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  • 1
    Language: English
    In: The American Journal of Cardiology, 15 January 2013, Vol.111(2), pp.273-277
    Description: The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism (PE) has not been investigated. Because the lungs are very sensitive to thrombolysis, we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator. The purpose of the present study was to evaluate the role of this “safe dose” thrombolysis in the reduction of pulmonary artery pressure in moderate PE. During a 22-month period, 121 patients with moderate PE were randomized to receive a “safe dose” of tissue plasminogen activator plus anticoagulation (thrombolysis group [TG], n = 61 patients) or anticoagulation alone (control group [CG], n = 60). The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months. Pulmonary hypertension and the composite end point developed in 9 of 58 patients (16%) in the TG and 32 of 56 patients (57%) in the CG (p 〈0.001) and 9 of 58 patients (16%) in the TG and 35 of 56 patients (63%) in the CG (p 〈0.001), respectively. The secondary end points were total mortality, the duration of hospital stay, bleeding at the index hospitalization, recurrent PE, and the combination of mortality and recurrent PE. The duration of hospitalization was 2.2 ± 0.5 days in the TG and 4.9 ± 0.8 days in the CG (p 〈0.001). The combination of death plus recurrent PE was 1 (1.6%) in TG and 6 (10%) in the CG (p = 0.0489). No bleeding occurred in any group, and despite a positive trend in favor of a “safe dose” thrombolysis, no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently. In conclusion, the results from the present prospective randomized trial suggests that “safe dose” thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months.
    Keywords: Medicine
    ISSN: 0002-9149
    E-ISSN: 1879-1913
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  • 2
    Language: English
    In: Journal of Vascular Surgery, 2011, Vol.53(1), pp.147-149
    Description: A growing number of patients who are on systemic anticoagulation with warfarin require endovenous thermal ablation for reflux disease in the great saphenous vein (GSV). Little is known about the effects of anticoagulation on periprocedural bleeding and long-term closure rates of the treated veins. This study evaluated the effects of uninterrupted anticoagulation in patients undergoing endovenous thermal ablation. In this prospective observational study, 88 limbs of patients on warfarin (anticoagulation group [AG]) who underwent endovenous thermal ablation for GSV reflux disease were compared with 92 limbs in patients receiving no anticoagulation or antiplatelet agents (control group [CG]). Forty percent of AG patients were also receiving antiplatelet therapy. Periprocedural bleeding and closure rate at 1 year were evaluated. No major bleeding occurred in either group. Minor bleeding was noted in 8 of 88 procedures in the AG vs 4 of 92 in the CG ( = 0.24); all in patients receiving radiofrequency ablation. Four of the eight minor bleeds in the AG were noted in patients receiving “triple therapy” with warfarin, aspirin, and clopidogrel or ticlopidine. Triple therapy in the AG was associated with a higher risk of minor bleeding compared with the CG (relative risk, 13.0; 95% confidence interval, 4.10-41.19, 〈 .001). All treated venous segments remained closed at the 1-year follow-up in both groups. In this relatively small, nonrandomized study comparing endovenous thermal ablation in patients with and without warfarin, no differences were found in periprocedural risk of major bleeding or closure rate of the treated venous segments. Minor bleeding was increased in patients receiving triple therapy with warfarin, aspirin, and a thienopyridine who underwent radiofrequency ablation.
    Keywords: Medicine
    ISSN: 0741-5214
    E-ISSN: 1097-6809
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  • 3
    Language: English
    In: CardioVascular and Interventional Radiology, 2013, Vol.36(6), pp.1586-1590
    Description: Byline: Mohsen Sharifi (1,2), Curt Bay (2), Sasan Nowroozi (1), Suzanne Bentz (1), Gayle Valeros (1), Sara Memari (1) Keywords: Argatroban; Deep vein thrombosis; Infusion catheter; Percutaneous endovenous intervention; Thrombolysis; tPA Abstract: Purpose Catheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT. Methods Thirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28 +- 6 h of presentation. The dose of tPA was 0.75--1 mg/h through the infusion port and that of argatroban at 0.3--1 ug/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22 months. Results There was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91 %). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE. Conclusion Concomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT. Author Affiliation: (1) Arizona Cardiovascular Consultants, 3850 E Baseline Road, Bldg1, Suite 102, Mesa, AZ, 85206, USA (2) A. T. Still University, 5850 East Still Circle, Mesa, AZ, 85206, USA Article History: Registration Date: 17/01/2013 Received Date: 25/09/2012 Accepted Date: 10/01/2013 Online Date: 02/02/2013
    Keywords: Argatroban ; Deep vein thrombosis ; Infusion catheter ; Percutaneous endovenous intervention ; Thrombolysis ; tPA
    ISSN: 0174-1551
    E-ISSN: 1432-086X
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  • 4
    Language: English
    In: Thrombosis Research, April 2015, Vol.135(4), pp.607-609
    Description: Heparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC. We retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19 ± 3 months. There were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient. In patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis.
    Keywords: Heparin- Induced Thrombocytopenia ; New Oral Anticoagulants ; Deep Venous Thrombosis ; Medicine
    ISSN: 0049-3848
    E-ISSN: 1879-2472
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  • 5
    Language: English
    In: BMC Bioinformatics, 01 December 2017, Vol.18(S14), pp.93-102
    Description: Abstract Background Blockage of some ion channels and in particular, the hERG (human Ether-a’-go-go-Related Gene) cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Candidate drugs that are determined not to cause cardiac ion channel blockage are more likely to pass successfully through clinical phases II and III trials (and preclinical work) and not be withdrawn even later from the marketplace due to cardiotoxic effects. The objective of the present study is to develop an SAR (Structure-Activity Relationship) model that can be used as an early screen for torsadogenic (causing TdP arrhythmias) potential in drug candidates. The method is performed using descriptors comprised of atomic NMR chemical shifts (13C and 15N NMR) and corresponding interatomic distances which are combined into a 3D abstract space matrix. The method is called 3D-SDAR (3-dimensional spectral data-activity relationship) and can be interrogated to identify molecular features responsible for the activity, which can in turn yield simplified hERG toxicophores. A dataset of 55 hERG potassium channel inhibitors collected from Kramer et al. consisting of 32 drugs with TdP risk and 23 with no TdP risk was used for training the 3D-SDAR model. Results An artificial neural network (ANN) with multilayer perceptron was used to define collinearities among the independent 3D-SDAR features. A composite model from 200 random iterations with 25% of the molecules in each case yielded the following figures of merit: training, 99.2%; internal test sets, 66.7%; external (blind validation) test set, 68.4%. In the external test set, 70.3% of positive TdP drugs were correctly predicted. Moreover, toxicophores were generated from TdP drugs. Conclusion A 3D-SDAR was successfully used to build a predictive model for drug-induced torsadogenic and non-torsadogenic drugs based on 55 compounds. The model was tested in 38 external drugs.
    Keywords: Artificial Neural Network ; Cardiac Arrhythmia ; Cardiotoxicity ; Herg ; Ion Channels ; Multilayer Perceptron ; Biology
    E-ISSN: 1471-2105
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  • 6
    Language: English
    In: American Journal of Emergency Medicine, October 2016, Vol.34(10), pp.1963-1967
    Description: Pulseless electrical activity (PEA) during cardiac arrest portends a poor prognosis. There is a paucity of data in the use of thrombolytic therapy in PEA and cardiopulmonary arrest due to confirmed pulmonary embolism (PE). We evaluated the outcome of low-dose systemic thrombolysis with tissue plasminogen activator (tPA) in patients presenting with PEA due to PE. During a 34-month period, we treated 23 patients with PEA and cardiopulmonary arrest due to confirmed massive PE. All patients received 50 mg of tPA as intravenous push in 1 minute while cardiopulmonary resuscitation was ongoing. The time from initiation of cardiopulmonary resuscitation to administration of tPA was 6.5 ± 2.1 minutes. Return of spontaneous circulation occurred in 2 to 15 minutes after tPA administration in all but 1 patient. There was no minor or major bleeding despite chest compression. Of the 23 patients, 2 died in the hospital, and at 22 ± 3 months of follow-up, 20 patients (87%) were still alive. The right ventricular/left ventricular ratio and pulmonary artery systolic pressure dropped from 1.79 ± 0.27 and 58.10 ± 7.99 mm Hg on admission to 1.16 ± 0.13 and 40.25 ± 4.33 mm Hg within 48 hours, respectively ( 〈 .001 for both comparisons). There was no recurrent venous thromboembolism or bleeding during hospitalization or at follow-up. Rapid administration of 50 mg of tPA is safe and effective in restoration of spontaneous circulation in PEA due to massive PE leading to enhanced survival and significant reduction in pulmonary artery pressures.
    Keywords: Medicine
    ISSN: 0735-6757
    E-ISSN: 1532-8171
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  • 7
    Language: English
    In: Catheterization and Cardiovascular Interventions, 01 April 2010, Vol.75(5), pp.685-689
    Description: Venous thromboembolic disease is an underdiagnosed disease spectrum with a high mortality and morbidity. Despite significant advances in cardiovascular interventions, venous occlusive disease has not received the attention it deserves from the interventional cardiology community. We describe an 82‐year‐old man with massive left lower extremity DVT who underwent successful percutaneous endovenous intervention (PEVI) with rapid resolution of symptoms. We like to use this case as a call to action and raise awareness of the importance of PEVI in the treatment of extensive venous occlusive disease. © 2009 Wiley‐Liss, Inc.
    Keywords: Deep Venous Thrombosis ; Thrombectomy ; Thrombolytic Therapy
    ISSN: 1522-1946
    E-ISSN: 1522-726X
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  • 8
    Language: English
    In: Medical Engineering and Physics, December 2017, Vol.50, pp.22-28
    Description: Elbow articular cartilage withstands high compressive and shear forces while protecting the bone from excessive loading. Better understanding of elbow cartilage contact mechanics can provide insight into cartilage degeneration. In this study a tactile pressure sensor was used to measure the contact pressure distribution within the ulno-humeral joint of two cadaver specimens at 20° flexion angle across three different axial loads of 80 N, 110 N, and 140 N. Corresponding 3D finite element (FE) models were constructed from magnetic resonance imaging (MRI) and contact analysis was performed for each specimen with boundary and loading conditions identical to the experiment. Direct comparison between FE results and experimental measurements was conducted for the validation of the FE models and a sensitivity analysis was employed for assessing the effect of cartilage parameters on the model's outputs. The results showed a good agreement between the FE models and the experiments in terms of contact characteristics. The sensitivity analysis demonstrated that outcomes of the model, particularly peak contact pressure is more sensitive to the Poisson's ratio rather than to Young's modulus under static conditions. This result suggests that selection of Poisson's ratio is very critical for accurate prediction of contact mechanics within the ulno-humeral joint.
    Keywords: Ulno-Humeral Joint ; Elbow Joint ; Articular Cartilage ; Contact Mechanics ; Finite Element Analysis ; Parametric Study ; Medicine ; Engineering ; Chemistry
    ISSN: 1350-4533
    E-ISSN: 1873-4030
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  • 9
    Language: English
    In: Journal of Endovascular Therapy, April 2012, Vol.19(2), pp.273-280
    Description: Purpose To present midterm results from a randomized study comparing the safety and efficacy of percutaneous endovenous intervention (PEVI) + anticoagulation vs. anticoagulation alone in the reduction of venous thromboembolism (VTE) and post-thrombotic syndrome (PTS) in acute symptomatic proximal deep venous thrombosis (DVT). Methods The TORPEDO trial was a randomized study to demonstrate superiority of PEVI in the reduction of the VTE and PTS at 6 months; in that trial, 183 patients (103 men; mean age 61±11 years) with symptomatic proximal DVT were randomized to receive PEVI + anticoagulation (n=91) or anticoagulation alone (n=92). PEVI consisted of one or more of a combination of thrombectomy, balloon venoplasty, stenting, and/or local low-dose thrombolytic therapy. Results At 6 months, recurrent VTE developed in 2.3% of the PEVI + anticoagulation group vs. 14.8% in the anticoagulation only group (p=0.003); PTS developed in 3.4% vs. 27.2% (p〈0.001), respectively. At a mean follow-up of 3065 months (range 12–41), 88 patients in the PEVI + anticoagulation group and 81 patients in the anticoagulation only group reached target follow-up. Recurrent VTE developed in 4 (4.5%) of the 88 PEVI + anticoagulation patients vs. 13 (16%) of the 81 patients receiving anticoagulation only (p=0.02). PTS developed in 6 (6.8%) of the PEVI + anticoagulation group vs. 24 (29.6%) of the anticoagulation only group (p〈0.001). Conclusion In patients with proximal DVT, PEVI is superior to anticoagulation alone in the reduction of VTE and PTS. This benefit, which appears early in the course of treatment, extends to 〉2.5 years.
    Keywords: Venous Thrombolysis ; Post-Thrombotic Syndrome ; Recurrent Deep Venous Thrombosis ; Venous Thromboembolism ; Percutaneous Endovenous Intervention ; Thrombectomy ; Venoplasty ; Anticoagulation ; Stent ; Thrombolysis
    ISSN: 1526-6028
    E-ISSN: 1545-1550
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  • 10
    Language: English
    In: Clinical chemistry, March 2007, Vol.53(3), pp.456-64
    Description: This study was undertaken to determine the association of serum C-reactive protein (CRP) with generalized and abdominal obesity, body fat composition, the metabolic syndrome, and oxidative stress markers among young people. We conducted a population-based study of 512 young people, aged 10-18 years. We obtained anthropometric and blood pressure measurements. Fasting blood sugar, total cholesterol (TC), HDL-cholesterol, triglycerides, CRP, malondialdehyde (MDA), and conjugated diene (CDE) were quantified. LDL-cholesterol (LDL-C) was calculated for samples with TG 〈 or =4.52 mmol/L RESULTS: Mean triglycerides, waist and hip circumferences, percentage body fat, subcutaneous fat, and systolic blood pressure increased significantly with increasing body mass index (BMI). In contrast, the mean LDL and TC were higher in underweight than normal weight individuals, and then increased significantly from normal to higher BMI categories. Mean HDL cholesterol significantly decreased with increasing BMI. Overall, CRP, MDA, and CDE were significantly correlated with measures of abdominal obesity. Serum CRP, MDA, and CDE significantly increased in the upper quartiles of waist circumference. Study participants with higher CRP concentrations were more likely to have metabolic syndrome and high oxidative stress markers. We found a significant positive association between CRP and oxidative stress markers in healthy young people, as well as an increase in these markers in the upper quartiles of waist circumference, but not BMI. Oxidative stress and CRP may interact in the early inflammatory processes of atherosclerosis.
    Keywords: Oxidative Stress ; Atherosclerosis -- Metabolism ; C-Reactive Protein -- Analysis
    ISSN: 0009-9147
    E-ISSN: 15308561
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