewed as an extension of the spectral element method. The approximation of cusps in the wave function and the formulation of multicenter nuclei singularities are efficiently dealt with by the combination of a coordinate transformation and a piecewise variational spectral approximation. The complete system can be efficiently inverted by established iterative methods for elliptical partial differential equations; an application of the method is presented for atomic, diatomic, and triatomic systems, and comparisons are made to the literature when possible. In particular, local density approximations are studied within the context of Kohn-Sham density functional theory, and are presented for selected subsets of atomic and diatomic molecules as well as the ozone molecule.

  3. Stress and stem cells.

    PubMed

    Tower, John

    2012-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress.

  4. Stem Cells and Aging.

    PubMed

    Koliakos, George

    2017-02-01

    The article is a presentation at the 4th Conference of ESAAM, which took place on October 30-31, 2015, in Athens, Greece. Its purpose was not to cover all aspects of cellular aging but to share with the audience of the Conference, in a 15-minute presentation, current knowledge about the rejuvenating and repairing somatic stem cells that are distinct from other stem cell types (such as embryonic or induced pluripotent stem cells), emphasize that our body in old age cannot take advantage of these rejuvenating cells, and provide some examples of novel experimental stem cell applications in the field of rejuvenation and antiaging biomedical research.

  5. Stress and stem cells

    PubMed Central

    Tower, John

    2013-01-01

    The unique properties and functions of stem cells make them particularly susceptible to stresses and also lead to their regulation by stress. Stem cell division must respond to the demand to replenish cells during normal tissue turnover as well as in response to damage. Oxidative stress, mechanical stress, growth factors, and cytokines signal stem cell division and differentiation. Many of the conserved pathways regulating stem cell self-renewal and differentiation are also stress-response pathways. The long life span and division potential of stem cells create a propensity for transformation (cancer) and specific stress responses such as apoptosis and senescence act as antitumor mechanisms. Quiescence regulated by CDK inhibitors and a hypoxic niche regulated by FOXO transcription factor function to reduce stress for several types of stem cells to facilitate long-term maintenance. Aging is a particularly relevant stress for stem cells, because repeated demands on stem cell function over the life span can have cumulative cell-autonomous effects including epigenetic dysregulation, mutations, and telomere erosion. In addition, aging of the organism impairs function of the stem cell niche and systemic signals, including chronic inflammation and oxidative stress. PMID:23799624

  6. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  7. Information on Stem Cell Research

    MedlinePlus

    ... Home » Current Research » Focus on Research Focus on Stem Cell Research Stem cells possess the unique ability to differentiate ... virus infection. To search the complete list of stem cell research projects funded by NIH please go to NIH ...

  8. Stem Cell Transplants (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants A ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  9. Real-time assessment of myocardial viability in the catheterization laboratory using the intracoronary electrograms recorded by the PTCA guidewire in patients with left ventricular dysfunction: comparison with delayed-enhancement magnetic resonance imaging.

    PubMed

    Petrucci, Ettore; Balian, Vruyr; Bocchieri, Andrea

    2014-09-01

    This study aimed to determine whether the intracoronary electrograms (IC-EGMs) recorded using a standard percutaneous coronary intervention guidewire could provide myocardial viability information. The revascularization of dysfunctional but viable myocardium may confer prognostic benefits compared with medical therapy in patients with post-ischemic heart failure. However, knowledge of myocardial viability is often unavailable at the time of the procedure. The peak-to-peak voltage of 317 IC-EGMs recordings from 25 patients with a previous myocardial infarction and systolic dysfunction were matched with corresponding delayed-enhancement magnetic resonance imaging sites using a 17-segment model of the left ventricle. Sixty-seven recordings were obtained from segments classified as complete scar on delayed-enhancement magnetic resonance imaging (group A), 162 from partially viable segments (group B), and 88 from fully viable segments (group C). Three high-pass (HP) filters (0.5, 30, and 100 Hz) were applied to the signals to modulate their spatial resolution. For all filters, the peak-to-peak voltage significantly decreased from group C to group B to group A (p < 0.001 for all comparisons). When receiver-operating characteristic analysis was used to compare nonviable (group A) with viable (group B + C) segments, the optimal discriminating voltages were 4.6, 2.2, and 0.78 mV for, respectively, HP-0.5, HP-30, and HP-100 filters, with a sensitivity of 92%, 94%, and 99% and a specificity of 70%, 79%, and 69%. The amplitude of the IC-EGMs discriminates viable from nonviable left ventricular segments. Because this technique is simple and inexpensive and provides real-time results, it is potentially useful to aid decision making in the catheterization laboratory. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Investigating Preservice STEM Teacher Conceptions of STEM Education

    NASA Astrophysics Data System (ADS)

    Radloff, Jeff; Guzey, Selcen

    2016-10-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the literature suggests no leading conception of STEM education, and little is known about how preservice STEM teachers are conceptualizing STEM education. In order to explore preservice STEM teacher conceptions of STEM education, preservice teachers at a large, Midwestern research university were given an open-ended survey eliciting both textual and visual responses. Here, we report and discuss the results of employing this instrument in relation with the current STEM conceptualization literature.

  11. Myeloproliferative neoplasm stem cells.

    PubMed

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2, CALR, or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC.

  12. Making STEM Connections

    ERIC Educational Resources Information Center

    Stump, Sheryl L.; Bryan, Joel A.; McConnell, Tom J.

    2016-01-01

    Integrated approaches to education in science, technology, engineering, and mathematics (STEM), especially those set in the context of real-world situations, can motivate and deepen students' learning of the STEM subjects (National Academy of Engineering and National Research Council 2014). This article describes two integrated investigations used…

  13. STEM Careers Ambassadors

    ERIC Educational Resources Information Center

    Eaton, Denise

    2011-01-01

    This article is designed to help teachers feel more confident in their work with STEM Ambassadors to further enhance enrichment activities. Skills shortages in Science, Technology, Engineering, Maths (STEM) and the Built Environment are well documented, and will continue to be an issue whether people are in a period of recession or recovery. The…

  14. STEM School Discourse Patterns

    ERIC Educational Resources Information Center

    Tofel-Grehl, Colby; Callahan, Carolyn M.

    2016-01-01

    Analysis of discursive practices in science classrooms within STEM schools may provide meaningful information about the nature of these classrooms and, potentially, their uniqueness. Full descriptions of current practice can serve as a foundation for exploring the differences in instructional norms within STEM specialized schools and across…

  15. Teaching STEM by Design

    ERIC Educational Resources Information Center

    Billiar, Kristen; Hubelbank, Jeanne; Oliva, Thomas; Camesano, Terri

    2014-01-01

    Developing innovative science, technology, engineering and mathematics (STEM) curricula that elicit student excitement for learning is a continuous challenge for K-12 STEM teachers. Generating these lessons while meeting conflicting pedagogical objectives and constraints of time, content, and cost from various parties is truly a challenging task…

  16. Bringing STEM to Life

    ERIC Educational Resources Information Center

    Berkeihiser, Mike; Ray, Dori

    2013-01-01

    The interdisciplinary approach that science, technology, engineering and mathematics (STEM) projects inspire in both teachers and students "brings to light a larger picture that promotes real-world scientific applications, which has in turn been shown to increase undergraduate persistence in STEM." The high school students have been…

  17. Designing for STEM Integration

    ERIC Educational Resources Information Center

    Berland, Leema K.

    2013-01-01

    We are increasingly seeing an emphasis on STEM integration in high school classrooms such that students will learn and apply relevant math and science content while simultaneously developing engineering habits of mind. However, research in both science education and engineering education suggests that this goal of truly integrating STEM is rife…

  18. Colorectal cancer stem cells.

    PubMed

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  19. Designing for STEM Integration

    ERIC Educational Resources Information Center

    Berland, Leema K.

    2013-01-01

    We are increasingly seeing an emphasis on STEM integration in high school classrooms such that students will learn and apply relevant math and science content while simultaneously developing engineering habits of mind. However, research in both science education and engineering education suggests that this goal of truly integrating STEM is rife…

  20. Bringing STEM to Life

    ERIC Educational Resources Information Center

    Berkeihiser, Mike; Ray, Dori

    2013-01-01

    The interdisciplinary approach that science, technology, engineering and mathematics (STEM) projects inspire in both teachers and students "brings to light a larger picture that promotes real-world scientific applications, which has in turn been shown to increase undergraduate persistence in STEM." The high school students have been…

  1. STEM School Discourse Patterns

    ERIC Educational Resources Information Center

    Tofel-Grehl, Colby; Callahan, Carolyn M.

    2016-01-01

    Analysis of discursive practices in science classrooms within STEM schools may provide meaningful information about the nature of these classrooms and, potentially, their uniqueness. Full descriptions of current practice can serve as a foundation for exploring the differences in instructional norms within STEM specialized schools and across…

  2. Making STEM Connections

    ERIC Educational Resources Information Center

    Stump, Sheryl L.; Bryan, Joel A.; McConnell, Tom J.

    2016-01-01

    Integrated approaches to education in science, technology, engineering, and mathematics (STEM), especially those set in the context of real-world situations, can motivate and deepen students' learning of the STEM subjects (National Academy of Engineering and National Research Council 2014). This article describes two integrated investigations used…

  3. Lock For Valve Stem

    NASA Technical Reports Server (NTRS)

    Burley, Richard K.; Guirguis, Kamal S.

    1991-01-01

    Simple, cheap device locks valve stem so its setting cannot be changed by unauthorized people. Device covers valve stem; cover locked in place with standard padlock. Valve lock made of PVC pipe and packing band. Shears, drill or punch, and forming rod only tools needed.

  4. State of STEM

    NASA Image and Video Library

    2013-02-13

    NASA Deputy Administrator Lori Garver listens to a question during the first-ever State of Science, Technology, Engineering and Math Event (SoSTEM) held at the Eisenhower Executive Office Building, Wednesday, Feb. 13, 2013 in Washington. Garver was part of a panel that took questions from a crowd of STEM students. Photo Credit: (NASA/Bill Ingalls)

  5. STEM Careers Ambassadors

    ERIC Educational Resources Information Center

    Eaton, Denise

    2011-01-01

    This article is designed to help teachers feel more confident in their work with STEM Ambassadors to further enhance enrichment activities. Skills shortages in Science, Technology, Engineering, Maths (STEM) and the Built Environment are well documented, and will continue to be an issue whether people are in a period of recession or recovery. The…

  6. Expanding STEM Education | Poster

    Cancer.gov

    Editor’s note: This article is written as a reflection on experiential STEM education by a student who completed her Werner H. Kirsten internship in June 2015. Here, she advocates for incorporating hands-on experience into STEM curricula. If the only way for high school students to learn science, technology, engineering, and mathematics (STEM) is through textbooks, then count me out. But how then do you get students to learn STEM outside of the classroom? The focus of this article is to advocate for high school STEM education through experiential learning. Tom Freston, one of the founders and the chief executive officer (CEO) of MTV Productions, said in an interview in Men’s Journal that “innovation is taking two things that already exist and...

  7. Intraoperative Stem Cell Therapy

    PubMed Central

    Coelho, Mónica Beato; Cabral, Joaquim M.S.; Karp, Jeffrey M.

    2013-01-01

    Stem cells hold significant promise for regeneration of tissue defects and disease-modifying therapies. Although numerous promising stem cell approaches are advancing in clinical trials, intraoperative stem cell therapies offer more immediate hope by integrating an autologous cell source with a well-established surgical intervention in a single procedure. Herein, the major developments in intraoperative stem cell approaches, from in vivo models to clinical studies, are reviewed, and the potential regenerative mechanisms and the roles of different cell populations in the regeneration process are discussed. Although intraoperative stem cell therapies have been shown to be safe and effective for several indications, there are still critical challenges to be tackled prior to adoption into the standard surgical armamentarium. PMID:22809140

  8. Expanding STEM Education | Poster

    Cancer.gov

    Editor’s note: This article is written as a reflection on experiential STEM education by a student who completed her Werner H. Kirsten internship in June 2015. Here, she advocates for incorporating hands-on experience into STEM curricula. If the only way for high school students to learn science, technology, engineering, and mathematics (STEM) is through textbooks, then count me out. But how then do you get students to learn STEM outside of the classroom? The focus of this article is to advocate for high school STEM education through experiential learning. Tom Freston, one of the founders and the chief executive officer (CEO) of MTV Productions, said in an interview in Men’s Journal that “innovation is taking two things that already exist and...

  9. Hydrogen multicenter bond in oxide and nitride semiconductors

    NASA Astrophysics Data System (ADS)

    Janotti, Anderson

    2009-03-01

    Hydrogen is a very reactive atom, occurring in virtually all organic and in many inorganic compounds. It can form a purely covalent bond, in which two hydrogen atoms share a pair of electrons in a two-electron two-center bond, as well as polar covalent bonds, such as in an H2O molecule. In solids, hydrogen is usually considered as an interstitial impurity. In elemental semiconductors, such as silicon, hydrogen forms a three-center bond when located at the bond center. In compound semiconductors, hydrogen bonds to the anionic species in p-type material, and to the cationic species in n-type. Thus far, hydrogen in solids has been found to form chemical bonds with one, two, or at most three other atoms. Higher coordination numbers are exceedingly rare and have been reported only for clusters. In this talk we will show that hydrogen is capable of forming multicenter bonds in solids, occupying substitutional sites. As examples, we discuss substitutional hydrogen impurities in oxides (ZnO, MgO, SnO2, TiO2) [1,2] and nitrides (InN, AlN, GaN) [3]. Based on first-principles calculations we show that hydrogen replaces oxygen (nitrogen) and forms genuine chemical bonds with multiple metal atoms, in truly multicoordinated configurations. These multicenter bonds are surprisingly strong despite the large hydrogen-metal distances when compared to typical values in hydrogen two-center bonds. Hydrogen in the multicenter bond configuration is a shallow donor in a number of materials. In conducting oxides, it provides a consistent explanation for the observed dependence of electrical conductivity on oxygen partial pressure, thus resolving a long-standing controversy on the role of point defects in unintentional n-type conductivity [1,2]. [4pt] [1] A. Janotti and C. G Van de Walle, Nature Materials 6, 44 (2007). [0pt] [2] A. K. Singh, A. Janotti, M. Scheffler, and C. G. Van de Walle, Phys. Rev. Lett. 101, 055502 (2008). [0pt] [3] A. Janotti and C. G. Van de Walle, Appl. Phys. Lett. 92

  10. [On plant stem cells and animal stem cells].

    PubMed

    You, Yun; Jiang, Chao; Huang, Lu-Qi

    2014-01-01

    A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both kingdoms, stem cells are defined by their clonogenic properties and are maintained by intercellular signals. The signaling molecules are different in plants and animals stem cell niches, but the roles of argonaute and polycomb group proteins suggest that there are some molecular similarities.

  11. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    NASA Astronaut Joe Acaba, left, is interviewed by National Geographic Kids reporter Trevor Jehl ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  12. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    NASA Astronaut Joe Acaba, left, is interviewed by TIME for Kids reporter Grace Clark ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  13. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Environmentalist and third-year law student at Elon University School of Law Tyrone Davis speaks at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  14. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    White House innovation expert Cristin Dorgelo speaks at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  15. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Defense Advanced Research Projects Agency (DARPA) Gill Pratt speaks at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  16. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    NASA associate administrator for education and former astronaut Leland Melvin speaks at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. Factors predicting survival in ALS: a multicenter Italian study.

    PubMed

    Calvo, Andrea; Moglia, Cristina; Lunetta, Christian; Marinou, Kalliopi; Ticozzi, Nicola; Ferrante, Gianluca Drago; Scialo, Carlo; Sorarù, Gianni; Trojsi, Francesca; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Chiò, Adriano; Sansone, Valeria Ada; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Monsurrò, Maria Rosaria; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fini, Nicola; Mandrioli, Jessica

    2017-01-01

    The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

  18. Descriptive epidemiology of the Multicenter ACL Revision Study (MARS) cohort.

    PubMed

    Wright, Rick W; Huston, Laura J; Spindler, Kurt P; Dunn, Warren R; Haas, Amanda K; Allen, Christina R; Cooper, Daniel E; DeBerardino, Thomas M; Lantz, Brett Brick A; Mann, Barton J; Stuart, Michael J

    2010-10-01

    Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Cross-sectional study; Level of evidence, 2. After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (<1%), and no response (<1%). Previous graft present at the time of injury was 70% autograft, 27% allograft, 2% combination, and 1% unknown. Sixty-two percent were more than 2 years removed from their last reconstruction. Graft choice for revision ACL reconstruction was 45% autograft, 54% allograft, and more than 1% both allograft and autograft. Meniscus and/or chondral damage was found in 90% of patients. The MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most common mode of failure. Allograft graft choice is more common

  19. Multicenter Validation of an MMSE-MoCA Conversion Table.

    PubMed

    Bergeron, David; Flynn, Kelsey; Verret, Louis; Poulin, Stéphane; Bouchard, Rémi W; Bocti, Christian; Fülöp, Tamàs; Lacombe, Guy; Gauthier, Serge; Nasreddine, Ziad; Laforce, Robert Jr

    2017-05-01

    Accumulating evidence points to the superiority of the MoCA over the MMSE as a cognitive screening tool. To facilitate the transition from the MMSE to the MoCA in clinical and research settings, authors have developed MMSE-MoCA conversion tables. However, it is unknown whether a conversion table generated from Alzheimer's disease (AD) patients would apply to patients with other dementia subtypes like vascular dementia or frontotemporal dementia. Furthermore, the reliability and accuracy of MMSE-MoCA conversion tables has not been properly evaluated. We retrospectively examined the MMSE-MoCA relationship in a large multicenter sample gathered from 3 Memory Clinics in Quebec, Canada (1492 patients). We produced an MMSE-MoCA conversion table using the equi-percentile method with log-linear smoothing. We then cross-validated our conversion table with the ADNI dataset (1202 patients) and evaluated its accuracy for future predictions. The MMSE-MoCA conversion table is consistent with previously published tables and has an intra-class correlation of 0.633 with the ADNI sample. However, we found that the MMSE-MoCA relationship is significantly modified by diagnosis (P < .01), with dementia subtypes associated with a dysexecutive syndrome showing a trend towards higher MMSE than other dementia syndromes for a given MoCA score. The large width of 95% confidence interval (CI) for a new prediction suggests questionable reliability for clinical use. In this study, we validated a conversion table between MMSE and MoCA using a large multicenter sample. Our results suggest caution in interpreting the tables in heterogeneous clinical populations, as the MMSE-MoCA relationship may be different across dementia subtypes. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  20. Multicenter study on the safety of bariatric endoscopy.

    PubMed

    Espinet Coll, Eduardo; Nebreda Durán, Javier; López-Nava Breviere, Gontrand; Ducóns García, Julio; Rodríguez-Téllez, Manuel; Crespo García, Javier; Marra-López Valenciano, Carlos

    2017-05-01

    Bariatric endoscopy includes a series of specific techniques focused on the management of obese patients. As a quality criterion, safety as expressed by a minimal incidence of serious complications is required in addition to efficacy. A descriptive, retrospective, multicenter review of the experience recorded at seven hospitals included in the Grupo Español de Endoscopia Bariátrica (GETTEMO) in order to document the incidence, cause, and resolution (including legal consequences) of serious complications reported for each bariatric technique, and according to endoscopist expertise. In all, 6,771 bariatric endoscopic procedures were collected, wherein 57 serious complications (0.84%) were identified. Balloons: Orbera®-Medsil®, 5/5,589; Spatz2® (older model): 44/225; Heliosphere®: 1/70; Obalon®: 0/107. Sutures: POSE®, 5/679; sleeve gastroplasty with Apollo® system: 0/55. Prostheses: Endobarrier®: 2/46. All complications were resolved with medical/endoscopic management except for five cases (0.07%) that required surgery. A single lawsuit occurred (esophageal perforation with Spatz2® balloon), which had a favorable outcome. There was no mortality, and apparently no differences were found according to endoscopist expertise level. In our multicenter experience, bariatric endoscopy may be considered as a safe procedure (0.84% of serious complications in all). However, some devices may induce a higher proportion of complications, such as 19.55% for Spatz2® balloons (already replaced) or 4.34% for Endobarrier® sleeves (at the upper limit of accepted safety), although our experience with the latter is limited. All complications were resolved with conservative medical management, and only exceptionally required surgery (0.07%). No technique-related mortality was seen, and only one lawsuit occurred. Further evolutionary studies are required on the novel endoscopic techniques presently emerging to authenticate our results.

  1. Perianal Crohn Disease in a Large Multicenter Pediatric Collaborative.

    PubMed

    Adler, Jeremy; Dong, Shiming; Eder, Sally J; Dombkowski, Kevin J

    2017-05-01

    Although perianal complications of Crohn disease (CD) are commonly encountered in clinical practice, the epidemiology of perianal CD among populations of children is poorly understood. We sought to characterize the prevalence of perianal disease in a large and diverse population of pediatric patients with CD. We conducted retrospective analyses from a prospective observational cohort, the ImproveCareNow Network (May 2006-October 2014), a multicenter pediatric inflammatory bowel disease quality improvement collaborative. Clinicians prospectively documented physical examination and phenotype classification at outpatient visits. Perianal examination findings and concomitant phenotype change were used to corroborate time of new-onset perianal disease. Results were stratified by age, sex, and race and compared across groups with logistic regression. Cumulative incidence was estimated using Kaplan-Meier analyses and compared between groups with Cox proportional hazard regression models. The registry included 7076 patients with CD (41% girls). Missing/conflicting entries resulted in 397 (6%) patient exclusions. Among the remaining 6679 cases, 1399 (21%) developed perianal disease. Perianal disease was more common among boys (22%) than girls (20%; P = 0.013) and developed sooner after diagnosis among those with later rather than early onset disease (P < 0.001). Perianal disease was also more common among blacks (26%) compared with whites (20%; P = 0.017). Asians with later onset CD developed perianal disease earlier in their disease course (P = 0.01). There was no association between disease location or nutritional status at diagnosis and later development of perianal disease. In this large multicenter collaborative, we found that perianal disease is more common among children with CD than previously recognized. Differences in the development of perianal disease were found across racial and other subgroups. Treatment strategies are needed to prevent

  2. Multicenter-type corrections to standard DFT exchange and correlation functionals

    NASA Astrophysics Data System (ADS)

    Tavernelli, Ivano; Lin, I.-Chun; Rothlisberger, Ursula

    2009-01-01

    We propose to express corrections to the standard approximations of the exchange-correlation functionals in the form of multiatom-centered functionals that can be related to the atoms-in-molecules theory of Bader and a multicenter density expansion. Unlike conventional functionals, the variables of these multicenter functionals are the positions and identities of the nuclei, which can unambiguously be determined from the topology of the electronic density. The proposed multicenter correction is used to provide a theoretical basis for the dispersion-corrected atom-centered potential (DCACP) approach used to improve van der Waals interactions in conventional density functional theory. Convergence to the correct long-range asymptotic behavior of the multicenter expansion for DCACPs is demonstrated in the test case of the H2 van der Waals dimer.

  3. Nuclear receptor regulation of stemness and stem cell differentiation

    PubMed Central

    Jeong, Yangsik

    2009-01-01

    Stem cells include a diverse number of toti-, pluri-, and multi-potent cells that play important roles in cellular genesis and differentiation, tissue development, and organogenesis. Genetic regulation involving various transcription factors results in the self-renewal and differentiation properties of stem cells. The nuclear receptor (NR) superfamily is composed of 48 ligand-activated transcription factors involved in diverse physiological functions such as metabolism, development, and reproduction. Increasing evidence shows that certain NRs function in regulating stemness or differentiation of embryonic stem (ES) cells and tissue-specific adult stem cells. Here, we review the role of the NR superfamily in various aspects of stem cell biology, including their regulation of stemness, forward- and trans-differentiation events; reprogramming of terminally differentiated cells; and interspecies differences. These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell). PMID:19696553

  4. Fish Stem Cell Cultures

    PubMed Central

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-01-01

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on “Fish Stem Cells and Nuclear Transfer”, we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer. PMID:21547056

  5. Multi-Center Electronic Structure Calculations for Plasma Equation of State

    SciTech Connect

    Wilson, B G; Johnson, D D; Alam, A

    2010-12-14

    We report on an approach for computing electronic structure utilizing solid-state multi-center scattering techniques, but generalized to finite temperatures to model plasmas. This approach has the advantage of handling mixtures at a fundamental level without the imposition of ad hoc continuum lowering models, and incorporates bonding and charge exchange, as well as multi-center effects in the calculation of the continuum density of states.

  6. Stem subsidence of polished and rough double-taper stems

    PubMed Central

    Yamada, Kengo; Hirosaki, Kenichi; Takano, Masahiro; Matsumoto, Tadami

    2009-01-01

    Background and purpose Many clinical reports have indicated that polished hip stems show better clinical results than rough stems of the same geometry. It is still unknown, however, what the mechanical effects are of different surface finishes on the cement at the cement-bone interface. We compared mechanical effects in an in vitro cemented hip arthroplasty model. Methods Two sizes of double-taper polished stems and matt-processed polished stems (rough stems) were fixed into composite femurs. A 1-Hz dynamic load was applied to the stems for 1 million cycles. An 8-h no-load period was set after every 16 h of load. Stem subsidence within the cement, and compressive force and horizontal cement creep at the cement-bone interface, were measured. Results Compared to rough stems, stem subsidence, compressive force and cement creep for polished stems were a maximum of 4, 12, and 7-fold greater, respectively. There was a strong positive correlation between stem subsidence and compressive force for polished stems. In contrast, a strong negative correlation was found between stem subsidence and compressive force for rough stems. There was also a statistically significant relationship between compressive force on the cement and cement creep for the polished stems, but no significant relationship was found for rough stems. Interpretation This is the first evidence that different surface finishes of stems can have different mechanical effects on the cement at the cement-bone interface. Stem subsidence in polished stems resulted in compressive force on the cement and cement creep. The mechanical effects that polished taper stems impart on cement at the cement-bone interface probably contribute to their good long-term fixation and excellent clinical outcome. PMID:19421909

  7. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Education Specialists Lynn Dotson, left, of the NASA Public Engagement Center, and Lester Morales, right, of Texas State University's NASA STEM Educator Professional Development Collaborative, explain the Rocketry Engineering Design Challenge to teachers participating in the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  8. Efficacy and safety of micafungin for febrile neutropenia in pediatric patients with hematological malignancies: a multicenter prospective study.

    PubMed

    Kobayashi, Ryoji; Suzuki, Nobuhiro; Yoshida, Makoto; Iizuka, Susumu; Suzuki, Daisuke; Sano, Hirozumi; Kudoh, Tooru

    2013-10-01

    Invasive fungal infections are a major cause of infectious mortality in neutropenic patients receiving chemotherapy or hematopoietic stem cell transplantation. However, little is known about the efficacy and safety of micafungin (MCFG), an echinocandin antifungal agent, in pediatric patients with febrile neutropenia (FN). This study was conducted as a prospective multicenter trial to evaluate the efficacy and safety of MCFG for FN in pediatric patients with hematological diseases. Efficacy was assessed based on the response to the 5 composite endpoints established by Walsh and colleagues in addition to body temperature and C-reactive protein values. Thirty episodes of FN were enrolled in the study. The median dose and duration of MCFG treatment were 3.0 mg/kg/d and 13.5 days, respectively. Using the criteria of Walsh and colleagues, MCFG was effective in 56.7% of the patients. No breakthrough invasive fungal infection occurred during MCFG treatment. Body temperatures on the last day of neutropenia during administration of MCFG and on the last day of MCFG therapy and C-reactive protein values after administration of MCFG were significantly lower than on the day MCFG therapy was started. Adverse effects in the form of mild liver dysfunction were seen in only 2 patients. MCFG is a very effective and safe antifungal drug for FN in children. Physicians should administer MCFG early in febrile episode in patients in whom first-line antibiotics are not effective in treating FN.

  9. Innovation and STEM Schools

    ERIC Educational Resources Information Center

    Roberts, Julia Link

    2015-01-01

    How do schools with a focus on science, technology, engineering, and mathematics (STEM) fit in with state goals to increase innovation and to boost the economy? This article briefly discusses how educators can encourage creativity and innovation.

  10. [STEM on Station Education

    NASA Technical Reports Server (NTRS)

    Lundebjerg, Kristen

    2016-01-01

    The STEM on Station team is part of Education which is part of the External Relations organization (ERO). ERO has traditional goals based around BHAG (Big Hairy Audacious Goal). The BHAG model is simplified to a saying: Everything we do stimulates actions by others to advance human space exploration. The STEM on Station education initiate is a project focused on bringing off the earth research and learning into classrooms. Educational resources such as lesson plans, activities to connect with the space station and STEM related contests are available and hosted by the STEM on Station team along with their partners such as Texas Instruments. These educational activities engage teachers and students in the current happenings aboard the international space station, inspiring the next generation of space explorers.

  11. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Teachers participate in the Rocketry Engineering Design Challenge during the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  12. State of STEM

    NASA Image and Video Library

    2013-02-13

    Bobak Ferdowsi, Flight Director, Mars Curiosity Rover, answers questions from Scholastic News young reporter Emily Shao prior to the start of the first-ever State of Science, Technology, Engineering and Math Event (SoSTEM) held at the Eisenhower Executive Office Building, Wednesday, Feb. 13, 2013 in Washington. Ferdowsi was part of a panel that took questions from a crowd of STEM students. Photo Credit: (NASA/Bill Ingalls)

  13. Hematopoietic Stem Cells Therapies.

    PubMed

    Chivu-Economescu, Mihaela; Rubach, Martin

    2017-01-01

    Stem cell-based therapies are recognized as a new way to treat various diseases and injuries, with a wide range of health benefits. The goal is to heal or replace diseased or destroyed organs or body parts with healthy new cells provided by stem cell transplantation. The current practical form of stem cell therapy is the hematopoietic stem cells transplant applied for the treatment of hematological disorders. There are over 2100 clinical studies in progress concerning hematopoietic stem cell therapies. All of them are using hematopoietic stem cells to treat various diseases like: cancers, leukemia, lymphoma, cardiac failure, neural disorders, auto-immune diseases, immunodeficiency, metabolic or genetic disorders. Several challenges are to be addressed prior to developing and applying large scale cell therapies: 1) to explain and control the mechanisms of differentiation and development toward a specific cell type needed to treat the disease, 2) to obtain a sufficient number of desired cell type for transplantation, 3) to overcome the immune rejection and 4) to show that transplanted cells fulfill their normal functions in vivo after transplants.

  14. Periluminal expression of a secreted transforming growth factor-β type II receptor inhibits in-stent neointima formation following adenovirus-mediated stent-based intracoronary gene transfer.

    PubMed

    Appleby, Clare E; Ranjzad, Parisa; Williams, Paul D; Kakar, Salik J; Driessen, Anita; Tijsma, Edze; Fernandes, Brian; Heagerty, Anthony M; Kingston, Paul A

    2014-05-01

    Transforming growth factor-β1 (TGF-β1) has been shown unequivocally to enhance neointima formation in carotid and ileo-femoral arteries. In our previous studies, however, TGF-β1 expression in coronary arteries actually reduced neointima formation without affecting luminal loss postangioplasty, while expression of a TGF-β1 antagonist (RIIs) in balloon-injured coronary arteries reduced luminal loss without affecting neointima formation. These observed effects may be a consequence of the mode of coronary artery gene transfer employed, but they may also represent differences in the modes of healing of coronary, carotid, and ileo-femoral arteries after endoluminal injury. To help clarify whether a gene therapy strategy to antagonize TGF-β might have application within the coronary vasculature, we have investigated the effect of high-level periluminal expression of RIIs using stent-based adenovirus-mediated intracoronary gene transfer. Porcine coronary arteries were randomized to receive a custom-made CoverStent preloaded with saline only, or with 1×10(9) infectious units of adenovirus expressing RIIs or β-galactosidase (lacZ). Vessels were analyzed 28 days poststenting, at which time angiographic in-stent diameter was significantly greater in RIIs-treated arteries, and in-stent luminal loss significantly reduced. Computerized morphometric minimum in-stent lumen area was ~300% greater in RIIs-exposed vessels than in lacZ or saline-only groups. This was because of significantly reduced neointima formation in the RIIs group. RIIs had no demonstrable effect on cellular proliferation or apoptosis, but greater normalized neointimal/medial collagen content was observed in RIIs-exposed arteries. These data highlight the qualitatively similar effect of TGF-β antagonism on neointima formation in injured coronary and noncoronary arteries, and suggest that since cellular proliferation is unaffected, TGF-β1 antagonism might prevent in-stent restenosis without the delayed

  15. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, right, is interviewed by National Geographic Kids reporter Trevor Jehl ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  16. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, left, is interviewed by TIME for Kids reporter Grace Clark ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  17. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy is interviewed by TIME for Kids reporter Kristen Rigsby, ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  18. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, speaks at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  19. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    NASA associate administrator for education and former astronaut Leland Melvin, left, watches as astronauts, Rick Mastracchio, screen left, and Michael Hopkins, deliver a message from the International Space Station (ISS) to attendees of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  20. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, talks with NASA's 2013 astronaut candidates at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  1. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, listens to a question during the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  2. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Montgomery Blair High School Student Newspaper “Silver Chips” Online Editor-in-Chief Aanchal Johri, right, and Photo Editor Emma Howells, left, from Silver Spring, MD. interview NASA Astronaut Joe Acaba at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  3. An open multicenter comparative randomized clinical study on chitosan.

    PubMed

    Mo, Xiaohui; Cen, John; Gibson, Elaine; Wang, Robin; Percival, Steven L

    2015-01-01

    Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next-generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management

  4. Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

    PubMed Central

    Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

    2015-01-01

    Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

  5. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  6. Valve stem and packing assembly

    DOEpatents

    Wordin, John J.

    1991-01-01

    A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents overtightening of the retaining nut and the resulting excessive friction between stem and stem packing.

  7. Valve stem and packing assembly

    DOEpatents

    Wordin, J.J.

    1991-09-03

    A valve stem and packing assembly is provided in which a rotatable valve stem includes a first tractrix surface for sliding contact with a stem packing and also includes a second tractrix surface for sliding contact with a bonnet. Force is applied by means of a spring, gland flange, and gland on the stem packing so the stem packing seals to the valve stem and bonnet. This configuration serves to create and maintain a reliable seal between the stem packing and the valve stem. The bonnet includes a second complementary tractrix surface for contacting the second sliding tractrix surface, the combination serving as a journal bearing for the entire valve stem and packing assembly. The journal bearing so configured is known as a Schiele's pivot. The Schiele's pivot also serves to maintain proper alignment of the valve stem with respect to the bonnet. Vertical wear between the surfaces of the Schiele's pivot is uniform at all points of contact between the second sliding tractrix surface and the second complementary tractrix surface of a bonnet. The valve stem is connected to a valve plug by means of a slip joint. The valve is opened and closed by rotating the valve stem. The slip joint compensates for wear on the Schiele's pivot and on the valve plug. A ledge is provided on the valve bonnet for the retaining nut to bear against. The ledge prevents over tightening of the retaining nut and the resulting excessive friction between stem and stem packing. 2 figures.

  8. Implementation of a "No Fly" safety culture in a multicenter radiation medicine department.

    PubMed

    Potters, Louis; Kapur, Ajay

    2012-01-01

    The safe delivery of radiation therapy requires multiple disciplines and interactions to perform flawlessly for each patient. Because treatment is individualized and every aspect of the patient's care is unique, it is difficult to regiment a delivery process that works flawlessly. The purpose of this study is to describe one safety-directed component of our quality program called the "No Fly Policy" (NFP). Our quality assurance program for radiation therapy reviewed the entire process of care prior, during, and after a patient's treatment course. Each component of care was broken down and rebuilt within a matrix of multidisciplinary safety quality checklists (QCL). The QCL process map was subsequently streamlined with revised task due dates and stopping rules. The NFP was introduced to place a holding pattern on treatment initiation pending reconciliation of associated stopping events. The NFP was introduced in a pilot phase using a Six-Sigma process improvement approach. Quantitative analysis on the performance of the new QCLs was performed using crystal reports in the Oncology Information Systems. Root cause analysis was conducted. Notable improvements in QCL performance were observed. The variances among staff in completing tasks reduced by a factor of at least 3, suggesting better process control. Steady improvements over time indicated an increasingly compliant and controlled adoption of the new safety-oriented process map. Stopping events led to rescheduling treatments with average and maximum delays of 2 and 4 days, respectively, with no reported adverse effects. The majority of stopping events were due to incomplete plan approvals stemming from treatment planning delays. Whereas these may have previously solicited last-minute interventions, including intensity modulated radiation therapy quality assurance, the NFP enabled nonpunitive, reasonable schedule adjustments to mitigate compromises in safe delivery. Implementation of the NFP has helped to mitigate

  9. A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma.

    PubMed

    Iyama, Satoshi; Sato, Tsutomu; Ohnishi, Hirofumi; Kanisawa, Yuji; Ohta, Shuichi; Kondo, Takeshi; Mori, Akio; Tsutsumi, Yutaka; Kuroda, Hiroyuki; Kakinoki, Yasutaka; Yamamoto, Satoshi; Takahashi, Tohru; Shindo, Motohiro; Torimoto, Yoshihiro; Sato, Kazuya; Iwasaki, Hiroshi; Haseyama, Yoshihito; Kohda, Kyuhei; Nagamachi, Yasuhiro; Hirayama, Yasuo; Sakai, Hajime; Hirata, Yasuji; Fukuhara, Takashi; Ikeda, Hiroshi; Kobune, Masayoshi; Kato, Junji; Kurosawa, Mitsutoshi

    2017-01-01

    Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan. A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study. Of the 125 ATL patients, 62 (46.6%) presented with the acute type, 51 (38.3%) with the lymphoma type, and 12 (9.0%) with the chronic type; the latter group included 7 unfavorable chronic cases. The median age at diagnosis was 68 years (range, 35-86 years). The median survival for those with acute, lymphoma, and unfavorable chronic types was 302, 279, and 921 days, respectively. Advanced age, high lactate dehydrogenase level, poor performance status (3-4), and the existence of B symptoms were unfavorable prognostic factors for overall survival (OS). Survival rate calculated from the day of diagnosis was significantly higher in patients treated with mogamulizumab. The OS of individuals receiving hematopoietic stem cell transplantation (HSCT) was superior to that of the non-HSCT group. The median interval between the last mogamulizumab dose and allogeneic HSCT was 38 days (range, 21-53 days). Of the 22 HSCT recipients who were not treated with mogamulizumab, overall acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD occurred in 12 (54.5%) and 3 (13.6%) patients, respectively. However, overall aGVHD and grade III-IV aGVHD developed in 8 (88.9%) and 3 (33.3%) of the 9 HSCT recipients treated with mogamulizumab, respectively. Mogamulizumab improves OS in patients with ATL, although its use in HSCT patients might trigger severe GVHD. Determining the optimal pre-HSCT mogamulizumab treatment regimen is thus a priority. Copyright © 2016 Elsevier Inc. All

  10. Fifth Annual Stem Cell Summit.

    PubMed

    Knowlton, Daniel

    2010-04-01

    The Fifth Annual Stem Cell Summit, held in New York, included topics covering new commercial developments in the research field of stem cell-based therapies. This conference report highlights selected presentations on embryonic and adult stem cells, stem cell-based therapies for the treatment of orthopedic and cardiovascular indications and inflammatory diseases, as well as technologies for processing and storing stem cells. Investigational therapies discussed include placental expanded (PLX) cells (Pluristem Therapeutics Inc), StemEx (Gamida-Teva Joint Venture/Teva Pharmaceutical Industries Ltd) and remestemcel-L (Osiris Therapeutics Inc/Genzyme Corp/JCR Pharmaceuticals Co Ltd/ Mochida Pharmaceutical Co Ltd).

  11. An International Randomized Multicenter Comparison of Nasal Potential Difference Techniques

    PubMed Central

    Solomon, George M.; Konstan, Michael W.; Wilschanski, Michael; Billings, Joanne; Sermet-Gaudelus, Isabelle; Accurso, Frank; Vermeulen, François; Levin, Elina; Hathorne, Heather; Reeves, Ginger; Sabbatini, Gina; Hill, Aubrey; Mayer-Hamblett, Nicole; Ashlock, Melissa; Clancy, John Paul

    2010-01-01

    Background: The transepithelial nasal potential difference (NPD) is used to assess cystic fibrosis transmembrane conductance regulator (CFTR) activity. Unreliability, excessive artifacts, and lack of standardization of current testing systems can compromise its use as a diagnostic test and outcome measure for clinical trials. Methods: To determine whether a nonperfusing (agar gel) nasal catheter for NPD measurement is more reliable and less susceptible to artifacts than a continuously perfusing nasal catheter, we performed a multicenter, randomized, crossover trial comparing a standardized NPD protocol using an agar nasal catheter with the same protocol using a continuously perfusing catheter. The data capture technique was identical in both protocols. A total of 26 normal adult subjects underwent NPD testing at six different centers. Results: Artifact frequency was reduced by 75% (P < .001), and duration was less pronounced using the agar catheter. The measurement of sodium conductance was similar between the two catheter methods, but the agar catheter demonstrated significantly greater CFTR-dependent hyperpolarization, because Δ zero Cl- + isoproterenol measurements were significantly more hyperpolarized with the agar catheter (224.2 ± 12.9 mV with agar vs 18.2 ± 9.1 mV with perfusion, P < .05). Conclusions: The agar nasal catheter approach demonstrates superior reliability compared with the perfusion nasal catheter method for measurement of NPD. This nonperfusion catheter method should be considered for adoption as a standardized protocol to monitor CFTR activity in clinical trials. PMID:20472865

  12. Multi-center airborne coherent atmospheric wind sensor (MACAWS)

    SciTech Connect

    Rothermel, J.; Menzies, R.T.; Tratt, D.M.

    1996-11-01

    The Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS) is an airborne scanning coherent Doppler lidar designed to acquire remote multi-dimensional measurements of winds and absolute aerosol backscatter in the troposphere and lower stratosphere. These measurements enable study of atmospheric dynamic processes and features at scales of motion that may be undersampled by, or may be beyond the capability of, existing or planned sensors. MACAWS capabilities enable more realistic assessments of concepts in global tropospheric wind measurement with satellite Doppler lidar, as well as a unique capability to validate the NASA Scatterometer currently scheduled for launch in late 1996. MACAWS consists of a Joule-class CO{sub 2} coherent Doppler lidar on a ruggedized optical table, a programmable scanner to direct the lidar beam in the desired direction, and a dedicated inertial navigation system to account for variable aircraft attitude and speed. MACAWS was flown for the first time in September 1995, over the eastern Pacific Ocean and western US. 33 refs., 2 figs.

  13. Clinical impact of 8 prospective, randomized, multicenter glaucoma trials.

    PubMed

    Panarelli, Joseph F; Banitt, Michael R; Sidoti, Paul A; Budenz, Donald L; Singh, Kuldev

    2015-01-01

    To determine the impact of 8 multicenter randomized clinical trials (RCTs) on glaucoma practice. An electronic survey was distributed to the members of the American Glaucoma Society (AGS). Each participant was asked 2 study-specific questions and 1 standard question common to all 8 RCTs assessing the study's impact on clinical practice. RCTs included in the survey were the Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma (CNTG) Study, European Glaucoma Prevention Study (EGPS), Early Manifest Glaucoma Trial (EMGT), Glaucoma Laser Trial (GLT), Ocular Hypertension Treatment Study (OHTS), and Tube Versus Trabeculectomy (TVT) Study. A 5-point Likert scale was used for rating all responses. The practice setting and duration of glaucoma practice was determined for all AGS members who responded. A total of 206 (23.0%) of 894 AGS members participated in the survey. Among those who responded, 46.4% were self classified as academic practitioners and 53.6% worked in a private practice setting. Mean Likert scores for the standard question evaluating the overall impact of the RCT were OHTS 4.47, CNTG Study 4.13, AGIS 3.78, TVT Study 3.53, EMGT 3.48, CIGTS 3.44, GLT 3.39, and 2.69 EGPS. Substantial differences were observed in the clinical impact of several RCTs in glaucoma. The reported impact of each study likely reflects several factors including study timing, design, conduct, and interpretation of results.

  14. Oral cancer in the UAE: a multicenter, retrospective study.

    PubMed

    Anis, Raeefa; Gaballah, Kamis

    2013-01-01

    Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential.

  15. Oral cancer in the UAE: a multicenter, retrospective study.

    PubMed

    Anis, Raeefa; Gaballah, Kamis

    2013-08-27

    To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential.

  16. Oral cancer in the UAE: a multicenter, retrospective study

    PubMed Central

    Anis, Raeefa; Gaballah, Kamis

    2013-01-01

    Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential. PMID:23985381

  17. Cardiac bioassist: results of the French multicenter cardiomyoplasty study.

    PubMed

    Chachques, Juan C; Jegaden, Olivier; Mesana, Thierry; Glock, Yves; Grandjean, Pierre A; Carpentier, Alain F

    2009-12-01

    The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic (48%), idiopathic (45%) or other (7%). Cardiomyoplasty was performed using the latissimus dorsi muscle which was electrostimulated after surgery. During follow-up, 88% of patients improved clinically. Hospital death occurred in 29 (14%) patients and was related to the severity of preoperative heart failure symptoms. Late mortality occurred in 99 patients due to heart failure (44%), sudden death (37%), or noncardiac causes (18%). Combined dynamic cardiomyoplasty and implantation of a cardiac rhythm management system was safely achieved in 22 patients, and 26 underwent heart transplantation for recurrent heart failure. Long-term functional improvements were observed in most patients, and the best outcome was achieved in those with isolated right ventricular failure. Dynamic cardiomyoplasty can be considered as a destination therapy or a mid- to long-term biological bridge to heart transplantation.

  18. The current state of facial prosthetics – A multicenter analysis.

    PubMed

    Thiele, Oliver C; Brom, Jörn; Dunsche, Anton; Ehrenfeld, Michael; Federspil, Philippe; Frerich, Bernhard; Hölzle, Frank; Klein, Martin; Kreppel, Matthias; Kübler, Alexander C; Kübler, Norbert R; Kunkel, Martin; Kuttenberger, Johannes; Lauer, Günter; Mayer, Boris; Mohr, Christopher; Neff, Andreas; Rasse, Michael; Reich, Rudolf H; Reinert, Siegmar; Rothamel, Daniel; Sader, Robert; Schliephake, Henning; Schmelzeisen, Rainer; Schramm, Alexander; Sieg, Peter; Terheyden, Hendrik; Wiltfang, Jörg; Ziegler, Christoph M; Mischkowski, Robert A; Zöller, Joachim E

    2015-09-01

    Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

  19. Emergency Care for Homeless Patients: A French Multicenter Cohort Study

    PubMed Central

    Feral-Pierssens, Anne-Laure; Aubry, Adeline; Truchot, Jennifer; Raynal, Pierre-Alexis; Boiffier, Mathieu; Hutin, Alice; Leleu, Agathe; Debruyne, Geraud; Joly, Luc-Marie; Juvin, Philippe; Riou, Bruno

    2016-01-01

    Objectives. To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. Methods. We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. Results. A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. Conclusions. We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients. PMID:26985613

  20. [National multicenter survey: the use of intravenous antimicrobial agents].

    PubMed

    Gutiérrez Zufiaurre, M N; García-Rodríguez, J A

    2006-12-01

    Infectious diseases are currently one of the major health problems worldwide. As a consequence, both nosocomial and community-acquired infections are responsible for a significant increase in workload and health costs for hospitals, particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The use of intravenous antimicrobial agents is common in hospitalized patients. In order to determine the use of antimicrobial agents and the most frequent procedures used for their administration in Spanish hospitals, a national multicenter survey was undertaken among ICU, Internal Medicine and Surgery health staff from 63 hospitals, in which data were collected on central and peripheral catheter manipulation and intravenous administration. Results showed that, in Spain, both catheter manipulation (insertion, maintenance and removal) and administration of antimicrobial agents are performed by the nursing staff following established protocols, particularly for central catheters. Moreover, the ICUs had the highest rates of catheter-bearing patients, as well as patients undergoing antimicrobial treatment, sometimes in combination. The use of intravenous antimicrobial agents in Spanish hospitals results in an increased workload for the nursing staff and higher health costs, not to mention the risk involved with the use of vascular catheters.

  1. [Motivations for a consultation before adoption: A multicenter study].

    PubMed

    Thieblemont, M; Francois, P; Poirier, V; Bosdure, E; Munck, M-R; Borsa-Dorion, A; Hazart, I; Moukagni-Pelzer, M; Brunel, D; Peyron, F; de Monleon, J-V

    2016-01-01

    While the number of international adoptions in France is decreasing, adopted children are older and in poorer health than they used to be. This phenomenon has resulted in an increase in the demand for preadoption consultations over the past several years. This study analyses the reasons for these consultations. Prospective multicenter study conducted from 1 January to 31 December 2013. Ten centers contributed to the study, i.e., 196 preadoption consultations. Seeking medical advice was the reason for 88% of the consultations, whether the advice was based on the study of an identified child's medical file (32%) or a country's healthcare characteristics, whether the country was identified (34%) or not (23%). In 6% of cases, the motive for preadoption consultations was social and familial, and in the last 5% it was to obtain general information about adoption and its procedures. In more than 40% of the cases, whether the child or the country identified, Russia is the subject of the consultation because of the complexity of the files and because of the dreaded but rarely mentioned fetal alcohol syndrome. The deterioration of adopted children's health is an additional worry for future adoption applicants. To provide them with the best information possible without making choices for them, specialists should have substantial experience in adoption before going into these preadoption consultations. Copyright © 2015. Published by Elsevier SAS.

  2. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.

    PubMed

    O'Connell, P J; Holmes-Walker, D J; Goodman, D; Hawthorne, W J; Loudovaris, T; Gunton, J E; Thomas, H E; Grey, S T; Drogemuller, C J; Ward, G M; Torpy, D J; Coates, P T; Kay, T W

    2013-07-01

    Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.

  3. Uterine rupture in pregnancies following myomectomy: A multicenter case series

    PubMed Central

    Kim, Hee-Sun; Oh, Soo-Young; Choi, Suk-Joo; Park, Hyun-Soo; Cho, Geum-Joon; Chung, Jin-Hoon; Seo, Yong-Soo; Jung, Sun-Young; Kim, Jung-Eun; Chae, Su-Hyun

    2016-01-01

    Objective The purpose of this case series was to retrospectively examine records of cases with uterine rupture in pregnancies following myomectomy and to describe the clinical features and pregnancy outcomes. Methods This study was conducted as a multicenter case series. The patient databases at 7 tertiary hospitals were queried. Records of patients with a diagnosis of uterine rupture in the pregnancy following myomectomy between January 2012 and December 2014 were retrospectively collected. The uterine rupture cases enrolled in this study were defined as follows: through-and-through uterine rupture or tear of the uterine muscle and serosa, occurrence from 24+0 to 41+6 weeks’ gestation, singleton pregnancy, and previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status. Results Fourteen pregnant women experienced uterine rupture during their pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks’ gestation occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases had fetal distress. Of the 14 uterine rupture cases, none occurred during labor. All mothers survived and had no sequelae, unlike the perinatal outcomes, although they were receiving blood transfusion or treatment for uterine artery embolization because of uterine atony or massive hemorrhage. Conclusion In women of childbearing age who are scheduled to undergo LTM or LSM, the potential risk of uterine rupture on subsequent pregnancy should be explained before surgery. Pregnancy in women after myomectomy should be carefully observed, and they should be adequately counseled during this period. PMID:27896247

  4. The Multi-Center Airborne Coherent Atmospheric Wind Sensor, MACAWS

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1997-01-01

    In 1992 the atmospheric lidar remote sensing groups of the NASA Marshall Space Flight Center, NOAA Environmental Technology Laboratory, and Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor, MACAWS, which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in the troposphere and lower stratosphere. A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise which were developed for previous atmospheric research by the respective institutions. The motivation for the MACAWS program Is three-fold: to obtain fundamental measurements of sub-synoptic scale processes and features which may be used as a basis to improve sub-grid scale parameterizations in large-scale models; to obtain similar datasets in order to improve the understanding and predictive capabilities on the mesoscale; and to validate (simulate) the performance of existing (planned) satellite-borne sensors. Examples of the latter include participation in the validation of the NASA Scatterometer and the assessment of prospective satellite Doppler lidar for global tropospheric wind measurement. Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  5. Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study

    PubMed Central

    Cabibbe, Andrea M.; Feuerriegel, Silke; Casali, Nicola; Drobniewski, Francis; Rodionova, Yulia; Bakonyte, Daiva; Stakenas, Petras; Pimkina, Edita; Augustynowicz-Kopeć, Ewa; Degano, Massimo; Ambrosi, Alessandro; Hoffner, Sven; Mansjö, Mikael; Werngren, Jim; Rüsch-Gerdes, Sabine; Niemann, Stefan; Cirillo, Daniela M.

    2014-01-01

    ABSTRACT Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZAr). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZAr strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZAr strains, (iii) mutations with an unclear role found in less than 70% of PZAr strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZAr; the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. PMID:25336456

  6. Multicenter clinical trial using next-generation Internet technology

    NASA Astrophysics Data System (ADS)

    Ingeholm, Mary-Lou; Levine, Betty A.; Eichler, Florian; Tu, Huacheng; Jimenez-Sanchez, Gerardo; Moser, Hugo

    2001-08-01

    The capacity to evaluate therapies in a multi-center clinical trial for a rare disease like X-linked adrenoleukodystrophy (ALD) can be improved by establishing a network for transmitting magnetic resonance imaging (MRI) data using current Internet and Next Generation Internet (NGI) technologies. A Digital Imaging and Communications in Medicine (DICOM) 3.0 application has been installed; it functions as a storage service class provider (SCP), query/retrieve SCP and central database. Sites with query/retrieve (Q/R) service class user (SCU) applications have access to the images. Using the DICOM Q/R SCU application, timing studies of image retrieval for a standard Internet connection and an NGI connection have been conducted. Standard Internet results indicate that performance is affected by bandwidth limitation and is constrained by network traffic, inhibiting the standard Internet as a useful tool for real-time therapy evaluation. NGI results indicate a higher and more consistent data throughput. The increased transmission speed along with the promise of improved quality of service offered by the NGI connection allows for physicians to discuss the images, correlate them with other disease findings, measure disease severity, and request additional MRI studies in real-time permitting a more efficient clinical evaluation strategy. The elimination of variability of transmission speed is no less significant, allowing the physicians to reserve the time needed for such consultations.

  7. Chronic gastritis in China: a national multi-center survey.

    PubMed

    Du, Yiqi; Bai, Yu; Xie, Pei; Fang, Jingyuan; Wang, Xiaozhong; Hou, Xiaohua; Tian, Dean; Wang, Chengdang; Liu, Yandi; Sha, Weihong; Wang, Bangmao; Li, Yanqing; Zhang, Guoliang; Li, Yan; Shi, Ruihua; Xu, Jianming; Li, Youming; Huang, Minghe; Han, Shengxi; Liu, Jie; Ren, Xu; Xie, Pengyan; Wang, Zhangliu; Cui, Lihong; Sheng, Jianqiu; Luo, Hesheng; Wang, Zhaohui; Zhao, Xiaoyan; Dai, Ning; Nie, Yuqiang; Zou, Yiyou; Xia, Bing; Fan, Zhining; Chen, Zhitan; Lin, Sanren; Li, Zhao-Shen

    2014-02-07

    Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy.

  8. Chronic gastritis in China: a national multi-center survey

    PubMed Central

    2014-01-01

    Background Chronic gastritis is one of the most common findings at upper endoscopy in the general population, and chronic atrophic gastritis is epidemiologically associated with the occurrence of gastric cancer. However, the current status of diagnosis and treatment of chronic gastritis in China is unclear. Methods A multi-center national study was performed; all patients who underwent diagnostic upper endoscopy for evaluation of gastrointestinal symptoms from 33 centers were enrolled. Data including sex, age, symptoms and endoscopic findings were prospectively recorded. Results Totally 8892 patients were included. At endoscopy, 4389, 3760 and 1573 patients were diagnosed to have superficial gastritis, erosive gastritis, and atrophic gastritis, respectively. After pathologic examination, it is found that atrophic gastritis, intestinal metaplasia and dysplasia were prevalent, which accounted for 25.8%, 23.6% and 7.3% of this patient population. Endoscopic features were useful for predicting pathologic atrophy (PLR = 4.78), but it was not useful for predicting erosive gastritis. Mucosal-protective agents and PPI were most commonly used medications for chronic gastritis. Conclusions The present study suggests non-atrophic gastritis is the most common endoscopic finding in Chinese patients with upper GI symptoms. Precancerous lesions, including atrophy, intestinal metaplasia and dysplasia are prevalent in Chinese patients with chronic gastritis, and endoscopic features are useful for predicting pathologic atrophy. PMID:24502423

  9. The Multi-Center Airborne Coherent Atmospheric Wind Sensor, MACAWS

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1997-01-01

    In 1992 the atmospheric lidar remote sensing groups of the NASA Marshall Space Flight Center, NOAA Environmental Technology Laboratory, and Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor, MACAWS, which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in the troposphere and lower stratosphere. A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise which were developed for previous atmospheric research by the respective institutions. The motivation for the MACAWS program Is three-fold: to obtain fundamental measurements of sub-synoptic scale processes and features which may be used as a basis to improve sub-grid scale parameterizations in large-scale models; to obtain similar datasets in order to improve the understanding and predictive capabilities on the mesoscale; and to validate (simulate) the performance of existing (planned) satellite-borne sensors. Examples of the latter include participation in the validation of the NASA Scatterometer and the assessment of prospective satellite Doppler lidar for global tropospheric wind measurement. Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  10. Guidelines for quality assurance in multicenter trials: a position paper.

    PubMed

    Knatterud, G L; Rockhold, F W; George, S L; Barton, F B; Davis, C E; Fairweather, W R; Honohan, T; Mowery, R; O'Neill, R

    1998-10-01

    In the wake of reports of falsified data in one of the trials of the National Surgical Adjuvant Project for Breast and Bowel Cancer supported by the National Cancer Institute, clinical trials came under close scrutiny by the public, the press, and Congress. Questions were asked about the quality and integrity of the collected data and the analyses and conclusions of trials. In 1995, the leaders of the Society for Clinical Trials (the Chair of the Policy Committee, Dr. David DeMets, and the President of the Society, Dr. Sylvan Green) asked two members of the Society (Dr. Genell Knatterud and Dr. Frank Rockhold) to act as co-chairs of a newly formed subcommittee to discuss the issues of data integrity and auditing. In consultation with Drs. DeMets and Green, the co-chairs selected other members (Ms. Franca Barton, Dr. C.E. Davis, Dr. Bill Fairweather, Dr. Stephen George, Mr. Tom Honohan, Dr. Richard Mowery, and Dr. Robert O'Neill) to serve on the subcommittee. The subcommittee considered "how clean clinical trial data should be, to what extent auditing procedures are required, and who should conduct audits and how often." During the initial discussions, the subcommittee concluded that data auditing was insufficient to achieve data integrity. Accordingly, the subcommittee prepared this set of guidelines for standards of quality assurance for multicenter clinical trials. We include recommendations for appropriate action if problems are detected.

  11. Neonatal invasive candidiasis: a prospective multicenter study of 118 cases.

    PubMed

    López Sastre, José B; Coto Cotallo, Gil D; Fernández Colomer, Belén

    2003-04-01

    A prospective multicenter study was conducted to assess the epidemiology of neonatal invasive candidiasis in Spain. In a total of 20,565 admissions to the 27 participating neonatal units over an 18-month period, systemic candidiasis was diagnosed in 118 (0.57%) neonates. Candida species were isolated from the blood in 79 infants, from the urine in 33, and from the cerebrospinal fluid in 4; in 2 cases, histologic evidence of deep tissue candidiasis was found at autopsy. Very-low-birth-weight (VLBW) infants (< or = 1500 g) showed a significantly higher incidence of systemic candidiasis (4.8%) than infants weighing > 1500 g (0.2%) ( p < 0.001). Candida albicans was the most frequent species (52.5%) followed by C. parapsilosis (23.7%), and C. tropicalis (7.6%). Only seven infants were treated with amphotericin B (initial dose 0.18 +/- 0.3 mg/kg, maximal daily dose 1.7 +/- 0.9 mg/kg) but treatment was stopped in three of them (43%) due to nephrotoxicity. Liposomal amphotericin B was given to 81 neonates and amphotericin B lipid complex to 29. There were no differences in mortality rate and in the incidence of adverse effects in relation to treatment with liposomal amphotericin B or amphotericin B lipid complex. The mortality rate was 10.2% and all deaths occurred in the VLBW cohort with candidemia.

  12. Epidemiology of melasma in Brazilian patients: a multicenter study.

    PubMed

    Hexsel, Doris; Lacerda, Davi A; Cavalcante, Andrea S; Machado Filho, Carlos A S; Kalil, Célia Luiza P V; Ayres, Eloísa L; Azulay-Abulafia, Luna; Weber, Magda B; Serra, Marcio S; Lopes, Nádya F P; Cestari, Tania F

    2014-04-01

    Melasma is an acquired, irregularly patterned, light to dark-brown hypermelanosis, with symmetric distribution mostly over the face. The aim of this study was to evaluate clinical characteristics and factors related to melasma in Brazilian patients. This was a cross-sectional, multicenter study performed in Brazil. Investigators examined and questioned 953 patients over 18 years of age on clinical characteristics and other factors related to their melasma. Melasma was more prevalent in women (97.5%) and in Fitzpatrick skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and III and family history of melasma had early onset of the disorder when compared with skin phototypes IV, V, and VI (P<0.0001). Similar results were also observed when these same groups were compared with the absence of family history (P<0.0001). Extra-facial melasma was more frequent in postmenopausal women compared with those who were not experiencing menopause (14.2% vs. 3.5%, P<0.0001). Data suggested that the age of melasma onset are related to skin phototypes and family history. Additionally, extra-facial melasma was more common in menopausal women. This is the first study on the epidemiology of melasma in Brazil involving a large sample of the population. These data can be a source of new relevant research on the cause and development of melasma. © 2013 The International Society of Dermatology.

  13. Antimicrobial prophylaxis during Hirudo medicinalis therapy: a multicenter study.

    PubMed

    Kruer, Rachel M; Barton, Cassie A; Roberti, Gregory; Gilbert, Brian; McMillian, Wesley D

    2015-03-01

    Medicinal leeches (Hirudo medicinalis) are indicated for salvage of tissue flaps, grafts, or replants when venous congestion threatens tissue viability. The purpose of this study was to evaluate the efficacy of prophylactic antimicrobial agents in patients who received medicinal leech therapy. A multicenter retrospective cohort study of all adult patients between January 1, 2010, and February 28, 2013, who received medicinal leech therapy was conducted. Antimicrobial prophylaxis was documented in 54 (91.5%) of the included patients, ciprofloxacin, trimethoprim-sulfamethoxazole, piperacillin-tazobactam, and ceftriaxone in 33 (61.1%), 18 (33.3%), 2 (3.7%), and 2 (3.7%) patients, respectively. Surgical site infection (SSI) was found in seven (11.9%) patients, all of whom received antimicrobial prophylaxis. Aeromonas spp. was isolated in four infections, and all isolates were resistant to the chosen prophylactic agent. The SSI incidence was similar between antimicrobial prophylaxis agents. Trimethoprim-sulfamethoxazole and ciprofloxacin appear equally effective at preventing leech-associated infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. 5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE (HARDESTY CAST IRON RECTANGULAR SLIDE GATE), LOOKING SOUTHWEST - High Mountain Dams in Bonneville Unit, Lost Lake Dam, Kamas, Summit County, UT

  15. 6. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (18' HARDESTY GATE), LOOKING SOUTHEAST - High Mountain Dams in Bonneville Unit, Long Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  16. 5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (28' WIDE HARDESTY CAST IRON SLIDE HEADGATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Duck Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  17. 5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND WHEEL (10' HARDESTY CAST IRON VERTICAL LIFT GATE), LOOKING WEST - High Mountain Dams in Bonneville Unit, Weir Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  18. 4. VIEW OF INCLINED OUTLET GATE, STEM, STEM GUIDE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW OF INCLINED OUTLET GATE, STEM, STEM GUIDE AND WHEEL (10' HARDESTY VERTICAL LIFT GATE), LOOKING NORTHWEST - High Mountain Dams in Bonneville Unit, Pot Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  19. 5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, LOOKING NORTHWEST - High Mountain Dams in Upalco Unit, Drift Lake Dam, Ashley National Forest, 11.4 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

  20. 7. VIEW OF UPRIGHT OUTLET GATE, WHEEL STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF UPRIGHT OUTLET GATE, WHEEL STEM AND STEM GUIDE (14' DIAMETER CIRCULAR CALCO CAST IRON SLIDE GATE), LOOKING SOUTHEAST - High Mountain Dams in Bonneville Unit, Fire Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  1. 7. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (15' HARDESTY MODEL 115 GATE), LOOKING NORTHWEST - High Mountain Dams in Bonneville Unit, Marjorie Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  2. 5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE, (12' DIAMETER HARDESTY MODEL 112 CIRCULAR GATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Island Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

  3. Substantially higher prevalence of postoperative peri­prosthetic fractures in octogenarians with hip fractures operated with a cemented, polished tapered stem rather than an anatomic stem

    PubMed Central

    Mukka, Sebastian; Mellner, Carl; Knutsson, Björn; Sayed-Noor, Arkan; Sköldenberg, Olof

    2016-01-01

    Background and purpose Recent studies have demonstrated a high incidence of postoperative periprosthetic femoral fracture (PPF) in elderly patients treated with 2 commonly used cemented, polished tapered stems. We compared the prevalence and incidence rate of PPF in a consecutive cohort of octagenerians with femoral neck fractures (FNFs) treated with either a collarless, polished tapered (CPT) stem or an anatomic matte stem (Lubinus SP2). Patients and methods In a multicenter, prospective cohort study, we included 979 hips in patients aged 80 years and above (72% females, median age 86 (80–102) years) with a femoral neck fracture as indication for surgery. 69% of the patients were classified as ASA class 3 or 4. Hip-related complications and repeat surgery were assessed at a median follow-up of 20 (0–24) months postoperatively. Results 22 hips (2.2%) sustained a PPF at a median of 7 (0–22) months postoperatively; 14 (64%) were Vancouver B2 fractures. 7 of the 22 surgically treated fractures required revision surgery, mainly due to deep infection. The cumulative incidence of PPFs was 3.8% in the CPT group, as compared with 0.2% in the SP2 group (p < 0.001). The risk ratio (RR) was 16 (95% CI: 2–120) using the SP2 group as denominator. Interpretation The CPT stem was associated with a higher risk of PPF than the SP2 stem. We suggest that the tapered CPT stem should not be used for the treatment of femoral neck fractures in patients over 80 years. PMID:27045318

  4. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, left, is interviewed by TIME for Kids reporter Kristen Rigsby, as Moira Vahey, Deputy Assistant Director for Strategic Communications at the White House Office of Science & Technology Policy, right, takes notes ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  5. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    NASA Astronaut Joe Acaba, center, moderates a panel discussion with NASA's 2013 astronaut candidates, from left, Christina M. Hammock, Andrew R. Morgan, Victor J. Glover, Jessica U. Meir, Tyler N. "Nick" Hague, Josh A. Cassada, Anne C. McClain, and, Nicole Aunapu Mann, at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  6. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    A student ask a question to NASA Astronaut Joe Acaba, center, and NASA's 2013 astronaut candidates, from left, Christina M. Hammock, Andrew R. Morgan, Victor J. Glover, Jessica U. Meir, Tyler N. "Nick" Hague, Josh A. Cassada, Anne C. McClain, and, Nicole Aunapu Mann, at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  7. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, left, is interviewed by Montgomery Blair High School Student Newspaper “Silver Chips” Online Editor-in-Chief Aanchal Johri, center, and Photo Editor Emma Howells, from Silver Spring, MD. ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  8. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, left, smiles along with 16-year-old Joey Hudy, a former White House Science Fair participant and self-described “Maker” at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  9. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, center, poses for a group photograph with NASA's 2013 astronaut candidates, from left, Josh A. Cassada, Nicole Aunapu Mann, Jessica U. Meir, Tyler N. "Nick" Hague, Holdren, Victor J. Glover, Christina M. Hammock, Andrew R. Morgan, and, Anne C. McClain at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  10. Dental pulp stem cells

    PubMed Central

    Ashri, Nahid Y.; Ajlan, Sumaiah A.; Aldahmash, Abdullah M.

    2015-01-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors. PMID:26620980

  11. Melanoma stem cells.

    PubMed

    Roesch, Alexander

    2015-02-01

    The cancer stem cell concept significantly broadens our understanding of melanoma biology. However, this concept should be regarded as an integral part of a holistic cancer model that also includes the genetic evolution of tumor cells and the variability of cell phenotypes within a dynamic tumor microenvironment. The biologic complexity and methodological difficulties in identifying cancer stem cells and their biomarkers are currently impeding the direct translation of experimental findings into clinical practice. Nevertheless, it is these methodological shortcomings that provide a new perspective on the phenotypic heterogeneity and plasticity of melanoma with important consequences for future therapies. The development of new combination treatment strategies, particularly with regard to overcoming treatment resistance, could significantly benefit from targeted elimination of cell subpopulations with cancer stem cell properties. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  12. Catalyzing stem cell research.

    PubMed

    Willemse, Lisa; Lyall, Drew; Rudnicki, Michael

    2008-09-01

    In 2001, the Stem Cell Network was the first of its kind, a bold initiative to forge and nurture pan-Canadian collaborations involving researchers, engineers, clinicians and private and public sector partners. Canada's broad and deep pool of stem cell talent proved to be a fertile ground for such an initiative, giving rise to a strong, thriving network that, 7 years later, can list innovative cell expansion and screening technologies, early-phase clinical trials for stroke, pulmonary hypertension, muscular dystrophy and cornea replacement, and leading discourse on ethical, legal and social issues among its accomplishments. As it moves into its second and final phase of funding, the Stem Cell Network continues to push boundaries and has set its sights on overcoming the obstacles that impede the transfer of research findings to clinical applications, commercial products and public policy.

  13. Expanding STEM Opportunities through Inclusive STEM-Focused High Schools

    ERIC Educational Resources Information Center

    Means, Barbara; Wang, Haiwen; Wei, Xin; Lynch, Sharon; Peters, Vanessa; Young, Viki; Allen, Carrie

    2017-01-01

    Inclusive STEM high schools (ISHSs) (where STEM is science, technology, engineering, and mathematics) admit students on the basis of interest rather than competitive examination. This study examines the central assumption behind these schools--that they provide students from subgroups underrepresented in STEM with experiences that equip them…

  14. Reversing breast cancer stem cell into breast somatic stem cell.

    PubMed

    Wijaya, L; Agustina, D; Lizandi, A O; Kartawinata, M M; Sandra, F

    2011-02-01

    Stem cells have an important role in cell biology, allowing tissues to be renewed by freshly created cells throughout their lifetime. The specific micro-environment of stem cells is called stem cell niche; this environment influences the development of stem cells from quiescence through stages of differentiation. Recent advance researches have improved the understanding of the cellular and molecular components of the micro-environment--or niche--that regulates stem cells. We point out an important trend to the study of niche activity in breast cancers. Breast cancer has long been known to conserve a heterogeneous population of cells. While the majority of cells that make up tumors are destined to differentiate and eventually stop dividing, only minority populations of cells, termed cancer stem cell, possess extensive self renewal capability. These cancer stem cells possess characteristics of both stem cells and cancer cells. Breast cancer stem cells reversal to breast somatic stem cells offer a new therapy, that not only can stop the spread of breast cancer cells, but also can differentiate breast cancer stem cells into normal breast somatic stem cells. These can replace damaged breast tissue. Nevertheless, the complexity of realizing this therapy approach needs further research.

  15. Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

    PubMed Central

    Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

    2011-01-01

    Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

  16. Multipotent Stem Cell and Reproduction.

    PubMed

    Khanlarkhani, Neda; Baazm, Maryam; Mohammadzadeh, Farzaneh; Najafi, Atefeh; Mehdinejadiani, Shayesteh; Sobhani, Aligholi

    2016-01-01

    Stem cells are self-renewing and undifferentiated cell types that can be differentiate into functional cells. Stem cells can be classified into two main types based on their source of origin: Embryonic and Adult stem cells. Stem cells also classified based on the range of differentiation potentials into Totipotent, Pluripotent, Multipotent, and Unipotent. Multipotent stem cells have the ability to differentiate into all cell types within one particular lineage. There are plentiful advantages and usages for multipotent stem cells. Multipotent Stem cells act as a significant key in procedure of development, tissue repair, and protection. The accessibility and adaptability of these amazing cells create them a great therapeutic choice for different part of medical approaches, and it becomes interesting topic in the scientific researches to found obvious method for the most advantageous use of MSC-based therapies. Recent studies in the field of stem cell biology have provided new perspectives and opportunities for the treatment of infertility disorders.

  17. Stem cells and healthy aging.

    PubMed

    Goodell, Margaret A; Rando, Thomas A

    2015-12-04

    Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.

  18. Stem Cells and Female Reproduction

    PubMed Central

    Du, Hongling; Taylor, Hugh S.

    2011-01-01

    Several recent findings in stem cell biology have resulted in new opportunities for the treatment of reproductive disease. Endometrial regeneration can be driven by bone marrow derived stem cells. This finding has potential implications for the treatment of uterine disorders. It also supports a new theory for the etiology of endometriosis. The ovaries have been shown to contain stem cells that form oocytes in adults and can be cultured in vitro to develop mature oocytes. Stem cells from the fetus have been demonstrated to lead to microchimerism in the mother and implicated in several maternal diseases. Additionally the placenta may be another source of hematopoietic stem cell. Finally endometrial derived stem cells have been demonstrated to differentiate into non-reproductive tissues. While we are just beginning to understand stem cells and many key questions remain, the potential advantages of stem cells in reproductive biology and medicine are apparent. PMID:19208782

  19. Stem Cell Organoid Engineering

    PubMed Central

    Yin, Xiaolei; Mead, Benjamin E.; Safaee, Helia; Langer, Robert; Karp, Jeffrey M.; Levy, Oren

    2016-01-01

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies. PMID:26748754

  20. STEM on the radio

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-10-01

    Looking for an Internet radio station focusing on programing about science, technology, engineering, and math (STEM)? The U.S. National Science Foundation (NSF) announced on 26 September the launch of Science360 Radio, which it says is the first Internet radio stream dedicated to STEM programing. Science360 includes more than 100 radio shows and podcasts that are available on the Web as well as on iPhone and Android devices. The shows originate from a variety of sources, including NSF, other U.S. government agencies, science organizations, universities, and media outlets. For more information, see http://science360.gov/files/.

  1. GE STEM Teacher's Conference

    NASA Image and Video Library

    2017-07-13

    Teachers prepare to demonstrate the projects they built for the Rocketry Engineering Design Challenge during the 2017 GE Foundation High School STEM Integration Conference at the Center for Space Education at NASA's Kennedy Space Center. High school teachers from across the country took part in the week-long conference, which is designed to explore effective ways for teachers, schools and districts from across the country to integrate STEM throughout the curriculum. The conference is a partnership between GE Foundation and the National Science Teachers Association.

  2. Engineering Stem Cell Organoids.

    PubMed

    Yin, Xiaolei; Mead, Benjamin E; Safaee, Helia; Langer, Robert; Karp, Jeffrey M; Levy, Oren

    2016-01-07

    Organoid systems leverage the self-organizing properties of stem cells to create diverse multi-cellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.

  3. Cloning of Mammary Stem Cells

    DTIC Science & Technology

    2001-11-01

    these parity-induced cells do represent a totipotent mammary stem cell population per se, but these cells might support stem cell maintenance as... Stem Cells PRINCIPAL INVESTIGATOR: Dr. Kay-Uwe Wagner CONTRACTING ORGANIZATION: University of Nebraska Medical Center Omaha, Nebraska 68198-6810 REPORT...Mammary Stem Cells DAMD17-00-1-0641 6. AUTHOR(S) Dr. Kay-Uwe Wagner 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT

  4. Laser biomodulation on stem cells

    NASA Astrophysics Data System (ADS)

    Liu, Timon C.; Duan, Rui; Li, Yan; Li, Xue-Feng; Tan, Li-Ling; Liu, Songhao

    2001-08-01

    Stem cells are views from the perspectives of their function, evolution, development, and cause. Counterintuitively, most stem cells may arise late in development, to act principally in tissue renewal, thus ensuring an organisms long-term survival. Surprisingly, recent reports suggest that tissue-specific adult stem cells have the potential to contribute to replenishment of multiple adult tissues. Stem cells are currently in the news for two reasons: the successful cultivation of human embryonic stem cell lines and reports that adult stem cells can differentiate into developmentally unrelated cell types, such as nerve cells into blood cells. The spotlight on stem cells has revealed gaps in our knowledge that must be filled if we are to take advantage of their full potential for treating devastating degenerative diseases such as Parkinsons's disease and muscular dystrophy. We need to know more about the intrinsic controls that keep stem cells as stem cells or direct them along particular differentiation pathways. Such intrinsic regulators are, in turn, sensitive to the influences of the microenvironment, or niche, where stem cells normally reside. Both intrinsic and extrinsic signals regular stem cell fate and some of these signals have now been identified. Vacek et al and Wang et al have studied the effect of low intensity laser on the haemopoietic stem cells in vitro. There experiments show there is indeed the effect of low intensity laser on the haemopoietic stem cells in vitro, and the present effect is the promotion of haemopoietic stem cells proliferation. In other words, low intensity laser irradiation can act as an extrinsic signal regulating stem cell fate. In this paper, we study how low intensity laser can be used to regulate stem cell fate from the viewpoint of collective phototransduction.

  5. STEM--Beyond the Acronym

    ERIC Educational Resources Information Center

    Vasquez, Jo Anne

    2015-01-01

    When most educators think of STEM education, they think of fully integrated projects seamlessly combining all four disciplines--science, technology, engineering, and mathematics. Although such transdisciplinary STEM units are ideal, writes Vasquez, they are not the only way to give students valuable STEM experiences. She gives examples of two…

  6. STEM--Beyond the Acronym

    ERIC Educational Resources Information Center

    Vasquez, Jo Anne

    2015-01-01

    When most educators think of STEM education, they think of fully integrated projects seamlessly combining all four disciplines--science, technology, engineering, and mathematics. Although such transdisciplinary STEM units are ideal, writes Vasquez, they are not the only way to give students valuable STEM experiences. She gives examples of two…

  7. Overcoming Obstacles in Teaching STEM

    ERIC Educational Resources Information Center

    Rhodes, Scott

    2017-01-01

    Learning the intricacies of STEM subjects can be a challenge, but teaching these complex subjects presents its own unique set of obstacles. Considering the rising demand for educated STEM professionals, students' dissatisfaction with university-level STEM education is both alarming and eye-opening. Given that competition among universities is…

  8. Stem Cell Transplants (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Stem Cell Transplants KidsHealth > For Parents > Stem Cell Transplants A A A What's in this article? ... Recovery Coping en español Trasplantes de células madre Stem cells are cells in the body that have the ...

  9. Interlaboratory quality control of total HIV-1 DNA load measurement for multicenter reservoir studies.

    PubMed

    Gantner, Pierre; Mélard, Adeline; Damond, Florence; Delaugerre, Constance; Dina, Julia; Gueudin, Marie; Maillard, Anne; Sauné, Karine; Rodallec, Audrey; Tuaillon, Edouard; Plantier, Jean-Christophe; Rouzioux, Christine; Avettand-Fenoel, Véronique

    2017-11-01

    Viral reservoirs represent an important barrier to HIV cure. Accurate markers of HIV reservoirs are needed to develop multicenter studies. The aim of this multicenter quality control (QC) was to evaluate the inter-laboratory reproducibility of total HIV-1-DNA quantification. Ten laboratories of the ANRS-AC11 working group participated by quantifying HIV-DNA with a real-time qPCR assay (Biocentric) in four samples (QCMD). Good reproducibility was found between laboratories (standard deviation ≤ 0.2 log10 copies/10(6) PBMC) for the three positive QC that were correctly classified by each laboratory (QC1multicenter studies using this standardized assay. © 2017 Wiley Periodicals, Inc.

  10. A modular informatics platform for effective support of collaborative and multicenter studies in cardiology.

    PubMed

    Marinelli, Martina; Positano, Vincenzo; Lorenzoni, Valentina; Caselli, Chiara; Mangione, Maurizio; Marcheschi, Paolo; Puzzuoli, Stefano; Esposito, Natalia; L'Abbate, Giuseppe Andrea; Neglia, Danilo

    2016-12-01

    Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease.

  11. Multi-centered AdS3 solutions from Virasoro conformal blocks

    NASA Astrophysics Data System (ADS)

    Hulík, Ondřej; Procházka, Tomáš; Raeymaekers, Joris

    2017-03-01

    We revisit the construction of multi-centered solutions in three-dimensional anti-de Sitter gravity in the light of the recently discovered connection between particle worldlines and classical Virasoro conformal blocks. We focus on multi-centered solutions which represent the backreaction of point masses moving on helical geodesics in global AdS3, and argue that their construction reduces to a problem in Liouville theory on the disk with Zamolodchikov-Zamolodchikov boundary condition. In order to construct the solution one needs to solve a certain monodromy problem which we argue is solved by a vacuum classical conformal block on the sphere in a particular channel. In this way we construct multi-centered gravity solutions by using conformal blocks special functions. We show that our solutions represent left-right asymmetric configurations of operator insertions in the dual CFT. We also provide a check of our arguments in an example and comment on other types of solutions.

  12. Research priorities for a multi-center child abuse pediatrics network - CAPNET.

    PubMed

    Lindberg, Daniel M; Wood, Joanne N; Campbell, Kristine A; Scribano, Philip V; Laskey, Antoinette; Leventhal, John M; Pierce, Mary Clyde; Runyan, Desmond K

    2017-03-01

    Although child maltreatment medical research has benefited from several multi-center studies, the new specialty of child abuse pediatrics has not had a sustainable network capable of pursuing multiple, prospective, clinically-oriented studies. The Child Abuse Pediatrics Network (CAPNET) is a new multi-center research network dedicated to child maltreatment medical research. In order to establish a relevant, practical research agenda, we conducted a modified Delphi process to determine the topic areas with highest priority for such a network. Research questions were solicited from members of the Ray E. Helfer Society and study authors and were sorted into topic areas. These topic areas were rated for priority using iterative rounds of ratings and in-person meetings. The topics rated with the highest priority were missed diagnosis and selected/indicated prevention. This agenda can be used to target future multi-center child maltreatment medical research.

  13. Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

    NASA Astrophysics Data System (ADS)

    Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; McCaul, E. W., Jr.

    1993-01-01

    This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall

  14. The Multi-center Airborne Coherent Atmospheric Wind Sensor.

    NASA Astrophysics Data System (ADS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James N.; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1998-04-01

    In 1992 the atmospheric lidar remote sensing groups of the National Aeronautics and Space Administration Marshall Space Flight Center, the National Oceanic and Atmospheric Administration/Environmental Technology Laboratory (NOAA/ETL), and the Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in three-dimensional volumes in the troposphere and lower stratosphere.A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise that were developed for previous atmospheric research by the respective institutions. For example, the laser transmitter is that of the mobile ground-based Doppler lidar system developed and used in atmospheric research for more than a decade at NOAA/ETL.The motivation for MACAWS is threefold: 1) to obtain fundamental measurements of subsynoptic-scale processes and features to improve subgrid-scale parameterizations in large-scale models, 2) to obtain datasets in order to improve the understanding of and predictive capabilities for meteorological systems on subsynoptic scales, and 3) to validate (simulate) the performance of existing (planned) satellite-borne sensors.Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following system improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  15. Managing Multi-center Flow Cytometry Data for Immune Monitoring.

    PubMed

    White, Scott; Laske, Karoline; Welters, Marij Jp; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21-23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables automated

  16. Reducing between scanner differences in multi-center PET studies.

    PubMed

    Joshi, Aniket; Koeppe, Robert A; Fessler, Jeffrey A

    2009-05-15

    This work is part of the multi-center Alzheimer's Disease Neuroimaging Initiative (ADNI), a large multi-site study of dementia, including patients having mild cognitive impairment (MCI), probable Alzheimer's disease (AD), as well as healthy elderly controls. A major portion of ADNI involves the use of [(18)F]-fluorodeoxyglucose (FDG) with positron emission tomography (PET). The objective of this paper is the reduction of inter-scanner differences in the FDG-PET scans obtained from the 50 participating PET centers having fifteen different scanner models. In spite of a standardized imaging protocol, systematic inter-scanner variability in PET images from various sites is observed primarily due to differences in scanner resolution, reconstruction techniques, and different implementations of scatter and attenuation corrections. Two correction steps were developed by comparison of 3-D Hoffman brain phantom scans with the 'gold standard' digital 3-D Hoffman brain phantom: i) high frequency correction; where a smoothing kernel for each scanner model was estimated to smooth all images to a common resolution and ii) low frequency correction; where smooth affine correction factors were obtained to reduce the attenuation and scatter correction errors. For the phantom data, the high frequency correction reduced the variability by 20%-50% and the low frequency correction further reduced the differences by another 20%-25%. Correction factors obtained from phantom studies were applied to 95 scans from normal control subjects obtained from the participating sites. The high frequency correction reduced differences similar to the phantom studies. However, the low frequency correction did not further reduce differences; hence further refinement of the procedure is necessary.

  17. Managing Multi-center Flow Cytometry Data for Immune Monitoring

    PubMed Central

    White, Scott; Laske, Karoline; Welters, Marij JP; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1–5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21–23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables

  18. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study

    PubMed Central

    Halbach, Nicky; Julu, Peter; Witt‐Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F.; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-01-01

    Many studies have attempted to establish the genotype–phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well‐defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype–phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non‐invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence‐based management in RTT. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:27354166

  19. Maternal near-miss: a multicenter surveillance in Kathmandu Valley.

    PubMed

    Rana, Ashma; Baral, Gehanath; Dangal, Ganesh

    2013-01-01

    Multicenter surveillance has been carried out on maternal near-miss in the hospitals with sentinel units. Near-miss is recognized as the predictor of level of care and maternal death. Reducing Maternal Mortality Ratio is one of the challenges to achieve Millennium Development Goal. The objective was to determine the frequency and the nature of near-miss events and to analyze the near-miss morbidities among pregnant women. A prospective surveillance was done for a year in 2012 at nine hospitals in Kathmandu valley. Cases eligible by definition were recorded as a census based on WHO near-miss guideline. Similar questionnaires and dummy tables were used to present the results by non-inferential statistics. Out of 157 cases identified with near-miss rate of 3.8 per 1000 live births, severe complications were postpartum hemorrhage 62 (40%) and preeclampsia-eclampsia 25 (17%). Blood transfusion 102 (65%), ICU admission 85 (54%) and surgery 53 (32%) were common critical interventions. Oxytocin was main uterotonic used both prophylactically and therapeutically at health facilities. Total of 30 (19%) cases arrived at health facility after delivery or abortion. MgSO4 was used in all cases of eclampsia. All laparotomies were performed within three hours of arrival. Near-miss to maternal death ratio was 6:1 and MMR was 62. Study result yielded similar pattern amongst developing countries and same near-miss conditions as the causes of maternal death reported by national statistics. Process indicators qualified the recommended standard of care. The near-miss event could be used as a surrogate marker of maternal death and a window for system level intervention.

  20. Variable costs of ICU patients: a multicenter prospective study.

    PubMed

    Rossi, Carlotta; Simini, Bruno; Brazzi, Luca; Rossi, Giancarlo; Radrizzani, Danilo; Iapichino, Gaetano; Bertolini, Guido

    2006-04-01

    To analyze the costs of treating critically ill patients. Multicenter, observational, prospective, cohort, bottom-up study on variable costs in 51 ICUs. A total of 1,034 patients aged over 14 years who either spent less than 48 h in the ICU or had multiple trauma, major abdominal surgery, ischemic stroke, chronic obstructive pulmonary disease, cardiac failure, isolated head injury, acute lung injury/adult respiratory distress syndrome (ALI/ARDS), nontraumatic intracranial hemorrhage or coronary surgery. Data recorded for each patient: length of ICU stay, and cost in euros of all diagnostic and therapeutic procedures, drugs and equipment used, and consultations by physicians from other units. To express cost-efficiency we calculated for each diagnostic group the cost per surviving patient (expenditure for all patients/number of surviving patients) and money loss per patient (expenditure for patients who died/total number of patients). Median costs for a multiple trauma patient were euro 4076 and for coronary surgery patient euro 380. The variability is largely due to different lengths of ICU stay. Cost per surviving patient was higher for ALI/ARDS, nontraumatic intracranial hemorrhage, multiple trauma, and emergency abdominal surgery. Money loss per patient was higher for ALI/ARDS and lower for multiple trauma. Planned coronary and major abdominal surgery and short-stay patients were treated most cost-efficiently. Cost of treatment in an ICU varies widely for different types of patients. Strategies are needed to contain the major determinants of high costs and low cost-efficiency.

  1. Determination of serum albumin, analytical challenges: a French multicenter study.

    PubMed

    Rossary, Adrien; Blondé-Cynober, Françoise; Bastard, Jean-Philippe; Beauvieux, Marie-Christine; Beyne, Pascale; Drai, Jocelyne; Lombard, Christine; Anglard, Ingrid; Aussel, Christian; Claeyssens, Sophie; Vasson, Marie-Paule

    2017-06-01

    Among the biological markers of morbidity and mortality, albumin holds a key place in the range of criteria used by the High Authority for Health (HAS) for the assessment of malnutrition and the coding of information system medicalization program (PMSI). If the principle of quantification methods have not changed in recent years, the dispersion of external evaluations of the quality (EEQ) data shows that the standardization using the certified reference material (CRM) 470 is not optimal. The aim of this multicenter study involving 7 sites, conducted by a working group of the French Society of Clinical Biology (SFBC), was to assess whether the albuminemia values depend on the analytical system used. The albumin from plasma (n=30) and serum (n=8) pools was quantified by 5 different methods [bromocresol green (VBC) and bromocresol purple (PBC) colorimetry, immunoturbidimetry (IT), immunonephelometry (IN) and capillary electrophoresis (CE)] using 12 analyzers. Bland and Altman's test evaluated the difference between the results obtained by the different methods. For example, a difference as high as 13 g/L was observed for the same sample between the methods (p <0.001) in the concentration range of 30 to 35 g/L. The VBC overestimates albumin across the range of values tested compared to PBC (p <0.05). PBC method gives similar results to IN for values lower than 40 g/L. For IT methods, one of the technical/analyzer tandem underestimates the albumin values inducing a difference of performance between the immunoprecipitation methods (IT vs IN, p <0.05). Although, the albumin results are related to the technical/analyzer tandem used. This variability is usually not taken into account by the clinician. Thus, clinicians and biologists have to be aware and have to check, depending on the method used, the albumin thresholds identified as risk factors for complications related to malnutrition and PMSI coding.

  2. Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.

    PubMed

    Manfredini, Fabio; Mallamaci, Francesca; D'Arrigo, Graziella; Baggetta, Rossella; Bolignano, Davide; Torino, Claudia; Lamberti, Nicola; Bertoli, Silvio; Ciurlino, Daniele; Rocca-Rey, Lisa; Barillà, Antonio; Battaglia, Yuri; Rapanà, Renato Mario; Zuccalà, Alessandro; Bonanno, Graziella; Fatuzzo, Pasquale; Rapisarda, Francesco; Rastelli, Stefania; Fabrizi, Fabrizio; Messa, Piergiorgio; De Paola, Luciano; Lombardi, Luigi; Cupisti, Adamasco; Fuiano, Giorgio; Lucisano, Gaetano; Summaria, Chiara; Felisatti, Michele; Pozzato, Enrico; Malagoni, Anna Maria; Castellino, Pietro; Aucella, Filippo; Abd ElHafeez, Samar; Provenzano, Pasquale Fabio; Tripepi, Giovanni; Catizone, Luigi; Zoccali, Carmine

    2017-04-01

    Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P<0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P=0.001 between groups). The cognitive function score (P=0.04) and quality of social interaction score (P=0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis. Copyright © 2017 by the American Society of Nephrology.

  3. Methylphenidate in Pregnancy: A Multicenter, Prospective, Comparative, Observational Study.

    PubMed

    Diav-Citrin, Orna; Shechtman, Svetlana; Arnon, Judy; Wajnberg, Rebecka; Borisch, Cornelia; Beck, Evelin; Richardson, Jonathan Luke; Bozzo, Pina; Nulman, Irena; Ornoy, Asher

    2016-09-01

    Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention-deficit disorder with or without hyperactivity (ADD/ADHD). Data on its use in human pregnancy are limited. The primary objective of the study was to evaluate the risk of major congenital anomalies after pregnancy exposure to methylphenidate for medical indications. In a prospective, comparative, multicenter observational study performed in 4 participating Teratology Information Services (in Jerusalem, Berlin, Newcastle upon Tyne, and Toronto) between 1996 and 2013, methylphenidate-exposed pregnancies were compared with pregnancies counseled for nonteratogenic exposure (NTE) after matching by maternal age, gestational age, and year at initial contact. 382 methylphenidate-exposed pregnancies (89.5% in the first trimester) were followed up. The overall rate of major congenital anomalies was similar between the groups (10/309 = 3.2% [methylphenidate] vs 13/358 = 3.6% [NTE], P = .780). The rates of major congenital anomalies (6/247 = 2.4% [methylphenidate] vs 12/358 = 3.4% [NTE], P = .511) and cardiovascular anomalies (2/247 = 0.8% [methylphenidate] vs 3/358 = 0.8% [NTE], P = .970) were also similar after exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period). There was a higher rate of miscarriages and elective terminations of pregnancy in the methylphenidate group. Significant predictors for the miscarriages using Cox proportional hazards model were methylphenidate exposure (adjusted hazard ratio [HR] = 1.98; 95% CI, 1.23-3.20; P = .005) and past miscarriage (adjusted HR = 1.35; 95% CI, 1.18-1.55; P < .001). The present study suggests that methylphenidate does not seem to increase the risk for major malformations. Further studies are required to establish its pregnancy safety and its possible association with miscarriages.

  4. Influenza vaccination coverage among medical residents: an Italian multicenter survey.

    PubMed

    Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele

    2014-01-01

    Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

  5. Intravascular retained surgical items: a multicenter study of risk factors.

    PubMed

    Moffatt-Bruce, Susan D; Ellison, E Christopher; Anderson, Harry L; Chan, Liza; Balija, Tara M; Bernescu, Irina; Cipolla, James; Marchigiani, Raffaele; Seamon, Mark J; Cook, Charles H; Steinberg, Steven M; Stawicki, Stanislaw P

    2012-11-01

    Retained surgical items (RSIs) have been previously studied in patients undergoing major surgical procedures. This is the first study that specifically examines potential risk factors for intravascular RSI (ivRSI). Multicenter retrospective review of 83 RSIs was performed. Among these, 13 cases involved ivRSI. Cases in the ivRSI group were compared with a group of similar control cases to determine potential risk factors for ivRSI, including procedural factors (urgency and complicating factors), patient factors (body mass index), equipment failure (structural or functional), and safety variances. Fisher's exact testing was performed. Thirteen ivRSI cases and 14 controls were examined. There were no differences between the two groups with regard to age, gender, or body mass index. ivRSI items included guide wires (8/13), catheter/catheter fragments (4/13), and a coil (1/13). The incidence of unexpected procedural factors was significantly higher among ivRSI cases (10/13) than among controls (3/14) (P < 0.007). Equipment failure occurred in five ivRSI cases, with none among controls (P < 0.016). There were no differences between the two groups with regard to number of urgent procedures, bleeding >500 mL, evening procedures, or trainee involvement. Both groups had a very high proportion of safety variances (8 in ivRSI and 11 in control group, P = not significant). In addition, seven of 13 ivRSIs were missed on initial confirmatory postprocedural imaging. Unexpected procedural factors and equipment failure are significantly associated with ivRSI. Of concern, over half of all ivRSIs were missed on confirmatory postprocedural imaging. Strict adherence to established protocols and stringent radiographic review for intravascular procedures is required to prevent ivRSI. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Immediate Postoperative Oral Nutrition Following Esophagectomy: A Multicenter Clinical Trial.

    PubMed

    Weijs, Teus J; Berkelmans, Gijs H K; Nieuwenhuijzen, Grard A P; Dolmans, Annemarie C P; Kouwenhoven, Ewout A; Rosman, Camiel; Ruurda, Jelle P; van Workum, Frans; van Det, Marc J; Silva Corten, Luis C; van Hillegersberg, Richard; Luyer, Misha D P

    2016-10-01

    Immediate start of oral intake is beneficial following colorectal surgery. However, following esophagectomy the safety and feasibility of immediate oral intake is unclear, thus these patients are still kept nil by mouth. This study therefore aimed to determine the feasibility and safety of oral nutrition immediately after esophagectomy. A multicenter, prospective trial was conducted in 3 referral centers between August 2013 and May 2014, including 50 patients undergoing a minimally invasive esophagectomy. Oral nutrition was started postoperatively immediately (clear liquids on postoperative day [POD] 0, liquid nutrition on POD 1 to 6, solid food from POD 7). Nonoral enteral nutrition was started when <50% of caloric need was met on postoperative day POD 5 or when oral intake was impossible. A comparison was made with a retrospective cohort (n = 50) with a per-protocol delayed start of oral intake until POD 4 to 7. The median caloric intake at POD 5 was 58% of required. In 38% of the patients nonoral nutrition was started, mainly due to complications (36%). The pneumonia rate was 28% following immediate oral intake and 40% following delayed oral intake (p = 0.202). The aspiration pneumonia rate was 4% in both groups. The anastomotic leakage rate was 14% after immediate oral intake versus 24% following delayed oral intake (p = 0.202). The 90-day mortality rate was 2% in both groups. Hospital stay and intensive care unit stay were significantly shorter following immediate oral intake. Immediate start of oral nutrition following esophagectomy seems to be feasible and does not increase complications compared to a retrospective cohort and literature. However, if complications arise an alternative nutritional route is required. This explorative study shows that a randomized controlled trial is needed. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Histologic features of secondary syphilis: A multicenter retrospective review.

    PubMed

    Flamm, Alexandra; Parikh, Kruti; Xie, Qiang; Kwon, Eun Ji; Elston, Dirk M

    2015-12-01

    Secondary syphilis has a wide spectrum of clinical and histologic manifestations. We sought to determine the frequency of histopathological features characterizing secondary syphilis, and which are most common in specimens displaying few diagnostic findings. In a multicenter, retrospective analysis of biopsy-proven secondary syphilis, cases were subcategorized by the number of histologic characteristics present. The 106 cases mostly had 5 to 7 of the features studied. Many features were scarcer in cases with 5 or fewer features, including endothelial swelling (87.7% overall vs 72.4% ≤5 features), plasma cells (69.8% vs 48.3%), and elongated rete ridges (75.5% vs 27.6%). Specimens with 5 or fewer features were more likely to be truncal (61.1% vs 34.4% overall), demonstrate rete ridge effacement (44.8% vs 19.8%), and have pityriasis rosea (33.3% vs 17.2%) or drug eruption (33.3% vs 10.9%) in the clinical differential. An interstitial inflammatory pattern was the most common characteristic of specimens with 5 or fewer features (75.9%). This was a retrospective review. The independent value of many histologic features of syphilis may be overestimated. Combinations of endothelial swelling, interstitial inflammation, irregular acanthosis, and elongated rete ridges should raise the possibility of syphilis, along with the presence of vacuolar interface dermatitis with a lymphocyte in nearly every vacuole and lymphocytes with visible cytoplasm. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Cabergoline for Cushing's disease: a large retrospective multicenter study.

    PubMed

    Ferriere, A; Cortet, C; Chanson, P; Delemer, B; Caron, P; Chabre, O; Reznik, Y; Bertherat, J; Rohmer, V; Briet, C; Raingeard, I; Castinetti, F; Beckers, A; Vroonen, L; Maiter, D; Cephise-Velayoudom, F L; Nunes, M L; Haissaguerre, M; Tabarin, A

    2017-03-01

    The efficacy of cabergoline in Cushing's disease (CD) is controversial. The aim of this study was to assess the efficacy and tolerability of cabergoline in a large contemporary cohort of patients with CD. We conducted a retrospective multicenter study from thirteen French and Belgian university hospitals. Sixty-two patients with CD received cabergoline monotherapy or add-on therapy. Symptom score, biological markers of hypercortisolism and adverse effects were recorded. Twenty-one (40%) of 53 patients who received cabergoline monotherapy had normal urinary free cortisol (UFC) values within 12 months (complete responders), and five of these patients developed corticotropic insufficiency. The fall in UFC was associated with significant reductions in midnight cortisol and plasma ACTH, and with clinical improvement. Compared to other patients, complete responders had similar median baseline UFC (2.0 vs 2.5xULN) and plasma prolactin concentrations but received lower doses of cabergoline (1.5 vs 3.5 mg/week, P < 0.05). During long-term treatment (>12 months), cabergoline was withdrawn in 28% of complete responders because of treatment escape or intolerance. Overall, sustained control of hypercortisolism was obtained in 23% of patients for 32.5 months (19-105). Nine patients on steroidogenesis inhibitors received cabergoline add-on therapy for 19 months (1-240). Hypercortisolism was controlled in 56% of these patients during the first year of treatment with cabergoline at 1.0 mg/week (0.5-3.5). About 20-25% of CD patients are good responders to cabergoline therapy allowing long-term control of hypercortisolism at relatively low dosages and with acceptable tolerability. No single parameter, including the baseline UFC and prolactin levels, predicted the response to cabergoline. © 2017 European Society of Endocrinology.

  9. Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

    NASA Technical Reports Server (NTRS)

    Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; Mccaul, E. W., Jr.

    1993-01-01

    This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall

  10. Readmissions after general surgery: a prospective multicenter audit.

    PubMed

    Lee, Matthew J; Daniels, Sarah L; Wild, Jonathan R L; Wilson, Timothy R

    2017-03-01

    Readmission rates after surgical procedures are viewed as a marker of quality of care and as a driver to improve outcomes in the United Kingdom, they are not remunerated. However, readmissions are not wholly avoidable. The aim of this study was to develop a regional overview of readmissions to determine the proportion that might be avoidable and to examine predictors of readmissions at a unit level. We undertook a prospective multicenter audit of readmissions following National Health Service funded general surgical procedures in five National Health Service hospitals and three independent sector providers over a 2-wk period. Basic demographic and procedure data were captured. Readmissions to hospitals were identified through acute admissions lists. Reason for readmission was identified, and the readmission data assessed by a senior surgical doctor as to whether it was avoidable. We identified 752 operations in the study period with all followed up to 30 d. The overall rate of readmissions was 4.7%, with 40% of these judged as being potentially avoidable. Pain and wound problems accounted for the vast majority of avoidable readmissions. The number of unavoidable readmissions was correlated with the workload of each center (r = 0.63, P = 0.06) and as with the higher (British United Provident Association) complexity of surgery (r = 0.90, P = 0.01). Patient and demographic factors were not associated with readmissions. This prospective audit describes readmission rates after general surgery. Volume and complexity of work are associated with readmission rates. A large proportion of readmissions could be reduced by attention to analgesia and outpatient arrangements for wound management. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Multicenter Comparison of Seven 25OH Vitamin D Automated Immunoassays

    PubMed Central

    Lippi, Giuseppe; Salvagno, Gian Luca; Fortunato, Antonio; Dipalo, Mariella; Aloe, Rosalia; Da Rin, Giorgio; Giavarina, Davide

    2015-01-01

    Summary Background The measurement of 25OH vitamin D continues to grow in clinical laboratories. The aim of this multi-center study was to compare the results of seven automated commercial immunoassays with a reference HPLC technique. Methods One hundred and twenty consecutive outpatient serum samples were centrifuged, divided in aliquots, frozen and shipped to the participating laboratories. 25OH Vitamin D was measured with a reference HPLC system and with seven automated commercial immunoassays (Roche Cobas E601, Beckman Coulter Unicel DXI 800, Ortho Vitros ES, DiaSorin Liaison, Siemens Advia Centaur, Abbott Architect i System and IDS iSYS). Results Compared to the reference method, the regression coefficients ranged from 0.923 to 0.961 (all p<0.001). The slope of Deming fit ranged from 0.95 to 1.06, whereas the intercept was comprised between −15.2 and 9.2 nmol/L. The bias from the reference HPLC technique varied from −14.5 to 8.7 nmol/L. The minimum performance goal for bias was slightly exceeded by only one immunoassay. The agreement between HPLC and the different immunoassays at 50 nmol/L 25OH Vitamin D varied between 0.61 and 0.85 (all p<0.001). The percentage of samples below this cut-off was significantly different with only one immunoassay. Conclusions The excellent correlation with the reference HPLC technique attests that all seven automated immunoassays may be reliably used for routine assessment of 25OH-D in clinical laboratories. The significant bias among the different methods seems mostly attributable to the lack of standardization and calls for additional efforts for improving harmonization of 25OH-D immunoassays. PMID:28356846

  12. Awareness of surgical costs: a multicenter cross-sectional survey.

    PubMed

    Bade, Kim; Hoogerbrug, Jonathan

    2015-01-01

    Resource scarcity continues to be an important problem in modern surgical practice. Studies in North America and Europe have found that medical professionals have limited understanding of the costs of medical care. No cost awareness studies have been undertaken in Australasia or specifically focusing on the surgical team. This study determined the cost of a range of commonly used diagnostic tests, procedures, and hospital resources associated with care of the surgical patient. The surgical teams' awareness of these costs was then assessed in a multicenter cross-sectional survey. In total, 14 general surgical consultants, 14 registrars, and 25 house officers working in three New Zealand hospitals were asked to estimate the costs of 14 items commonly associated with patient care. Cost estimations were considered correct if within 25% plus or minus of the actual cost. Accuracy was assessed by calculating the median, mean, and absolute percentage discrepancy. A total of 57 surveys were completed. Of which, four were incomplete and were not included in the analysis. Cost awareness was generally poor, and members of the surgical team were rarely able to estimate the costs to within 25%. The mean absolute percentage error was 0.87 (95% CI: 0.58-1.18) and underestimates were most common. There was no significant difference in estimate accuracy between consultants, registrars, or house officers, or between consultants working in both public/private practice compared with those working in public practice alone. There is poor awareness of surgical costs among consultant surgeons, registrars, and junior physicians working in Australasia. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  13. The Global Enteric Multicenter Study (GEMS): Impetus, Rationale, and Genesis

    PubMed Central

    Levine, Myron M.; Kotloff, Karen L.; Nataro, James P.; Muhsen, Khitam

    2012-01-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12 600 analyzable cases and 12 600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467 000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease. PMID:23169934

  14. The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis.

    PubMed

    Levine, Myron M; Kotloff, Karen L; Nataro, James P; Muhsen, Khitam

    2012-12-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12,600 analyzable cases and 12,600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467,000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease.

  15. A Multicenter Reference Intervals Study for Specific Proteins in China

    PubMed Central

    Qin, Xuzhen; Tang, Guodong; Qiu, Ling; Li, Peng Chang; Xia, Liangyu; Chen, Ming; Tao, Zhihua; Li, Shijun; Liu, Min; Wang, Liang; Gao, Shang; Yu, Songlin; Cheng, Xinqi; Han, Jianhua; Hou, Li’an; Kawano, Reo; Ichihara, Kiyoshi

    2015-01-01

    Abstract A multicenter study conducted in healthy population of 6 cities from the 4 corners and central China for 7 serum-specific proteins to identify the sources of variation and establish the reference intervals on 2 automation platforms. A total of 3148 subjects aged 19 to 64 years old were enrolled in this study to ensure at least 120 participants in each 10-year age group and each city. The majority of samples were transported to central laboratory and measured on both Beckman AU5800 and Immage 800 analytical systems. Three-level nested ANOVA, multiple regression analysis, and the scatter plot were used to explore the variations from sex, age, region, BMI, cigarette smoking, and so on. The latent abnormal value exclusion (LAVE) method was applied at the time of computing RIs as a method for secondary exclusion. Regionality was not observed in any of the immunoassay in China. Variations for sex were significant for IgM among the immune analytes. For CRP and hsCRP results with turbidimetry method (Beckman Coulter AU5800) were lower than the nephelometry method (Beckman Immage). The LAVE method did not affect the RIs computed for the majority of analytes except C4, CRP, and hsCRP. In the scatter plot at the age of 45 years old C3, C4, and IgM reached an inflection point, accordingly RIs were separated by the age group. With the lack of regional differences and the well-standardized status of test results, the RIs of C3, IgG, IgA, IgM derived from this nationwide study can be used for the entire Chinese population. C4, CRP, and hsCRP were affected by different platforms and gender was a significant source of variation for IgM, so they had separated RIs. PMID:26656356

  16. NUT carcinoma in children and adults: A multicenter retrospective study.

    PubMed

    Lemelle, Lauriane; Pierron, Gaëlle; Fréneaux, Paul; Huybrechts, Sophie; Spiegel, Alexandra; Plantaz, Dominique; Julieron, Morbize; Dumoucel, Sophie; Italiano, Antoine; Millot, Fréderic; Le Tourneau, Christophe; Leverger, Guy; Chastagner, Pascal; Carton, Matthieu; Orbach, Daniel

    2017-06-23

    Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer is underdiagnosed and poorly treated. The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy. This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti-NUT nuclear staining (>50%). This series of 12 patients had a median age of 18.1 years (ranges: 12.3-49.7 years). The primary tumor was located in the chest in eight patients, the head and neck in three patients, and one patient had a multifocal tumor. Nine patients presented regional lymph node involvement and eight distant metastases. One-half of patients were initially misdiagnosed. Specific NUT antibody was positive in all cases tested. A transient response to chemotherapy was observed in four of 11 patients. Only two patients were treated by surgery and five received radiotherapy with curative intent. At the end of follow-up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95% confidence interval [CI]: 2.1-17.7). NUT carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful to propose the optimal therapeutic strategy. © 2017 Wiley Periodicals, Inc.

  17. Randomized comparison of ticagrelor versus prasugrel in patients with acute coronary syndrome and planned invasive strategy--design and rationale of the iNtracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 trial.

    PubMed

    Schulz, Stefanie; Angiolillo, Dominick J; Antoniucci, David; Bernlochner, Isabell; Hamm, Christian; Jaitner, Juliane; Laugwitz, Karl-Ludwig; Mayer, Katharina; von Merzljak, Barbara; Morath, Tanja; Neumann, Franz-Josef; Richardt, Gert; Ruf, Judith; Schömig, Gisela; Schühlen, Helmut; Schunkert, Heribert; Kastrati, Adnan

    2014-02-01

    In acute coronary syndromes (ACS), a dual antiplatelet regimen with an adenosine diphosphate (ADP) receptor antagonist plus aspirin has become the cornerstone of treatment. The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater, more rapid and consistent platelet inhibition compared to their predecessor clopidogrel. Based on their advantages over clopidogrel in two landmark studies, both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation. Due to differences in ACS populations and conditions investigated, the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy cannot be reliably estimated from independent trials. To date, no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists. The aim of this multicenter, randomized, open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy.

  18. A Problem with STEM

    ERIC Educational Resources Information Center

    Marder, Michael

    2013-01-01

    Striking differences between physics and biology have important implications for interdisciplinary science, technology, engineering, and mathematics (STEM) education. The author is a physicist with interdisciplinary connections. The research group in which he works, the Center for Nonlinear Dynamics at the University of Texas at Austin, is…

  19. STEM Comes to Preschool

    ERIC Educational Resources Information Center

    Moomaw, Sally; Davis, Jaumall A.

    2010-01-01

    Math and science and the related technology and engineering are natural pairings. These four disciplines form the acronym STEM (Science, Technology, Engineering, and Math) and can be readily combined into an integrated curriculum for early childhood classrooms. Many educators believe that children learn best when disciplines are interconnected. An…

  20. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--shorthand for "science, technology, engineering, and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in an internationally competitive, 21st-century economy. But building and implementing programs that…

  1. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--the catchy shorthand for "science, technology, engineering and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in preparing students for an internationally competitive, 21st-century economy. But while the…

  2. STEM Sense and Nonsense

    ERIC Educational Resources Information Center

    Charette, Robert N.

    2015-01-01

    If you can believe the daily flood of mass media stories, journal articles, and white papers, the United States is facing a STEM worker crisis. Business leaders and politicians warn that the nation is falling hopelessly behind in the global economic race because our students are unprepared for and uninterested in science, technology, engineering,…

  3. Advancing Diversity in STEM

    ERIC Educational Resources Information Center

    Hill, Paul L.; Shaw, Rose A.; Taylor, Jan R.; Hallar, Brittan L.

    2011-01-01

    Although progress has been made, greater efforts are needed to promote faculty diversity at the college and university levels, especially in STEM fields. Thus, it is important to elucidate best practices both for increasing awareness of diversity issues pertaining to higher education and for implementing change. This article focuses on the…

  4. "Excellence" in STEM Education

    ERIC Educational Resources Information Center

    Clark, Aaron C.

    2012-01-01

    So what does it take to achieve excellence in STEM education? That is the title of the author's presentation delivered at International Technology and Engineering Educators Association's (ITEEA's) FTEE "Spirit of Excellence" Breakfast on March 16, 2012, in Long Beach, California. In preparation for this presentation, the author went back and read…

  5. A Problem with STEM

    ERIC Educational Resources Information Center

    Marder, Michael

    2013-01-01

    Striking differences between physics and biology have important implications for interdisciplinary science, technology, engineering, and mathematics (STEM) education. The author is a physicist with interdisciplinary connections. The research group in which he works, the Center for Nonlinear Dynamics at the University of Texas at Austin, is…

  6. Advancing Diversity in STEM

    ERIC Educational Resources Information Center

    Hill, Paul L.; Shaw, Rose A.; Taylor, Jan R.; Hallar, Brittan L.

    2011-01-01

    Although progress has been made, greater efforts are needed to promote faculty diversity at the college and university levels, especially in STEM fields. Thus, it is important to elucidate best practices both for increasing awareness of diversity issues pertaining to higher education and for implementing change. This article focuses on the…

  7. Integrated STEM Assessment Model

    ERIC Educational Resources Information Center

    Bicer, Ali; Capraro, Robert M.; Capraro, Mary M.

    2017-01-01

    Previous research identified a strong correlation between mathematics and science performance albeit for small samples of students. Even though there was a high correlation between mathematics and science performance, researchers examining students' STEM achievement investigated mathematics and science achievement separately. The present study…

  8. "Excellence" in STEM Education

    ERIC Educational Resources Information Center

    Clark, Aaron C.

    2012-01-01

    So what does it take to achieve excellence in STEM education? That is the title of the author's presentation delivered at International Technology and Engineering Educators Association's (ITEEA's) FTEE "Spirit of Excellence" Breakfast on March 16, 2012, in Long Beach, California. In preparation for this presentation, the author went back and read…

  9. STEM Sense and Nonsense

    ERIC Educational Resources Information Center

    Charette, Robert N.

    2015-01-01

    If you can believe the daily flood of mass media stories, journal articles, and white papers, the United States is facing a STEM worker crisis. Business leaders and politicians warn that the nation is falling hopelessly behind in the global economic race because our students are unprepared for and uninterested in science, technology, engineering,…

  10. STEMMING the Gap

    ERIC Educational Resources Information Center

    Kahler, Jim; Valentine, Nancy

    2011-01-01

    America has a gap when it comes to youth pursuing science and technology careers. In an effort to improve the knowledge and application of science, technology, engineering, and math (STEM), after-school programs can work in conjunction with formal in-school curriculum to improve science education. One organization that actively addresses this…

  11. Bolden STEM Event

    NASA Image and Video Library

    2011-01-28

    NASA Administrator Charles Bolden speaks to students from Albert Hill Middle School during a visit to the MathScience Innovation Center, Friday, Jan. 28, 2011, in Richmond, Va. During his talk, Bolden highlighted the importance of science, technology, engineering and math, or STEM, as he shared his life experiences with the students. Photo Credit (NASA/Paul E. Alers)

  12. NASA STEM Event

    NASA Image and Video Library

    2013-01-19

    School children are taught to build their own spacecraft and habitat during a Science, Technology, Engineering, and Math (STEM) education event held at the Ritz-Carlton Hotel in Arlington, VA on Saturday, Jan. 19, 2013. Students were able to meet with Astronaut Leland Melvin, conduct experiments, build their own space jab, and touch a mockup space suit. Photo Credit: (NASA/Bill Ingalls)

  13. Bolden STEM Event

    NASA Image and Video Library

    2011-01-28

    NASA Administrator Charles Bolden visits with students from Albert Hill Middle School during a visit to the MathScience Innovation Center, Friday, Jan. 28, 2011, in Richmond, Va. During his visit, Bolden highlighted the importance of science, technology, engineering and math, or STEM, as he shared his life experiences with the students. Photo Credit:(NASA/Paul E. Alers)

  14. NASA STEM Event

    NASA Image and Video Library

    2013-01-19

    School children react to food shrinking in a vacuum chamber during an Science, Technology, Engineering, and Math (STEM) education event held at the Ritz-Carlton Hotel in Arlington, VA on Saturday, Jan. 19, 2013. Students were able to meet with Astronaut Melvin, conduct experiments, build their own space jab, and touch a mockup space suit. Photo Credit: (NASA/Bill Ingalls)

  15. STEM Comes to Preschool

    ERIC Educational Resources Information Center

    Moomaw, Sally; Davis, Jaumall A.

    2010-01-01

    Math and science and the related technology and engineering are natural pairings. These four disciplines form the acronym STEM (Science, Technology, Engineering, and Math) and can be readily combined into an integrated curriculum for early childhood classrooms. Many educators believe that children learn best when disciplines are interconnected. An…

  16. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--the catchy shorthand for "science, technology, engineering and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in preparing students for an internationally competitive, 21st-century economy. But while the…

  17. Helping STEM Take Root

    ERIC Educational Resources Information Center

    Schachter, Ron

    2011-01-01

    STEM--shorthand for "science, technology, engineering, and mathematics"--has been part of the school improvement discussion for more than a decade, as educational leaders and policy makers have underscored the importance of these areas in an internationally competitive, 21st-century economy. But building and implementing programs that…

  18. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

    PubMed

    Chen, Robert; Palmer, Joycelynne M; Martin, Peter; Tsai, Nicole; Kim, Young; Chen, Bihong T; Popplewell, Leslie; Siddiqi, Tanya; Thomas, Sandra H; Mott, Michelle; Sahebi, Firoozeh; Armenian, Saro; Leonard, John; Nademanee, Auayporn; Forman, Stephen J

    2015-12-01

    This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

  19. Analytically reduced form of multicenter integrals from Gaussian transforms. [in atomic and molecular physics

    NASA Technical Reports Server (NTRS)

    Straton, Jack C.

    1989-01-01

    The four-dimensional Fourier-Feynman transformations previously used in analytically reducing the general class of integrals containing multicenter products of 1s hydrogenic orbitals, Coulomb or Yukawa potentials, and plane waves, are replaced by the one-dimensional Gaussian transformation. This reduces the previously required double-diagonalization of the quadratic form of the multicenter integrals to only one diagonalization, yielding a simpler reduced form of the integral. The present work also extends the result to include all s states and pairs of states with l not equal to zero summed over the m quantum number.

  20. Stem cell mobilization.

    PubMed

    Cottler-Fox, Michele H; Lapidot, Tsvee; Petit, Isabelle; Kollet, Orit; DiPersio, John F; Link, Dan; Devine, Steven

    2003-01-01

    Successful blood and marrow transplant (BMT), both autologous and allogeneic, requires the infusion of a sufficient number of hematopoietic progenitor/stem cells (HPCs) capable of homing to the marrow cavity and regenerating a full array of hematopoietic cell lineages in a timely fashion. At present, the most commonly used surrogate marker for HPCs is the cell surface marker CD34, identified in the clinical laboratory by flow cytometry. Clinical studies have shown that infusion of at least 2 x 10(6) CD34(+) cells/kg recipient body weight results in reliable engraftment as measured by recovery of adequate neutrophil and platelet counts approximately 14 days after transplant. Recruitment of HPCs from the marrow into the blood is termed mobilization, or, more commonly, stem cell mobilization. In Section I, Dr. Tsvee Lapidot and colleagues review the wide range of factors influencing stem cell mobilization. Our current understanding focuses on chemokines, proteolytic enzymes, adhesion molecules, cytokines and stromal cell-stem cell interactions. On the basis of this understanding, new approaches to mobilization have been designed and are now starting to undergo clinical testing. In Section II, Dr. Michele Cottler-Fox describes factors predicting the ability to mobilize the older patient with myeloma. In addition, clinical approaches to improving collection by individualizing the timing of apheresis and adjusting the volume of blood processed to achieve a desired product are discussed. Key to this process is the daily enumeration of blood CD34(+) cells. Newer methods of enumerating and mobilizing autologous blood HPCs are discussed. In Section III, Dr. John DiPersio and colleagues provide data on clinical results of mobilizing allogeneic donors with G-CSF, GM-CSF and the combination of both as relates to the number and type of cells collected by apheresis. Newer methods of stem cell mobilization as well as the relationship of graft composition on immune reconstitution

  1. [Melanocyte stem cells in adults].

    PubMed

    Aubin-Houzelstein, Geneviève; Djian-Zaouche, Johanna; Panthier, Jean-Jacques

    2008-01-01

    Melanocyte stem cells have been recently localized in mice, in the outer root sheath of the lower permanent portion of the hair follicle. Specific depletion of melanocyte stem cell population is responsible for natural hair greying in aging mice and humans. Melanocyte stem cells also seem to drive the growth of malignant melanomas. A few mutations, either spontaneous or genetically engineered, accelerate the natural process of hair greying with age. These mutations allowed the identification of genes and signalling pathways controlling emergence, maintenance and/or differentiation of melanocyte stem cells. This review summarizes recent studies on the melanocyte stem cells and defines a few major unanswered questions in the field.

  2. Gravitropism in Leafy Dicot Stems

    NASA Technical Reports Server (NTRS)

    Salisbury, F. B.

    1985-01-01

    A polarizing research microscope with rotating stage and associated camera equipment were ordered, and techniques of fixation and preparation of specimens were perfected for studying possible changes in orientation of cellulose microfibrils in cell walls of gravistimulated dicot stems. Acid ethephon solutions or acid without ethephon caused elongation of stem tissues where they were applied; stems bent away from the side of application. Acid solutions applied to the bottom of horizontal stems greatly delayed bending. Research in tissue sensitivity changes during gravitropic bending of soybean hypocotyls while immersed in auxin and in castor bean stems is also reported.

  3. Gravitropism in Leafy Dicot Stems

    NASA Technical Reports Server (NTRS)

    Salisbury, F. B.

    1985-01-01

    A polarizing research microscope with rotating stage and associated camera equipment were ordered, and techniques of fixation and preparation of specimens were perfected for studying possible changes in orientation of cellulose microfibrils in cell walls of gravistimulated dicot stems. Acid ethephon solutions or acid without ethephon caused elongation of stem tissues where they were applied; stems bent away from the side of application. Acid solutions applied to the bottom of horizontal stems greatly delayed bending. Research in tissue sensitivity changes during gravitropic bending of soybean hypocotyls while immersed in auxin and in castor bean stems is also reported.

  4. Stem Cells in Mammalian Gonads.

    PubMed

    Wu, Ji; Ding, Xinbao; Wang, Jian

    Stem cells have great value in clinical application because of their ability to self-renew and their potential to differentiate into many different cell types. Mammalian gonads, including testes for males and ovaries for females, are composed of germline and somatic cells. In male mammals, spermatogonial stem cells maintain spermatogenesis which occurs continuously in adult testis. Likewise, a growing body of evidence demonstrated that female germline stem cells could be found in mammalian ovaries. Meanwhile, prior studies have shown that somatic stem cells exist in both testes and ovaries. In this chapter, we focus on mammalian gonad stem cells and discuss their characteristics as well as differentiation potentials.

  5. Inflammation and cancer stem cells.

    PubMed

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei

    2014-04-10

    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Panels participants, from left, Dr. John P. Holdren, Assistant to the President for Science and Technology and Director of the White House Office of Science & Technology Policy, former White House Science Fair participant Joey Hudy, Environmentalist and third-year law student at Elon University School of Law Tyrone Davis, White House innovation expert Cristin Dorgelo, and Defense Advanced Research Projects Agency (DARPA) Gill Pratt, take a question from the audience during the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Photo Credit: (NASA/Bill Ingalls)

  7. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Environmentalist and third-year law student at Elon University School of Law Tyrone Davis is interviewed by TIME for Kids reporter Grace Clark ahead of the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Davis sat with the First Lady at the President’s 2014 State of the Union Address. As a Fellow with the Environmental Defense Fund in 2010, he helped show Elizabeth City State University how to save more than $31,000 a year and 200 tons of carbon emissions reductions annually by using technology and efficiency solutions. Photo Credit: (NASA/Bill Ingalls)

  8. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Joey Hudy, Anthem, AZ, 16-year-old self-described “Maker” answers a question from the audience at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Joey sat with the First Lady at the President’s 2014 State of the Union Address after his first shot to fame in 2012 when he attended the White House Science Fair where the President took a turn using his “extreme marshmallow cannon” to launch a marshmallow across the East Room of the White House. Photo Credit: (NASA/Bill Ingalls)

  9. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    Montgomery Blair High School Student Newspaper “Silver Chips” Online Editor-in-Chief Aanchal Johri, right, and Photo Editor Emma Howells, left, from Silver Spring, MD. interview Joey Hudy, Anthem, AZ, 16-year-old self-described “Maker” at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Joey sat with the First Lady at the President’s 2014 State of the Union Address after his first shot to fame in 2012 when he attended the White House Science Fair where the President took a turn using his “extreme marshmallow cannon” to launch a marshmallow across the East Room of the White House. Photo Credit: (NASA/Bill Ingalls)

  10. State of STEM (SoSTEM) Address

    NASA Image and Video Library

    2014-01-29

    National Geographic Kids reporter Trevor Jehl, right, interviews Joey Hudy, Anthem, AZ, 16-year-old self-described “Maker” at the annual White House State of Science, Technology, Engineering, and Math (SoSTEM) address, Wednesday, Jan. 29, 2014, in the South Court Auditorium in the Eisenhower Executive Office Building on the White House complex in Washington. Joey sat with the First Lady at the President’s 2014 State of the Union Address after his first shot to fame in 2012 when he attended the White House Science Fair where the President took a turn using his “extreme marshmallow cannon” to launch a marshmallow across the East Room of the White House. Photo Credit: (NASA/Bill Ingalls)

  11. Intracoronary Doppler: Clinical Application And Future Directions

    NASA Astrophysics Data System (ADS)

    Whitlow, Patrick L.; Raymond, Russell E.; Tuzcu, E. Murat

    1989-08-01

    Because coronary arteriography may underestimate the severity of coronary artery disease, other methods to assess the physiologic significance of a coronary lesion have been sought. Experimental data have confirmed that the ratio of peak flow to resting flow, coronary vasodilator reserve (CVDR), is a quantitative measure of the functional significance of a coronary a stenosis.