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Sample records for aggressive antithrombotic therapy

  1. Pharmacogenetics in Oral Antithrombotic Therapy.

    PubMed

    Maier, Cheryl L; Duncan, Alexander; Hill, Charles E

    2016-09-01

    Certain antithrombotic drugs exhibit high patient-to-patient variability that significantly impacts the safety and efficacy of therapy. Pharmacogenetics offers the possibility of tailoring drug treatment to patients based on individual genotypes, and this type of testing has been recommended for 2 oral antithrombotic agents, warfarin and clopidogrel, to influence use and guide dosing. Limited studies have identified polymorphisms that affect the metabolism and activity of newer oral antithrombotic drugs, without clear evidence of the clinical relevance of such polymorphisms. This article provides an overview of the current status of pharmacogenetics in oral antithrombotic therapy. PMID:27514462

  2. Antithrombotic Therapy for Atrial Fibrillation

    PubMed Central

    You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

    2012-01-01

    Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized

  3. Perioperative Management of Antithrombotic Therapy

    PubMed Central

    Douketis, James D.; Spyropoulos, Alex C.; Spencer, Frederick A.; Mayr, Michael; Jaffer, Amir K.; Eckman, Mark H.; Dunn, Andrew S.

    2012-01-01

    Background: This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure. Methods: The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C). Conclusions: Perioperative antithrombotic management is based on risk assessment for thromboembolism and

  4. [Managing antithrombotic therapy in vitreoretinal surgery].

    PubMed

    Gallice, M; Rouberol, F; Albaladejo, P; Brillat Zaratzian, E; Palombi, K; Aptel, F; Romanet, J-P; Chiquet, C

    2015-01-01

    Given the growing number of patients on antithrombotic therapy we are increasingly confronted with the management of this therapy before, during and after vitreoretinal surgery. In the absence of a consensus, the decision to withdraw antithrombotic therapy is based on the cardiovascular thromboembolism risk versus the theoretical risk of bleeding if the antithrombotic treatment is continued. As suggested by the literature, antiplatelet therapy (acetylsalicylic acid or clopidogrel) may be safely continued for vitreoretinal surgery, including retinal detachment repair. However, the risk/benefit ratio for patients being treated with two antiplatelet therapies is unknown. It appears that an International Normalized Ratio (INR) less than 3 for patients treated with anticoagulant therapy does not increase the perioperative risk of ocular bleeding. This risk has not been evaluated in patients treated by new antithrombotic therapies (prasugrel, ticagrelor as antiplatelet medication, or dabigatran, rivaroxaban, apixaban as anticoagulant therapy), and there is a need to study it further. PMID:25577431

  5. A new paradigm shift in antithrombotic therapy

    PubMed Central

    Pudusseri, Anita; Shameem, Raji; Spyropoulos, Alex C.

    2013-01-01

    Decades after the introduction of oral anti-coagulants namely the vitamin K antagonist (VKA) Warfarin and antiplatelet agents such as Aspirin and Plavix, new classes of direct, small molecule, novel oral anti-coagulant medications and antiplatelet P2Y12 receptor inhibitors have recently become available. For the novel oral anticoagulants (NOAC), these agents can be separated by direct thrombin inhibitors such as Dabigatran and direct Factor Xa inhibitors such as Rivaroxaban and Apixaban. For next generation antiplatelet agents such as Ticagrelor and Prasugrel, these new P2Y12 receptor inhibitors form the cornerstone of therapy for patients with acute coronary syndrome (ACS) or undergoing percutaneous interventions. These novel oral antithrombotics are revolutionizing the field of stroke prevention, atrial fibrillation (AF), the management of venous thromboembolism (VTE) and treatment of ACS. This article reviews the current research developed in order to identify therapeutic effects and establish net clinical benefits of these new oral antithrombotics. PMID:24155721

  6. Antithrombotic Therapy for VTE Disease

    PubMed Central

    Kearon, Clive; Comerota, Anthony J.; Prandoni, Paolo; Bounameaux, Henri; Goldhaber, Samuel Z.; Nelson, Michael E.; Wells, Philip S.; Gould, Michael K.; Dentali, Francesco; Crowther, Mark; Kahn, Susan R.

    2012-01-01

    Background: This article addresses the treatment of VTE disease. Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID:22315268

  7. Antithrombotic Therapy After Peripheral Vascular Intervention.

    PubMed

    Hu, Peter; Jones, Schuyler

    2016-03-01

    Cardioprotective medications and risk-factor modification are the hallmarks of treatment for all patients with peripheral artery disease (PAD). If symptoms are life-limiting and/or do not respond to conservative treatment, endovascular or surgical revascularization can be considered especially for patients with critical limb ischemia or acute limb ischemia. The rates of peripheral vascular intervention (PVI) have risen dramatically over the past few decades and much of this care have shifted from inpatient hospital settings to outpatient settings and office-based clinics. While PVI rates have surged and technology advancements have dramatically changed the face of PVI, the data behind optimal antithrombotic therapy following PVI is scant. Currently in the USA, most patients are treated with indefinite aspirin therapy and a variable duration of clopidogrel (or other P2Y12 inhibitor)-typically 1 month, 3 months, or indefinite therapy. More observational analyses and randomized clinical trials evaluating clinically relevant outcomes such as cardiovascular morbidity/mortality and the risk of bleeding are needed to guide the optimal role and duration of antithrombotic therapy post-PVI. PMID:26841788

  8. Antithrombotic Therapy in Neonates and Children

    PubMed Central

    Monagle, Paul; Chan, Anthony K. C.; Goldenberg, Neil A.; Ichord, Rebecca N.; Journeycake, Janna M.; Nowak-Göttl, Ulrike

    2012-01-01

    Background: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. Methods: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Results: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). Conclusions: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies. PMID:22315277

  9. Antithrombotic and Thrombolytic Therapy for Valvular Disease

    PubMed Central

    Sun, Jack C.; Fremes, Stephen E.; Rubens, Fraser D.; Teoh, Kevin H.

    2012-01-01

    Background: Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low

  10. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    PubMed Central

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

    2012-01-01

    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  11. Antithrombotic and Anticoagulant Therapy for Atrial Fibrillation.

    PubMed

    Dzeshka, Mikhail S; Lip, Gregory Y H

    2016-04-01

    As atrial fibrillation (AF) substantially increases the risk of stroke and other thromboembolic events, most AF patients require appropriate antithrombotic prophylaxis. Oral anticoagulation (OAC) with either dose-adjusted vitamin K antagonists (VKAs) (eg, warfarin) or non-VKA oral anticoagulants (eg, dabigatran, apixaban, rivaroxaban) can be used for this purpose unless contraindicated. Therefore, risk assessment of stroke and bleeding is an obligatory part of AF management, and risk has to be weighed individually. Antiplatelet drugs (eg, aspirin and clopidogrel) are inferior to OAC, both alone and in combination, with a comparable risk of bleeding events. PMID:26968670

  12. Antithrombotic therapy and survival in patients with malignant disease

    PubMed Central

    Kakkar, A K; Macbeth, F

    2010-01-01

    A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group. PMID:20386547

  13. Periprocedural antithrombotic therapy during various types of percutaneous cardiovascular interventions

    PubMed Central

    Widimský, P.; Kočka, V.; Roháč, F.; Osmančík, P.

    2016-01-01

    Percutaneous catheter-based interventions became a critically important part of treatment in modern cardiology, improving quality of life as well as saving many life. Due to the introduction of foreign materials to the circulation (either temporarily or permanently) and due to a certain damage to the endothelium or endocardium, the risk of thrombotic complications is substantial and thus some degree of antithrombotic therapy is needed during all these procedures. The intensity (dosage, combination, and duration) of periprocedureal antithrombotic treatment largely varies based on the type of procedure, clinical setting, and comorbidities. This manuscript summarizes the current therapeutic approach to prevent clotting (and bleeding) during a large spectrum of interventions: acute and elective coronary interventions, acute stroke interventions and elective carotid stenting, electrophysiology procedures, interventions for structural heart disease, and peripheral arterial interventions. PMID:27418971

  14. Factor XI and Contact Activation as Targets for Antithrombotic Therapy

    PubMed Central

    Gailani, David; Bane, Charles E.; Gruber, Andras

    2015-01-01

    Summary The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa, or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and factor X. These drugs do not distinguish between thrombin generation contributing to thrombosis from thrombin generation required for hemostasis. Thus, anticoagulants increase bleeding risk, and many patients who would benefit from therapy go untreated because of comorbidities that place them at unacceptable risk for hemorrhage. Studies in animals demonstrate that components of the plasma contact activation system contribute to experimentally-induced thrombosis, despite playing little or no role in hemostasis. Attention has focused on factor XII, the zymogen of a protease (factor XIIa) that initiates contact activation when blood is exposed to foreign surfaces; and factor XI, the zymogen of the protease factor XIa, which links contact activation to the thrombin generation mechanism. In the case of factor XI, epidemiologic data indicate this protein contributes to stroke and venous thromboembolism, and perhaps myocardial infarction, in humans. A phase 2 trial showing that reduction of factor XI may be more effective than low-molecular-weight heparin at preventing venous thrombosis during knee replacement surgery provides proof of concept for the premise that an antithrombotic effect can be uncoupled from an anticoagulant effect in humans by targeting components of contact activation. Here we review data on the role of factor XI and factor XII in thrombosis, and results of pre-clinical and human trials for therapies targeting these proteins. PMID:25976012

  15. Update on Antithrombotic Therapy for Stroke Prevention in Atrial Fibrillation

    PubMed Central

    Ovbiagele, Bruce

    2010-01-01

    Opinion statement Atrial fibrillation (AF) is the most common cardiac arrhythmia in the elderly, affecting 1 in 20 adults over the age of 70 years. Stroke is a major yet highly preventable complication of AF, and the strokes related to AF often are disabling and fatal. Warfarin is the treatment of choice in high-risk patients with AF, and its superior efficacy over aspirin for preventing stroke in these patients is widely recognized. However, several eligible patients with AF are not being treated with warfarin or are being treated inadequately, largely because of concerns regarding the attendant strict monitoring, drug interactions, and risk of major bleeding. As such, alternative antithrombotic therapies that can rival or exceed the efficacy of warfarin, yet compare favorably with its administration and side effect profile, are being sought. One such strategy, the use of a combination antiplatelet regimen, for stroke prevention in high-risk patients with nonvalvular AF was investigated recently in two clinical trials. This article reviews the role of combination antiplatelet regimens in stroke prevention for patients with AF. Other therapies discussed include oral anticoagulation, single antiplatelet therapies, oral anticoagulation plus antiplatelet treatment, direct thrombin inhibitors, and factor Xa inhibitors. PMID:20461116

  16. Gender differences in cardiovascular therapy: focus on antithrombotic therapy and percutaneous coronary intervention.

    PubMed

    Gutiérrez-Chico, Juan Luis; Mehilli, Julinda

    2013-11-01

    The epidemiology of coronary artery disease (CAD) differs between women and men: female cardiac patients are older and have poorer risk profiles than their male counterparts. This results in a preferential exclusion of women from participation in clinical trials, reducing their power to detect differences in performance of cardiovascular therapies in women. In general, all the antiplatelet and anticoagulant medications used in cardiac patients are equally effective in men and women, although women tend to experience a higher relative benefit due to their poorer risk profile. In particular, women with CAD benefit the most from interventional treatment combined with modern antithrombotic drugs. No gender-related differences in the reduction of thromboembolic risk with more potent antithrombotic drugs have been reported. On the other hand, a clear trend to a higher incidence of bleeding complications has been consistently reported in women, which might be related to a more frequent over-dosage of antithrombotic treatment in women than in men. Women are therefore one of the subgroups that might benefit the most from careful dose adjustment of available antithrombotic drugs. However, the development of a gender-based dosage guideline remains an unmet need in cardiology. PMID:24155117

  17. [Perioperative complications of transurethral resection of bladder tumor in patients receiving antithrombotic therapy].

    PubMed

    Wada, Naoki; Okazaki, Satoshi; Kobayashi, Shin; Hashizume, Kazumi; Hori, Junichi; Azumi, Makoto; Kita, Masafumi; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2014-11-01

    We examined perioperative complications of transurethral resection of bladder tumor (TURBT) in patients receiving antithrombotic therapy. We retrospectively studied 276 patients who underwent TURBT in our institute from January 2007 to March 2013. The study group consisted of 105 patients (38%) who were receiving antithrombotic agents, and the other 171 patients (62%) without antithrombotic agents were assigned to the control group. The period of discontinuation of antithrombotic agents complied with our institutional rule. The most frequently used agent was aspirin (69 patients : 66%), followed by warfarin (25 patients : 24%). Fourteen patients receiving warfarin (56%) needed heparin bridging therapy. There was no significant difference in average operative time (51 minutes versus 54 minutes), or average days to removal of urethral catheter (3.7 days versus 3.3 days) between the study and control groups. Hemorrhagic and ischemic complications were noted in 11 (10.5%) and 2 (1.9%) patients in the study group and 11 (6.4%) and none (0%) of the patients in the control group, respectively, with no significant difference between the 2 groups. However, prevalence of hemorrhagic complications in patients receiving heparin bridging therapy (21.4%) was significantly higher than that in the control group. Ischemic complications in the study group included chest pain suggestive of angina in one patient and acute myocardial infarction leading to death in another patient. We should pay attention to hemorrhagic complications in patients receiving heparin bridging therapy and keep in mind the possibility of lethal ischemic complications after discontinuation of antithrombotic agents. PMID:25511938

  18. Patient Values and Preferences in Decision Making for Antithrombotic Therapy: A Systematic Review

    PubMed Central

    Mulla, Sohail; Akl, Elie A.; Jankowski, Milosz; Vandvik, Per Olav; Ebrahim, Shanil; McLeod, Shelley; Bhatnagar, Neera; Guyatt, Gordon H.

    2012-01-01

    Background: Development of clinical practice guidelines involves making trade-offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy. Methods: We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate. Results: We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment. Conclusion: Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area. PMID:22315262

  19. Tutorial in oral antithrombotic therapy: Biology and dental implications

    PubMed Central

    Fakhri, Hamid R.; Janket, Sok J.; Baird, Alison E.; Dinnocenzo, Richard; Meurman, Jukka H.

    2013-01-01

    Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants. Method: We searched Medline using search terms “antithrombotic”, “antihemostasis” or “anticoagulation” and combined them with the search results of “dental”, “oral surgery” or “periodontal”. We restricted the results to “human” and “English”. Results: The early coagulation cascade, the new cell-based coagulation model, the pharmacokinetics and pharmacodynamics of conventional antithrombotics, and new oral anticoagulants were reviewed. The new direct factor Xa inhibitors and the direct thrombin inhibitor (s), called direct oral anticoagulants (DOAs) have rapid onset of action, fast elimination on cessation, and fewer drug-drug or drug-food interactions than warfarin. However, the lack of antidotes raises concerns that some dental procedures may trigger serious hemorrhagic events. Additionally, careful perioperative withdrawal and resumption protocols for the DOAs are reviewed, because DOAs’ blood levels are dependent on renal function. Also, various reversal strategies in the event of excessive bleedings are summarized. Perioperative management of dental patients taking new DOAs and conventional oral anticoagulants are also discussed. However, the perioperative strategies for DOAs are yet to be validated in randomized trials. Key words:Coagulation cascade, cell-based coagulation model, factor Xa inhibitors, direct thrombin inhibitors, prothrombin complex concentrates. PMID:23524440

  20. Holmium Laser Enucleation of the Prostate: Comparison of Immediate Postoperative Outcomes in Patients with and without Antithrombotic Therapy

    PubMed Central

    Bishop, Conrad V.; Liddell, Heath; Ischia, Joseph; Paul, Eldho; Appu, Sree; Frydenberg, Mark; Pham, Trung

    2013-01-01

    Objective To compare the immediate postoperative outcomes of patients with benign prostatic hyperplasia undergoing Holmium laser enucleation of the prostate (HOLEP) with and without full anticoagulation or antiplatelet therapy at the time of surgery. Materials and Methods A retrospective review was performed on a series of consecutive patients undergoing HOLEP at our institution by a single surgeon from February 2004 to September 2010. Demographic, surgical, pathological and outcome data were collected. Two cohorts were identified on the basis of antithrombotic therapy at the time of surgery. Patients who continued on aspirin, aspirin/dipyridamole, clopidogrel and warfarin throughout the surgery were included in the antithrombotic cohort. Univariate analysis was performed to determine differences in outcomes between the 2 cohorts. Results Total 125 consecutive patients underwent HOLEP with 52 patients on antithrombotic therapy at the time of surgery and 73 patients were not on antithrombotic therapy during surgery. Patients in the antithrombotic group were older (75.1 ±7.5 vs. 71.7 ± 8.3 years; p = 0.02) and had a higher median ASA physical status (3 (3-3) vs. 2 (2-3), p < 0.0001). The mean operating time and median specimen volume were not significantly different between the 2 cohorts. The median length of stay (2 (1-3) vs. 1 (1-2) d, p = 0.014) was longer in the antithrombotic cohort. The transfusion rate (7.7 vs. 0%, p = 0.028) was predictably higher in the antithrombotic cohort. No patients required re-operation for bleeding. Conclusions The use of HOLEP in patients on antithrombotic therapy is safe despite the higher surgical risk profile of that particular patient population and the potential increased risk for significant bleeding. PMID:24917753

  1. Antithrombotic Therapy for the CardioWest Temporary Total Artificial Heart

    PubMed Central

    Ensor, Christopher R.; Cahoon, William D.; Crouch, Michael A.; Katlaps, Gundars J.; Hess, Michael L.; Cooke, Richard H.; Gunnerson, Kyle J.; Kasirajan, Vigneshwar

    2010-01-01

    The CardioWest™ temporary total artificial heart serves as a viable bridge to orthotopic heart transplantation in patients who are experiencing end-stage refractory biventricular heart failure. This device is associated with a low, albeit still substantial, risk of thrombosis. Platelet interactions with artificial surfaces are complex and result in continuous activation of contact proteins despite therapeutic anticoagulation. We searched the medical literature (publication dates, January 1962–October 2009) in order to evaluate means of mitigating adverse events that have occurred after implantation of the CardioWest temporary total artificial heart. We conclude that the use of a multitargeted antithrombotic approach, involving anticoagulation (bivalirudin and warfarin) and antiplatelet therapy (dipyridamole and aspirin), can mitigate the procoagulative effects of mechanical circulatory assist devices, particularly those that are associated with the CardioWest temporary total artificial heart. Careful monitoring with use of a variant multisystem approach, involving efficacy tests (thrombelastography and light transmittance aggregometry), safety tests (laboratory analyses), and warfarin genomics, may maximize the therapeutic actions and minimize the bleeding risks that are associated with the multitargeted antithrombotic approach. The development and monitoring of individualized antithrombotic regimens require that informed health professionals appreciate the complexities and grasp the hazards that are associated with these therapies. PMID:20401285

  2. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

    PubMed

    Levine, Mark N; Raskob, Gary; Beyth, Rebecca J; Kearon, Clive; Schulman, Sam

    2004-09-01

    This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. PMID:15383476

  3. Factor XI as a target for antithrombotic therapy

    PubMed Central

    Bane, Charles E.; Gailani, David

    2014-01-01

    Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

  4. Management of antithrombotic therapy during cardiac implantable device surgery.

    PubMed

    AlTurki, Ahmed; Proietti, Riccardo; Birnie, David H; Essebag, Vidal

    2016-06-01

    Anticoagulants are commonly used drugs that are frequently encountered during device placement. Deciding when to halt or continue the use of anticoagulants is a balance between the risks of thromboembolism versus bleeding. Patients taking warfarin with a high risk of thromboembolism should continue to take their warfarin without interruption during device placement while ensuring their international normalized ratio remains below 3. For patients who are taking warfarin and have low risk of thromboembolism, either interrupted or continued warfarin may be used, with no evidence to clearly support either strategy. There is little evidence to support continuing direct acting oral anticoagulants (DOACs) for device implantation. The timing of halting these medications depends largely on renal function. If bleeding occurs, warfarin׳s anticoagulation effect is reversible with vitamin K and activated prothrombin complex concentrate. There are no DOAC reversal agents currently available, but some are under development. Regarding antiplatelet agents, aspirin alone can be safely continued while clopidogrel alone may also be continued, but with a slightly higher bleeding risk. Dual antiplatelet therapy for bare-metal stent/drug-eluting stent implanted within 4 weeks/6 months, respectively, should be continued due to high risk of stent thrombosis; however, if they are implanted after this period, then clopidogrel can be halted 5 days before the procedure and resumed soon after, while aspirin is continued. If the patient is taking both aspirin and warfarin, aspirin should be halted 5 days prior to the procedure, while warfarin is continued. PMID:27354859

  5. Antithrombotic therapy in nonvalvular atrial fibrillation: a narrative review.

    PubMed

    Sá, Susana P D; Rodrigues, Rui P; Santos-Antunes, João; Rocha Gonçalves, Francisco; Nunes, José Pedro L

    2011-12-01

    Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients. PMID:22094310

  6. [Antithrombotic therapy after myocardial infarction: arguments for the use of acetylsalicylic acid and coumarin derivatives].

    PubMed

    Waskowsky, W M; Brouwer, A; Verheugt, F W A

    2005-01-01

    Patients who survived myocardial infarction and who are being treated with the current optimal therapy (antithrombotics, statins and beta-blockers), have a 10-20% chance of death, re-infarction and stroke within in the first year. A possible explanation for this could be an increased activation and generation ofthrombin for at least 6 months following the cardiovascular event preceding preventative therapy. Acetylsalicylic acid and clopidogrel do not affect activation by thrombin of the platelet aggregation and the clotting cascade. The additional use of cumarin derivatives could therefore reduce the chance of recurring thrombotic events, and subsequently improve prognosis. Since the nineteen-nineties several randomised trials have been conducted to study the clinical relevance ofcumarin derivatives both with and without acetylsalicylic acid, in patients who had had a myocardial infarction. The conclusions of these studies were not unambiguous. If the international normalized ratio (INR) was kept > 2 for a long period, by means of frequent check-ups and effective dosage adjustment, the chance of death, recurrent myocardial infarction or stroke was 30-50% lower than when acetylsalicylic acid only was used. The risk of bleeding was raised by 2-4 times, but there were no life-threatening episodes of bleeding. In view of the recent development of anticoagulant agents, for which monitoring seems to be becoming unnecessary, identification of patients who would benefit most from a combined antithrombotic strategy is warranted. PMID:15688836

  7. Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

    PubMed

    Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

    2016-03-01

    To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients. PMID:27134306

  8. Optimizing adjunctive antithrombotic and anticoagulant therapy in primary PCI for STEMI.

    PubMed

    Deharo, Pierre; Rahbi, Hazim; Cuisset, Thomas

    2016-06-01

    The pharmacological management of patients with ST elevation myocardial infarction (STEMI) poses a significant challenge to the clinician. While mechanical reperfusion with primary percutaneous coronary intervention (PPCI) has proved its superiority over fibrinolysis, the best antithrombotic strategy surrounding the procedure remains a matter of debate. Due to the high risk of bleeding induced by antithrombotic drugs, the pharmacological management of STEMI needs to focus on an optimal strategy that reduces the rate of coronary thrombotic events without leading to excess bleeding. Intravenous anticoagulants are recommended for all patients presenting with STEMI. Low molecular heparin may be preferred over unfractionated heparin in the setting of PPCI. Recent data suggest that anticoagulation with bivalirudin can be utilized as an alternative strategy to heparin and Gp2b3a but this should be limited to patients at high risk of bleeding. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. New P2Y12 inhibitors (prasugrel and ticagrelor) have restricted clopidogrel use to situations where these potent agents are contraindicated. Whilst all oral antiplatelet agents have been used with an initial loading dose in STEMI, the time of their administration remains a controversial issue. In everyday practice, intravenous antiplatelet agents appear less consensual. While Gp2b3a receptor inhibitors use has been restricted to bailout situations, the place of cangrelor is not yet defined in real life daily practice. PMID:26934662

  9. Appropriate antiplatelet and antithrombotic therapy in patients with acute coronary syndromes: recent updates to the ACC/AHA guidelines.

    PubMed

    Mehta, Shamir R

    2002-12-01

    Thrombosis is the most important pathological mechanism of acute coronary syndromes (ACS). In addition to standard antithrombotic treatment with aspirin and heparin, clopidogrel, glycoprotein IIb/IIIa inhibitors, and low-molecular-weight have a therapeutic benefit in ACS patients. Updated American College of Cardiology/American Heart Association guidelines for the management of ACS patients were published in mid-2002, and this article summarizes the rationale for the recommendations outlined in these guidelines for the use of antithrombotic and antiplatelet therapies. PMID:12668860

  10. Antithrombotic therapy in the primary and secondary prevention of coronary-related death and infarction: focus on gender differences.

    PubMed

    Clyne, C A

    1990-01-01

    Much of our understanding of the role of antithrombotic therapy for postmyocardial infarction patients comes from studies which often included few or no women. Despite this shortcoming there are data available which identify gender differences in risk factors, presentation, natural history and treatment results for myocardial infarction. The use of anticoagulants and antiplatelet agents in the prevention and management of myocardial infarction has evolved over 30 years of investigation. The major randomized, controlled and blinded studies of antithrombotics and myocardial infarction are reviewed, with special emphasis on the female population. PMID:2198101

  11. Aggressive Adolescents Benefit from Massage Therapy.

    ERIC Educational Resources Information Center

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Shaw, Jon A.; Rothe, Eugenio M.; Castellanos, Daniel; Mesner, Linda

    2002-01-01

    Seventeen aggressive adolescents were assigned to a massage therapy group or a relaxation therapy group to receive 20-minute therapy sessions, twice a week for five weeks. The massaged adolescents had lower anxiety after the first and last sessions. By the end of the study, they also reported feeling less hostile and they were perceived by their…

  12. Stroke and Bleeding Risk Associated With Antithrombotic Therapy for Patients With Nonvalvular Atrial Fibrillation in Clinical Practice

    PubMed Central

    An, JaeJin; Niu, Fang; Lang, Daniel T; Jazdzewski, Kristin P; Le, Paul T; Rashid, Nazia; Meissner, Brian; Mendes, Robert; Dills, Diana G; Aranda, Gustavus; Bruno, Amanda

    2015-01-01

    Background The quality of antithrombotic therapy for patients with nonvalvular atrial fibrillation during routine medical care is often suboptimal. Evidence linking stroke and bleeding risk with antithrombotic treatment is limited. The purpose of this study was to evaluate the associations between antithrombotic treatment episodes and outcomes. Methods and Results A retrospective longitudinal observational cohort study was conducted using patients newly diagnosed with nonvalvular atrial fibrillation with 1 or more stroke risk factors (CHADS2 ≥1) in Kaiser Permanente Southern California between January 1, 2006 and December 31, 2011. A total of 1782 stroke and systemic embolism (SE) and 3528 major bleed events were identified from 23 297 patients during the 60 021 person-years of follow-up. The lowest stroke/SE rates and major bleed rates were observed in warfarin time in therapeutic range (TTR) ≥55% episodes (stroke/SE: 0.87 [0.71 to 1.04]; major bleed: 4.91 [4.53 to 5.28] per 100 person-years), which was similar to the bleed rate in aspirin episodes (4.95 [4.58 to 5.32] per 100 person-years). The warfarin TTR ≥55% episodes were associated with a 77% lower risk of stroke/SE (relative risk=0.23 [0.18 to 0.28]) compared to never on therapy; and the warfarin TTR <55% and on-aspirin episodes were associated with a 20% lower and with a 26% lower risk of stroke/SE compared to never on therapy, respectively. The warfarin TTR <55% episodes were associated with nearly double the risk of a major bleed compared to never on therapy (relative risk=1.93 [1.74 to 2.14]). Conclusions Continuation of antithrombotic therapy as well as maintaining an adequate level of TTR is beneficial to prevent strokes while minimizing bleeding events. PMID:26187996

  13. Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy.

    PubMed

    Holster, I L; Kuipers, E J; Tjwa, E T T L

    2013-01-01

    Patients on antithrombotic therapy (ATT) have the highest risk of ongoing bleeding and mortality. Hemospray (Cook Medical, Winston-Salem, North Carolina, USA) is a novel hemostatic agent for the treatment of upper gastrointestinal bleeding (UGIB). Initial reports on its use appear promising in terms of initial hemostasis and rebleeding rates. It is unknown whether this also pertains to patients on ATT. The aim of the current study therefore was to evaluate the efficacy of Hemospray in the treatment of UGIB in patients taking ATTs. A total of 16 unselected consecutive patients with UGIB who were treated with Hemospray were analyzed (eight taking ATT for various indications and eight not on ATT). Initial hemostasis was achieved after Hemospray application in 5 /8 patients on ATT (63 %) and in all eight patients not on therapy (P = 0.20). Rebleeding rates were similar in both groups. These preliminary data on the use of Hemospray in the management of UGIB are promising in both patients with and without ATT; however, caution should be exercised for its use in patients on ATT with spurting arterial bleeding. PMID:23208778

  14. Impact of preoperative antithrombotic therapy on blood management after implantation of primary total knee arthroplasty.

    PubMed

    Leitner, Lukas; Musser, Ewald; Kastner, Norbert; Friesenbichler, Jörg; Hirzberger, Daniela; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

    2016-01-01

    Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss. PMID:27488941

  15. Impact of preoperative antithrombotic therapy on blood management after implantation of primary total knee arthroplasty

    PubMed Central

    Leitner, Lukas; Musser, Ewald; Kastner, Norbert; Friesenbichler, Jörg; Hirzberger, Daniela; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

    2016-01-01

    Red blood cell concentrates (RCC) substitution after total knee arthroplasty (TKA) is correlated with multifold of complications and an independent predictor for higher postoperative mortality. TKA is mainly performed in elderly patients with pre-existing polymorbidity, often requiring permanent preoperative antithrombotic therapy (PAT). The aim of this retrospective analysis was to investigate the impact of demand for PAT on inpatient blood management in patients undergoing TKA. In this study 200 patients were retrospectively evaluated after TKA for differences between PAT and non-PAT regarding demographic parameters, preoperative ASA score > 2, duration of operation, pre-, and intraoperative hemoglobin level, and postoperative parameters including amount of wound drainage, RCC requirement, and inpatient time. In a multivariate logistic regression analysis the independent influences of PAT, demographic parameters, ASA score > 2, and duration of the operation on RCC demand following TKA were analyzed. Patients with PAT were significantly older, more often had an ASA > 2 at surgery, needed a higher number of RCCs units and more frequently and had lower perioperative hemoglobin levels. Multivariate logistic regression revealed PAT was an independent predictor for RCC requirement. PAT patients are more likely to require RCC following TKA and should be accurately monitored with respect to postoperative blood loss. PMID:27488941

  16. Complex antithrombotic therapy: determinants of patient preference and impact on medication adherence

    PubMed Central

    Abraham, Neena S; Naik, Aanand D; Street, Richard L; Castillo, Diana L; Deswal, Anita; Richardson, Peter A; Hartman, Christine M; Shelton, George; Fraenkel, Liana

    2015-01-01

    Purpose For years, older patients have been prescribed multiple blood-thinning medications (complex antithrombotic therapy [CAT]) to decrease their risk of cardiovascular events. These therapies, however, increase risk of adverse bleeding events. We assessed patient-reported trade-offs between cardioprotective benefit, gastrointestinal bleeding risk, and burden of self-management using adaptive conjoint analysis (ACA). As ACA could be a clinically useful tool to obtain patient preferences and guide future patient-centered care, we examined the clinical application of ACA to obtain patient preferences and the impact of ACA on medication adherence. Patients and methods An electronic ACA survey led 201 respondents through medication risk–benefit trade-offs, revealing patients’ preferences for the CAT risk/benefit profile they valued most. The post-ACA prescription regimen was categorized as concordant or discordant with elicited preferences. Adherence was measured using VA pharmacy refill data to measure persistence of use prior to and 1 year following preference-elicitation. Additionally, we analyzed qualitative interviews of 56 respondents regarding their perception of the ACA and the preference elicitation experience. Results Participants prioritized 5-year cardiovascular benefit over preventing adverse events. Medication side effects, medication-associated activity restrictions, and regimen complexity were less important than bleeding risk and cardioprotective benefit. One year after the ACA survey, a 15% increase in adherence was observed in patients prescribed a preference-concordant CAT strategy. An increase of only 6% was noted in patients prescribed a preference-discordant strategy. Qualitative interviews showed that the ACA exercise contributed to increase inpatient activation, patient awareness of preferences, and patient engagement with clinicians about treatment decisions. Conclusion By working through trade-offs, patients actively clarified their

  17. Stroke in atrial fibrillation: update on pathophysiology, new antithrombotic therapies, and evolution of procedures and devices.

    PubMed

    Savelieva, Irina; Bajpai, Abhay; Camm, A John

    2007-01-01

    Atrial fibrillation (AF) is said to be an epidemic, affecting 1%-1.5% of the population in the developed world. The clinical significance of AF lies predominantly in a 5-fold increased risk of stroke. Strokes associated with AF are usually more severe and confer increased risk of morbidity, mortality, and poor functional outcome. Despite the advent of promising experimental therapies for selected patients with acute stroke, pharmacological primary prevention remains the best approach to reducing the burden of stroke. New antithrombotic drugs include both parenteral agents (e.g. a long-acting factor Xa inhibitor idraparinux) and oral anticoagulants, such as oral factor Xa inhibitors and direct oral thrombin inhibitors (ximelagatran, dabigatran). Ximelagatran had shown significant potential as a possible replacement to warfarin therapy, but has been withdrawn because of potential liver toxicity. Its congener dabigatran appears to have a better safety profile and has recently entered a phase III randomized clinical trial in AF. Oral factor Xa inhibitors (rivaroxaban, apixaban, YM150) inhibit factor Xa directly, without antithrombin III mediation, and may prove to be more potent and safe. Selective inhibitors of specific coagulation factors involved in the initiation and propagation of the coagulation cascade (factor IXa, factor VIIa, circulating tissue factor) are at an early stage of development. Additional new agents with hypothetical, although not yet proven, anticoagulation benefits include nematode anticoagulant peptide (NAPc2), protein C derivatives, and soluble thrombomodulin. A battery of novel mechanical approaches for the prevention of cardioembolic stroke has recently been evaluated, including various models of percutaneous left atrial appendage occluders which block the connection between the left atrium and the left atrial appendage, minimally invasive surgical isolation of the left atrial appendage, and implantation of the carotid filtering devices which

  18. Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

    PubMed Central

    Cui, Guozhen; Shan, Luchen; Guo, Lin; Chu, Ivan Keung; Li, Guohui; Quan, Quan; Zhao, Yun; Chong, Cheong Meng; Zhang, Zaijun; Yu, Pei; Hoi, Maggie Pui Man; Sun, Yewei; Wang, Yuqiang; Lee, Simon MingYuen

    2015-01-01

    Protein disulfide isomerase (PDI) family members including PDI and ERp57 emerge as novel targets for anti-thrombotic treatments, but chemical agents with selectivity remain to be explored. We previously reported a novel derivative of danshensu (DSS), known as ADTM, displayed strong cardioprotective effects against oxidative stress-induced cellular injury in vitro and acute myocardial infarct in vivo. Herein, using chemical proteomics approach, we identified ERp57 as a major target of ADTM. ADTM displayed potent inhibitory effects on the redox activity of ERp57, inhibited the adenosine diphosphate (ADP)-induced expressions of P-selectin and αIIbβ3 integrin, and disrupted the interaction between ERp57 and αIIbβ3. In addition, ADTM inhibited both arachidonic acid (AA)-induced and ADP-induced platelet aggregation in vitro. Furthermore, ADTM significantly inhibited rat platelet aggregation and thrombus formation in vivo. Taken together, ADTM represents a promising candidate for anti-thrombotic therapy targeting ERp57. PMID:26037049

  19. Cu(2+)-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy.

    PubMed

    Wu, Jianhui; Wang, Yuji; Wang, Yaonan; Zhao, Ming; Zhang, Xiaoyi; Gui, Lin; Zhao, Shurui; Zhu, Haimei; Zhao, Jinghua; Peng, Shiqi

    2015-01-01

    Thrombosis disease has been the leading cause of morbidity and mortality worldwide. In the discovery of antithrombotic agents, three complexes of Cu(2+) and repetitive arginine-glycine-aspartic acid (RGD) sequences, Cu(II)-Arg-Gly-Asp-Ser-Arg-Gly-Asp-Ser (Cu[II]-4a), Cu(II)-Arg-Gly-Asp-Val-Arg-Gly-Asp-Val (Cu[II]-4b), and Cu(II)-Arg-Gly-Asp-Phe-Arg-Gly-Asp-Phe (Cu[II]-4c), were previously reported, of which Cu(II)-4a and Cu(II)-4c possessed the highest in vitro and in vivo activity, respectively. Transmission electron microscopy (TEM) images visualized that Cu(II)-4a and Cu(II)-4c formed nanoaggregates and nanoparticles, respectively. However, the details of the formation of the nanospecies complexes and of the mechanism for inhibiting thrombosis remain to be clarified. For this purpose, this study designed a novel complex of Cu(II) and the RGD octapeptide, Arg-Gly-Asp-Phe-Arg-Gly-Asp-Ser (RGDFRGDS), consisting of Arg-Gly-Asp-Phe of Cu(II)-4c and Arg-Gly-Asp-Ser of Cu(II)-4a, to colligate their biological and nanostructural benefits. In contrast with Cu(II)-4a, -4b, and -4c, Cu(II)-RGDFRGDS (Cu(2+)-FS) had high antiplatelet and antithrombotic activities, with the formed nanoparticles having a porous surface. Additionally, this paper evidenced the dimer had the basic structural unit of Cu(2+)-FS in water, theoretically simulated the formation of Cu(2+)-FS nanoparticles, and identified that Cu(2+)-FS activity in decreasing glycoprotein IIb/IIIa, P-selectin, and IL-8 was responsible for the antithrombotic action. Finally, adherence onto the surface and entry into the cytoplasm were considered the steps of a two-step model for the blocking of platelet activation by Cu(2+)-FS nanoparticles. Findings indicated that the antiplatelet aggregation activity of Cu(2+)-FS was 10-52 times higher than that of RGDFRGDS, while the effective dose for antithrombotic action was 5,000 times lower than that of RGDFRGDS. PMID:25931819

  20. Cu2+-RGDFRGDS: exploring the mechanism and high efficacy of the nanoparticle in antithrombotic therapy

    PubMed Central

    Wu, Jianhui; Wang, Yuji; Wang, Yaonan; Zhao, Ming; Zhang, Xiaoyi; Gui, Lin; Zhao, Shurui; Zhu, Haimei; Zhao, Jinghua; Peng, Shiqi

    2015-01-01

    Thrombosis disease has been the leading cause of morbidity and mortality worldwide. In the discovery of antithrombotic agents, three complexes of Cu2+ and repetitive arginine-glycine-aspartic acid (RGD) sequences, Cu(II)-Arg-Gly-Asp-Ser-Arg-Gly-Asp-Ser (Cu[II]-4a), Cu(II)-Arg-Gly-Asp-Val-Arg-Gly-Asp-Val (Cu[II]-4b), and Cu(II)-Arg-Gly-Asp-Phe-Arg-Gly-Asp-Phe (Cu[II]-4c), were previously reported, of which Cu(II)-4a and Cu(II)-4c possessed the highest in vitro and in vivo activity, respectively. Transmission electron microscopy (TEM) images visualized that Cu(II)-4a and Cu(II)-4c formed nanoaggregates and nanoparticles, respectively. However, the details of the formation of the nanospecies complexes and of the mechanism for inhibiting thrombosis remain to be clarified. For this purpose, this study designed a novel complex of Cu(II) and the RGD octapeptide, Arg-Gly-Asp-Phe-Arg-Gly-Asp-Ser (RGDFRGDS), consisting of Arg-Gly-Asp-Phe of Cu(II)-4c and Arg-Gly-Asp-Ser of Cu(II)-4a, to colligate their biological and nanostructural benefits. In contrast with Cu(II)-4a, -4b, and -4c, Cu(II)-RGDFRGDS (Cu2+-FS) had high antiplatelet and antithrombotic activities, with the formed nanoparticles having a porous surface. Additionally, this paper evidenced the dimer had the basic structural unit of Cu2+-FS in water, theoretically simulated the formation of Cu2+-FS nanoparticles, and identified that Cu2+-FS activity in decreasing glycoprotein IIb/IIIa, P-selectin, and IL-8 was responsible for the antithrombotic action. Finally, adherence onto the surface and entry into the cytoplasm were considered the steps of a two-step model for the blocking of platelet activation by Cu2+-FS nanoparticles. Findings indicated that the antiplatelet aggregation activity of Cu2+-FS was 10–52 times higher than that of RGDFRGDS, while the effective dose for antithrombotic action was 5,000 times lower than that of RGDFRGDS. PMID:25931819

  1. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  2. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  3. Triple antithrombotic therapy in patients with atrial fibrillation undergoing coronary artery stenting: hovering among bleeding risk, thromboembolic events, and stent thrombosis

    PubMed Central

    2012-01-01

    Dual antiplatelet treatment with aspirin and clopidogrel is the antithrombotic treatment recommended after an acute coronary syndrome and/or coronary artery stenting. The evidence for optimal antiplatelet therapy for patients, in whom long-term treatment oral anticoagulation is mandatory, is however scarce. To evaluate the safety and efficacy of the various antithrombotic strategies adopted in this population, we reviewed the available evidence on the management of patients receiving oral anticoagulation, such as a vitamin-k-antagonists, referred for coronary artery stenting. Atrial fibrillation is the most frequent indication for oral anticoagulation. The need of starting antiplatelet therapy in this clinical scenario raises concerns about the combination to choose: triple therapy with warfarin, aspirin, and a thienopyridine being the most frequent and advised. The safety of this regimen appeared suboptimal because of an increased risk in hemorrhagic complications. On the other hand, the combination of oral anticoagulation and an antiplatelet agent is suboptimal in preventing thromboembolic events and stent thrombosis; dual antiplatelet therapy may be considered only when a high hemorrhagic risk and low thromboembolic risk are perceived. Indeed, the need for prolonged multiple-drug antithrombotic therapy increases the bleeding risks when drug eluting stents are used. Since current evidence derives mainly from small, single-center and retrospective studies, large-scale prospective multicenter studies are urgently needed. PMID:23075316

  4. Antithrombotic therapy for patients with nonvalvular atrial fibrillation undergoing percutaneous coronary intervention: a review.

    PubMed

    Krasner, Andrew; Halperin, Jonathan L

    2013-07-01

    Patients with atrial fibrillation who have risk factors for thromboembolism benefit from chronic oral anticoagulation therapy, and antiplatelet therapy alone is of relatively little benefit for prevention of ischemic stroke and systemic embolism. Patients undergoing percutaneous coronary intervention with drug-eluting stents require dual antiplatelet therapy with aspirin and a thienopyridine for 3 to 12 months or more prevention of stent thrombosis and recurrent ischemic events. When patients with atrial fibrillation undergo percutaneous coronary intervention, the need to combine dual antiplatelet therapy and warfarin raises the risk of major bleeding complications considerably. Recent trials have explored the option of omitting aspirin with promising results. The introduction of novel oral anticoagulants that specifically inhibit factor IIa (dabigatran) or factor Xa (rivaroxaban, apixaban, and edoxaban) and antiplatelet agents that inhibit the P(2)Y(12) receptor (prasugrel and ticagrelor) makes management of these patients even more challenging, but future trials addressing myriad alternative regimens may identify better tolerated strategies. PMID:23689944

  5. Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician

    PubMed Central

    Leiria, Tiago L. L.; Lopes, Renato D.; Williams, Judson B.; Katz, Jason N.; Kalil, Renato A. K.

    2013-01-01

    Patients with prosthetic heart valves require chronic oral anticoagulation. In this clinical scenario, physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. This paper reviews the main heart valve guidelines focusing on the use of oral anticoagulation in these patients. PMID:21327503

  6. A clinical decision aid for the selection of antithrombotic therapy for the prevention of stroke due to atrial fibrillation

    PubMed Central

    LaHaye, Stephen Andrew; Gibbens, Sabra Lynn; Ball, David Gerald Andrew; Day, Andrew George; Olesen, Jonas Bjerring; Skanes, Allan Cameron

    2012-01-01

    Aims The availability of new antithrombotic agents, each with a unique efficacy and bleeding profile, has introduced a considerable amount of clinical uncertainty with physicians. We have developed a clinical decision aid in order to assist clinicians in determining an optimal antithrombotic regime for the prevention of stroke in patients who are newly diagnosed with non-valvular atrial fibrillation. Methods and results The CHA2DS2-VASc and HAS-BLED scoring systems were used to assess patients’ baseline risks of stroke and major bleeding, respectively. The relative risks of stroke and major bleeding for each antithrombotic agent were then used to identify the agent associated with the lowest net risk. Individual patient factors such as the treatment threshold, bleeding ratio, and cost threshold modified the recommendations in order to generate a final recommendation. By considering both patient factors and clinical research concurrently, this clinical decision aid is able to provide specific advice to clinicians regarding an optimal stroke prevention strategy. The resulting treatment recommendation tables are consistent with the recommendations of the European Society of Cardiology and Canadian Cardiovascular Society Guidelines, which can be incorporated into either a paper-based or electronic format to allow clinicians to have decision support at the point of care. Conclusion The use of a clinical decision aid that considers both patient factors and evidence-based medicine will serve to bridge the knowledge gap and provide practical guidance to clinicians in the prevention of stroke due to atrial fibrillation. PMID:22752615

  7. [Antithrombotic recombinant antibodies].

    PubMed

    Muzard, Julien; Loyau, Stéphane; Ajzenberg, Nadine; Billiald, Philippe; Jandrot-Perrus, Martine

    2006-01-01

    Coronary syndromes, stroke and other ischaemic arterial diseases are the leading cause of death in the world and will probably remain it at least until 2020. Cardiovascular diseases kill 17 million people each year with an expected increase to 20 million in 2020 and 24 million in 2030. The global impact of recurrence and death during the 6 months following an acute coronary syndrome remains at 8-15% in the present state of medical practice. Acute ischaemic syndromes have a common aetiology that is the formation of a platelet-rich clot at the site of severe coronary stenosis and of eroded atherosclerotic plaques. Therapy consists of medical treatments associating thrombolysis, antiplatelet drugs, and the re-opening of the coronary artery by angioplasty. But these treatments do not prevent morbidity and mortality reaching 15% at 6 months. Finally the treatment of stroke is very limited. There is thus a real clinical need to improve existing treatments and to discover new molecules. Platelet activation is a critical step in ischaemic cardiovascular diseases. This is the reason why antiplatelet drugs are most often prescribed in these cases. Currently, only one recombinant antithrombotic antibody is used in therapy. This is a chimeric Fab, c7E3 or abciximab, which inhibits the final phase of platelet aggregation. Abciximab is prescribed in acute coronary syndromes treated by angioplasty. However, treatment by abciximab can induce severe complications, principally, hemorrages and thrombopenia. Other platelet receptors involved in the earlier steps of platelet activation, such as the phases of contact with and of activation by the subendothelium matrix, have been identified as potential targets for the development of antithrombotic antibodies and are described in this revue. PMID:17652972

  8. Inappropriate prescribing of antithrombotic therapy in Ethiopian elderly population using updated 2015 STOPP/START criteria: a cross-sectional study

    PubMed Central

    Getachew, Henok; Bhagavathula, Akshaya Srikanth; Abebe, Tamrat Befekadu; Belachew, Sewunet Admasu

    2016-01-01

    Background Inappropriate use of antiplatelets and anticoagulants among elderly patients increases the risk of adverse outcomes. The aim of this study was to assess the prevalence of inappropriate prescribing of antithrombotic therapy in hospitalized elderly patients. Methods A retrospective cross-sectional, single-center study was conducted at the Gondar University Hospital. A total of 156 hospitalized elderly patients fulfilling the inclusion/exclusion criteria were included in the study. The Screening Tool for Older Person’s Prescription/Screening Tool to Alert doctors to Right Treatment criteria version 2 were applied to patients’ data to identify the total number of inappropriate prescribing (IPs) including potentially inappropriate medications and potential prescribing omissions. Results A total of 70 IPs were identified in 156 patients who met the inclusion criteria. Of these, 36 (51.4%) were identified as potentially inappropriate medications by the Screening Tool for Older Person’s Prescription criteria. The prevalence of IP per patient indicated that 58 of the 156 (37.2%) patients were exposed to at least one IP. Of these, 32 (55.2%) had at least one potentially inappropriate medication and 33 (56.9%) had at least one potential prescribing omission. Patients hospitalized due to venous thromboembolism (adjusted odds ratio [AOR] =29.87, 95% confidence interval [CI], 1.26–708.6), stroke (AOR =7.74, 95% CI, 1.27–47.29), or acute coronary syndrome (AOR =13.48, 95% CI, 1.4–129.1) were less likely to be exposed to an IP. An increase in Charlson comorbidity index score was associated with increased IP exposure (AOR =0.60, 95% CI, 0.39–0.945). IPs were about six times more likely to absent in patients prescribed with antiplatelet only therapy (AOR =6.23, 95% CI, 1.90–20.37) than those receiving any other groups of antithrombotics. Conclusion IPs are less common in elderly patients primarily admitted due to venous thromboembolism, stroke, and acute

  9. New Antithrombotic Drugs

    PubMed Central

    Eikelboom, John W.; Samama, Meyer Michel

    2012-01-01

    This article focuses on new antithrombotic drugs that are in or are entering phase 3 clinical testing. Development of these new agents was prompted by the limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this article (1) outlines the rationale for development of new antithrombotic agents; (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs; and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents. PMID:22315258

  10. Outcomes of nonsurgical periodontal therapy in severe generalized aggressive periodontitis

    PubMed Central

    2014-01-01

    Purpose Aggressive periodontitis, especially in its severe form, was traditionally considered to have an unfavourable prognosis. It required a complex treatment and its stabilization was often achieved by surgical therapy. The aim of this study was to investigate the results of nonsurgical periodontal treatment in severe generalized forms of aggressive periodontitis. Methods Patients with advanced generalized aggressive periodontitis were included in the study. Probing depth (PD) of pockets ≥7 mm and clinical attachment level (CAL) of sites with attachment loss ≥5 mm were measured at baseline before nonsurgical periodontal treatment, at re-evaluation, and after treatment. The following other parameters were recorded: resolution of inflammation and bone fill. We compared the baseline values with re-evaluation and posttreatment values using the Friedman test. The Wilcoxon test with the Bonferroni correction was used for both re-evaluation and posttreatment values. Results Seven patients with 266 periodontal sites were examined. A significant difference was found between values, reported as medians with interquartile ranges, for PD at baseline (7.94 [7.33-8.19] mm) and both re-evaluation (4.33 [3.63-5.08] mm) and posttreatment (3.54 [3.33-4.11] mm) values (P=0.002). A significant difference was also found between values for CAL at baseline (9.02 [7.5-9.2] mm) and both re-evaluation (6.55 [6.30-6.87] mm) and posttreatment (6.45 [5.70-6.61] mm) (P=0.002). Inflammation was resolved and angular bone defects were repaired in all cases. Conclusions These therapeutic results suggest that this form of periodontitis could have positive outcomes after nonsurgical periodontal treatment. The reparative potential of tissue affected by severe aggressive periodontitis should encourage clinicians to save apparently hopeless teeth in cases of this form of periodontitis. Graphical Abstract PMID:25177522

  11. [Pro and contra: aggressive or conservative thrombosis therapy? - Pro aggressive thrombosis therapy].

    PubMed

    Grommes, J

    2014-10-01

    The post-thrombotic syndrome (PTS), long-term sequelae of a deep vein thrombosis (DVT), reduces quality of life and is of great socio-economic importance. Despite conservative treatment which does not directly facilitate recanalization more than 25% of patients develop PTS. Early thrombus removal may decrease the incidence and severity of PTS. Although the evidence for surgical thrombectomy is weak which allows an early and rapid recanalization, this therapy appears to reduce the risk of PTS and iliofemoral thrombosis. Systemic thrombolysis can reduce the incidence of PTS but it is no longer recommended due to serious bleeding complications. Previous studies with new endovascular catheter-guided procedures allowing local application of thrombolysis and thrombus aspiration displayed promising results. However, so far one prospective randomised study (CaVent study) with long-term results has revealed a significant reduction of PTS. The current evidence recommends early thrombus removal for patients at high risk for PTS. New endovascular procedures such as catheter-guided thrombolysis allow rapid thrombus removal but more prospective randomised studies are necessary to ensure the long-term success of this therapy. PMID:25313889

  12. Trial of Early Aggressive Therapy in Polyarticular Juvenile Idiopathic Arthritis

    PubMed Central

    Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.

    2011-01-01

    OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975

  13. The New Oral Anticoagulants for the Treatment of Venous Thromboembolism: A New Paradigm Shift in Antithrombotic Therapy

    PubMed Central

    Galanis, Taki; Keiffer, Gina; Merli, Geno

    2014-01-01

    Background Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition. Objective To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach. Methods A literature search in PubMed was conducted that identified Phase III clinical trials investigating the novel oral anticoagulant agents for the treatment of VTE. Results The new oral anticoagulant agents have been shown to be as safe and effective for the treatment of VTE as conventional therapies. Conclusions These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE. PMID:25352938

  14. Postextraction bleeding in a patient taking antithrombotics: report of a case.

    PubMed

    Wahl, Michael J; Schmitt, Margaret M

    2016-01-01

    Antithrombotic medications, including antiplatelets and anticoagulants, are used by millions of patients to prevent stroke or heart attack. When these patients present for dental surgery, a decision must be made whether to continue the antithrombotic medication and risk a bleeding problem or to interrupt the medication and risk an embolic complication such as a stroke or heart attack. In patients taking antithrombotic medications, a small risk of postoperative bleeding after dental extractions must be weighed against a small risk of stroke or heart attack when these medications are interrupted. This case report discusses an episode of minor postextraction bleeding in a patient taking combination anticoagulant and antiplatelet therapy. Antithrombotic therapy generally should not be interrupted for dental procedures, as the prognosis of potential postextraction bleeding that could result from antithrombotic continuation is almost always better than the prognosis of a potential stroke or heart attack that could follow antithrombotic interruption. PMID:27148659

  15. A review of antithrombotic therapy and the rationale and design of the randomized edoxaban in patients with peripheral artery disease (ePAD) trial adding edoxaban or clopidogrel to aspirin after femoropopliteal endovascular intervention.

    PubMed

    Tangelder, Marco J D; Nwachuku, Chuke E; Jaff, Michael; Baumgartner, Iris; Duggal, Anil; Adams, George; Ansel, Gary; Grosso, Michael; Mercuri, Michele; Shi, Minggao; Minar, Erich; Moll, Frans L

    2015-04-01

    Compared with the coronary setting, knowledge about antithrombotic therapies after endovascular treatment (EVT) is inadequate in patients with peripheral artery disease (PAD). Based on a review of trials and guidelines, which is summarized in this article, there is scant evidence that antithrombotic drugs improve outcome after peripheral EVT. To address this knowledge gap, the randomized, open-label, multinational edoxaban in patients with Peripheral Artery Disease (ePAD) study (ClinicalTrials.gov identifier NCT01802775) was designed to explore the safety and efficacy of a combined regimen of antiplatelet therapy with clopidogrel and anticoagulation with edoxaban, a selective and direct factor Xa inhibitor, both combined with aspirin. As of July 2014, 203 patients (144 men; mean age 67 years) from 7 countries have been enrolled. These patients have been allocated to once-daily edoxaban [60 mg for 3 months (or 30 mg in the presence of factors associated with increased exposure)] or clopidogrel (75 mg/d for 3 months). All patients received aspirin (100 mg/d) for the 6-month duration of the study. The primary safety endpoint is major or clinically relevant nonmajor bleeding; the primary efficacy endpoint is restenosis or reocclusion at the treated segment(s) measured at 1, 3, and 6 months using duplex ultrasound scanning. All outcomes will be assessed and adjudicated centrally in a masked fashion. The ePAD study is the first of its kind to investigate a combined regimen of antiplatelet therapy and anticoagulation through factor Xa inhibition with edoxaban. PMID:25809373

  16. Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis.

    PubMed

    Lau, Y C; Xiong, Q; Ranjit, P; Lip, G Y H; Blann, A D

    2016-08-01

    As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk. PMID:26942726

  17. Aggression control therapy for violent forensic psychiatric patients: method and clinical practice.

    PubMed

    Hornsveld, Ruud H J; Nijman, Henk L I; Hollin, Clive R; Kraaimaat, Floor W

    2008-04-01

    Aggression control therapy is based on Goldstein, Gibbs, and Glick's aggression replacement training and was developed for violent forensic psychiatric in- and outpatients (adolescents and adults) with a (oppositional-defiant) conduct disorder or an antisocial personality disorder. First, the conditions for promoting "treatment integrity" are examined. Then, target groups, framework, and procedure are described in detail, followed by the most important clinical findings during the period 2002 to 2006. Finally, new programme developments are mentioned, with aggression control therapy as a starting point. PMID:17636205

  18. Reinforcement Behavior Therapy by Kindergarten Teachers on Preschool Children’s Aggression: A Randomized Controlled Trial

    PubMed Central

    Yektatalab, Shahrzad; Alipour, Abdolrasool; Edraki, Mitra; Tavakoli, Pouran

    2016-01-01

    Background: Aggression is a kind of behavior that causes damage or harm to others. The prevalence of aggression is 8–20% in 3–6 years old children. The present study aimed to assess the effect of training kindergarten teachers regarding reinforcement behavior therapy on preschoolers’ aggression. Methods: In this cluster randomized control trial, 14 out of 35 kindergarten and preschool centers of Mohr city, Iran, were chosen using random cluster sampling and then randomly assigned to an intervention and a control group. All 370 kindergarten and preschool children in 14 kindergarten were assessed by preschoolers’ aggression questionnaire and 60 children who obtained a minimum aggression score of 117.48 for girls and 125.77 for boys were randomly selected. The teachers in the intervention group participated in 4 educational sessions on behavior therapy and then practiced this technique under the supervision of the researcher for two months. Preschoolers’ aggression questionnaire was computed in both intervention and control groups before and after a two-month period. Results: The results demonstrated a significant statistical difference in the total aggression score (P=0.01), verbal (P=0.02) and physical (P=0.01) aggression subscales scores in the intervention group in comparison to the control group after the intervention. But the scores of relational aggression (P=0.09) and impulsive anger (P=0.08) subscales were not statistically different in the intervention group compared to the controls. Conclusion: This study highlighted the importance of teaching reinforcement behavior therapy by kindergarten teachers in decreasing verbal and physical aggression in preschoolers. Trial Registration Number: IRCT2014042617436N1 PMID:26793733

  19. Antithrombotic Therapy in Cardiac Embolism

    PubMed Central

    Cervera, Álvaro; Chamorro, Ángel

    2010-01-01

    Anticoagulation is indicated in most cardioembolic ischemic strokes for secondary prevention. In many cardiac conditions, anticoagulation is also indication for primary stroke prevention, mainly when associated to vascular risk factors. Anticoagulation should be started as soon as possible, as it is safe even in moderate acute strokes. The efficacy of early anticoagulation after cardioembolic stroke in relation to outcome has not been assessed adequately, but there is evidence from animal models and clinical studies that anticoagulation with unfractionated heparin is associated with a better outcome mediated in part by its anti-inflammatory properties. PMID:21804782

  20. [Antithrombotic management in atrial fibrillation].

    PubMed

    Fauchier, Laurent; Taillandier, Sophie; Clementy, Nicolas

    2013-02-01

    There is increasing recognition of the value of oral anticoagulation for stroke prevention in atrial fibrillation (AF), and the availability of new oral anticoagulants that overcome the limitations of vitamin K antagonists (VKA). Stroke risk assessment using the CHA2DS2-Vasc score allows identification of patients who are at truly low risk (score = 0) who should need no antithrombotic therapy, while all others (CHA2DS2-Vasc score > or = 1 with a risk of thromboembolic event > 1% per year) would be considered for oral anticoagulation. The HAS-BLED score has been recently proposed to easily assess bleeding risk in AF patients. A score of > or = 3 indicates "high risk" and some caution and regular review of the patient are needed. It also makes the clinician think of correctable common bleeding risk factors. The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are new oral anticoagulants that are at least as efficacious and safe as VKA in non valvular AF. Their advantages are easier use, predictable anticoagulant effects, low propensity for food and drug interactions, and lower rates of intracranial bleeding than with VKA, but they should not be used in patients with kidney disease at the present time. Overall, one may expect that more AF patients will be appropriately treated with oral anticoagulation in the next years. PMID:23513780

  1. Targeting GPVI as a novel antithrombotic strategy

    PubMed Central

    Andrews, Robert K; Arthur, Jane F; Gardiner, Elizabeth E

    2014-01-01

    While platelet activation is essential to maintain blood vessel patency and minimize loss of blood upon injury, untimely or excessive activity can lead to unwanted platelet activation and aggregation. Resultant thrombosis has the potential to block blood vessels, causing myocardial infarction or stroke. To tackle this major cause of mortality, clinical therapies that target platelet responsiveness (antiplatelet therapy) can successfully reduce cardiovascular events, especially in people at higher risk; however, all current antiplatelet therapies carry an increased probability of bleeding. This review will evaluate new and emerging targets for antithrombotics, focusing particularly on platelet glycoprotein VI, as blockade or depletion of this platelet-specific receptor conveys benefits in experimental models of thrombosis and thromboinflammation without causing major bleeding complications. PMID:24899824

  2. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer.

    PubMed

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385-0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  3. The role and indications of aggressive locoregional therapy in metastatic inflammatory breast cancer

    PubMed Central

    Yan, Yi; Tang, Lili; Tong, Wei; Zhou, Jingyu

    2016-01-01

    We seek to confirm the effect and explore the indications of aggressive locoregional management in patients with metastatic inflammatory breast cancer (IBC). Between 2003 and 2014, we reviewed the records of 156 patients with metastatic IBC from five large centers of Breast Surgery in the region of central south of China. Clinicopathologic data were collected to access overall survival (OS), prognostic factors and the indications for locoregional treatment. 75 (48%) patients underwent aggressive locoregional therapy. Patients in locoregional therapy group had a median OS of 24 months compared with 17 months of those in no locoregional therapy group. 2-year OS rate of these two groups was 52% and 32%, separately. Locoregional therapy (HR = 0.556; 95% CI 0.385–0.803; p = 0.002) was confirmed to be an independent prognostic factor, which could significantly improve OS of patients with metastatic IBC. For locoregional therapy group, statistical differences were observed in all subgroups stratified by the factors that were significant in univariate analysis except in the subgroups of stable disease, Charlson comorbidity index ≥3 and cerebral metastasis. Therefore, systemic therapy efficacy, Charlson comorbidity index and cerebral metastasis status appeared to be important indexes for choice of locoregional therapy in different individuals. PMID:27174789

  4. An overview of antithrombotics in ischemic stroke.

    PubMed

    Schweickert, Patricia A; Gaughen, John R; Kreitel, Elizabeth M; Shephard, Timothy J; Solenski, Nina J; Jensen, Mary E

    2016-06-19

    The use of antithrombotic medications is an important component of ischemic stroke treatment and prevention. This article reviews the evidence for best practices for antithrombotic use in stroke with focused discussion on the specific agents used to treat and prevent stroke. PMID:27153001

  5. Variability of Antithrombotic Dosing Among Veterans Presenting With Acute Coronary Syndrome

    PubMed Central

    Plomondon, Mary E.; Lambert‐Kerzner, Anne C.; Jennewein, Xuefei; Fagan, Katherine; McCreight, Marina; Fehling, Kelty B.; Tsai, Thomas T.; Ho, P. Michael

    2015-01-01

    Background Antithrombotic therapy for acute coronary syndrome (ACS) patients is recommended by clinical practice guidelines. Appropriate dosing of antithrombotic therapy is necessary to ensure effectiveness and safety and is an American College of Cardiology/American Heart Association ST elevated myocardial infarction/non‐ST elevated myocardial infarction performance measure. This study describes the variability in dosing of unfractionated heparin (UH) and low‐molecular‐weight heparin (LMWH) in an integrated health care system with electronic medical records and computerized physician order entry (CPOE). Methods and Results This was a mixed‐methods study of veterans presenting with ACS at 135 Veterans Health Administration hospitals from 2009 to 2011. Patients hospitalized with ACS and received antithrombotic therapy were included (n=36 682). The cohort was 98% male with an average age of 66 years and median body mass index (BMI) of 28.6. The average percentage of patients by hospital who received an above‐recommended dose of either antithrombotic was 7.5% and ranged 0% to 32.0%. By individual therapy, the average percentage of patients by hospital who received an above‐recommended dose of UH was 1.2% and LMWH was 12.9%. Risk‐adjusted analyses demonstrated that older age and higher BMI were associated with lower risk for receiving a dose above recommended levels. Additionally, there was an association between antithrombotic ordered by a resident and higher risk of the patient receiving an above‐recommended dose. Qualitative interviews supported the quantitative findings by highlighting the need to use current patient weight and the need to adequately train providers on the use of CPOE to improve antithrombotic dosing. Conclusion This study found wide hospital variability in dosing of antithrombotics above the recommended level for patients treated for ACS. PMID:25917444

  6. SAFETY AND UTILITY OF ACUTE ELECTROCONVULSIVE THERAPY FOR AGITATION AND AGGRESSION IN DEMENTIA

    PubMed Central

    Acharya, Deepa; Harper, David G.; Achtyes, Eric D.; Seiner, Stephen J.; Mahdasian, Jack A.; Nykamp, Louis J.; Adkison, Lesley; Van der Schuur White, Lori; McClintock, Shawn M.; Ujkaj, Manjola; Davidoff, Donald A.; Forester, Brent P.

    2015-01-01

    Objective Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Methods Twenty-three participants admitted to McLean Hospital (Belmont, MA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory (CMAI)-short form, Neuropsychiatric Inventory (NPI)-Nursing Home Version, Cornell Scale for Depression in Dementia (CSDD), and the Clinical Global Impression Scale (CGI) at baseline, during, and after the ECT course. Results Regression analyses revealed a significant decrease from baseline to discharge on the CMAI (F(4, 8) =13.3; p=0.006) and NPI (F(4, 31)= 14.6; p<0.001). There was no statistically significant change in scores on the CSDD. The CGI scores on average changed from a rating of “markedly agitated/aggressive” at baseline to “borderline agitated/aggressive” at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants due to recurrence of agitation and for three participants due to adverse events. Conclusions ECT may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. PMID:24838521

  7. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer

    PubMed Central

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC. PMID:24328598

  8. Photodynamic therapy in the treatment of aggressive periodontitis: A systematic review

    PubMed Central

    Doufexi, Aikaterini-Ellisavet

    2016-01-01

    Background Aggressive periodontitis (AgP) is a severe form of periodontal diseases with rapid destruction of the supporting bone around teeth. The efficacy of PDT in suppressing periodontal pathogens may be crucial in adopting new protocols for the treatment of AgP. Thus, the aim of this systematic review was to investigate the possible role of PDT in the treatment of AgP as an adjunctive therapy or monotherapy. Material and Methods A systematic search of the literature was performed. Additionally, the references from all the selected full-text studies were searched for relevant articles. Two reviewers screened independently titles and abstracts or full text copies. Quality assessment of all the included studies was held. Results Initial screening of electronic databases yielded 418 potentially relevant publications. After screening of the titles and full-text examination, five studies were included in the systematic review. Four publications evaluated the effects of PDT adjunctive to SRP in patients with AgP: two of them compared the clinical outcomes of SRP and PDT with a control group that received therapy with SRP and antibiotics (metronidazole and amoxicillin); two publications included SRP and PDT in the test group, and SRP alone in the control group. In one study, PDT was tested as a monotherapy compared with SRP alone. Conclusions Within the limitations of this review, PDT may exhibit a beneficial role in the therapy of aggressive periodontitis after repeated applications. In the future, more methodologically sound, long-term randomized clinical trials are needed to be conducted. Key words:Photodynamic therapy, periodontitis, systematic review. PMID:26595837

  9. Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

    2005-01-01

    This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

  10. Maintenance therapy with interferon-alpha 2b, cyclophosphamide, and prednisone in aggressive diffuse large cell lymphoma.

    PubMed

    Avilés, Agustin; Neri, Natividad; Nambo, M Jesús; Castañeda, Claudia; Talavera, Alejandra; Huerta-Guzmán, Judith; Murillo, Edgar

    2004-04-01

    Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy. PMID:15186737

  11. Decision-making around antithrombotics for stroke prevention in atrial fibrillation: the health professionals' views.

    PubMed

    Wang, Yishen; Bajorek, Beata

    2016-08-01

    Background For stroke prevention in patients with atrial fibrillation (AF), the decision-making around antithrombotic therapy has been complicated by older age, multiple comorbidities, polypharmacy and the different pharmacological properties of warfarin and the nonvitamin K antagonist oral anticoagulants (NOACs). The complexity of decision-making has been associated with a reluctance by health professionals to use antithrombotic therapy, leading to poor clinical outcomes. In order to improve stroke prevention in patients with AF, the contemporary perspectives of health professionals on the decision-making around antithrombotic therapy needs exploration. Objective To elicit emerging themes describing health professionals' perspectives on the decision-making around antithrombotic therapy for stroke prevention in patients with AF. Setting Sydney metropolitan area of New South Wales, Australia. Method A qualitative study based on face-to-face interviews was conducted from August to October 2014. Seven pharmacists, seven specialists, six general practitioners and six nurses practising in the Sydney metropolitan area and managing antithrombotic therapy for AF were interviewed until theme saturation was achieved in each subgroup. Interview transcripts were analysed using manual inductive coding. Main outcome measure Emerging themes describing health professionals' perspectives on the decision-making around antithrombotic therapy for stroke prevention in patients with AF. Results Three overarching themes emerged. (1) Comprehensive assessment is necessary for decision-making but is not always implemented. Health professionals mostly focused on stroke risk assessment, not on the bleeding risk and medication safety issues. (2) Health professionals from different disciplines have different preferences for antithrombotic therapies. Although the majority of health professionals considered warfarin as the first-line therapy, NOACs were preferred by neurologists and

  12. [New developments in antithrombotic care].

    PubMed

    Wautrecht, J C

    2009-09-01

    For more than 50 years vitamin K antagonists (VKA) have been the gold standard for long-term oral anticoagulant treatment. New anticoagulants are now in extensive clinical development what will probably have a significant impact on daily practice in the near future. Compounds that specifically block activated factor X (FXa) or activated factor II (thrombin) have entered impressive phase III trials. Idraparinux is a long-active derivative from fondaparinux (synthetic pentasaccharide) and is administered subcutaneously. It inhibits indirectly FXa. Apixaban and rivaroxaban are small molecules that directly block FXa following oral administration. Dabigatran is another substance that is administered orally and directly inhibit thrombin. This article will review the potential interest of these new drugs in the modern antithrombotic care. In the meantime, we will briefly discuss two new tools that have been developed to optimalizing the classical VKA anticoagulation: anticoagulation clinics and point-of-care testing of INR that allows self-monitoring. PMID:19899386

  13. Unusually Aggressive Primary Testicular Diffuse Large B Cell Lymphoma with Post Therapy Extensive Metastasis

    PubMed Central

    Goel, Shalini; Mohapatra, Ishani; Gajendra, Smeeta; Gupta, Sunil

    2016-01-01

    Primary Testicular Lymphoma (PTL) is a rare intermediate to high grade tumour, diffuse large cell being the most common type. Unlike nodal Diffuse Large B-Cell Lymphoma (DLBCL), testicular DLBCL has a less aggressive course and better prognosis. Metastasis is uncommon in testicular DLBCL. Commonly involved sites are contralateral testes, Waldeyer’s ring, skin, lung, Central Nervous System (CNS) and prostate, however the kidneys, liver, bone marrow, pleura and bones are more rarely involved. We report a case of testicular DLBCL which has metastasized to skin and bone marrow with an aggressive clinical course in a year, in-spite of combined modality of therapy given to the patient. Bone marrow infiltration is common and well documented with nodal DLBCL, however there is no published literature for simultaneous bone marrow and skin infiltration in testicular DLBCL till date. Other large studies done in the west have shown that distinct metastasis is usually common but the median progression-free survival is usually in years. This case stresses on shorter period of progression after standard treatment protocol in this part of the world, thus highlighting the need for other extensive studies to define specific treatment protocol for testicular DLBCL.

  14. Which Patients With Mantle Cell Lymphoma Do Not Need Aggressive Therapy.

    PubMed

    Ruan, Jia; Martin, Peter

    2016-06-01

    Mantle cell lymphoma (MCL) is a heterogeneous disease, and it has been well-established over the last decade that a subset of patients can have indolent presentation. It is therefore important to adopt a risk-stratified approach in order to minimize unnecessary toxicities while maximizing survival and quality of life in selected MCL patients. This review provides an up-to-date assessment of clinical and pathologic entities associated with indolent disease course and delineates available biomarkers with predictive significance. Initial treatment decisions should be guided by risk assessment to discern patients who might do well with deferred therapy, from those who would require treatment with non-aggressive first-line regimens. PMID:27068437

  15. Effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) in Reducing Aggression of Individuals at the Juvenile Correction and Rehabilitation Center

    PubMed Central

    Milani, Atefeh; Nikmanesh, Zahra; Farnam, Ali

    2013-01-01

    Background: In the present era, delinquency in children and adolescents is undoubtedly a difficult and upsetting issue attracting the attention of many experts such as psychologists, sociologists, and criminologists. These experts often try to answer why a number of children and adolescents engage in various crimes such as aggressive and anti-social crimes. They also try to find out how these crimes can be prevented. Objectives: The present study investigates the effectiveness of mindfulness-based cognitive therapy training (MBCT) in reducing aggression in a juvenile correction and rehabilitation center of Zahedan province during years 1991 to 1992. Materials and Methods: This experimental study included an experimental and a control group with a pretest, posttest, and follow-up approach. The Buss and Perry aggression questionnaire (1992) was used for data collection. The sample group included 22 (10 experimental and 12 control groups) adolescent males in a juvenile correction and rehabilitation center of Zahedan province who were selected through a census method. Using a matching method based on the pre-test scores of the aggression questionnaire, they were then divided into two equivalent categories and were randomly assigned to the two groups. Mindfulness-based cognitive training took the group training in 8 sessions administered on experimental group. The follow-up test was conducted two weeks after the end of the posttest sessions. The results were analyzed using ANCOVA. Results: The results of ANCOVA showed that mindfulness-based cognitive training could significantly reduce aggression during posttest and follow-up test phases in the experimental group, compared to the control group (P < 0.01). Moreover, the results indicated the effectiveness of this method in significantly reducing anger, physical aggression, and hostility during posttest and follow-up test phases (P < 0.05). However, no significant reduction was observed in the verbal aggression subscale

  16. Safety of Antithrombotic Agents in Elderly Patients with Acute Coronary Syndromes.

    PubMed

    Rocca, Bianca; Husted, Steen

    2016-04-01

    There are unique challenges in the treatment and prevention of acute coronary syndromes (ACS) with antithrombotics in elderly patients: elderly patients usually require multiple drugs due to comorbidities, are highly susceptible to adverse drug reactions and drug-drug interactions, may have cognitive problems affecting compliance and complications, are especially exposed to the risk of falls and, most importantly, ageing is an independent risk factor for bleeding. Antithrombotic drugs, alone or in association, further and variously amplify age-related bleeding risk. Moreover, age-related changes in primary haemostasis may potentially affect the pharmacodynamics of some antiplatelet drugs. Thus, elderly subjects might be more or less sensitive to standard antiplatelet regimens depending on individual characteristics affecting antiplatelet drug response. Importantly, elderly patients are a rapidly growing population worldwide, have the highest incidence of ACS, but are poorly represented in clinical trials. As a consequence, evidence on antithrombotic drug benefits and risks is limited. Thus, in the real-world setting, older people are often denied antithrombotic drugs because of unjustified concerns, or might be over-treated and exposed to excessive bleeding risk. Personalized antithrombotic therapy in elderly patients is particularly critical, to minimize risks without affecting efficacy. PMID:26941087

  17. Patient's Guide to Perioperative Antithrombotic Therapy

    MedlinePlus

    ... most often are warfarin (Coumadin), clopidogrel (Plavix), and aspirin. How Are Blood-Thinning Medications Managed Before and ... or at home. What About Patients Who Take Aspirin and/or Clopidogrel (Plavix) to Thin Their Blood? "! ...

  18. Patient's Guide to Antithrombotic Therapy in Stroke

    MedlinePlus

    ... have had ischemic strokes. 5. How important is aspirin for a new stroke? ! Aspirin is a drug that “thins” the blood by ... cases, it is recommended that patients start taking aspirin within 48 hours of an ischemic stroke. While ...

  19. Patient's Guide to Antithrombotic and Thrombolytic Therapy

    MedlinePlus

    ... X Low-molecular-weight heparin X Fondaparinux X Warfarin (Coumadin) X Dabigatran (Pradaxa) X Rivaroxaban (Xarelto) X ... features of these blood thinners? X Heparin and warfarin have been used for more than 50 years, ...

  20. Survival After Solid Cancers in Antithrombotic Trials.

    PubMed

    Serebruany, Victor L; Tomek, Ales; Kim, Moo Hyun

    2015-09-15

    The impact of antithrombotics on cancer is currently under intense investigation because of the excess of solid cancers in trials after thienopyridines such as TRITON (prasugrel), DAPT (prasugrel and clopidogrel), PAR-1 thrombin antagonist in TRACER (vorapaxar), pyrimidines in PEGASUS (ticagrelor), and in APPRAISE-2 after apixaban. However, whether patient survival after solid cancer (SASC) in antithrombotic trials may be affected is unknown. We matched the 1-year SASC rate in antithrombotic trials reported by Food and Drug Administration with the census averages in Surveillance, Epidemiology, and End Results (SEER) Program by the US National Cancer Institute and World Health Organization (WHO) surveys. The Food and Drug Administration provided the SASC data for 3 trials with similar cancer survival of about 70% for the first year of follow-up in TRITON, APPRAISE-2, and ARISTOTEL. Adjusted cancers in TRITON with SEER (odds ratio 0.92; 95% confidence interval 0.53 to 1.59, p = 0.4351) and WHO (odds ratio 0.99; 95% confidence interval 0.57 to 1.7, p = 1.00) revealed very close if not identical SASC rates in antithrombotic trials compared to epidemiologic census estimates. In conclusion, SASC rates in patients enrolled in antithrombotic trials do not differ from SEER or World Health Organization averages. PMID:26189037

  1. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas. PMID:24287797

  2. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  3. Antithrombotic Agents in the Management of Sepsis.

    PubMed

    Iqbal, Omer; Tobu, Mahmut; Hoppenstead, Debra; Aziz, Salim; Messmore, Harry; Fareed, Jawed

    2002-09-01

    compared to the placebo group. Better understanding of the pathophysiologic mechanism of severe sepsis will provide better treatment options. Combination antithrombotic therapy may provide a multipronged approach for the treatment of severe sepsis. PMID:27264974

  4. Risk factors for postoperative bleeding after gastric endoscopic submucosal dissection in patients under antithrombotics

    PubMed Central

    Shindo, Yuji; Matsumoto, Satohiro; Miyatani, Hiroyuki; Yoshida, Yukio; Mashima, Hirosato

    2016-01-01

    AIM: To evaluate the risk factors for postoperative bleeding after gastric endoscopic submucosal dissection (ESD) based on the latest guidelines. METHODS: A total of 262 gastric neoplasms were treated by ESD at our center during a 2-year period from October 2012. We analyzed the data of these cases retrospectively to identify the risk factors for post-ESD bleeding. RESULTS: Of the 48 (18.3%) cases on antithrombotic treatment, 10 were still receiving antiplatelet drugs perioperatively, 13 were on heparin replacement after oral anticoagulant withdrawal, and the antithrombotic therapy was discontinued perioperatively in 25 cases. Postoperative bleeding occurred in 23 cases (8.8%). The postoperative bleeding rate in the heparin replacement group was 61.5%, significantly higher than that in the non-antithrombotic therapy group (6.1%). Univariate analysis identified history of antithrombotic drug use, heparin replacement, hemodialysis, cardiovascular disease, diabetes mellitus, elevated prothrombin time-international normalized ratio, and low hemoglobin level on admission as risk factors for post ESD bleeding. Multivariate analysis identified only heparin replacement (OR = 13.7, 95%CI: 1.2-151.3, P = 0.0329) as a significant risk factor for post-ESD bleeding. CONCLUSION: Continued administration of antiplatelet agents, based on the guidelines, was not a risk factor for postoperative bleeding after gastric ESD; however, heparin replacement, which is recommended after withdrawal of oral anticoagulants, was identified as a significant risk factor. PMID:27076874

  5. Antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: a systematic review and meta-analysis.

    PubMed

    Souza, Emmanuel; Medeiros, Ana Cláudia; Gurgel, Bruno César; Sarmento, Carlos

    2016-01-01

    The aim of this systematic review was to investigate whether the use of antimicrobial photodynamic therapy (aPDT) as an adjuvant to scaling and root planning (SRP) yields better results than SRP alone or associated with systemic antibiotics in the treatment of aggressive periodontitis (AgP). A meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statements and Cochrane Collaboration recommendations. The search for relevant studies (earliest record to January 2015) was carried out in seven databases, followed by a manual search. Methodological quality assessment of the studies selected was based on an analysis of the risk of bias. At each time point of follow-up, the existence of significant differences (p < 0.05) in clinical attachment level (CAL) gain and probing depth (PD) reduction (primary outcomes) between groups was assessed with RevMan software 5.0. Heterogeneity between studies was assessed by the Higgin test (I (2)). Four randomized controlled trials (RCTs) satisfied the eligibility criteria of this review. Only one study was found to have a low risk of bias. There were no significant differences in PD reduction (mean difference 0.33, 95 % confidence interval -0.32 to 0.98, p = 0.32) and CAL gain (mean difference 0.20, 95 % confidence interval -0.41 to 0.81, p = 0.53) between the test and control interventions. At present, therefore, when compared to SRP alone or associated with systemic antibiotics, the evidence suggests that the association of aPDT + SRP is of no additional benefit in the nonsurgical treatment of AgP. PMID:26563956

  6. Maintenance periodontal therapy after systemic antibiotic and regenerative therapy of generalized aggressive periodontitis. A case report with 10-year follow-up.

    PubMed

    Siqueira, Sergio Júnior; Ribeiro, Fernanda Vieira; Villalpando, Karina Teixeira; Cirano, Fabiano Ribeiro; Pimentel, Suzana Peres

    2015-05-01

    Aggressive periodontitis (AgP) is an inflammatory disease characterized by rapid attachment loss and bone destruction. This case report presents the 10-year results in a subject with generalized AgP treated by a regenerative periodontal therapeutic approach and the adjunctive use of antibiotics, following a systematic maintenance periodontal therapy. The use of enamel matrix derivatives (EMD) and adjunctive antibiotic therapy to treat AgP yielded improvements in clinical parameters and radiographic bony fill. This combined therapeutic approach following a systematic supportive periodontal therapy supports the long-term maintenance of teeth with previous advanced periodontal defects, demonstrating successful stability after 10-years follow-up. Clinical Relevance: The combined treatment protocol using EMD plus adjunctive antibiotic therapy, associated with a systematic supportive periodontal therapy, benefits the long-term maintenance of teeth with previous advanced periodontal defects in subjects presenting AgP, supporting this approach as an alternative in the treatment of AgP. PMID:26062264

  7. Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report

    PubMed Central

    UMEDA, KATSUTSUGU; SAIDA, SATOSHI; YAMAGUCHI, HIDEKI; OKAMOTO, SHINYA; OKAMOTO, TAKESHI; KATO, ITARU; HIRAMATSU, HIDEFUMI; IMAI, TSUYOSHI; KODAIRA, TAKESHI; HEIKE, TOSHIO; ADACHI, SOUICHI; WATANABE, KEN-ICHIRO

    2016-01-01

    Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID:26870296

  8. Antithrombotic Treatment in Neonatal Cerebral Sinovenous Thrombosis: Results of the International Pediatric Stroke Study

    PubMed Central

    Jordan, Lori C.; Rafay, Mubeen F.; Smith, Sabrina E.; Askalan, Rand; Zamel, Khaled M.; deVeber, Gabrielle; Ashwal, Stephen

    2010-01-01

    Objective To identify predictors of antithrombotic treatment in neonates with cerebral sinovenous thrombosis (CSVT) in a large multi-national study. Study Design Neonates with CSVT from 10 countries were enrolled in the International Pediatric Stroke Study from 2003-2007. Term neonates with CSVT who presented with neurologic symptoms or signs of systemic illness and neuroimaging evidence of thrombus or flow interruption within cerebral venous system were included. Results Of 341 neonates enrolled, 84 had isolated CSVT. Neuroimaging findings, available in 67/84 neonates, included: venous ischemic infarction in 5, hemorrhagic infarction or other intracranial hemorrhage in 13, both infarction and hemorrhage in 26, and no parenchymal lesions in 23. Treatment data, available in 81/84 neonates, included antithrombotic medications in 52% (n=43), comprising heparin (n=14), low molecular weight heparin (n=34), warfarin (n=1) and aspirin (n=2). By univariate logistic regression analysis, deep venous system thrombosis (p=0.05) and location in the United States (p=0.001) predicted non-treatment. Presence of infarction, hemorrhage, dehydration, systemic illness, and age did not predict treatment or non-treatment. In multivariate analysis only geographic location remained significant. Conclusions In neonatal CSVT, regional antithrombotic treatment practices demonstrate considerable variability and uncertainty about the indications for antithrombotic therapy. Additional studies to determine appropriate treatments are warranted. PMID:20149389

  9. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  10. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  11. The Utility of Platelet and Coagulation Testing of Antithrombotics: Fusing Science with Patient Care

    PubMed Central

    Jennings, Lisa K; Kotha, Jayaprakash

    2013-01-01

    Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I-III Regulatory, Quality, ManufacturingPostmarketing Phase IV There is an increasing need for the standardization of platelet function and coagulation testing for the assessment of antithrombotic therapies. Investigators continue to strive to identify ideal laboratory testing and monitoring procedures for acquired and inherited platelet function defects as well as for evaluating patient status when treated with existing or emerging antithrombotics. These therapies are used primarily in the treatment of ischemic complications. In patients receiving antithrombotic therapy, the balance between hemostasis and thrombosis is a challenge as there is an ongoing risk for bleeding when patients are receiving antiplatelet agents or anticoagulants to lessen their risk for secondary thrombotic events. There are several diverse tests for monitoring anticoagulant therapy; however, as new agents are developed, more specific tests will be required to directly assess these agents in relationship to overall coagulation status. Research in the platelet biology field is ongoing to provide point-of-care methodologies for the assessment of platelet reactivity in terms of both bleeding and thrombosis risk. Currently there are no instruments that reliably assess the risk of bleeding. The challenges that routinely faced are the complexity of physiology, the need for standardization of platelet testing methodology, and the necessity for appropriate interpretation of the test results. PMID:24489427

  12. Optimizing Stroke Prevention in Patients With Atrial Fibrillation: A Cluster-Randomized Controlled Trial of a Computerized Antithrombotic Risk Assessment Tool in Australian General Practice, 2012–2013

    PubMed Central

    Magin, Parker J.; Hilmer, Sarah N.; Krass, Ines

    2016-01-01

    Introduction Clinicians have expressed a need for tools to assist in selecting treatments for stroke prevention in patients with atrial fibrillation. The objective of this study was to evaluate the impact of a computerized antithrombotic risk assessment tool (CARAT) on general practitioners’ prescribing of antithrombotics for patients with atrial fibrillation. Methods A prospective, cluster-randomized controlled trial was conducted in 4 regions (in rural and urban settings) of general practice in New South Wales, Australia (January 2012–June 2013). General practitioner practices were assigned to an intervention arm (CARAT) or control arm (usual care). Antithrombotic therapy prescribing was assessed before and after application of CARAT. Results Overall, the antithrombotic therapies for 393 patients were reviewed by 48 general practitioners; we found no significant baseline differences in use of antithrombotics between the control arm and intervention arm. Compared with control patients, intervention patients (n = 206) were 3.1 times more likely to be recommended warfarin therapy (over any other treatment option; P < .001) and 2.8 times more likely to be recommended any anticoagulant (in preference to antiplatelet; P = .02). General practitioners agreed with most (75.2%) CARAT recommendations; CARAT recommended that 75 (36.4%) patients change therapy. After application of CARAT, the proportion of patients receiving any antithrombotic therapy was unchanged from baseline (99.0%); however, anticoagulant use increased slightly (from 89.3% to 92.2%), and antiplatelet use decreased (from 9.7% to 6.8%). Conclusion Tools such as CARAT can assist clinicians in selecting antithrombotic therapies, particularly in upgrading patients from antiplatelets to anticoagulants. However, the introduction of novel oral anticoagulants has complicated the decision-making process, and tools must evolve to weigh the risks and benefits of these new therapy options. PMID:27418212

  13. The Rosenzweig Picture-Frustration Study "Extra-Aggression" Score as an Indicator in Cognitive Restructuring Therapy for Male Perpetrators of Domestic Violence

    ERIC Educational Resources Information Center

    Norman, Michael; Ryan, Lawrence J.

    2008-01-01

    It was hypothesized that male perpetrators of domestic violence in the early stages of a 1-year process of cognitive restructuring therapy would manifest on the Rosenzweig Picture-Frustration Study higher levels of extra-aggressiveness than in later stages of the therapy process. A sample of male batterers in the process of treatment took the…

  14. Cognitive behavioral therapy to reduce overt aggression behavior in Chinese young male violent offenders.

    PubMed

    Chen, Chen; Li, Chun; Wang, Hong; Ou, Jian-Jun; Zhou, Jian-Song; Wang, Xiao-Ping

    2014-01-01

    This 9-week study was designed to determine whether a commercial cognitive-behavioral training program could effectively reduce overt aggression behavior in Chinese young male violent offenders. Sixty-six participants were randomly assigned to receive routine intervention alone (control group) or routine intervention plus Williams LifeSkills Training (WLST group) in a 1:1 ratio. The primary outcome was change scores on the Modified Overt Aggression Scale (MOAS) from baseline to one week following end of training. Secondary outcomes were change scores on the Barratt Impulsiveness Scale-11 (BIS-11) and Cook-Medley Hostility Scale (CMHS). There were significant between-group differences in change of MOAS total score (P < .001) and all sub-scores (Ps < .01) except aggression against property. Between-group differences were also observed in change of BIS-11 and CMHS total score (Ps < 0.05). All results favored the WLST group. These findings suggest WLST has the potential to be an effective intervention to reduce overt aggressive behavior in young male violent offenders. PMID:24375428

  15. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer

    PubMed Central

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs. PMID:22149431

  16. Reevaluation of antithrombotic fruits and vegetables: great variation between varieties.

    PubMed

    Yamamoto, Junichiro; Ijiri, Yoshinobu; Tamura, Yukinori; Iwasaki, Masahiro; Murakami, Masahiro; Okada, Yoshio

    2016-01-01

    In the quest for prevention of atherothrombotic diseases, an antithrombotic diet may offer a promising approach. The major stumbling block in finding an effective diet is the lack of pathophysiological relevant techniques to detect potential antithrombotic effects of various diet components. Platelet function and coagulation/fibrinolysis tests currently in use do not allow assessment of global thrombotic status and their value in screening diet-components for antithrombotic effects. Recently, we combined the point-of-care shear-induced ex vivo thrombosis test (Global Thrombosis Test-GTT) with the Flow-mediated Vasodilation (FMV) in vivo test and found that the combination improved the assessment of thrombotic status in humans and could be used for screening diet-components for antithrombotic effects. In the present experiments, a combination of GTT, hemostatometry, laser-induced thrombosis tests and FMV were employed for screening. The results show that the overall antithrombotic effect is determined by the effect on thrombus formation and endogenous thrombolytic activities. This study showed a great variation in the observed antithrombotic effect between the tested varieties. Antithrombotic activities were independent from polyphenolic content or antioxidant activities. The presented experimental techniques seem to be suitable for establishing an antithrombotic diet, which may be effective in the prevention of atherothrombotic cardiovascular diseases in humans. PMID:27431269

  17. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

    PubMed

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L; Shea, Thomas C; Liomba, N George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  18. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

    PubMed Central

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  19. Long-term antithrombotic pharmacotherapy following ST-elevation myocardial infarction.

    PubMed

    Buccheri, Sergio; Capodanno, Davide

    2016-06-01

    The selection and optimal duration of pharmacological agents to counteract thrombotic processes activated in patients with ST-elevation myocardial infarction (STEMI) still remain a debated issue in current clinical practice. Recently published trials have highlighted the potential benefits of dual-antiplatelet therapy (DAPT) extended beyond the currently recommended 12-months term. Anticoagulation with non-vitamin K oral anticoagulants in addition to DAPT has also been explored. Importantly, benefits of prolonged antithrombotic management strategies could be offset by harms following bleeding complications, therefore careful assessment of a patient benefit-risk profile must be used to drive individualized medical decisions. Appraising current available evidence is useful to inform clinical practice and to optimize the pharmacological management of patients with STEMI. Accordingly, we provide an overview of the literature focusing on long-term antithrombotic management strategies in patients with a recent or prior myocardial infarction, with a primary focus on STEMI. PMID:26934659

  20. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    SciTech Connect

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a shorter

  1. Dialectical behavior therapy deployed: an aggressive alternative to traditional mental health on the noncontiguous battlefield.

    PubMed

    Parrish, Brian D

    2008-01-01

    This paper provides a description of the Witmer Wellness Center, the first successful military application of dialectical behavior therapy in a theater of war. Dialectical behavior therapy is a dynamic and provocative evidenced-based modification of cognitive behavioral treatment developed by Dr Marsha Linehan for patients with severe emotional dysregulation. One of the primary concepts of dialectical behavior therapy is that self-harming behaviors are learned, and provide evidence of maladaptive coping that is reinforced in an invalidating environment. Dialectical behavior therapy recommends a hierarchy of goals to effectively address the behaviors associated with dysregulation. Chief among these goals is reducing risk of violence to self or others. Dialectical behavior therapy is especially well-suited for the complex and dynamic environment of the noncontiguous battlefield with its chronic threat of ultraviolence, strain of nonresponse, shifting rules of engagement, and extended duration and frequency of combat deployments. The Witmer Wellness Center program uses an intensive outpatient organizational structure and minimal, but innovative, modifications to standard dialectical behavior therapy designed to meet the special requirements of Warriors in a combat zone. The Wellness Center program was designed and implemented during Operation Iraqi Freedom 07-09, at a time during the troop surge when suicide rates among US forces had reached an unprecedented level. PMID:20088061

  2. Temporal trends in the use of antithrombotics at admission.

    PubMed

    Madsen, Christian Medom; Jantzen, Christopher; Lauritzen, Jes Bruun; Abrahamsen, Bo; Jorgensen, Henrik L

    2016-08-01

    Background and purpose - Currently, no clear evidence exists on the pattern of use of antithrombotics at admission in hip fracture patients and how this has changed over time. We investigated temporal trends in-and factors associated with-the use of antithrombotics in patients admitted with a fractured hip. Patients and methods - This was a population-based cohort study including all patients aged 18 years or above who were admitted with a hip fracture in Denmark from 1996 to 2012. The Danish national registries were used to collect information on medication use, vital status, and comorbidity. Results - From 1996 to 2012, the proportion of patients using antithrombotics in general increased by a factor of 2.3 from 19% to 43% (p < 0.001). More specifically, the use of anticoagulants increased by a factor of 6.8 and the use of antiplatelets increased by a factor of 2.1. When we adjusted for possible confounders, the use of antithrombotics still increased for every calendar year (relative risk (RR) = 1.03, CI: 1.03-1.04; p < 0.001). Age, sex, and Charlson comorbidity index were all associated with the use of antithrombotics (all p < 0.001). Interpretation - The proportion of hip fracture patients using antithrombotics at admission has increased substantially in Denmark over the last 2 decades. This highlights the need for evidence-based guidelines on how to handle patients using antithrombotics to ensure safe surgery and to avoid surgical delay. PMID:27301556

  3. Risk of Hemorrhage during Needle-Based Ophthalmic Regional Anesthesia in Patients Taking Antithrombotics: A Systematic Review

    PubMed Central

    Takaschima, Augusto; Marchioro, Patricia; Sakae, Thiago M.; Porporatti, André L.; Mezzomo, Luis André; De Luca Canto, Graziela

    2016-01-01

    Background Patients undergoing ophthalmic surgery are usually elderly and, due to systemic disease, may be on long-term therapy, such as antithrombotic agents. Rates of hemorrhagic complications associated with invasive procedures may be increased by the use of anticoagulants and antiplatelet agents. Objective To compare the incidence of hemorrhagic complications in patients undergoing needle-based ophthalmic regional anesthesia between patients on antithrombotic therapy and those not on such therapy. Methods A systematic review was conducted by two independent reviewers based on searches of Cochrane, LILACS, PubMed, Scopus, Web of Science, and the “gray” literature (Google Scholar). The end search date was May 8, 2015, across all databases. Results Five studies met the eligibility criteria. In three studies, individual risk of bias was low, and in two of them, moderate. In all studies, no differences regarding mild to moderate incidence of hemorrhagic complications were found between patients using antithrombotics (aspirin, clopidogrel, and warfarin) and those not using them. Rates of severe hemorrhagic complication were very low (0.04%) in both groups, supporting the safety of needle blocks, even in patients using antithrombotics. High heterogeneity across studies prevented meta-analysis. Limitations to these results include low statistical power in three experimental studies and a large 95% confidence interval in the two retrospective cohorts. Conclusion In this review, none of the selected studies showed significant bleeding related to needle-based ophthalmic regional anesthesia in association with the use of aspirin, clopidogrel, or vitamin K inhibitors. Since the available data is not powerful enough to provide a reliable evaluation of the true effect of antithrombotics in this setting, new studies to address these limitations are necessary. PMID:26800356

  4. Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

    PubMed

    Taverna, Josephine A; Yun, Seongseok; Jonnadula, Jayasree; Saleh, Ahlam; Riaz, Irbaz Bin; Abraham, Ivo; Yeager, Andrew M; Persky, Daniel O; McBride, Ali; Haldar, Subrata; Anwer, Faiz

    2016-07-01

    Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas. PMID:26899562

  5. Identification of targeted therapy for an aggressive subgroup of muscle-invasive bladder cancers.

    PubMed

    Lebret, Thierry; Neuzillet, Yann; Houede, Nadine; Rebouissou, Sandra; Bernard-Pierrot, Isabelle; De Reynies, Aurélien; Benhamou, Simone; Allory, Yves; Radvanyi, François

    2015-01-01

    Rebouissou et al. recently provided preclinical evidence that a subset of patients with muscle-invasive bladder cancer might benefit from anti-epidermal growth factor receptor (EGFR) therapy and reported diagnostic tools for identifying these patients in the clinical setting. This work also identified relevant experimental models that may be useful for future basic and clinical research on this subgroup of tumors. PMID:27308521

  6. How do we manage high-grade T1 bladder cancer? Conservative or aggressive therapy?

    PubMed Central

    Kim, Seon-Kyu; Kim, Wun-Jae

    2016-01-01

    High-grade T1 bladder cancer has a poor prognosis due to a higher incidence of recurrence and progression than other nonmuscle invasive bladder cancer; thus patients with high-grade T1 have to be carefully monitored and managed. If patients are diagnosed with high-grade T1 at initial transurethral resection (TUR), a second TUR is strongly recommended regardless of whether muscle layer is present in the specimen because of the possibility of understating due to incomplete resection. Since high-grade T1 disease shows diverse clinical courses, individual approaches are recommended for treatment. In cases with low risk of progression, cystectomy could represent overtreatment and deteriorate quality of life irreversibly, while, in those with high risk, bacillus Calmette-Guérin (BCG) therapy may worsen survival by delaying definitive therapy. Therefore, a strategy for predicting prognosis based on the risk of progression is needed for managing high-grade T1 disease. Molecular risk classifiers predicting the risk of progression and response to BCG may help identify the optimal management of high-grade T1 disease for each individual. PMID:27326407

  7. The Relationship Between the Level of Program Integrity and Pre- and Post-Test Changes of Responsive-Aggression Regulation Therapy (Re-ART) Outpatient: A Pilot Study.

    PubMed

    Hoogsteder, Larissa M; van Horn, Joan E; Stams, Geert Jan J M; Wissink, Inge B; Hendriks, Jan

    2016-03-01

    Responsive-Aggression Regulation Therapy (Re-ART) Outpatient is a cognitive behavioral-based intervention for adolescents and young adults (16-24 years) with severe aggressive behavioral problems. This pilot study (N = 26) examined the level of program integrity (PI; that is, the delivery of the intervention as it is originally intended) of Re-ART. We also investigated the pre- and post-test changes in several outcome variables, and the relation between the level of PI and these changes. Participants were recruited from three different outpatient forensic settings. Results showed that the PI of half of the treatments was not sufficient (e.g., the intensity of the program was too low and some standard modules were not offered). In addition, this pilot study demonstrated that sufficient PI was related to positive changes in aggression, cognitive distortions, social support, coping (reported by therapist), and distrust (responsiveness to treatment). PMID:25326466

  8. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer.

    PubMed

    Dal Pra, Alan; Locke, Jennifer A; Borst, Gerben; Supiot, Stephane; Bristow, Robert G

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  9. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  10. LXR as a novel antithrombotic target

    PubMed Central

    Spyridon, Michael; Moraes, Leonardo A.; Jones, Chris I.; Sage, Tanya; Sasikumar, Parvathy; Bucci, Giovanna

    2011-01-01

    Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease. PMID:21411760

  11. Translation and Clinical Development of Antithrombotic Aptamers.

    PubMed

    Nimjee, Shahid M; Povsic, Thomas J; Sullenger, Bruce A; Becker, Richard C

    2016-06-01

    Thrombosis is a necessary physiological process to protect the body from uncontrolled bleeding. Pathological thrombus formation can lead to devastating clinical events including heart attack, stroke, deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. Numerous drugs have been developed to inhibit thrombosis. These have been targeted to coagulation factors along with proteins and receptors that activate platelets. While these drugs are effective at preventing blood clotting, their major side effect is inadvertent hemorrhage that can result in significant morbidity and mortality. There exists a need for anticoagulants that are not only effective at preventing thrombosis but can also be readily reversed. Aptamers offer a potential solution, representing a new class of drug agents that can be isolated to any protein and where antidote oligonucleotides can be designed based on the sequence of the aptamer. We present a summary of the anticoagulant and antithrombotic aptamers that have been identified and their stage of development and comment on the future of aptamer-based drug development to treat thrombosis. PMID:26882082

  12. Antithrombotic strategies in patients undergoing percutaneous coronary intervention for acute coronary syndrome

    PubMed Central

    Pham, Son V; Pham, Phuong-Chi T; Pham, Phuong-Mai T; Miller, Jeffrey M; Pham, Phuong-Thu T; Pham, Phuong-Anh T

    2010-01-01

    In patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS), both periprocedural acute myocardial infarction and bleeding complications have been shown to be associated with early and late mortality. Current standard antithrombotic therapy after coronary stent implantation consists of lifelong aspirin and clopidogrel for a variable period depending in part on the stent type. Despite its well-established efficacy in reducing cardiac-related death, myocardial infarction, and stroke, dual antiplatelet therapy with aspirin and clopidogrel is not without shortcomings. While clopidogrel may be of little beneficial effect if administered immediately prior to PCI and may even increase major bleeding risk if coronary artery bypass grafting is anticipated, early discontinuation of the drug may result in insufficient antiplatelet coverage with thrombotic complications. Optimal and rapid inhibition of platelet activity to suppress ischemic and thrombotic events while minimizing bleeding complications is an important therapeutic goal in the management of patients undergoing percutaneous coronary intervention. In this article we present an overview of the literature on clinical trials evaluating the different aspects of antithrombotic therapy in patients undergoing PCI and discuss the emerging role of these agents in the contemporary era of early invasive coronary intervention. Clinical trial acronyms and their full names are provided in Table 1. PMID:20856846

  13. The Effects of Aggression on Symptom Severity and Treatment Response in a Trial of Cognitive Behavioral Therapy for Panic Disorder

    PubMed Central

    Cassiello-Robbins, Clair; Conklin, Laren R.; Anakwenze, Ujunwa; Gorman, Jack M.; Woods, Scott W.; Shear, M. Katherine; Barlow, David H.

    2015-01-01

    Background Previous research suggests that patients with panic disorder exhibit higher levels of aggression than patients with other anxiety disorders. This aggression is associated with more severe symptomatology and interpersonal problems. However, few studies have examined whether higher levels of aggression are associated with a worse treatment response in this population. Methods The present study sought to examine the association of aggression with panic disorder symptom severity in a sample of 379 patients who participated in a trial examining long-term strategies for the treatment of panic disorder. Results We found that aggression was significantly associated with higher baseline levels of panic disorder symptoms, anxiety, depression, and functional impairment. Further, we found that patients higher in aggression did not achieve the same level of improvement in general anxiety symptoms during treatment compared to patients lower in aggression, even when controlling for baseline anxiety symptom severity. Conclusion These results suggest that more research is needed concerning patients with anxiety disorders with higher aggression, as they may be a group in need of additional treatment considerations. PMID:25987198

  14. Efficacy of Photodynamic Therapy and Lasers as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis – A Clinical and Microbiologic Short Term Study

    PubMed Central

    Sarkar, Indranil; Rajan, Padma; Pai, Jagdish; Malagi, Sachin; Bharmappa, Radhika; Kamath, Vinesh

    2016-01-01

    Introduction Aggressive periodontitis comprises a group of rare, severe, rapidly progressive form of periodontitis. Conventional treatment includes mechanical debridement augmented with adjunctive antimicrobial therapy. Development of antibiotic resistance has led to use of lasers. Photodynamic therapy (PDT) is a novel non-invasive therapeutic approach with increased site and pathogen specificity. This study compares PDT and Lasers as an adjunct to conventional Scaling in the treatment of patients with aggressive periodontitis. Materials and Methods Fifteen untreated aggressive periodo-ntitis patients were randomly assigned in a split mouth design for one of the following treatment modalities: 1) SRP alone; (2) SRP + Diode Laser irradiation with 810 nm at 1W, continuous mode for 30 sec per tooth; (3) SRP + PDT on “0” day; (4) SRP + PDT on “0”, 7th and 21st day. The clinical parameters included PI, BOP, PPD, CAL recorded at the baseline & 3rd month. The site with greatest probing pocket depth (PPD) was selected from each quadrant for bacterial sampling and cultured for Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis & Prevotella intermedia. Results Statistically significant reduction in clinical & microbial parameters was seen. Sites 4 showed a greater reduction compared to other groups. Conclusion Photodynamic therapy is a valuable treatment modality adjunctive to conventional scaling and root planing. PMID:27042576

  15. [Advances in antithrombotic treatment--antithrombotics with anti-Xa effect].

    PubMed

    Bátorová, A

    2009-03-01

    The use of anticoagulants in the prophylaxis and treatment of arterial and venous thrombosis has substantially expanded during the last years. Increasing knowledge about the inherited and acquired thrombophilia and the risk factors predisposing to the recurrency of thromboembolic events result in a new indications for primary and secondary thromboprophylaxis with prolonged or even life-long duration. The limitations of classical anticoagulans, heparin and vitamin K antagonists support the development of medicaments with a specific antithrombotic action. The new generation anticoagulants inhibit in a specific way either particular coagulation enzyme or hemostasis activation step. Based on the in vitro studies and extensive clinical observations the activated factor Xa (FXa) seems to be one of the most advantageous targets for a specific action of perspective antithrombotic agents. Two selective F Xa inhibitors have been approved for clinical use: fondaparinux is an indirect parenteral F Xa inhibitor, and most recently approved rivaroxaban is the first oral anti-Xa inhibitor. Other anti-Xa molecules are under development for either parenteral (idraparinux, DX-9065a) or oral use (razaxaban, apixaban, rivaroxaban, LY-51, 7717, BMS-56247 a DU-176b). PMID:19378862

  16. An echo-guided case report of rapid regression of unstable mobile thrombus aortic atheroma after aggressive statin and antiplatelet combination therapy.

    PubMed

    Dʼaloia, Antonio; Vizzardi, Enrico; Caretta, Giorgio; Zanini, Gregoriana; Bugatti, Silvia; Curnis, Antonio; Dei Cas, Livio

    2014-01-01

    We describe a case report that documented the efficacy and safety of medical therapy in stabilizing and resolving a complex and unstable aortic atheroma after a relatively short period. The patient had a large protruding, mobile, calcified nonulcerated atheroma involving the descending aorta and was therefore treated with aggressive combination therapy with high statin dosages (atorvastatin = 80 mg) and dual antiplatelet treatment (clopidogrel = 75 mg and aspirin = 100 mg). At follow-up, the echocardiogram showed a significant regression in the atheroma volume, with no signs suggestive of ulceration on its surface with the complete mobile component resolution. PMID:23817345

  17. BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

    PubMed

    Zheng, Hua-chuan; Li, Jing; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Wu, Ya-zhou; Takano, Yasuo; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Gou, Wen-feng

    2015-08-14

    Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer. PMID:26050197

  18. Perioperative management of antithrombotic treatment during implantation or revision of cardiac implantable electronic devices: the European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI).

    PubMed

    Deharo, Jean-Claude; Sciaraffia, Elena; Leclercq, Christophe; Amara, Walid; Doering, Michael; Bongiorni, Maria G; Chen, Jian; Dagres, Nicolaus; Estner, Heidi; Larsen, Torben B; Johansen, Jens B; Potpara, Tatjana S; Proclemer, Alessandro; Pison, Laurent; Brunet, Caroline; Blomström-Lundqvist, Carina

    2016-05-01

    The European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI) was a prospective European survey of consecutive adults who had undergone implantation/surgical revision of a cardiac implantable electronic device (CIED) on chronic antithrombotic therapy (enrolment March-June 2015). The aim of the survey was to investigate perioperative treatment with oral anticoagulants and antiplatelets in CIED implantation or surgical revision and to determine the incidence of complications, including clinically significant pocket haematomas. Information on antithrombotic therapy before and after surgery and bleeding and thromboembolic complications occurring after the intervention was collected at first follow-up. The study population comprised 723 patients (66.7% men, 76.9% aged ≥66 years). Antithrombotic treatment was continued during surgery in 489 (67.6%) patients; 6 (0.8%) had their treatment definitively stopped; 46 (6.4%) were switched to another antithrombotic therapy. Heparin bridging was used in 55 out of 154 (35.8%) patients when interrupting vitamin K antagonist (VKA) treatment. Non-vitamin K oral anticoagulant (NOAC) treatment was interrupted in 88.7% of patients, with heparin bridging in 25.6%, but accounted for only 25.3% of the oral anticoagulants used. A total of 108 complications were observed in 98 patients. No intracranial haemorrhage or embolic events were observed. Chronic NOAC treatment before surgery was associated with lower rates of minor pocket haematoma (1.4%; P= 0.042) vs. dual antiplatelet therapy (13.0%), VKA (11.4%), VKA + antiplatelet (9.2%), or NOAC + antiplatelet (7.7%). Similar results were observed for bleeding complications (P= 0.028). Perioperative management of patients undergoing CIED implantation/surgical revision while on chronic antithrombotic therapy varies, with evidence of a disparity between guideline recommendations and practice patterns in Europe. Haemorrhagic complications were significantly

  19. The Antithrombotic and Fibrinolytic Effect of Natto in Hypercholesterolemia Rats

    PubMed Central

    Park, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Yeo, Ik-Hyun

    2012-01-01

    Antithrombotic and fibrinolytic activity of natto was evaluated on platelet aggregation in vitro and in vivo. Natto showed inhibitory effects on platelet aggregation induced by adenosine 5′diphosphate (ADP) and collagen. Orally administered natto also showed fibrinolytic activity in hypercholesterolemia rats. Normal levels of natto, when administered for four weeks, shortened euglobulin clot lysis time (ECLT) and prolonged partial thromboplastin time (PATT) significantly compared to non-treated group. In addition, the natto treatment decreased total cholesterol in serum. These results showed that intake of normal levels of natto can elicit antithrombotic and fibrinolytic effects, suggesting its consumption may improve blood circulation. PMID:24471066

  20. Clinical Factors Influencing the Efficacy of Systemic Moxifloxacin in the Therapy of Patients With Generalized Aggressive Periodontitis: A Multilevel Analysis From a Clinical Trial

    PubMed Central

    Ardila, Carlos M.; Guzmán, Isabel C.

    2016-01-01

    Background: It has been reported that clinical results of mechanical periodontal treatment could differ between subjects and among different sites of the tooth in the patient. The objective of this multilevel analysis is to investigate clinical factors at subject and sites of the tooth that influence variations in clinical attachment (CAL) increase and probing depth (PD) diminution of adjunctive moxifloxacin (MOX) at six months post-treatment in generalized aggressive periodontitis. Methods: This clinical trial included 40 patients randomly distributed to two therapy protocols: scaling and root planing alone or combined with MOX. Multilevel linear models for continuous variables were formulated to evaluate the clinical impact of the hierarchical configuration of periodontal data. Results: Six months following therapy, the divergences between both protocols were statistically significant in PD diminution and CAL increase, favouring the MOX therapy (p<0.001). Besides, the multilevel analysis revealed that adjunctive MOX at the subject level, non-molar and the interaction non-molar x MOX at the tooth level, interproximal sites and the interaction interproximal sites x MOX at the site level, were statistically significant factors in determining CAL increase and PD diminution. Conclusions: The main cause of variability in CAL gain and PD reduction following adjunctive MOX was attributable to the tooth level. Adjunctive MOX and their interactions with non-molar and interproximal sites showed higher clinical benefits at the tooth and site levels which could be essential for PD reduction and CAL gain in generalized aggressive periodontitis subjects. PMID:26493435

  1. Antithrombotic Drugs: Pharmacology and Implications for Dental Practice

    PubMed Central

    Becker, Daniel E.

    2013-01-01

    Appropriate preoperative assessment of the dental patient should always include an analysis of the patient's medications. This article reviews the actions and indications for the various categories of antithrombotic medications and considers actual risks for postoperative bleeding and potential interactions with drugs the dental provider might administer or prescribe. PMID:23763563

  2. New antithrombotic drugs: potential for use in oncology.

    PubMed

    Levine, Mark N

    2009-10-10

    For more than 50 years, heparin and vitamin K antagonists (VKAs) have been the anticoagulant drugs used to prevent and treat thrombosis. Low molecular weight heparins (LMWHs) are more recent and have been available for approximately 20 years. Patients with cancer are members of a unique patient population because of their high risk for thrombosis and the risk of anticoagulant-related bleeding. With the currently available antithrombotic agents, patients with cancer still have unmet needs in terms of the prevention and treatment of thrombosis. Although long-term LMWH is the treatment of choice for patients with cancer who have acute, symptomatic venous thromboembolism (VTE), some patients still experience recurrent VTE. More effective antithrombotic agents are needed for such patients. Convenient (ie, oral and with no laboratory monitoring), effective, and safe agents are needed to prevent thrombosis in patients taking chemotherapy and antiangiogenic drugs and in patients with central vein catheters. There are a number of new antithrombotic agents that have been studied in recent years and will soon be available for certain diseases. They target either activated factor X (ie, factor Xa) or activated thrombin, and some of them have potential therapeutic value in patients with cancer. In this article, the clinical research model used for the development of a new antithrombotic agent is discussed along with the results of recent trials that evaluate these new agents in high-risk populations. PMID:19738103

  3. Nitric oxide-releasing NSAIDs: GI-safe antithrombotics.

    PubMed

    Wallace, J L; Del Soldato, P; Cirino, G; Muscará, M N

    1999-04-01

    Aspirin is increasingly being used for long-term prophylaxis of myocardial infarction and stroke, but its use is limited by toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. While proven effective in prophylaxis of stroke and myocardial infarction, the efficacy of aspirin is limited. Addition of a nitric oxide-releasing moiety to several non-steroidal anti-inflammatory drugs results in a profound reduction in their toxicity in the gastrointestinal tract and kidney. A similar derivatization of aspirin has recently been shown to result in a more potent, gastrointestinal-sparing antithrombotic drug. Two such compounds (NCX-4215 and NCX-4016; NicOx SA) have undergone detailed evaluation thus far. In each case, the NO-aspirin has shown improved anti-aggregatory activity while not inducing detectable gastric damage. The compounds have also been shown to exert protective effects in the gastrointestinal tract exposed to other injurious agents. The NO-aspirin derivatives significantly inhibit leukocyte adherence to the vascular endothelium, which may contribute to their anti-thrombotic activity. NO-releasing derivatives of aspirin and naproxen also exhibit beneficial effects in experimental hypertension, which would also contribute to improved anti-thrombotic activity. NO-releasing derivatives of NSAIDs offer great potential as gastrointestinal-sparing anti-thrombotic drugs. PMID:16158351

  4. In vitro antithrombotic activities of peanut protein hydrolysates.

    PubMed

    Zhang, Shao Bing

    2016-07-01

    The antithrombotic activities of peanut protein hydrolysates were investigated using a microplates assay. When peanut proteins were hydrolyzed to a limited extent by various enzymes, their thrombin inhibitory abilities were significantly enhanced. However, the resultant hydrolysates showed significantly different activities even at the same degrees of hydrolysis. The hydrolysates generated by Alcalase 2.4L displayed the best antithrombotic activities and the hydrolysis process was further optimized by response surface methodology. The antithrombotic activities were increased to 86% based on a protein concentration of 50mg/ml under the optimal conditions: pH 8.5, enzyme concentration of 5000IU/g of peanut proteins, and 2h hydrolysis time at 50°C. The Alcalase 2.4L crude hydrolysates were then fractionated successively by preparative and semi-preparative reverse-phase high-performance liquid chromatography (RP-HPLC). The peptide fraction collected inhibited thrombin-catalyzed coagulation of fibrinogen completely at a concentration of 0.4mg/ml, with an antithrombotic activity close to that of heparin at quite a low concentration (0.2mg/ml). This peptide fraction was further analyzed by online reverse-phase ultra-performance liquid chromatography (RP-UPLC) coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and three new peptides were identified as Ser-Trp-Ala-Gln-Leu, Gly-Asn-His-Glu-Ala-Gly-Glu and Cys-Phe-Asn-Glu-Tyr-Glu, respectively. This research provided an effective way to produce antithrombotic peptides from peanut proteins, and also helped to elucidate the structure-function relationships of peanut peptides. PMID:26920259

  5. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08.

    PubMed

    Hitz, Felicitas; Zucca, Emanuele; Pabst, Thomas; Fischer, Natalie; Cairoli, Anne; Samaras, Panagiotis; Caspar, Clemens B; Mach, Nicolas; Krasniqi, Fatime; Schmidt, Adrian; Rothermundt, Christian; Enoiu, Milica; Eckhardt, Katrin; Berardi Vilei, Simona; Rondeau, Stephanie; Mey, Ulrich

    2016-07-01

    An increasing number of older patients are suffering from aggressive lymphoma. Effective and more tolerable treatment regimens are urgently needed for this growing patient population. Patients with aggressive lymphoma not eligible for anthracycline-based first-line therapy or intensive salvage regimens were treated with the rituximab-bendamustine-lenalidomide (R-BL) regimen (rituximab 375 mg/m(2)  day 1, bendamustine 70 mg/m(2)  d 1, 2, lenalidomide 10 mg d 1-21) for six cycles every 4 weeks. Forty-one patients with a median age of 75 (range 40-94) years were enrolled: 33 patients had substantial co-morbidities. 13 patients were not eligible for anthracycline-based first-line chemotherapy, 28 patients had relapsed/refractory disease. The primary endpoint, overall response, was achieved by 25 (61%) patients (95% confidence interval 45-76%). Grade ≥ 3 toxicity comprised haematological (59%), skin (15%), constitutional (15%) and neurological (12%) events. 9 patients died during trial treatment: 5 from lymphoma progression, 2 from toxicity, 2 with sudden death. After a median follow-up of 25·9 (interquartile range 20·4-31·6) months, 13 patients were still alive. Median overall survival was 14·5 months. In conclusion, R-BL can be considered a treatment option for elderly patients with treatment naïve or relapsed/refractory aggressive lymphoma not eligible for standard aggressive regimens. PMID:27018242

  6. Patient's Guide to Antithrombotic Therapy in Atrial Fibrillation

    MedlinePlus

    ... tests to measure the drugs’ blood thinning e ects (measured using the international nomalized ratio [INR]) to ... is the INR?”and “What factors can a ect INR control?” X Dabigatran (Pradaxa) and Rivaroxban (Xarelto) ...

  7. Safe use of antithrombotics for stroke prevention in atrial fibrillation: consideration of risk assessment tools to support decision-making

    PubMed Central

    Bajorek, Beata

    2014-01-01

    Clinical guidelines advocate stroke prevention therapy in atrial fibrillation (AF) patients, specifically anticoagulation. However, the decision to initiate treatment is based on the risk (bleeding) versus benefit (prevention of stroke) of therapy, which is often difficult to assess. This review identifies available risk assessment tools to facilitate the safe and optimal use of antithrombotic therapy for stroke prevention in AF. Using key databases and online clinical resources to search the literature (1992–2012), 19 tools have been identified and published to date: 11 addressing stroke risk, 7 addressing bleeding risk and 1 integrating both risk assessments. The stroke risk assessment tools (e.g. CHADS2, CHA2DS2-VASc) share common risk factors: age, hypertension, previous cerebrovascular attack. The bleeding risk assessment tools (e.g. HEMORR2HAGES, HAS-BLED) share common risk factors: age, previous bleeding, renal and liver impairment. In terms of their development, six of the stroke risk assessment tools have been derived from clinical studies, whilst five are based on refinement of existing tools or expert consensus. Many have been evaluated by prospective application to data from real patient cohorts. Bleeding risk assessment tools have been derived from trials, or generated from patient data and then validated via further studies. One identified tool (i.e. Computerised Antithrombotic Risk Assessment Tool [CARAT]) integrates both stroke and bleeding, and specifically considers other key factors in decision-making regarding antithrombotic therapy, particularly those increasing the risk of medication misadventure with treatment (e.g. function, drug interactions, medication adherence). This highlights that whilst separate tools are available to assess stroke and bleeding risk, they do not estimate the relative risk versus benefit of treatment in an individual patient nor consider key medication safety aspects. More effort is needed to synthesize these

  8. Antithrombotic effects of bromophenol, an alga-derived thrombin inhibitor

    NASA Astrophysics Data System (ADS)

    Shi, Dayong; Li, Xiaohong; Li, Jing; Guo, Shuju; Su, Hua; Fan, Xiao

    2010-01-01

    Thrombin, the ultimate proteinase of the coagulation cascade, is an attractive target for the treatment of a variety of cardiovascular diseases. A bromophenol derivative named (+)-3-(2,3-dibromo-4, 5-dihydroxy-phenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroiso-benzofuran 1, isolated from the brown alga Leathesia nana exhibited significant thrombin inhibitory activity. In this study, we investigated the inhibition of human thrombin in vitro with this bromophenol derivative, and its antithrombotic efficacy in vivo using the arteriovenous shunt model and the ferric chloride-induced arterial thrombosis model in rats. The results show that the bromophenol derivative is a potential inhibitor of thrombin (IC50=1.03 nmol/L). In antithrombotic experiments in vivo, the bromophenol derivative also shows good effect comparing with the control group. These data indicate that the bromophenol derivative is a potential drug for prophylaxis and the treatment of thrombotic diseases.

  9. The future of glycoprotein VI as an antithrombotic target.

    PubMed

    Zahid, M; Mangin, P; Loyau, S; Hechler, B; Billiald, P; Gachet, C; Jandrot-Perrus, M

    2012-12-01

    The treatment of acute coronary syndromes has been considerably improved in recent years with the introduction of highly efficient antiplatelet drugs. However, there are still significant limitations: the recurrence of adverse vascular events remains a problem, and the improvement in efficacy is counterbalanced by an increased risk of bleeding, which is of particular importance in patients at risk of stroke. One of the most attractive targets for the development of new molecules with potential antithrombotic activity is platelet glycoprotein (GP)VI, because its blockade appears to ideally combine efficacy and safety. This review summarizes current knowledge on GPVI regarding its structure, its function, and its role in physiologic hemostasis and thrombosis. Strategies for inhibiting GPVI are presented, and evidence of the antithrombotic efficacy and safety of GPVI antagonists is provided. PMID:23020554

  10. Two new compounds from Crataegus pinnatifida and their antithrombotic activities.

    PubMed

    Zhou, Chen-Chen; Huang, Xiao-Xiao; Gao, Pin-Yi; Li, Fei-Fei; Li, Dian-Ming; Li, Ling-Zhi; Song, Shao-Jiang

    2014-01-01

    One new sesquiterpene, (1α,4aβ,8aα)-1-isopropanol-4a-methyl-8-methylenedecahydronaphthalene (1), with one new phenylpropanoid, threo-2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol (2), along with four known phenylpropanoids were isolated from Crataegus pinnatifida. The structures of compounds 1 and 2 were elucidated on the basis of 1D, 2D NMR analyses, and HR-ESI-MS. The antithrombotic activity in vitro of all isolates was assayed, and only compound 1 exhibited potent antithrombotic activity by inhibiting platelet aggregation in rat plasma by 81.4% at 1 mg/ml. PMID:24161196

  11. Hydroxychloroquine as an anti-thrombotic in antiphospholipid syndrome.

    PubMed

    Belizna, Cristina

    2015-04-01

    Elective therapeutic approaches are required since recurrent thrombosis remains a major challenge in the management of antiphospholipid syndrome (APS) despite an efficient anticoagulation. Several data suggest that hydroxychloroquine (HCQ) could play a role in the prevention of thrombosis. The goal of this review is to point out the different aspects that could suggest the usefulness and the efficacy of HCQ for the prevention of thrombosis relapse in APS. By Medline research we collected important data dealing with potential anti-thrombotic effects of HCQ. The mechanisms of action of HCQ, and clinical and experimental data in systemic lupus erythematosus (SLE) and APS are discussed. As HCQ reduces the risk of thrombosis in both SLE patients and animal models of APS (1-7), and possibly decreases the titre of aPL [8], its beneficial role as a potential antithrombotic could be suggested. PMID:25534016

  12. Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron Radiation Therapy Combined with Aggressive Anterior Surgical Resection for Retroperitoneal Sarcomas

    PubMed Central

    Yoon, Sam S.; Chen, Yen-Lin; Kirsch, David G.; Maduekwe, Ugwuji N.; Rosenberg, Andrew E.; Nielsen, G. Petur; Sahani, Dushyant V.; Choy, Edwin; Harmon, David C.; DeLaney, Thomas F.

    2010-01-01

    Background We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection. Methods Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin. Results Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence. Conclusions Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease. PMID:20151216

  13. Antithrombotic Treatments for Stroke Prevention in Elderly Patients With Nonvalvular Atrial Fibrillation: Drugs and Doses.

    PubMed

    Kilickap, Mustafa; Bosch, Jackie; Eikelboom, John W; Hart, Robert G

    2016-09-01

    Atrial fibrillation (AF) is a common cardiac rhythm disturbance and is associated with a 5-fold increased risk of stroke. The most important risk factors for stroke in patients with AF are previous stroke and age ≥ 75 years. Canadian guidelines recommend anticoagulant therapy for patients with AF who are older than the age of 65 years, but the elderly often remain undertreated, primarily because of concerns regarding bleeding. Non-vitamin K oral anticoagulants appear to be safer, at least as efficacious, and more convenient than warfarin, and are a cost-effective alternative for elderly patients with AF. We review the evidence for the use of antithrombotic agents for stroke prevention in elderly patients (age ≥ 75 years) with nonvalvular AF. PMID:27568871

  14. A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs.

    PubMed

    Zhu, Xiao-Yu; Liu, Hong-Cui; Guo, Sheng-Ya; Xia, Bo; Song, Ru-Shun; Lao, Qiao-Cong; Xuan, Yao-Xian; Li, Chun-Qi

    2016-08-01

    Thrombosis is a leading cause of death and the development of effective and safe therapeutic agents for thrombotic diseases has been proven challenging. In this study, taking advantage of the transparency of larval zebrafish, we developed a larval zebrafish thrombosis model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days post fertilization) were treated with phenylhydrazine (PHZ) and a testing drug for 24 h. Tested drugs were administered into the zebrafish either by direct soaking or circulation microinjection. Antithrombotic efficacy was quantitatively evaluated based on our previously patented technology characterized as an image analysis of the heart red blood cells stained with O-dianisidine staining. Zebrafish at 2 dpf treated with PHZ at a concentration of 1.5 μM for a time period of 24 h were determined as the optimum conditions for the zebrafish thrombosis model development. Induced thrombosis in zebrafish was visually confirmed under a dissecting stereomicroscope and quantified by the image assay. All 6 human antithrombotic drugs (aspirin, clopidogrel, diltiazem hydrochloride injection, xuanshuantong injection, salvianolate injection, and astragalus injection) showed significant preventive and therapeutic effects on zebrafish thrombosis (p < 0.05, p < 0.01, & p < 0.001) in this zebrafish thrombosis model. The larval zebrafish thrombosis model developed and validated in this study could be used for in vivo thrombosis studies and for rapid screening and efficacy assessment of antithrombotic drugs. PMID:27333081

  15. Evaluation of antithrombotic effect: Importance of testing components and methodologies.

    PubMed

    Yamamoto, Junichiro; Tamura, Yukinori; Ijiri, Yoshinobu; Iwasaki, Masahiro; Murakami, Masahiro; Matsuo, Osamu

    2015-08-01

    The beneficial antithrombotic effect of some dietary components may offer the most promising approach of prevention of cardiovascular diseases and arterial thrombosis. The major stumbling block in finding effective dietary components is the lack of physiologically relevant techniques which can detect potential antithrombotic effect in humans. The presently used platelet function and coagulation tests do not allow the assessment of global thrombotic status and their value in screening dietary components for antithrombotic effect is questionable. Most of these in vitro tests ignore the effect of flow and shear stress, thrombin generation and vascular endothelium, the major contributors to arterial thrombogenesis in humans. As a gold standard, we employed the helium-neon (He-Ne) laser-induced thrombosis test in murine carotid artery and mesenteric microvessels, as the pathomechanism of this test closely reflects arterial thrombogenesis in humans. Results obtained with laser thrombosis test were compared with various shear-induced in vitro platelet function tests which use native blood (Haemostatometry, Thrombotic Status Analyser, Global Thrombosis Test-GTT). Contribution of vascular endothelium to thrombogenesis was assessed by measuring flow-mediated vasodilation (FMV) in vivo. The combination of the two shear-induced ex vivo thrombosis tests (Haemostatometry and GTT) with FMV correlated most closely with the laser-thrombosis test. Our findings suggest that combining the commercially available point-of-care GTT with the FMV test could provide a better assessment of the overall thrombotic status than either of the two tests alone. PMID:26370524

  16. Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients

    PubMed Central

    Klein Hesselink, E.N.; Links, T.P.

    2015-01-01

    Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine. PMID:26279993

  17. Antithrombotic Medication for Cardioembolic Stroke Prevention

    PubMed Central

    Font, M. Àngels; Krupinski, Jerzy; Arboix, Adrià

    2011-01-01

    Embolism of cardiac origin accounts for about 20% of ischemic strokes. Nonvalvular atrial fibrillation is the most frequent cause of cardioembolic stroke. Approximately 1% of population is affected by atrial fibrillation, and its prevalence is growing with ageing in the modern world. Strokes due to cardioembolism are in general severe and prone to early recurrence and have a higher long-term risk of recurrence and mortality. Despite its enormous preventive potential, continuous oral anticoagulation is prescribed for less than half of patients with atrial fibrillation who have risk factors for cardioembolism and no contraindications for anticoagulation. Available evidence does not support routine immediate anticoagulation of acute cardioembolic stroke. Anticoagulation therapy's associated risk of hemorrhage and monitoring requirements have encouraged the investigation of alternative therapies for individuals with atrial fibrillation. New anticoagulants being tested for prevention of stroke are low-molecular-weight heparins (LMWH), unfractionated heparin, factor Xa inhibitors, or direct thrombin inhibitors like dabigatran etexilate and rivaroxaban. The later exhibit stable pharmacokinetics obviating the need for coagulation monitoring or dose titration, and they lack clinically significant food or drug interaction. Moreover, they offer another potential that includes fixed dosing, oral administration, and rapid onset of action. There are several concerns regarding potential harm, including an increased risk for hepatotoxicity, clinically significant bleeding, and acute coronary events. Therefore, additional trials and postmarketing surveillance will be needed. PMID:21822469

  18. Effect of Surgical Periodontal Therapy on Serum C-reactive Protein Levels Using ELISA in Both Chronic and Aggressive Periodontitis Patient

    PubMed Central

    Gupta, Bharat; Patil, Neha; Yadav, Manoj; Tripathi, Shashank; Sinha, Saurabh; Sharma, Saurabh; Gupta, Saurabh

    2015-01-01

    Background Periodontitis can be defined as a local inflammatory process which mediates destruction of periodontal tissues & is triggered by bacterial insult. In periodontal infections, the levels of C reactive proteins are elevated as compared to the levels in a periodontally healthy individual. The study was done to determine the relative levels of serum CRP in aggressive, chronic and periodontally healthy subjects and to evaluate the effect of surgical periodontal therapy on serum C-reactive protein levels. Materials and Methods Serum samples were collected from 150 participants (50 healthy control patients (non-periodontitis), 50 patients with chronic periodontitis and aggressive periodontitis. Serum C- reactive protein levels were assessed by means of immunoturbidimetric assay at baseline for subjects in all the 3 groups and 3 months after completion of surgical therapy. Results The mean baseline C-reactive protein (CRP) concentrations in the Groups I, II and III were 1.65±0.57 mg/L, 3.03±2.14 mg/L and 3.09±2.27 mg/L respectively. After treatment, the mean C-reactive protein (CRP) levels in Groups II and III reduced from 3.03±1.67 mg/L to 1.46±1.67 mg/L and from 3.09±1.21 to 1.43±1.21 mg/L respectively. Similar results were found for probing depth and all indexes in Group II and III after treatment. Also, the mean attachment loss in Groups II and III reduced, so the results were highly significant. Conclusion Successful periodontal treatment results in significant decrease in serum C-reactive protein (CRP) levels in otherwise healthy subjects. PMID:26557605

  19. Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials

    PubMed Central

    Subbiah, Ishwaria M.; Falchook, Gerald S.; Kaseb, Ahmed O.; Hess, Kenneth R.; Tsimberidou, Apostolia M.; Fu, Siqing; Subbiah, Vivek; Hong, David S.; Naing, Aung; Sarina, A. Piha-Paul; Akmal, Owais; Janku, Filip; Kurzrock, Razelle

    2015-01-01

    PURPOSE Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapeutic options. Given the rapid advanced in drug development and emergence of novel agents, we analyzed the characteristics and outcomes of HCC patients treated on early phase trials with an emphasis on targeted therapies. METHODS We reviewed the records of consecutive HCC patients evaluated in the Phase I Clinical Trials Program at MD Anderson from March 2004. RESULTS Thirty-nine patients were not treated due to poor performance status (n = 22, 56%) and decision to pursue alternate therapies (n = 10, 27%). Of 61 treated patients (median age, 60 years; median prior therapies, 3), eight patients (13%) attained stable disease lasting ≥6 months; four (7%) had a partial response, mainly with anti-angiogenic or multikinase inhibitors. Median Phase I progression-free survival (PFS) was 2.6 months versus 4.4 months (p 0.019) and 4.1 months (p 0.27) for their first-, and second-line FDA-approved therapy. Molecular analysis showed frequent PTEN loss (10/19 patients, 53%) and P53 mutation (4/4 patients tested). On multivariate analysis, independent factors predicting shorter survival were white ethnicity/race (p 0.031), cirrhosis (p 0.016), and serum sodium (p 0.0013). CONCLUSIONS In our heavily-pretreated HCC patients, the phase I PFS was comparable to that of 2nd-line therapy, highlighting a potential role for clinical trials after progression on first-line therapy. The response rate (SD>6 months/PR) of 20% was observed with early signals of activity in regimens combining inhibitors of angiogenesis, multiple kinases and mTOR with preliminary molecular analysis revealing prevalence of PTEN loss. PMID:26164085

  20. Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges.

    PubMed

    Serebruany, Victor L; Cherepanov, Vasily; Cabrera-Fuentes, Hector A; Kim, Moo Hyun

    2015-11-25

    The role of anticoagulants and antiplatelet agents in tumour growth and prognosis is not new, and currently under intense investigation. Some randomised data strongly suggest that this association exists, but it is complex, and not necessarily pointed at the same direction. The potential mechanisms responsible for such harmful association include a direct hazard of novel antithrombotics on cancer, indirect promotion of tumour growth, easier metastatic dissemination due to instability of platelet-tumour cell aggregates, or/and inability to keep cancer cells locally in situ are considered. The latest randomised evidence ultimately rejected the drug-specific cancer risks, clearly indicating the class-effect. In lay terms "cancers follow bleeding", which seems to be true for antithrombotic agents in general. Significant excess of solid cancers which was similar after prasugrel in TRITON, and with vorapaxar in TRACER trials was confirmed by the FDA reviews. Later, extra cancer deaths reported following clopidogrel and prasugrel in DAPT, and after ticagrelor in PEGASUS are also of concern. However, there are remaining controversies with regard to published cancer risks after ticagrelor (PLATO), or another vorapaxar trial (TRA2P), while full disclosure of separate clopidogrel and prasugrel cancer data in DAPT is still lacking. In short, if we apply moderate antiplatelet strategies for over two years, or aggressive regimens including triple therapy for much less than one year, the solid cancer risks emerge. Currently, more delicate platelet inhibition, and shorter exposure to dual oral antiplatelet agents should prevail. PMID:26559427

  1. On the mechanism of antithrombotic action of flavonoids.

    PubMed

    Gryglewski, R J; Korbut, R; Robak, J; Swies, J

    1987-02-01

    Flavonols (quercetin and rutin) and flavanes (cyanidol and meciadonol) were studied for their effect on non-enzymatic lipid peroxidation, lipoxygenase and cyclo-oxygenase activities, binding to albumin and platelet membranes. These biochemical properties of four flavonoids were compared with respect to their antithrombotic action in vivo and their efficacy at influencing the platelet-endothelium interaction in vitro. All four flavonoids inhibited the ascorbate-stimulated formation of malondialdehyde by boiled rat liver microsomes (quercetin greater than rutin approximately cyanidol approximately meciadonol) and inhibited platelet lipoxygenase activity (quercetin greater than cyanidol greater than meciadonol greater than rutin) whereas only flavonols, but not flavanes, stimulated cyclo-oxygenase and were bound to platelet membranes. The same two flavonols dispersed platelet thrombi which were adhering to the rabbit aortic endothelium in vitro (EC50 for quercetin was 80 nM and for rutin 500 nM) and prevented platelets from aggregation over blood-superfused collagen strip in vivo (ED50 for quercetin was 5 nmol/kg and for rutin 33 nmol/kg i.v.). Cyanidol and meciadonol were not effective as anti-thrombotic agents. It is concluded that activated platelets adhering to vascular endothelium generate lipid peroxides and oxygen-free radicals which inhibit endothelial biosynthesis of prostacyclin and destroy endothelium-derived relaxing factor (EDRF). Flavonols are anti-thrombotic because they are selectively bound to mural platelet thrombi and owing to their free radical scavenging properties resuscitate biosynthesis and action of endothelial prostacyclin and EDRF. Thus, flavonols release the thrombolytic and vasoprotective endothelial mediators only in these vascular segments which are covered by a carpet of aggregating platelets. PMID:3101704

  2. IL12 and IL27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors1

    PubMed Central

    Zhu, Shiguo; Lee, Dean Anthony; Li, Shulin

    2010-01-01

    Eradication of residual malignancies and metastatic tumors via a systemic approach is the key for successfully treating cancer and increasing the cancer patient survival. Systemic administration of IL12 protein in an acute large dose is effective but toxic. Systemic administration of IL12 gene by persistently expressing a low level of IL12 protein may reduce the systemic toxicity, but only eradicates IL12 sensitive tumors. Here, we discovered that sequential administration of IL12 and IL27 encoding DNA, referred to as sequential IL12-IL27 gene therapy, not only eradicated IL12 sensitive tumors from 100% of mice but also eradicated the highly malignant 4T1 tumors from 33% of treated mice in multiple independent experiments. This IL12-IL27 sequential gene therapy is not only superior to IL12-IL12 sequential gene therapy for eliminating tumors, but also for inducing CTL activity, increasing T cell infiltration into tumors, and yielding a large number of tumor-specific IFNγ positive CD8 T cells. Notably, depletion of either T- or NK-cells during the IL27 treatment phase reverses tumor eradication, suggesting an NK-cell requirement for this sequential gene therapy-mediated tumor eradication. Both reversal of the administration sequence and co-administration of IL12 and IL27 impaired the tumor eradication in 4T1 tumor bearing mice. This IL12-IL27 sequential gene therapy, via sequential administration of IL12 and IL27 encoding plasmid DNA into tumor-bearing mice through intramuscular electroporation, provides a simple but effective approach for eliminating inaccessible residual tumors. PMID:20139275

  3. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma.

    PubMed

    Zoellner, A-K; Fritsch, S; Prevalsek, D; Engel, N; Hubmann, M; Reibke, R; Rieger, C T; Hellmuth, J C; Haas, M; Mumm, F; Herold, T; Ledderose, G; Hiddemann, W; Dreyling, M; Hausmann, A; Tischer, J

    2015-05-01

    Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory. PMID:25642765

  4. Study on antithrombotic and antiplatelet activities of low molecular weight fucoidan from Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue

    2012-06-01

    The antithrombotic and antiplatelet effects of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica were compared in order to examine the influence of chemical character on their antithrombotic activity and the possible mechanism. Both LMW fucoidan fractions exhibited favorable antithrombotic activity in an Fecl3-induced arterial thrombosis. The antithrombotic activity of LMW fucoidan was related with decrease of TXB2 and whole blood viscosity and hematocrit. LMW fucoidan showed a correlation between anticoagulant, antiaggregant and antithrombotic effects in vivo. For LMW fucoidan, antithrombotic activity required high dose of 5-10 nmol kg-1, concomitantly with increase in anticoagulant activity and inhibition of platelet aggregation. Administration of LMW fucoidan significantly promoted the 6-keto-PGF1α content and decreased the TXB2 content, indicating its inhibition of tissue factor pathway and regulation of metabolism of arachidonic acid. By comparison, highly sulfated fucoidan LF2 with Mw 3900 seemed to be a more suitable choice for antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic risk in vivo.

  5. Newer clinically available antithrombotics and their antidotes.

    PubMed

    Lévy, Samuel

    2014-09-01

    New oral anticoagulants (NOACs) have emerged as an alternative therapy to warfarin in the treatment of arterial and venous thromboembolism and in stroke prevention in patients with non-valvular atrial fibrillation (AF). Three of them, i.e., dabigatran, rivaroxaban, and apixaban, have been approved for clinical use in North America and in a number of European countries. In non-valvular AF, their approval was based on large randomized trials showing that they are non-inferior or even, in some instances, superior to warfarin. Dabigatran is a direct thrombin (factor IIa) inhibitor; rivaroxaban and apixaban are direct factor Xa inhibitors. Before using NOACs, it is recommended to become familiar with their pharmacological characteristics and their metabolism. The absence of specific antidotes is often cited as part of the possible weaknesses of NOACs. Antidotes are perceived to be useful in emergency situations such as life-threatening bleeding or non-elective major surgery. NOACs do not require blood monitoring, and therefore, patient compliance to the treatment is essential. For the present time, there are no specific antidotes available for the three NOACs approved for clinical use. However, phase I or phase II research studies in this area are ongoing. For dabigatran, a specific antidote has been tested in a rat model of anticoagulation, and a study in healthy male volunteers has been recently reported. For rivaroxaban, prothrombin complex concentrates (PCCs) have been found to completely reverse the prolongation of the prothrombin time induced by this NOAC. For apixaban, recombinant factor VII was found in an experimental study using human blood to be superior to activated PCC (aPCC) and PCC. More specific antidotes for rivaroxaban and apixaban are in phases I and II evaluation. The management of patients suffering from a major bleeding or requiring a non-elective major surgery includes non-specific reversal agents and is discussed in the light of a recent position

  6. Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, Tanin; Bunworasate, Udomsak; Nakorn, Thanyaphong Na; Rojnuckarin, Ponlapat

    2006-07-01

    With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5

  7. Antithrombotic activity of Vitis labrusca extract on rat platelet aggregation.

    PubMed

    Kwon, Se-Uk; Lee, Hoon-Yeon; Xin, Mingjie; Ji, Su-Jeong; Cho, Hyoung-Kwon; Kim, Dae-Sung; Kim, Dae-Ki; Lee, Young-Mi

    2016-03-01

    Vitis labrusca is a grapevine that has antioxidant, neuroprotective, hepatoprotective, and anticarcinogenic activity. However, the antithrombotic effect of Vitis labrusca leaves on platelets is yet to be ascertained. We investigated the inhibitory effect of V. labrusca leaf extract (VLE) on platelet aggregation in vitro and ex vivo. The thromboxane B2 (TXB2) and serotonin concentrations were measured by ELISA. The flavonoids content was measured by ultraperformance liquid chromatography (UPLC). The antithrombotic activity of VLE was evaluated using various agonists in vitro. VLE strongly inhibited adenosine diphosphate (ADP)-induced platelet aggregation. In rats, VLE treatment (100 mg/kg) reduced ADP-stimulated platelet aggregation, without affecting tail bleeding and coagulation time. Moreover, VLE significantly suppressed TXB2 and serotonin secretion. UPLC analysis indicated that VLE contains quercetin, isorhamnetin, and rutin. Our results indicate that VLE possesses antiplatelet activity via the suppression of TXB2 and serotonin, without affecting bleeding. Further, we identified the flavonoids present in VLE. Thus, VLE may be a potential agent for the prevention of cardiovascular diseases. PMID:26340455

  8. Downstream Processing, Formulation Development and Antithrombotic Evaluation of Microbial Nattokinase.

    PubMed

    Kapoor, Rohit; Harde, Harshad; Jain, Sanyog; Panda, Amulya Kumar; Panda, Bibhu Prasad

    2015-07-01

    The present research work describes the downstreaming of nattokinase (NK) produced by Bacillus subtilis under solid state fermentation; and the role of efficient oral formulation of purified NK in the management of thrombotic disorders. Molecular weight of purified NK was estimated to be 28 kDa with specific activity of 504.4 FU/mg. Acid stable nattokinase loaded chitosan nanoparticles (sNLCN) were fabricated for oral delivery of this enzyme. Box-Behnken design (BBD) was employed to investigate and validate the effect of process (independent) variables on the quality attributes (dependent variables) of nanoparticles. The integrity, conformational stability and preservation of fibrinolytic activity of NK (in both free and sNLCN forms) were established by SDS-PAGE, CD analysis and in vitro clot lytic examination, respectively. A 'tail thrombosis model' demonstrated significant decrease in frequency of thrombosis in Wistar rats upon peroral administration of sNLCN in comparison with negative control and free NK group. Furthermore, coagulation analysis, namely the measurement of prothrombin and activated partial thromboplastin time illustrated that sNLCN showed significantly (p < 0.001) higher anti-thrombotic potential in comparison to the free NK. Further, sNLCN showed anti-thrombotic profile similar to warfarin. This study signifies the potential of sNLCN in oral delivery of NK for the management of thrombotic disorders. PMID:26307844

  9. Antiplatelet, Antithrombotic, and Fibrinolytic Activities of Campomanesia xanthocarpa

    PubMed Central

    Klafke, Jonatas Zeni; Arnoldi da Silva, Mariane; Fortes Rossato, Mateus; Trevisan, Gabriela; Banderó Walker, Cristiani Isabel; Martins Leal, Cláudio Alberto; Olschowsky Borges, Diego; Chitolina Schetinger, Maria Rosa; Noal Moresco, Rafael; Medeiros Frescura Duarte, Marta Maria; Soares dos Santos, Adair Roberto; Nazário Viecili, Paulo Ricardo; Ferreira, Juliano

    2012-01-01

    In a previous work based on popular belief, Campomanesia xanthocarpa Berg., popularly known as “guavirova”, showed to have a potential effect in the control of a number of conditions associated with cardiovascular diseases. The aim of the present work was to investigate the effects of C. xanthocarpa extract (CXE) on antiplatelet, antithrombotic and fibrinolytic activities in mice and in human blood. Mice were treated orally for 5 days with CXE or acetylsalicylic acid and at the end of the treatment period animals were challenged for bleeding, acute thromboembolism and ulcerogenic activity. In addition, we have assessed the prothrombin time and activated partial thromboplastin time (aPTT) after oral administration. In in vitro assays, antiplatelet effects of CXE was evaluated on platelet aggregation, and fibrinolytic activity of the extract was observed by mice or human artificial blood clot degradation. Platelet citotoxicity of the extract was also determined by the LDH assay. Results demonstrated that CXE has a significant protective effect on thrombosis. It also inhibits platelet aggregation without demonstrating cytotoxicity on platelets. CXE slightly prolonged aPTT and showed no ulcerogenic activity after oral administration. In addition, CXE showed a fibrinolytic activity. Thus, C. xanthocarpa showed antiplatelet, antithrombotic and fibrinolytic activities in mice. PMID:21915188

  10. Antithrombotic Effects of Amaranthus hypochondriacus Proteins in Rats.

    PubMed

    Sabbione, Ana Clara; Rinaldi, Gustavo; Añón, María Cristina; Scilingo, Adriana A

    2016-03-01

    Cardiovascular disease (CVD) is a major cause of disability and premature death throughout the world. Diets with antithrombotic components offer a convenient and effective way of preventing and reducing CVD incidence. The aim of the present work was to assess in vivo and ex vivo effects of Amaranthus hypochondriacus proteins on platelet plug formation and coagulation cascade. Amaranth proteins were orally administrated to rats (AG, 8 animals) and bleeding time was determined showing no significant difference compared with control rats (CG, 7 animals). However, results show a strong tendency, suggesting that amaranth proteins are involved in the inhibition of thrombus formation. Non-anticoagulated blood extracted from animals was analyzed with the hemostatometer, where AG parameters obtained were twice the values showed by CG. The clotting tests, thrombin time (TT) and activated partial thromboplastin time (APTT), presented a 17 and 14% clotting formation increase respectively when comparing AG with CG. The ex-vivo assays confirm the hypothesis inferring that amaranth proteins are a potential antithrombotic agent. PMID:26627100

  11. Antithrombotic functions of small molecule-capped gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Tian, Yue; Zhao, Yuyun; Zheng, Wenfu; Zhang, Wei; Jiang, Xingyu

    2014-07-01

    Here we report the antithrombotic functions of pyrimidinethiol-capped gold nanoparticles (Au_DAPT NPs). They can prolong coagulation parameters when injected intravenously in normal mice. Applied in two typical thrombosis models, mice tail thrombosis and pulmonary thromboembolism, gold NPs can inhibit both thrombosis and improve the survival rates of mice tremendously, without increasing the bleeding risk. The anticoagulant mechanisms include inhibiting the platelet aggregation as well as interfering with thrombin and fibrin generation.Here we report the antithrombotic functions of pyrimidinethiol-capped gold nanoparticles (Au_DAPT NPs). They can prolong coagulation parameters when injected intravenously in normal mice. Applied in two typical thrombosis models, mice tail thrombosis and pulmonary thromboembolism, gold NPs can inhibit both thrombosis and improve the survival rates of mice tremendously, without increasing the bleeding risk. The anticoagulant mechanisms include inhibiting the platelet aggregation as well as interfering with thrombin and fibrin generation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01937g

  12. Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

    PubMed Central

    2012-01-01

    Background Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best-practice model that applies major elements of case management and patient education, can improve antithrombotic management in primary healthcare in terms of reducing major thromboembolic and bleeding events. Methods This 24-month cluster-randomized trial will be performed with 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, healthcare assistants, and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, healthcare assistants will be trained in case management and will use the Coagulation-Monitoring List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment as usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life, and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients’ assessment of chronic illness care, self-reported adherence to medication, general practitioners’ and healthcare assistants’ knowledge, and patients’ knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible

  13. The role of comprehensive geriatric assessment and functional status in evaluating the patterns of antithrombotic use among older people with atrial fibrillation.

    PubMed

    Mazzone, A; Bo, M; Lucenti, A; Galimberti, S; Bellelli, G; Annoni, G

    2016-01-01

    Aim of the study is to investigate the use of antithrombotic drugs in older patients with atrial fibrillation (AF) at the time of hospital discharge. We enrolled 399 ≥65 years old patients with AF consecutively admitted to our acute geriatric unit from September 2012 to February 2014. Utilization of antithrombotic drugs, comorbidities, functional, mental and nutritional status were evaluated through a comprehensive geriatric assessment (CGA). A Logistic regression model was used to assess variables associated with antithrombotic use. On admission, 198 patients (49.6%) used oral anticoagulants (OAC), 125 (21.3%) antiplatelets, 32 (8%) low weight molecular heparin (LMWH) and 44 (11%) none of them. At discharge the proportion of patients on OAC increased to 55.7%. Age>90years (OR=2.57, CI=1.28-5.16, p-value=0.008), severe functional impairment (OR=3.38, CI=1.63-7.01, p-value=0.001), polypharmacy (OR=2.07, CI=1.1-3.86, p-value=0.023), HAS-BLED score (OR=1.64, CI=1.09-2.47, p-value=0.019) and ≥1 OAC contraindication (OR=5.01, CI=2.68-9.34, p-value<0.001) were all associated with OAC underuse. In conclusion, OAC is underused in geriatric patients with AF, while antiplatelet, LMWH and no antithrombotic therapy are relatively overused. Factors associated with the decision to not prescribe OAC lie on a mix of clinical and geriatric variables, among which functional status is particularly relevant. PMID:27131228

  14. Antithrombotic treatment in elderly patients with atrial fibrillation.

    PubMed

    Suárez Fernández, C; Camafort, M; Cepeda Rodrigo, J M; Díez-Manglano, J; Formiga, F; Pose Reino, A; Tiberio, G; Mostaza, J M

    2015-04-01

    Atrial fibrillation (AF) in the elderly is a complex condition due to the high number of frequently associated comorbidities, such as cardiovascular and kidney disease, cognitive disorders, falls and polypharmacy. Except when contraindicated, anticoagulation is necessary for preventing thromboembolic events in this population. Both vitamin K antagonists and direct oral anticoagulants (dabigatran, rivaroxaban and apixaban) are indicated in this context. Renal function should be closely monitored for this age group when these drugs are used. In recent years, various clinical practice guidelines have been published on patients with AF. The majority of these guidelines make specific recommendations on the clinical characteristics and treatment of elderly patients. In this update, we review the specific comments on the recommendations concerning antithrombotic treatment in elderly patients with nonvalvular AF. PMID:25618495

  15. Recombinant Protein Production of Earthworm Lumbrokinase for Potential Antithrombotic Application

    PubMed Central

    Wang, Kevin Yueju; Wang, Nan; Liu, Dehu

    2013-01-01

    Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered as a potent and effective supplement for supporting healthy blood circulation. Lumbrokinases are a group of enzymes that were isolated and purified from different species of earthworms. These enzymes are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Many lumbrokinase (LK) genes have been cloned and characterized. Advances in genetic technology have provided the ability to produce recombinant LK and have made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic application. In this review, we focus on expression systems that can be used for lumbrokinase production. In particular, the advantages of using a transgenic plant system to produce edible lumbrokinase are described. PMID:24416067

  16. Antithrombotic activities of ferulic acid via intracellular cyclic nucleotide signaling.

    PubMed

    Hong, Qian; Ma, Zeng-Chun; Huang, Hao; Wang, Yu-Guang; Tan, Hong-Ling; Xiao, Cheng-Rong; Liang, Qian-De; Zhang, Han-Ting; Gao, Yue

    2016-04-15

    Ferulic acid (FA) produces protective effects against cardiovascular dysfunctions. However, the mechanisms of FA is still not known. Here we examined the antithrombotic effects of FA and its potential mechanisms. Anticoagulation assays and platelet aggregation was evaluated in vitro and in vivo. Thromboxane B2 (TXB2), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate (cGMP) was determined using enzyme immunoassay kits. Nitric oxide (NO) production was measured using the Griess reaction. Protein expression was detected by Western blotting analysis. Oral administration of FA prevented death caused by pulmonary thrombosis and prolonged the tail bleeding and clotting time in mice,while, it did not alter the coagulation parameters, including the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). In addition, FA (50-200µM) dose-dependently inhibited platelet aggregation induced by various platelet agonists, including adenosine diphosphate (ADP), thrombin, collagen, arachidonic acid (AA), and U46619. Further, FA attenuated intracellular Ca(2)(+) mobilization and TXB2 production induced by the platelet agonists. FA increased the levels of cAMP and cGMP and phosphorylated vasodilator-stimulated phosphoprotein (VASP) while decreased phospho-MAPK (mitogen-activated protein kinase) and phosphodiesterase (PDE) in washed rat platelets, VASP is a substrate of cyclic nucleotide and PDE is an enzyme family responsible for hydrolysis of cAMP/cGMP. These results suggest that antithrombotic activities of FA may be regulated by inhibition of platelet aggregation, rather than through inhibiting the release of thromboplastin or formation of thrombin. The mechanism of this action may involve activation of cAMP and cGMP signaling. PMID:26948317

  17. Aggression in borderline personality disorder.

    PubMed

    Látalová, K; Prasko, J

    2010-09-01

    This review examined aggressive behavior in Borderline Personality Disorder (BPD) and its management in adults. Aggression against self or against others is a core component of BPD. Impulsiveness is a clinical hallmark (as well as a DSM-IV-TR diagnostic criterion) of BPD, and aggressive acts by BPD patients are largely of the impulsive type. BPD has high comorbidity rates with substance use disorders, Bipolar Disorder, and Antisocial Personality Disorder; these conditions further elevate the risk for violence. Treatment of BDP includes psychodynamic, cognitive behavioral, schema therapy, dialectic behavioral, group and pharmacological interventions. Recent studies indicate that many medications, particularly atypical antipsychotics and anticonvulsants, may reduce impulsivity, affective lability as well as irritability and aggressive behavior. But there is still a lack of large, double blind, placebo controlled studies in this area. PMID:20390357

  18. Spirulan from blue-green algae inhibits fibrin and blood clots: its potent antithrombotic effects.

    PubMed

    Choi, Jun-Hui; Kim, Seung; Kim, Sung-Jun

    2015-05-01

    We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases. PMID:25651404

  19. Antithrombotic activities of fucosylated chondroitin sulfates and their depolymerized fragments from two sea cucumbers.

    PubMed

    Liu, Xiaoxiao; Hao, Jiejie; Shan, Xindi; Zhang, Xiao; Zhao, Xiaoliang; Li, Qinying; Wang, Xiaojiang; Cai, Chao; Li, Guoyun; Yu, Guangli

    2016-11-01

    Fucosylated chondroitin sulfate (FCS), a glycosaminoglycan extracted from the body wall of sea cucumber, is a promising antithrombotic agent. The chemical structures of FCSc isolated from sea cucumber Cucumaria frondosa and its depolymerized fragment (dFCSc) were characterized for the first time. Additionally, anticoagulant and antithrombotic activities were evaluated in vitro and in vivo. The results demonstrated that dFCSc exhibited better antithrombotic-hemorrhagic ratio than native FCSc on the electrical induced arterial thrombosis model in rats. Compared to FCSt obtained from Thelenota ananas, FCSc possessed different sulfation patterns but similar antithrombotic effects. Therefore, sulfation pattern of FCS might not affect anticoagulation and antithrombosis as much as molecular weight may. Our results proposed a new point of view to understand the structure-activity relationship of FCS as alternative agents. PMID:27516281

  20. DLBS1033, A Protein Extract from Lumbricus rubellus, Possesses Antithrombotic and Thrombolytic Activities

    PubMed Central

    Trisina, Jessica; Sunardi, Febrina; Suhartono, Maggy T.; Tjandrawinata, Raymond R.

    2011-01-01

    The medicinal value of earthworm has been widely known since the history of Asian ancient medicine. This present study aims to determine the mechanism of action and effect of a standardized extract of Lumbricus rubellus named as DLBS1033. The fibrinogen degradation, antiplatelet aggregation, and ex vivo antithrombotic assay using human blood were performed to study antithrombotic activity. Fibrin plate and clot lysis assay were also done to examine thrombolytic properties. DLBS1033 was found to possess fibrinogenolytic activity on α-, β-, and γ-chain of fibrinogen. It also induced antiplatelet aggregation and prolonged blood clotting time, which further confirmed its antithrombotic properties. In addition, thrombolytic properties of DLBS1033 were shown with its fast and long-acting fibrinolytic activity, as well as its effective blood clot lysis activities. In conclusion, DLBS1033 conferred antithrombotic and thrombolytic action which could be used as a safe and promising oral thrombolytic drug. PMID:21403877

  1. The antithrombotic factor singlet oxygen/light (1O2/h nu).

    PubMed

    Stief, T W; Fareed, J

    2000-01-01

    Activated phagocytes (especially polymorphonuclear granulocytes (PMNs)) by respiratory oxidative/photonic burst (activation of NADPH-oxidase and myeloper-oxidase) generate large amounts of oxidants of the hypochlorite-/chloramine-type, which are physiologic sources for singlet oxygen (1O2), a nonradical-excited (photon (h nu) emitting) oxygen species [Weiss SJ, NEJM 1989;320:365-376]. In vitro experiments show that 1O2 (1) inhibits coagulation by inactivation of thrombocytes, fibrinogen, factor V, factor VIII, and factor X and (2) activates fibrinolysis by inactivation of the main fibrinolysis inhibitors plasminogen activator inhibitor (PAI)-1 and alpha-2-antiplasmin, and by activation of single-chain urokinase by plasmin and oxidized fibrin. Additionally, this work suggests that 1O2/h nu acts antithrombotically, inducing selective thrombolysis in vivo (i.e., thrombolysis induced by 0.1 to 0.5 mmol/l chloramine within 30 to 60 minutes without changes of the plasmatic hemostasis system). 1O2 might activate flowing to (on the endothelium) rolling PMN, increasing their chance to get in contact with fibrin/platelet aggregates deposited on the endothelial layer. Via 1O2 generation, the thrombus-activated phagocytes might call for (acute, physiologic) inflammation/fibrinolysis amplification, resulting in the "moving front" of PMN, which infiltrates and destroys the thrombus. 1O2 seems to (partially) participate in the reactivity of nitric oxide, another prooxidative agent. The inhibition of physiologic amounts of 1O2 by blood cholesterol might be involved in the pathogenesis of atherothrombosis. Consequently, it is suggested that activated PMNs modulate hemostasis, shifting it into an antithrombotic state; this cellular part of fibrinolysis seems to be of greater physiologic importance than the plasmatic one. Impaired PMN function (e.g., as occurring in patients with antineutrophil cytoplasmic antibodies or under cytostatic treatments) often results in serious thrombotic

  2. Appropriate Use of Antithrombotic Medication in Canadian Patients With Nonvalvular Atrial Fibrillation.

    PubMed

    Bell, Alan D; Gross, Peter; Heffernan, Michael; Deschaintre, Yan; Roux, Jean-Francois; Purdham, Daniel M; Shuaib, Ashfaq

    2016-04-01

    This national chart audit of 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices sought to examine the management of Canadian patients with AF through an evidence-based, guideline-recommended approach. The appropriate use of oral anticoagulants (OACs) in this patient population and the potential factors guiding OAC choice were examined. Suboptimal dosing was seen. In patients on warfarin, 30.9% had not achieved a time in therapeutic range (TTR) in excess of 65% and, despite current Canadian guideline recommendations, were continued on warfarin rather than one of the novel OACs. In patients who received no antithrombotic therapy, 65.5% met criteria for treatment with an OAC. In addition, 62.8% of patients who were treated with acetylsalicylic acid monotherapy met guideline criteria for the use of an OAC. In those patients treated with an OAC, 24.8% were not on the recommended dose based on the product monograph or, if on warfarin, had a TTR <65%. Of the patients on novel OACs (NOACs), 7.4% of patients were underdosed, whereas overdosing was seen in 4.3%. Factors that may have contributed to dosing outside recommendations included underestimation of stroke risk, overestimation of bleed risk, compliance concerns, and lack of provincial reimbursement. In conclusion, significant correctable gaps remain in optimal treatment for stroke prevention in AF. PMID:26879070

  3. Adlerian Therapy with Aggressive Children.

    ERIC Educational Resources Information Center

    Kizer, Betty

    Alfred Adler devised a theory that was holistic, social, teleological, and phenomenological. Adler believed that the basis of problems with children originated in the child's inability to cooperate with society, feelings of inferiority, and a lack of a goal in life. Adler felt the child's life should be examined through the child's eyes.…

  4. CLINICAL AND PHARMACEUTICAL ASPECTS OF THE USE OF ANTITHROMBOTIC DRUGS IN PATIENTS SUFFERING FROM ISCHEMIC HEART DISEASE (REVIEW).

    PubMed

    Zhunussov, Y

    2016-02-01

    The review article discusses the possibilities and evidence base of the use of antithrombotic drugs in common clinical practice. Presents information about the basic clinical trials of the effectiveness of antithrombotic medications (CAPRIE, CURE, VA, RISC, ISIS2, PLATO) in the treatment and secondary prevention of the consequences of atherothrombosis. Also presents the algorithms for prescription of antithrombotic drugs and the principles of rational use of antiplatelet agents. PMID:27001783

  5. CONCEPT ANALYSIS: AGGRESSION

    PubMed Central

    Liu, Jianghong

    2006-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  6. Concept analysis: aggression.

    PubMed

    Liu, Jianghong

    2004-01-01

    The concept of aggression is important to nursing because further knowledge of aggression can help generate a better theoretical model to drive more effective intervention and prevention approaches. This paper outlines a conceptual analysis of aggression. First, the different forms of aggression are reviewed, including the clinical classification and the stimulus-based classification. Then the manifestations and measurement of aggression are described. Finally, the causes and consequences of aggression are outlined. It is argued that a better understanding of aggression and the causal factors underlying it are essential for learning how to prevent negative aggression in the future. PMID:15371137

  7. Usefulness of platelet function tests to predict bleeding with antithrombotic medications.

    PubMed

    Gorog, Diana A; Otsui, Kazunori; Inoue, Nobutaka

    2015-01-01

    The pharmacological inhibition of platelets has always been regarded as a double-edged sword: the challenge of balancing the antithrombotic effect against the bleeding risk. Potent antiplatelet agents and novel oral anticoagulants, sometimes in combination, are increasingly used in the treatment of cardiovascular disease and for thromboprophylaxis in atrial fibrillation. Although such treatment has reduced the risk of thrombotic events, the potential for major bleeding has increased, and a technique to identify those at increased bleeding risk is greatly needed. Platelet function tests (PFTs), most frequently VerifyNow and also the vasodilator-stimulated phosphoprotein -phosphorylation assay, have been used to identify low on-treatment platelet reactivity, to identify individuals who may be at increased bleeding risk. Such results predict nuisance bleeding, but many individuals have low on-treatment platelet reactivity and yet do not exhibit major or even minor bleeding. Although PFTs may be useful in assessing populations, they do not allow identification of individual patients at risk of bleeding on either antiplatelet or novel oral anticoagulant therapy, nor do they allow the tailoring of such therapy to optimize the risk:benefit ratio. Thrombin plays a cardinal role in both arterial thrombus formation and hemostasis, yet most PFTs fail to assess the contribution of thrombin, because they employ anticoagulated blood. Techniques such as the calibrated automated thrombogram and the point-of-care global thrombosis test, performed on native blood, which measure endogenous thrombin potential, seem to show the most promise for profiling bleeding risk, as tests that most physiologically assess the effects of medications on thrombin. PMID:25839991

  8. Withdrawal of Antithrombotic Agents and Its Impact on Ischemic Stroke Occurrence

    PubMed Central

    Broderick, Joseph P.; Bonomo, Jordan B.; Kissela, Brett M.; Khoury, Jane C.; Moomaw, Charles J.; Alwell, Kathleen; Woo, Daniel; Flaherty, Matthew L.; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Kleindorfer, Dawn O.

    2011-01-01

    Background Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication. Methods and Results Patient records from the population-based Greater Cincinnati / Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review. Results In 2005, 2,197 cases of ischemic stroke among residents of the region were identified via hospital discharge records. Of the 2,197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal: 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes following withdrawal, 71 (62.3%) were first-ever, and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period. Conclusions The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance. PMID:21719769

  9. Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study

    PubMed Central

    Gulati, Sasha; Solheim, Ole; Carlsen, Sven M.; Øie, Lise R.; Jensberg, Heidi; Gulati, Agnete M.; Giannadakis, Charalampis; Jakola, Asgeir S.; Salvesen, Øyvind

    2015-01-01

    Background A wide range of antithrombotic medications can be used in the prevention and treatment of thrombosis. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage may have particularly devastating consequences with high morbidity, disability and mortality rates. The incidence and risks of intracranial hemorrhage in patients on antithrombotic treatments from regular clinical practice outside clinical trials remain largely unknown. It is not known if results from clinical trials can be extrapolated to everyday clinical practice. We will conduct a nationwide study to investigate the risks and incidence rates of intracranial hemorrhage in users oral antithrombotic drugs in Norway from 2008 through 2014.   Methods and design The aim of this nationwide study is to investigate the incidence rates of intracranial hemorrhage requiring hospitalization in users of oral antithrombotic drugs. The study will be conducted within the approximately 4.7 million inhabitants of Norway from January 1 st, 2008, to December 31 st, 2014. Treatment and outcome data are obtained from the Norwegian patient registry and the Norwegian prescription database.   Trial registration number Clinicaltrials.gov (NCT02481011) PMID:26918124

  10. Clinical Utility of Antithrombotic Prophylaxis in ART Procedures: An Italian Experience

    PubMed Central

    Grandone, Elvira; Villani, Michela; Tiscia, Giovanni L.; Dentali, Francesco; Colaizzo, Donatella; Cappucci, Filomena; Fischetti, Lucia; Ageno, Walter; Margaglione, Maurizio

    2014-01-01

    Background The usefulness of antithrombotic prophylaxis in management of Assisted Reproductive Technologies (ART) is questionable. Objectives We prospectively examined the contribution of an antithrombotic prophylaxis in influencing clinical pregnancy and live-birth in an unselected cohort of women approaching ART. Patients/Methods 1107 women with fertility problems and a valid indication for ART were recruited. Baseline and follow-up information of obstetric outcomes and antithrombotic treatment were collected. Results and Conclusions Median follow-up time was 34.5 months (range: 2–143). During the follow-up period, 595 (53.8%) women underwent ART (total 1234 cycles); 202 (33.9%) women achieved a pregnancy for a total of 255 clinical pregnancies. The concomitant use of LMWH and aspirin was significantly associated with a higher rate of clinical pregnancies (p: 0.003, OR: 4.9, 95% CI: 1.7–14.2). The pregnancy rate was also significantly increased by the use of LMWH alone (p: 0.005, OR: 2.6, 95% CI: 1.3–5.0). Carriership of inherited or acquired thrombophilia did not affect clinical outcomes of the ART. The efficacy of antithrombotic treatment was confirmed when the outcome “ live-birth” was considered. Present data suggest a potential benefit of antithrombotic prophylaxis during ART in improving the number of live-births. PMID:24870449

  11. Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

    PubMed

    Chen, Qiu-Fang; Li, Yun-Zhan; Wang, Xin-Hui; Su, You-Rui; Cui, Shuang; Miao, Ming-Xing; Jiang, Zhen-Zhou; Jiang, Mei-Ling; Jiang, Ai-Dou; Chen, Xiang; Xu, Yun-Gen; Gong, Guo-Qing

    2016-06-15

    The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro. With the method of continuous infusion of thrombin intravenous, we successfully established a rat hypercoagulable model and evaluated the effect of HY023016 or dabigatran etexilate in vivo. HY023016 was able to inhibit thrombin- or ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates in dose-dependent manner. Dabigatran etexilate was unable to affect ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates. Based on rat hypercoagulable model, dabigatran etexilate could reverse thrombin-induced circulatory system hypercoagulable state in a concentration-dependent manner. Dabigatran etexilate also inhibited electrical stimulation induced formation of arterial thrombus in rat under hypercoagulable state, and extracorporal circulation-induced formation of thrombus in dose-dependent manner. Compared with dabigatran etexilate, HY023016 showed nearly equal or even better antithrombotic activity, regardless of reversing the cycle of rat hypercoagulable state or inhibiting platelet-leukocyte aggregation. In surrmary, HY023016 could effectively improve hypercoagulable state of circulatory system. PMID:27085896

  12. Effects of antithrombotic drugs in patients with left ventricular thrombi: assessment with indium-111 platelet imaging and two-dimensional echocardiography

    SciTech Connect

    Stratton, J.R.; Ritchie, J.L.

    1984-03-01

    Patients with left ventricular thrombi not caused by recent myocardial infarction were prospectively studied by indium-111 platelet imaging and two-dimensional echocardiography to determine the reproducibility of these techniques and the short-term effects of sulfinpyrazone (200 mg four times daily), aspirin (325 mg three times daily) plus dipyridamole (75 mg three times daily), and full-dose warfarin. At baseline, all patients underwent indium-111 platelet imaging and echocardiography, and the results were positive for thrombus. In six patients on no antithrombotic drug therapy, repeat platelet scans and echocardiographic studies at 6.0 +/- 3.3 weeks remained positive and were unchanged. In seven patients studied on sulfinpyrazone, three platelet scans became negative, two became equivocal, and two were unchanged; the presence and size of thrombus was constant by echocardiography in all seven patients. Of the six patients studied on aspirin plus dipyridamole, one platelet scan became negative, those of three became equivocal, and two were unchanged; all echocardiographic findings remained positive, but one patient had decreased thrombus size. Among four warfarin-treated patients, three had resolution of platelet deposition and one was unchanged; by echocardiography, thrombus resolved in one patient, was decreased in size in one, and was unchanged in two. We conclude that, in the absence of antithrombotic drug therapy, platelet imaging and echocardiographic findings are stable in patients with left ventricular thrombi not caused by recent myocardial infarction. Sulfinpyrazone, aspirin plus dipyridamole, and warfarin all interrupt platelet deposition in some patients with chronic left ventricular thrombi.

  13. Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda.

    PubMed

    Chen, Chen-Huan; Chen, Mien-Cheng; Gibbs, Harry; Kwon, Sun U; Lo, Sidney; On, Young Keun; Rosman, Azhari; Suwanwela, Nijasri C; Tan, Ru San; Tirador, Louie S; Zirlik, Andreas

    2015-07-15

    Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients. PMID:25978611

  14. Non-Antithrombotic Medical Options in ACS: Old Agents and New Lines on the Horizon

    PubMed Central

    Soukoulis, Victor; Boden, William E.; Smith, Sidney C.; O'Gara, Patrick T.

    2014-01-01

    Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply-demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into “disease-modifying” agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as beta-blockers and inhibitors of the reninangiotensin-aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic pre- and post-conditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, anti-thrombotic agents, and the use of high-intensity statins. PMID:24902977

  15. Selecting the optimal antithrombotic regimen for patients with acute coronary syndromes undergoing percutaneous coronary intervention

    PubMed Central

    Parikh, Shailja V; Keeley, Ellen C

    2009-01-01

    The wide variety of anticoagulant and antiplatelet agents available for clinical use has made choosing the optimal antithrombotic regimen for patients with acute coronary syndromes undergoing percutaneous coronary intervention a complex task. While there is no single best regimen, from a risk-benefit ratio standpoint, particular regimens may be considered optimal for different patients. We review the mechanisms of action for the commonly prescribed antithrombotic medications, summarize pertinent data from randomized trials on their use in acute coronary syndromes, and provide an algorithm (incorporating data from these trials as well as risk assessment instruments) that will help guide the decision-making process. PMID:19707287

  16. Antithrombotic agents in the treatment of severe sepsis.

    PubMed

    Iqbal, Omer; Messmore, Harry; Fareed, Jawed; Ahmad, Sarfraz; Hoppensteadt, Debra; Hazar, Shadid; Tobu, Mahmut; Aziz, Salim; Wehrmacher, William

    2002-05-01

    mortality when compared to the placebo group. A better understanding of the pathophysiologic mechanism of severe sepsis will provide better treatment options, and combination antithrombotic treatment may provide a multipronged approach for the treatment of severe sepsis. PMID:15989540

  17. What Is Aggressive Violence?

    ERIC Educational Resources Information Center

    Singer, Dorothy G.; Luca, Wendy

    1985-01-01

    Responses to a questionnaire dealing with what constitutes aggressive violence on television indicate that health care providers tend to rate items describing acts on television as more aggressive than television writers, producers, and executives do. (MBR)

  18. Exploiting the antithrombotic effect of the (pro)thrombin inhibitor bothrojaracin.

    PubMed

    Assafim, Mariane; Frattani, Flávia S; Ferreira, Marcos S; Silva, Dione M; Monteiro, Robson Q; Zingali, Russolina B

    2016-09-01

    Bothrojaracin is a 27 kDa C-type lectin-like protein from Bothrops jararaca snake venom. It behaves as a potent thrombin inhibitor upon high-affinity binding to thrombin exosites. Bothrojaracin also forms a stable complex with prothrombin that can be detected in human plasma. Formation of the zymogen-inhibitor complex severely decreases prothrombin activation and contributes to the anticoagulant activity of bothrojaracin. In the present study, we employed two rodent models to evaluate the antithrombotic effect of bothrojaracin in vivo: stasis-induced thrombosis and thrombin-induced pulmonary thromboembolism. It was observed that bothrojaracin interacts with rat prothrombin in plasma. Ex-vivo assays showed stable complex formation even after 24 h of a single bothrojaracin dose. As a result, bothrojaracin showed significant antithrombotic activity in a rat venous thrombosis model elicited by thromboplastin combined with stasis. The antithrombotic activity of bothrojaracin (1 mg/kg) persisted for up to 24 h and it was associated with moderate bleeding as assessed by a tail transection method. Formation of bothrojaracin-prothrombin complex has been also observed following intravenous administration of the inhibitor into mice. As a result, bothrojaracin effectively protected mice from thrombin-induced fatal thromboembolism. We conclude that bothrojaracin is a potent antithrombotic agent in vivo and may serve as a prototype for the development of new zymogen-directed drugs that could result in prolonged half-life and possible decreased hemorrhagic risk. PMID:27179421

  19. Antithrombotic Activity of a New Hypoglycemic Compound Limiglidole in Mouse Model of Cell Thrombosis.

    PubMed

    Kucheryavenko, A F; Spasov, A A; Smirnov, A V

    2015-05-01

    Antithrombotic activity of hypoglycemic compound limiglidole that exhibits antiplatelet activity 2-fold exceeded activity of antiplatelet agent acetylsalicylic acid in the mouse model of systemic collagen-epinephrine thrombosis. Limiglidole signifi cantly reduced the relative and mean area of blood clots in the sections of mouse lungs. PMID:26033587

  20. Neurobiological Patterns of Aggression.

    ERIC Educational Resources Information Center

    Hunt, Robert D.

    1993-01-01

    Describes chemical model for patterns of aggressive behavior. Addresses cultural, neurobiological, and cognitive factors that affect violent children. Identifies five patterns of aggression (overaroused, impulsive, affective, predatory, and instrumental) and examines these dimensions of aggression for each pattern: baseline, precipitators,…

  1. An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect

    PubMed Central

    Fraga-Silva, Rodrigo Araujo; Costa-Fraga, Fabiana P; De Sousa, Frederico B; Alenina, Natalia; Bader, Michael; Sinisterra, Ruben D; Santos, Robson A S

    2011-01-01

    INTRODUCTION AND OBJECTIVE: The heptapeptide angiotensin-(1-7) is a component of the renin-angiotensin system, which promotes many beneficial cardiovascular effects, including antithrombotic activity. We have recently shown that the antithrombotic effect of angiotensin-(1-7) involves receptor Mas-mediated NO-release from platelets. Here, we describe an orally active formulation based on angiotensin-(1-7) inclusion in cyclodextrin [Ang-(1-7)- CyD] as an antithrombotic agent. Cyclodextrins are pharmaceutical tools that are used to enhance drug stability, absorption across biological barriers and gastric protection. METHOD: To test the antithrombotic effect of Ang-(1-7)-CyD, thrombus formation was induced in the abdominal vena cava of spontaneously hypertensive rats that were pretreated either acutely or chronically with Ang-(1-7)-CyD. Male Mas-knockout and wild-type mice were used to verify the role of the Mas receptor on the effect of Ang-(1-7)-CyD. RESULTS: Acute or chronic oral treatment with Ang-(1-7)-CyD promoted an antithrombotic effect (measured by thrombus weight; all values are, respectively, untreated vs. treated animals) in spontaneously hypertensive rats (acute: 2.86 ± 0.43 mg vs. 1.14 ± 0.40 mg; chronic: 4.27 ± 1.03 mg vs. 1.39 ± 0.68 mg). This effect was abolished in Mas-knockout mice (thrombus weight in Mas wild-type: 0.76 ± 0.10 mg vs. 0.37 ± 0.02 mg; thrombus weight in Mas-knockout: 0.96 ± 0.11 mg vs. 0.87 ± 0.14 mg). Furthermore, the antithrombotic effect of Ang-(1-7)-CyD was associated with an increase in the plasma level of Angiotensin-(1-7). CONCLUSION: These results show for the first time that the oral formulation Ang-(1-7)-CyD has biological activity and produces a Mas-dependent antithrombotic effect. PMID:21789389

  2. Long Complete Remission Achieved with the Combination Therapy of Cisplatin and Gemcitabine in a Patient with Aggressive Natural Killer Cell Leukemia

    PubMed Central

    Koepke, John

    2015-01-01

    Aggressive natural killer cell leukemia (ANKL) is a rare and often lethal lymphoproliferative disorder. Patients may present with constitutional symptoms, jaundice, skin infiltration, lymphadenopathy, and hepatosplenomegaly. ANKL can progress quickly to multiorgan failure and survival is usually measured in weeks. Although a rapid and accurate diagnosis is critical, unfortunately there is no hallmark diagnostic marker of ANKL. We report a case of a 48-year-old male who was able to obtain a complete remission following cisplatin-based chemotherapy. We describe the details of the chemotherapy regimens used and a literature review of the treatment of ANKL. PMID:25694835

  3. TransRadial Education And Therapeutics (TREAT): Shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention. A report from the Cardiac Safety Research Consortium

    PubMed Central

    Hess, Connie N.; Rao, Sunil V.; Kong, David F.; Miller, Julie M.; Anstrom, Kevin J.; Bertrand, Olivier F.; Collet, Jean-Philippe; Effron, Mark B.; Eloff, Benjamin C.; Fadiran, Emmanuel O.; Farb, Andrew; Gilchrist, Ian C.; Holmes, David R.; Jacobs, Alice K.; Kaul, Prashant; Newby, L. Kristin; Rutledge, David R.; Tavris, Dale R.; Tsai, Thomas T.; White, Roseann M.; Peterson, Eric D.; Krucoff, Mitchell W.

    2013-01-01

    Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions. PMID:23453103

  4. Increasing Parent Satisfaction of Children's Therapy through an Audio-Visual Investigation of Reactions to Children's Aggressive, Assertive or Passive Anger Responses.

    ERIC Educational Resources Information Center

    Anderson, Fay B.

    This document presents a practicum designed to address the problems encountered when a child in nondirective play therapy becomes able to express emotions and parents, unable to accept their child's new expressions of anger, withdraw the child from therapy at a time when he or she is most vulnerable. The development and implementation of a program…

  5. Relational aggression in marriage.

    PubMed

    Carroll, Jason S; Nelson, David A; Yorgason, Jeremy B; Harper, James M; Ashton, Ruth Hagmann; Jensen, Alexander C

    2010-01-01

    Drawing from developmental theories of relational aggression, this article reports on a study designed to identify if spouses use relationally aggressive tactics when dealing with conflict in their marriage and the association of these behaviors with marital outcomes. Using a sample of 336 married couples (672 spouses), results revealed that the majority of couples reported that relationally aggressive behaviors, such as social sabotage and love withdrawal, were a part of their marital dynamics, at least to some degree. Gender comparisons of partner reports of their spouse's behavior revealed that wives were significantly more likely to be relationally aggressive than husbands. Structural equation modeling demonstrated that relational aggression is associated with lower levels of marital quality and greater marital instability for both husbands and wives. Implications are drawn for the use of relational aggression theory in the future study of couple conflict and marital aggression. PMID:20698028

  6. [Recognizing and assessing aggressive behaviour in dogs].

    PubMed

    Schalke, E; Hackbarth, H

    2006-03-01

    Within the population the sensitivity to aggressive behaviour in dogs has increased. The authorities are confronted with a problem: if any incident occurs it is their task to decide whether the dogs involved constitute a threat to other people or whether the charge is only the result of a quarrel between neighbours. For this reason, an examination of the dogs with regard to their aggressive behaviour is necessary. Seen from the biological point of view, aggressive behaviour is one of four possibilities a dog can chose from to solve a conflict. The dog's intention in showing aggressive behaviour is to eliminate disturbances and to maintain a distance in space and time. Aggressive behaviour might also be necessary to acquire or defend resources essential to the dog's life. This is to secure its survival and its success in reproduction. One can see from this that aggressive behaviour is a very important and biologically necessary adjustment factor. However, when living together with man aggressive behaviour might become a problem. For the assessment and the therapy of the problem it is necessary to exa-mine the behaviour shown by the dog with regard to its cause. To be able to do this an exact anamnesis, a medical check, and an examination of the dog on the basis of its display in special situations are necessary. For this reason, exclusively veterinarians with a special further education in the field of behaviour should carry out the examination of dogs. PMID:16669189

  7. Effect of Antithrombotic Agents on the Patency of PTFE-Covered Stents in the Inferior Vena Cava: An Experimental Study

    SciTech Connect

    Makutani, Shiro; Kichikawa, Kimihiko; Uchida, Hideo; Maeda, Munehiro; Konishi, Noboru; Hiasa, Yoshio; Yoshikawa, Tomohiro; Kimura, Yukio

    1999-05-15

    Purpose: To evaluate the efficacy of antithrombotic agents in the prevention of stenosis of polytetrafluoroethylene (PTFE)-covered stents in the venous system. Methods: Spiral Z stents covered with PTFE (PTFE-covered stents) were placed in the inferior vena cava (IVC) of 34 dogs. Nineteen dogs, used as a control group, were sacrificed at 2, 4, and 12 weeks. Fifteen dogs, previously given antithrombotic agents [cilostazol (n= 5), warfarin potassium (n= 5), cilostazol plus warfarin potassium (n= 5)] were sacrificed at 4 weeks, and then examined angiographically and histopathologically. The effect of the antithrombotic agents was compared between groups. Results: The patency rate of the antithrombotic agent group was 93% (14/15), which was higher than the control group rate of 63% (12/19). The mean stenosis rate of the patent stent at both ends and at the midportion was lower at 4 weeks in the antithrombotic agent group than in the control group. In particular, the mean stenosis rate in the cilostazol plus warfarin potassium group was significantly lower than the control group (Tukey's test, p < 0.05). The mean neointimal thickness of the patent stent at both ends and at the midportion was thinner at 4 weeks in the antithrombotic agent group than in the control group. In particular, the thickness of the neointima in the cilostazol plus warfarin potassium group was significantly decreased when compared with the control group (Tukey's test p < 0.05). At 4 weeks, endothelialization in the antithrombotic agent group tended to be almost identical to that in the control group. Conclusion: The present study suggests that administration of an antithrombotic agent is an effective way of preventing the stenosis induced by a neointimal thickening of PTFE-covered stents in the venous system.

  8. Authoritarianism and sexual aggression.

    PubMed

    Walker, W D; Rowe, R C; Quinsey, V L

    1993-11-01

    In Study 1, 198 men completed the Right Wing Authoritarianism, Sex Role Ideology, Hostility Towards Women, Acceptance of Interpersonal Violence, Adversarial Sexual Beliefs, and Rape Myth Acceptance scales, as well as measures of past sexually aggressive behavior and likelihood of future sexual aggression. As predicted, authoritarianism and sex role ideology were as closely related to self-reported past and potential future sexually aggressive behavior as were the specifically sexual and aggression-related predictors. Among 134 men in Study 2, authoritarianism and sex guilt positively correlated with each other and with self-reported past sexual aggression. In both studies, the relationship of authoritarianism and sexual aggression was larger in community than in university samples. PMID:8246111

  9. European Society of Cardiology Guideline-Adherent Antithrombotic Treatment and Risk of Mortality in Asian Patients with Atrial Fibrillation.

    PubMed

    Li, Cheng-Hung; Liu, Chia-Jen; Chou, Annie Y; Chao, Tze-Fan; Tuan, Ta-Chuan; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Liao, Jo-Nan; Chen, Tzeng-Ji; Wu, Tsu-Juey; Chen, Shih-Ann

    2016-01-01

    This study compared the risk of mortality in atrial fibrillation (AF) patients treated adherent to the 2012 European Society of Cardiology (ESC) guidelines for stroke prevention and those who were not treated according to guideline recommendations. This study used the Taiwan National Health Insurance Research Database. From 1996 to 2011, 354,649 newly diagnosed AF patients were identified as the study population. Among the study cohort, 45,595 and 309,054 patients were defined as Guideline-Adherent and Non-Adherent groups, respectively. During the follow up of 1,480,280 person-years, 133,552 (37.7%) patients experienced mortality. The risk of mortality was lower among AF patients whose treatment was adherent to the guideline recommendation for stroke prevention than those whose treatment was not (annual risk of mortality = 4.3% versus 10.0%) with an adjusted hazard ratio of 0.62 (95% confidence interval = 0.61-0.64, p value < 0.001) after adjusting for age, gender, CHA2DS2-VASc score and antiplatelet therapy. The findings were consistently observed after propensity matching analysis. In conclusion, the risk of mortality was lower for AF patients who were treated according to the antithrombotic recommendations of the 2012 ESC guidelines, guided by the CHA2DS2-VASc score. Better efforts to implement guidelines would lead to improved outcomes for patients with AF. PMID:27498702

  10. European Society of Cardiology Guideline-Adherent Antithrombotic Treatment and Risk of Mortality in Asian Patients with Atrial Fibrillation

    PubMed Central

    Li, Cheng-Hung; Liu, Chia-Jen; Chou, Annie Y.; Chao, Tze-Fan; Tuan, Ta-Chuan; Chen, Su-Jung; Wang, Kang-Ling; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Chung, Fa-Po; Liao, Jo-Nan; Chen, Tzeng-Ji; Wu, Tsu-Juey; Chen, Shih-Ann

    2016-01-01

    This study compared the risk of mortality in atrial fibrillation (AF) patients treated adherent to the 2012 European Society of Cardiology (ESC) guidelines for stroke prevention and those who were not treated according to guideline recommendations. This study used the Taiwan National Health Insurance Research Database. From 1996 to 2011, 354,649 newly diagnosed AF patients were identified as the study population. Among the study cohort, 45,595 and 309,054 patients were defined as Guideline-Adherent and Non-Adherent groups, respectively. During the follow up of 1,480,280 person-years, 133,552 (37.7%) patients experienced mortality. The risk of mortality was lower among AF patients whose treatment was adherent to the guideline recommendation for stroke prevention than those whose treatment was not (annual risk of mortality = 4.3% versus 10.0%) with an adjusted hazard ratio of 0.62 (95% confidence interval = 0.61–0.64, p value < 0.001) after adjusting for age, gender, CHA2DS2-VASc score and antiplatelet therapy. The findings were consistently observed after propensity matching analysis. In conclusion, the risk of mortality was lower for AF patients who were treated according to the antithrombotic recommendations of the 2012 ESC guidelines, guided by the CHA2DS2-VASc score. Better efforts to implement guidelines would lead to improved outcomes for patients with AF. PMID:27498702

  11. [A clinical experience of V-A bypass using a new antithrombotic coating material].

    PubMed

    Kawahito, K; Ino, T; Ide, H; Adachi, H; Mizuhara, A; Yamaguchi, A

    1992-07-01

    To perform V-A bypass with minimal systemically administered heparin, we used a equipment coated by fluorine-acryl-styrene-urethane-silicone graft copolymer. A 67 year old woman developed right heart failure after CABG was treated for 25 hours on V-A bypass without oxygenator by using this new antithrombotic coating material. During V-A bypass, hemodynamics were stable. Not coagulative nor hemolytic disorder was observed. And she did not suffer from thrombotic nor hemorrhagic complications. Scanning electron microscopy of coated equipment demonstrated only minor deposits on the surface, and morphologic study of platelet was almost normal. By using this new antithrombotic material it is possible to perform V-A bypass with minimal heparinization, thus avoiding the risk of major coagulation complications. PMID:1506705

  12. Antithrombotic alternatives for stroke prevention in atrial fibrillation: critical differences and remaining questions

    PubMed Central

    Kalus, James S

    2013-01-01

    Three therapeutic alternatives for prevention of stroke in patients with atrial fibrillation are available in dabigatran (an oral direct thrombin inhibitor), rivaroxaban, and apixaban (both oral blood coagulation factor Xa inhibitors). Compared with warfarin, these new agents have a more predictable pharmacodynamic response and fewer major clinically relevant drug–drug interactions. These agents also have few, if any, food–drug interactions, and infrequent or no need for routine laboratory monitoring. These agents also bring new disadvantages, particularly lack of clearly defined reversal strategies, inability to effectively monitor patient response, and higher cost. Selection of the most appropriate oral antithrombotic agent for a given patient is dependent on clinician knowledge of the similarities and critical differences between the available antithrombotic medications. PMID:24432039

  13. Biocatalytic approaches to a key building block for the anti-thrombotic agent ticagrelor.

    PubMed

    Hugentobler, Katharina G; Sharif, Humera; Rasparini, Marcello; Heath, Rachel S; Turner, Nicholas J

    2016-09-14

    three complementary biocatalytic routes were examined for the synthesis of the cyclopropyl amine (1R,2S)-2, which is a key building block for the anti-thrombotic agent ticagrelor 1. By employing either a ketoreductase, amidase or lipase biocatalyst, the key building blocks for synthesis of the amine 2 were obtained in 99.9, 92.5 and 46.3 ee, respectively. PMID:27470519

  14. Integration of molecular and enzymatic catalysts on graphene for biomimetic generation of antithrombotic species

    NASA Astrophysics Data System (ADS)

    Xue, Teng; Peng, Bo; Xue, Min; Zhong, Xing; Chiu, Chin-Yi; Yang, Si; Qu, Yongquan; Ruan, Lingyan; Jiang, Shan; Dubin, Sergey; Kaner, Richard B.; Zink, Jeffrey I.; Meyerhoff, Mark E.; Duan, Xiangfeng; Huang, Yu

    2014-02-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene-haemin-glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π-π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene-haemin-glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices.

  15. [Testing system design and analysis for the execution units of anti-thrombotic device].

    PubMed

    Li, Zhelong; Cui, Haipo; Shang, Kun; Liao, Yuehua; Zhou, Xun

    2015-02-01

    In an anti-thrombotic pressure circulatory device, relays and solenoid valves serve as core execution units. Thus the therapeutic efficacy and patient safety of the device will directly depend on their performance. A new type of testing system for relays and solenoid valves used in the anti-thrombotic device has been developed, which can test action response time and fatigue performance of relay and solenoid valve. PC, data acquisition card and test platform are used in this testing system based on human-computer interaction testing modules. The testing objectives are realized by using the virtual instrument technology, the high-speed data acquisition technology and reasonable software design. The two sets of the system made by relay and solenoid valve are tested. The results proved the universality and reliability of the testing system so that these relays and solenoid valves could be accurately used in the antithrombotic pressure circulatory equipment. The newly-developed testing system has a bright future in the aspects of promotion and application prospect. PMID:25997290

  16. Antithrombotic and Antioxidant Activity of Amaranth Hydrolysate Obtained by Activation of an Endogenous Protease.

    PubMed

    Sabbione, Ana Clara; Ibañez, Sabrina M; Martínez, E Nora; Añón, María Cristina; Scilingo, Adriana A

    2016-06-01

    Ingestion of diets with antithrombotic and antioxidant components offer a convenient and effective way to prevent and reduce the incidence of cardiovascular diseases. The aim of the present work was to obtain an amaranth hydrolysate by the activation of an endogenous aspartic protease, to establish adequate experimental conditions, and to evaluate its antithrombotic and antioxidant activity in order to assess its potential application as an ingredient in functional foods. The results obtained not only confirmed the presence of an endogenous protease in the amaranth isolate, but also allowed us to select an adequate incubation conditions (pH 2, 40 °C, 16 h). The hydrolysate obtained (degree of hydrolysis 5.3 ± 0.4 %) showed potential antithrombotic activity (IC50 = 5.9 ± 0.1 mg soluble protein/mL) and had more antioxidant activity than the isolate, indicating that the activation of the protease released bioactive peptides from amaranth proteins. Decreasing the pH is a simple and cheap process and is another way to obtain potential functional ingredients with bioactive compounds. PMID:27023251

  17. The hypolipidemic effect and antithrombotic activity of Mucuna pruriens protein hydrolysates.

    PubMed

    Herrera Chalé, Francisco; Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David; Acevedo Fernández, Juan José; Segura Campos, Maira Rubi

    2016-01-01

    Hydrolysates and peptide fractions (PF) obtained from M. pruriens protein concentrates with commercial and digestive enzymatic systems were studied for their hypolipidemic and antithrombotic activities. Hydrolysates obtained with Pepsin-Pancreatin (PP) and their peptide fractions inhibited cholesterol micellar solubility with a maximum value of 1.83% in PP. Wistar rats were used to evaluate the hypolipidemic effect of hydrolysates and PF. The higher reductions of cholesterol and triglyceride levels were exhibited by PP and both peptide fractions <1 kDa obtained from PP and Alcalase®-Flavourzyme® hydrolysate (AF) at a dose of 15 mg kg(-1) of animal weight. PF > 10 kDa from both hydrolysates showed the maximum antithrombotic activity with values of 33.33% for PF > 10 kDa from AF and 31.72% for PF > 10 kDa from PP. The results suggest that M. pruriens bioactive peptides with the hypolipidemic effect and antithrombotic activity might be utilized as nutraceuticals. PMID:26505152

  18. Nanoencapsulation of Red Ginseng Extracts Using Chitosan with Polyglutamic Acid or Fucoidan for Improving Antithrombotic Activities.

    PubMed

    Kim, Eun Suh; Lee, Ji-Soo; Lee, Hyeon Gyu

    2016-06-15

    The potential of nanoencapsulation using bioactive coating materials for improving antithrombotic activities of red ginseng extract (RG) was examined. RG-loaded chitosan (CS) nanoparticles were prepared using antithrombotic materials, polyglutamic acid (PGA) or fucoidan (Fu). Both CS-PGA (P-NPs, 360 ± 67 nm) and CS-Fu nanoparticles (F-NPs, 440 ± 44 nm) showed sustained ginsenoside release in an acidic environment and improved ginsenoside solubility by approximately 122.8%. Both in vitro rabbit and ex vivo rat platelet aggregation of RG (22.3 and 41.5%) were significantly (p < 0.05) decreased within P-NPs (14.4 and 30.0%) and F-NPs (12.3 and 30.3%), respectively. Although RG exhibited no effect on in vivo carrageenan-induced mouse tail thrombosis, P-NPs and F-NPs demonstrated significant effects, likely the anticoagulation activity of PGA and Fu. Moreover, in the in vivo rat arteriovenous shunt model, P-NPs (156 ± 6.8 mg) and F-NPs (160 ± 3.2 mg) groups showed significantly lower thrombus formation than that of RG (190 ± 5.5 mg). Therefore, nanoencapsulation using CS, PGA, and Fu is a potential for improving the antithrombotic activity of RG. PMID:27181678

  19. Anticoagulant and antithrombotic activities of low-molecular-weight propylene glycol alginate sodium sulfate (PSS).

    PubMed

    Xin, Meng; Ren, Li; Sun, Yang; Li, Hai-hua; Guan, Hua-Shi; He, Xiao-Xi; Li, Chun-Xia

    2016-05-23

    Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action. PMID:26974373

  20. Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects.

    PubMed

    Cipriani, Thales R; Gracher, Ana Helena P; de Souza, Lauro M; Fonseca, Roberto J C; Belmiro, Celso L R; Gorin, Philip A J; Sassaki, Guilherme L; Iacomini, Marcello

    2009-05-01

    Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1-->4)-linked alpha-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent antithrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit alpha-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent. PMID:19404539

  1. Neuropsychiatry of Aggression

    PubMed Central

    Lane, Scott D.; Kjome, Kimberly L.; Moeller, F. Gerard

    2010-01-01

    Synopsis Aggression is a serious medical problem that can place both the patient and the health care provider at risk. Aggression can result from medical, neurologic and or psychiatric disorders. A comprehensive patient evaluation is needed. Treatment options include pharmacotherapy as well as non-pharmacologic interventions, both need to be individualized to the patient. PMID:21172570

  2. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy through…

  3. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

    Since many acts of aggression in society are more than simply an aggressor-victim encounter, the role played by third person instigated aggression also needs examination. The purpose of this study was to develop a laboratory procedure to systematically investigate instigation. In a competitive reaction time task, high and low Machiavellian Males…

  4. Angry and Aggressive Students

    ERIC Educational Resources Information Center

    Larson, Jim

    2008-01-01

    Students who engage in physical aggression in school present a serious challenge to maintaining a safe and supportive learning environment. Unlike other forms of student aggression, fighting is explicit, is violent, and demands attention. A fight between students in a classroom, hallway, or the lunchroom brings every other activity to a halt and…

  5. Girls' Aggressive Behavior

    ERIC Educational Resources Information Center

    Owens, Larry; Shute, Rosalyn; Slee, Phillip

    2004-01-01

    In contrast to boys' bullying behavior which is often overt and easily visible, girls' aggression is usually indirect and covert. Less research has been conducted on the types of bullying that girls usually engage in. Using focus groups composed of teenaged girls, Dr. Owens and colleagues examine the nature of teenage girls' indirect aggression.

  6. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  7. Aggression: Psychopharmacologic Management

    PubMed Central

    Conlon, Patrick; Frommhold, Kristine

    1989-01-01

    Aggression may be part of a variety of psychiatric diagnoses. The appropriate treatment requires that the physician recognize the underlying cause. Pharmacologic agents may form part of the overall treatment of the patient. The number of possible drugs for treating aggression has expanded rapidly, and it is important that the physician be familiar with the various options avilable. PMID:21248947

  8. CHOP versus CHOP plus ESHAP and high-dose therapy with autologous peripheral blood progenitor cell transplantation for high-intermediate-risk and high-risk aggressive non-Hodgkin's lymphoma.

    PubMed

    Intragumtornchai, T; Prayoonwiwat, W; Numbenjapon, T; Assawametha, N; O'Charoen, R; Swasdikul, D

    2000-12-01

    The purpose of the study was to compare conventional cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy with CHOP (3 courses) plus etoposide/methylprednisolone/high-dose cytarabine/cisplatin (ESHAP), high-dose therapy (HDT), and autologous peripheral blood progenitor cell transplantation (PBPCT) as front-line treatment for poor-prognosis aggressive non-Hodgkin's lymphoma (NHL). Between May 1, 1995, and April 30, 1998, 58 patients, aged 15-55 years, newly diagnosed with poor-prognosis aggressive NHL (category F-H by the Working Formulation) were enrolled. According to the age-adjusted international prognostic index, 65% of the patients were high-risk cases and 35% made up the high-intermediate group. After 3 courses of CHOP, 25 of 48 patients were randomized to continue with CHOP, and 23 were randomized to receive 2-4 cycles of ESHAP followed by HDT and PBPCT. There was no significant difference in the rate of complete remission between the two groups (36%, 95% confidence interval [CI]: 18%-57% in CHOP vs. 43%, 95% CI: 23%-65% in ESHAP/HDT) (P = 0.77). With a median follow-up duration of 39 months, the 4-year failure-free survival (FFS) was superior in the ESHAP/HDT group (38%, 95% CI: 18%-58% vs. 15%, 95% CI: 4%-32%) (P = 0.04). The disease-free survival was marginally different in favor of the ESHAP/HDT arm (90%, 95% CI: 47%-98% vs. 37%, 95% CI: 7%-69%) (P = 0.06). The 4-year overall survival between the two treatment arms was comparable (51%, 95% CI: 28%-70% for ESHAP/HDT vs. 30%, 95% CI: 13%-48% for CHOP) (P = 0.25). Treatment-related mortalities were not significantly different between both groups (17%, 95% CI: 5%-39% for ESHAP/HDT vs. 8%, 95% CI: 1%-26% for CHOP) (P = 0.41). However, only 61% of the patients assigned to the ESHAP/HDT arm underwent HDT and PBPCT. As compared with CHOP, the corporate regimen of CHOP/ESHAP/HDT seems to improve the FFS in patients with newly diagnosed, poor-prognosis aggressive NHL. PMID:11707834

  9. Salmonella-Based Therapy Targeting Indoleamine 2,3-Dioxygenase Coupled with Enzymatic Depletion of Tumor Hyaluronan Induces Complete Regression of Aggressive Pancreatic Tumors.

    PubMed

    Manuel, Edwin R; Chen, Jeremy; D'Apuzzo, Massimo; Lampa, Melanie G; Kaltcheva, Teodora I; Thompson, Curtis B; Ludwig, Thomas; Chung, Vincent; Diamond, Don J

    2015-09-01

    Bacterial-based therapies are emerging as effective cancer treatments and hold promise for refractory neoplasms, such as pancreatic ductal adenocarcinoma (PDAC), which has not shown significant improvement in therapy for more than 25 years. Using a novel combination of shIDO-ST, a Salmonella-based therapy targeting the immunosuppressive molecule indoleamine 2,3-dioxygenase (IDO), with an enzyme, PEGPH20, which depletes extracellular matrix hyaluronan, we observed extended survival with frequent total regression of autochthonous and orthotopic PDAC tumors. This observation was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not seen using a scrambled control (shScr-ST). Purified splenic PMNs from PEGPH20/shIDO-ST-treated mice exhibited significant IDO knockdown and were able to kill tumor targets ex vivo through mechanisms involving FasL and serine proteases. In addition, CD8(+) T cells were observed to contribute to late control of pancreatic tumors. Collectively, our data demonstrate that entry of shIDO-ST and PMNs into otherwise impermeable desmoplastic tumors is facilitated by PEGPH20-mediated HA removal, further highlighting an important component of effective treatment for PDAC. PMID:26134178

  10. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)*

    PubMed Central

    Lejeune, A.; Skorupski, K.; Frazier, S.; Vanhaezebrouck, I.; Rebhun, R. B.; Reilly, C. M.; Rodriguez, C. O.

    2016-01-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease-free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months. PMID:23721492

  11. Toxicity of aggressive multimodality therapy including cisplatinum, bleomycin and methotrexate with radiation and/or surgery for advanced head and neck cancer

    SciTech Connect

    Weichselbaum, R.R.; Posner, M.R.; Ervin, T.J.; Fabian, R.L.; Miller, D.

    1982-05-01

    A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one of whom required hospitalization. Late complications, possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weigh increased toxicity.

  12. Linkages between Aggression and Children's Legitimacy of Aggression Beliefs.

    ERIC Educational Resources Information Center

    Erdley, Cynthia A.; Asher, Steven R.

    To determine whether Slaby and Guerra's (1988) measure of aggression would reliably assess younger children's belief about aggression and whether children's belief about the legitimacy of aggression relates to their self-reports of it and to their levels of aggression as evaluated by peers, 781 fourth and fifth graders were asked to complete an…

  13. Aggressive Attitudes Predict Aggressive Behavior in Middle School Students.

    ERIC Educational Resources Information Center

    McConville, David W.; Cornell, Dewey G.

    2003-01-01

    This prospective study found that self-reported attitudes toward peer aggression among 403 middle school students were both internally consistent and stable over time (7 months). Aggressive attitudes were correlated with four outcome criteria for aggressive behavior: student self-report of peer aggression; peer and teacher nominations of bullying;…

  14. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  15. Holy Basil Leaf Extract Decreases Tumorigenicity and Metastasis of Aggressive Human Pancreatic Cancer Cells in vitro and in vivo: Potential Role in Therapy

    PubMed Central

    Shimizu, Tomohiro; Torres, María P.; Chakraborty, Subhankar; Souchek, Joshua J.; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K.; Hauke, Ralph J; Batra, Surinder K.

    2013-01-01

    There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

  16. Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: potential role in therapy.

    PubMed

    Shimizu, Tomohiro; Torres, María P; Chakraborty, Subhankar; Souchek, Joshua J; Rachagani, Satyanarayana; Kaur, Sukhwinder; Macha, Muzafar; Ganti, Apar K; Hauke, Ralph J; Batra, Surinder K

    2013-08-19

    There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum ("Holy Basil") has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p<0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future. PMID:23523869

  17. Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model.

    PubMed Central

    Takiguchi, Y.; Asai, F.; Wada, K.; Hayashi, H.; Nakashima, M.

    1995-01-01

    1. The antithrombotic effect of a new specific thrombin inhibitor, CX-397, was examined in a photochemically-induced arterial thrombosis model in the rat femoral artery and compared with that of heparin. 2. Pretreatment with CX-397 (10, 20 and 40 micrograms kg-1 min-1, i.v.) from 15 min before the experiment prolonged the time required for thrombotic occlusion of the artery in a dose-dependent manner. The antithrombotic efficacy of CX-397 was associated with modest increases in activated partial thromboplastin time (APTT) and template bleeding time. 3. On the other hand, heparin at a dose of 450 micrograms kg-1 markedly prolonged APTT and the bleeding time, but did not inhibit thrombo-occlusion. 4. CX-397 selectively inhibited platelet aggregation and concurrent secretion of 5-hydroxytryptamine (5-HT) and thromboxane A2 (TXA2) production from platelets in response to thrombin, but not to collagen and ADP, in a dose-dependent manner (5-100 ng ml-1). 5. CX-397 at 10 micrograms kg-1 combined with vapiprost, a TXA2 receptor antagonist, at 0.1 mg kg-1 significantly prevented occlusion, whereas, at these doses, neither drug alone had much effect. 6. These results demonstrate that CX-397 may prove to be more efficient for preventing platelet-rich thrombosis than heparin. Thrombin may play an important role in the rat thrombosis model. 7. The additive antithrombotic effect of the combination of thrombin inhibitor and TXA2 receptor antagonist at low doses suggests that thrombin and TXA2 may work in concert to produce thrombosis. Images Figure 3 PMID:8680743

  18. Prothrombotic risk factors and antithrombotic therapy in children with ischemic stroke

    PubMed Central

    Askar, Gamal A.; Abu Faddan, Naglaa H.; Kamal, Taghreed M.

    2015-01-01

    Objective: Congenital and acquired prothrombotic disorders have been highlighted in a recent series of cerebrovascular stroke (CVS), with a controversial role in pathogenesis. The aim is to study some prothrombotic risk factors [activated protein C (APC) resistance, von Willebrand factor (vWF), anticardiolpin (ACL) antibodies and plasma homocysteine] in children with ischemic stroke, and to evaluate the role of aspirin and low molecular weight heparin (LMWH) in its management in relation to outcome. Methods: A total of 37 cases aged from 1 month to 15 years ( mean ± standard deviation 26.2 ± 35.7 months), diagnosed as ischemic stroke (>24 hours) were recruited. Complete blood count, prothrombin time and concentration, partial thromboplastin time, serum electrolytes, random blood sugar, C-reactive protein, electrocardiogram and echocardiography were done. Levels of APC resistance, vWF, ACL antibodies [immunoglobulin G (IgG) and immunoglobulin M (IgM)] and plasma homocysteine were estimated. A total of 25 cases received aspirin 3–5 mg /kg/d and 12 patients received LMWH as initial dose at 75 international units (IU)/kg subcutaneously (SC) then 10–25 IU/kg/day for 15 days in a nonrandomized fashion. Results: The levels of APC resistance, vWF, ACL antibodies (IgG and IgM) and plasma homocysteine were significantly higher in stroke cases than in controls. There was no significant difference between cases treated with aspirin and those with LMWH in all prothrombotic factors. Significant positive correlations were found between vWF and ACL antibodies (IgG and IgM) levels before treatment. Significant decrease in cognitive function was detected between cases treated with LMWH and those treated with aspirin. Conclusion: Ischemic CVS in children is multifactorial. Thrombophilia testing should be performed in any child with CVS. Early use of aspirin improves the prognosis and has less effect on cognitive function. PMID:25922619

  19. Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy

    PubMed Central

    Angelillo-Scherrer, Anne; Burnier, Laurent; Flores, Nathalie; Savi, Pierre; DeMol, Maria; Schaeffer, Paul; Herbert, Jean-Marc; Lemke, Greg; Goff, Stephen P.; Matsushima, Glenn K.; Earp, H. Shelton; Vesin, Christian; Hoylaerts, Marc F.; Plaisance, Stéphane; Collen, Désiré; Conway, Edward M.; Wehrle-Haller, Bernhard; Carmeliet, Peter

    2005-01-01

    Mechanisms regulating thrombus stabilization remain largely unknown. Here, we report that loss of any 1 of the Gas6 receptors (Gas6-Rs), i.e., Tyro3, Axl, or Mer, or delivery of a soluble extracellular domain of Axl that traps Gas6 protects mice against life-threatening thrombosis. Loss of a Gas6-R does not prevent initial platelet aggregation but impairs subsequent stabilization of platelet aggregates, at least in part by reducing “outside-in” signaling and platelet granule secretion. Gas6, through its receptors, activates PI3K and Akt and stimulates tyrosine phosphorylation of the β3 integrin, thereby amplifying outside-in signaling via αIIbβ3. Blocking the Gas6-R–αIIbβ3 integrin cross-talk might be a novel approach to the reduction of thrombosis. PMID:15650770

  20. Antiplatelet Therapy in TAVI: Current Clinical Practice and Recommendations.

    PubMed

    Magkoutis, Nikolaos A; Fradi, Sabi; Azmoun, Alexandre; Ramadan, Ramsi; Ben Ouanes, Sami; Vavuranakis, Manolis; Vrachatis, Dimitrios A; Papaioannou, Theodore G; Tousoulis, Dimitrios; Ghostine, Saïd

    2016-01-01

    Transcatheter aortic valve implantation (TAVI) is all the more used therapeutic option for patients suffering from symptomatic severe aortic valvular stenosis declined by surgeons because of high surgical risk. Given the high bleeding and ischemic risk of this vulnerable population, their antithrombotic treatment becomes a crucial issue. There is no consensus on antithrombotic treatment after TAVI and dual antiplatelet therapy (DAPT) with aspirin (indefinitely) and clopidogrel (1-6 months) is, in general, recommended. With regards to patients with an indication for oral anticoagulation (OAC), a combination of OAC plus aspirin or clopidogrel is commonly suggested. This review underscores that it is extremely difficult to compare different antithrombotic regimens in patients undergoing TAVI because of their variable demographic characteristics. Nevertheless, available data suggest that DAPT results to more bleeding events. Still, whether it positively affects ischemic episodes is doubtful. Ongoing trials are expected to draw a clearer picture on the field. PMID:26898915

  1. The top 4 advances in antithrombotic care in the last year.

    PubMed

    Turpie, Alexander G G

    2008-01-01

    Important clinical data with a significant impact on the clinical management of venous thromboembolism (VTE) were presented at The International Society of Thrombosis and Haemostasis (ISTH) meeting, held in Geneva, Switzerland in July of 2007. In addition, 2 new guidelines for the management of patients with acute coronary syndromes (ACS) were published in 2007, and will have a significant impact on daily practice. Finally, the approval of new practice-changing, paradigm-shifting oral anticoagulants is on the horizon. This article will review the top 4 advances in antithrombotic care and discuss their impact on the clinical management of VTE. PMID:18834617

  2. Platelet collagen receptors and coagulation. A characteristic platelet response as possible target for antithrombotic treatment.

    PubMed

    Heemskerk, Johan W M; Kuijpers, Marijke J E; Munnix, Imke C A; Siljander, Pia R M

    2005-04-01

    Collagen is a unique agonist of platelets, because it acts as an immobilized ligand that only causes platelet activation after stable adhesion. This review addresses the present understanding of how platelet interaction with collagen supports the process of thrombin generation and coagulation. Only some of the collagen-adhered platelets, that is, those showing profound changes in shape and shedding microparticles (resembling apoptotic cells), appear to contribute to the procoagulant activity of platelets. The main signaling receptor for collagen, glycoprotein VI, plays a key role in the platelet procoagulant response during thrombus formation; this is a reason why new anti-glycoprotein-VI antibodies are promising antithrombotic tools. PMID:16039967

  3. Response-Adapted Therapy for Aggressive non-Hodgkin's Lymphomas based on early [18F] FDG-PET Scanning: ECOG-ACRIN Cancer Research Group Study (E3404)

    PubMed Central

    Swinnen, Lode J.; Li, Hailun; Quon, Andrew; Gascoyne, Randy; Hong, Fangxin; Ranheim, Erik A.; Habermann, Thomas M.; Kahl, Brad S.; Horning, Sandra J.; Advani, Ranjana H.

    2015-01-01

    A persistently positive positron emission tomography (PET) scan during therapy for diffuse large B-cell lymphoma (DLBCL) is predictive of treatment failure. A response-adapted strategy consisting of an early treatment change to four cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) was studied in the Eastern Cooperative Oncology Group E3404 trial. Previously untreated patients with DLBCL stage III, IV, or bulky II, were eligible. PET scan was performed after 3 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and scored as positive or negative by central review during the fourth cycle. PET-positive patients received 4 cycles of R-ICE, PET-negative patients received 2 more cycles of R-CHOP. A ≥45% 2-year progression-free survival (PFS) for mid-treatment PET-positive patients was viewed as promising. Of 74 patients, 16% were PET positive, 79% negative. The PET positivity rate was much lower than the 33% expected. Two-year PFS was 70%; 42% (90% confidence interval [CI], 19-63%) for PET-positives and 76% (90% CI 65-84%) for PET-negatives. Three-year overall survival (OS) was 69% (90% CI 43-85%) and 93% (90% CI 86-97%) for PET-positive and –negative cases, respectively. The 2-year PFS for mid-treatment PET-positive patients intensified to R-ICE was 42%, with a wide confidence interval due to the low proportion of positive mid-treatment PET scans. Treatment modification based on early PET scanning should remain confined to clinical trials. PMID:25823885

  4. Folic-acid metabolism and DNA-repair phenotypes differ between neuroendocrine lung tumors and associate with aggressive subtypes, therapy resistance and outcome

    PubMed Central

    Werner, Robert; Vollbrecht, Claudia; Hager, Thomas; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Christoph, Daniel Christian

    2016-01-01

    Purpose 25% of all lung cancer cases are neuroendocrine (NELC) including typical (TC) and atypical carcinoid (AC), large-cell neuroendocrine (LCNEC) and small cell lung cancer (SCLC). Prognostic and predictive biomarkers are lacking. Experimental Design Sixty patients were used for nCounter mRNA expression analysis of the folic-acid metabolism (ATIC, DHFR, FOLR1, FPGS, GART, GGT1, SLC19A1, TYMS) and DNA-repair (ERCC1, MLH1, MSH2, MSH6, XRCC1). Phenotypic classification classified tumors (either below or above the median expression level) with respect to the folic acid metabolism or DNA repair. Results Expression of FOLR1, FPGS, MLH1 and TYMS (each p<0.0001) differed significantly between all four tumor types. FOLR1 and FPGS associated with tumor differentiation (both p<0.0001), spread to regional lymph nodes (FOLR1 p=0.0001 and FPGS p=0.0038), OS and PFS (FOLR1 p<0.0050 for both and FPGS p<0.0004 for OS). Phenotypic sorting revealed the Ft-phenotype to be the most prominent expression profile in carcinoids, whereas SCLC presented nearly univocal with the fT and LCNEC with fT or ft. These results were significant for tumor subtype (p<0.0001). Conclusions The assessed biomarkers and phenotypes allow for risk stratification (OS, PFS), diagnostic classification and enhance the biological understanding of the different subtypes of neuroendocrine tumors revealing potential new therapy options and clarifying known resistance mechanisms. PMID:27064343

  5. Adolescents’ Aggression to Parents: Longitudinal Links with Parents’ Physical Aggression

    PubMed Central

    Margolin, Gayla; Baucom, Brian R.

    2014-01-01

    Purpose To investigate whether parents’ previous physical aggression (PPA) exhibited during early adolescence is associated with adolescents’ subsequent parent-directed aggression even beyond parents’ concurrent physical aggression (CPA); to investigate whether adolescents’ emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. Methods Adolescents (N = 93) and their parents participated in a prospective, longitudinal study. Adolescents and parents reported at waves 1–3 on four types of parents’ PPA (mother-to-adolescent, father-to-adolescent, mother-to-father, father-to-mother). Wave 3 assessments also included adolescents’ emotion dysregulation, attitudes condoning aggression, and externalizing behaviors. At waves 4 and 5, adolescents and parents reported on adolescents’ parent-directed physical aggression, property damage, and verbal aggression, and on parents’ CPA Results Parents’ PPA emerged as a significant indicator of adolescents’ parent-directed physical aggression (odds ratio [OR]: 1.25, 95% confidence interval [CI]: 1.0–1.55; p = .047), property damage (OR: 1.29, 95% CI: 1.1–1.5, p = .002), and verbal aggression (OR: 1.35, 95% CI: 1.15–1.6, p < .001) even controlling for adolescents’ sex, externalizing behaviors, and family income. When controlling for parents’ CPA, previous mother-to-adolescent aggression still predicted adolescents’ parent-directed physical aggression (OR: 5.56, 95% CI: 1.82–17.0, p = .003), and father-to-mother aggression predicted adolescents’ parent-directed verbal aggression (OR: 1.86, 95% CI: 1.0–3.3, p = .036). Emotion dysregulation and attitudes condoning aggression did not produce direct or moderated effects. Conclusions Adolescents’ parent-directed aggression deserves greater attention in discourse about lasting, adverse effects of even minor forms of parents’ physical aggression. Future research should investigate parent-directed aggression as

  6. Antithrombotic effects of the effective components group of Xiaoshuantongluo formula in vivo and in vitro.

    PubMed

    Zhao, Yan; Chu, Xiao; Pang, Xiao-Bin; Wang, Shao-Hua; DU, Guan-Hua

    2015-02-01

    The present study was designed to investigate the antithrombotic effects and underlying mechanisms of the effective components group (ECG) of Xiaoshuantongluo recipe (XECG) and to further verify the rationality and feasibility of ECG-guided methodology in traditional Chinese medicine (TCM) research. The arterial thrombosis model induced by ferric chloride (FeCl3) oxidation and the venous thrombosis model induced by inferior vena cava ligation were established to evaluate the antithrombotic potential of XECG. Our results indicated that XECG significantly prolonged the time to occlusion, activated partial thromboplastin time (APTT), and prothrombin time (PT), and markedly inhibited adenosine diphosphate (ADP)-induced platelet aggregation in the 20% FeCl3-induced arterial thrombosis model. The superoxide dismutase (SOD) activity was significantly increased and the levels of malondialdehyde (MDA) and nitric oxide (NO) were dramatically decreased in the plasma of arterial thrombosis rats after XECG treatment for 12 days. Furthermore, XECG markedly reduced the weight of thrombus formed by inferior vena cava ligation. Additionally, XECG exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and protective effect on mitochondrial lipid peroxidation. In summary, XECG played an important role in the prevention of thrombosis through interacting with multiple targets, including inhibition of platelet aggregation and coagulation and repression of oxidative stress. The ECG-guided methodology was validated as a feasible tool in TCM research. PMID:25769892

  7. Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions

    PubMed Central

    Zhang, Chao; Zhang, Lin; Zhang, Youcai; Sun, Na; Jiang, Shaoyi; Fujihara, Timothy J.; Sun, Yan

    2016-01-01

    An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall. PMID:27195826

  8. Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Zhang, Lin; Zhang, Youcai; Sun, Na; Jiang, Shaoyi; Fujihara, Timothy J.; Sun, Yan

    2016-05-01

    An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall.

  9. Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions.

    PubMed

    Zhang, Chao; Zhang, Lin; Zhang, Youcai; Sun, Na; Jiang, Shaoyi; Fujihara, Timothy J; Sun, Yan

    2016-01-01

    An antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall. PMID:27195826

  10. Microbiology of aggressive periodontitis.

    PubMed

    Könönen, Eija; Müller, Hans-Peter

    2014-06-01

    For decades, Aggregatibacter actinomycetemcomitans has been considered the most likely etiologic agent in aggressive periodontitis. Implementation of DNA-based microbiologic methodologies has considerably improved our understanding of the composition of subgingival biofilms, and advanced open-ended molecular techniques even allow for genome mapping of the whole bacterial spectrum in a sample and characterization of both the cultivable and not-yet-cultivable microbiota associated with periodontal health and disease. Currently, A. actinomycetemcomitans is regarded as a minor component of the resident oral microbiota and as an opportunistic pathogen in some individuals. Its specific JP2 clone, however, shows properties of a true exogenous pathogen and has an important role in the development of aggressive periodontitis in certain populations. Still, limited data exist on the impact of other microbes specifically in aggressive periodontitis. Despite a wide heterogeneity of bacteria, especially in subgingival samples collected from patients, bacteria of the red complex in particular, and those of the orange complex, are considered as potential pathogens in generalized aggressive periodontitis. These types of bacterial findings closely resemble those found for chronic periodontitis, representing a mixed polymicrobial infection without a clear association with any specific microorganism. In aggressive periodontitis, the role of novel and not-yet-cultivable bacteria has not yet been elucidated. There are geographic and ethnic differences in the carriage of periodontitis-associated microorganisms, and they need to be taken into account when comparing study reports on periodontal microbiology in different study populations. In the present review, we provide an overview on the colonization of potential periodontal pathogens in childhood and adolescence, and on specific microorganisms that have been suspected for their role in the initiation and progression of aggressive

  11. Anonymity, Deindividuation and Aggression.

    ERIC Educational Resources Information Center

    Baron, Robert S.

    Several writers suggest that reducing one's sense of individuality reduces social restraints. The author suggests that the effect of uniformity of appearance on aggression is unclear when anonymity is held constant. This poses a problem of interpretation given that a distinction must be made between lack of individuality and anonymity. One must…

  12. Intellectual Competence and Aggression.

    ERIC Educational Resources Information Center

    Huesmann, L. Rowell; Yarmel, Patty Warnick

    Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…

  13. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  14. Stability of Aggressive Behavior.

    ERIC Educational Resources Information Center

    Eron, Leonard D.; Huesmann, L. Rowell

    As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

  15. Relational Aggression among Students

    ERIC Educational Resources Information Center

    Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.

    2011-01-01

    "Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…

  16. Parents' Aggressive Influences and Children's Aggressive Problem Solutions with Peers

    ERIC Educational Resources Information Center

    Duman, Sarah; Margolin, Gayla

    2007-01-01

    This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…

  17. Relational Aggression and Physical Aggression among Adolescent Cook Islands Students

    ERIC Educational Resources Information Center

    Page, Angela; Smith, Lisa F.

    2016-01-01

    Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…

  18. The management of adult aggressive non-Hodgkin's lymphomas.

    PubMed

    Couderc, B; Dujols, J P; Mokhtari, F; Norkowski, J L; Slawinski, J C; Schlaifer, D

    2000-07-01

    Aggressive non-Hodgkin's lymphona include diffuse large B-cell lymphoma, anaplastic large cell lymphona, and different peripheral T-cell lymphomas. An international prognostic index has been developed including age, serum LDH, performance status, and extranodal involvement. For localized aggressive lymphoma, the preferred treatment is 3-4 CHOP and radiation therapy, with a cure rate of 70-80%. For disseminated aggressive lymphoma, current regimens have a cure rate of less than 40%. Innovative strategies, including dose escalation, autologus stem cell support, new drugs, and immunotherapy are being explored to improve these results. PMID:10863150

  19. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

    White subjects were aggressive toward Black opponents when contest results appeared to reflect elements of reverse discrimination; but they showed less aggressive behavior toward Black opponents when they thought their loss was due to their opponents' superior ability. (RL)

  20. Coping with Agitation and Aggression

    MedlinePlus

    Alzheimer ’s Caregiving Tips Coping with Agitation and Aggression People with Alzheimer’s disease may become agitated or aggressive as the disease gets worse. Agitation means that a person is restless or worried. ...

  1. Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo.

    PubMed

    Kramkowski, K; Leszczynska, A; Przyborowski, K; Kaminski, T; Rykaczewska, U; Sitek, B; Zakrzewska, A; Proniewski, B; Smolenski, R T; Chabielska, E; Buczko, W; Chlopicki, S

    2016-05-01

    The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery. Sodium nitrite (NaNO2, 0.17 mmol/kg twice daily for 3 days, p.o) was administered with or without one of the XOR-inhibitors: allopurinol (ALLO) and febuxostat (FEB) (100 and 5 mg/kg, p.o., for 3 days). Nitrite treatment (0.17 mmol/kg), which was associated with a significant increase in NOHb, nitrite/nitrate plasma concentration, resulted in a substantial decrease in thrombus weight (TW) (0.48 ± 0.03 mg vs. vehicle [VEH] 0.88 ± 0.08 mg, p < 0.001) without a significant hypotensive effect. The anti-thrombotic effect of nitrite was partially reversed by FEB (TW = 0.63 ± 0.06 mg, p < 0.05 vs. nitrites), but not by ALLO (TW = 0.43 ± 0.02 mg). In turn, profound anti-platelet effect of nitrite measured ex vivo using collagen-induced whole-blood platelet aggregation (70.5 ± 7.1% vs. VEH 100 ± 4.5%, p < 0.05) and dynamic thromboxaneB2 generation was fully reversed by both XOR-inhibitors. In addition, nitrite decreased plasminogen activator inhibitor-1 concentration (0.47 ± 0.13 ng/ml vs. VEH 0.62 ± 0.04 ng/ml, p < 0.05) and FEB/ALLO reversed this effect. In vitro the anti-platelet effect of nitrite (1 mM) was reversed by FEB (0.1 mM) under hypoxia (0.5%O2) and normoxia (20%O2). Nitrite treatment had no effect on coagulation parameters. In conclusion, the nitrite-induced anti-platelet effect in rats in vivo is mediated by XOR, but XOR does not fully account for the anti-thrombotic effects of nitrite. PMID:26374946

  2. Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    PubMed Central

    Amann, Birgit H.

    2016-01-01

    Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when

  3. Serotonin and Aggressiveness in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin (5-HT) regulates aggressive behavior in animals. This study examined if 5-HT regulation of aggressiveness is gene-dependent. Chickens from two divergently selected lines KGB and MBB (Kind Gentle Birds and Mean Bad Birds displaying low and high aggressiveness, respectively) and DXL (Dekalb ...

  4. Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans

    PubMed Central

    Lee, Wonhwa; Lee, JungIn; Kulkarni, Roshan; Kim, Mi-Ae; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

    2016-01-01

    The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants. PMID:26905699

  5. Children's normative beliefs about aggression and aggressive behavior.

    PubMed

    Huesmann, L R; Guerra, N G

    1997-02-01

    Normative beliefs have been defined as self-regulating beliefs about the appropriateness of social behaviors. In 2 studies the authors revised their scale for assessing normative beliefs about aggression, found that it is reliable and valid for use with elementary school children, and investigated the longitudinal relation between normative beliefs about aggression and aggressive behavior in a large sample of elementary school children living in poor urban neighborhoods. Using data obtained in 2 waves of observations 1 year apart, the authors found that children tended to approve more of aggression as they grew older and that this increase appeared to be correlated with increases in aggressive behavior. More important, although individual differences in aggressive behavior predicted subsequent differences in normative beliefs in younger children, individual differences in aggressive behavior were predicted by preceding differences in normative beliefs in older children. PMID:9107008

  6. Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial.

    PubMed

    Choi, Ae-Na; Lee, Myeong Soo; Lee, Jung-Sook

    2010-06-01

    We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

  7. Group Music Intervention Reduces Aggression and Improves Self-esteem in Children with Highly Aggressive Behavior: A Pilot Controlled Trial

    PubMed Central

    Lee, Myeong Soo; Lee, Jung-Sook

    2010-01-01

    We investigated the effects of group music intervention on aggression and self-esteem in children with highly aggressive behavior. Forty-eight children were allocated to either a music intervention group or an untreated control group. The music intervention group received 50 min of music intervention twice weekly for 15 consecutive weeks. The outcome measures were Child Behavior Checklist Aggression Problems Scale (Parents), Child Aggression Assessment Inventory (Teachers) and Rosenberg Self-esteem Scale. After 15 weeks, the music intervention group showed significant reduction of aggression and improvement of self-esteem compared with the control group. All outcome measures were significantly lower in the music intervention group than prior to treatment, while there was no change in the control group. These findings suggest that music can reduce aggressive behavior and improve self-esteem in children with highly aggressive behavior. Music intervention is an easily accessible therapy for children and as such may be an effective intervention for aggressive behavior. Further more, objective and replicable measures are required from a randomized controlled trial with a larger sample size and active comparable control. PMID:18955314

  8. Motives in Sexual Aggression: The Chinese Context.

    ERIC Educational Resources Information Center

    Tang, Catherine So-Kum; And Others

    1993-01-01

    Compared sexual and aggressive motives for sexual aggression in Chinese college students. Male undergraduates (N=146) completed self-report measures. Results suggest that sex guilt and aggressive guilt acted as inhibitors for their respective drives and sexual aggression resulted from aggressive, rather than sexual, motives. Sexual aggression may…

  9. Effectiveness of ECT combined with risperidone against aggression in schizophrenia.

    PubMed

    Hirose, S; Ashby, C R; Mills, M J

    2001-03-01

    Aggressive behavior in schizophrenic patients can often be problematic not only for the patients themselves, but for their families and others. This study examined the effect of electroconvulsive therapy (ECT) in combination with risperidone in an open trial in 10 male schizophrenic patients with significant aggressive behaviors. Patients were given bilateral ECT five times a week in combination with risperidone. The mean total number of times of ECT was 6.6 (range 5-9). The aggressive behavior in five of the six patients, who showed positive symptoms, was rapidly ameliorated within 12 days. The ECT/risperidone regimen also eliminated aggressive behavior in four patients showing no positive symptoms within 10 days. These treatment effects lasted for at least 6 months in 9 (of the 10) patients. The results suggest that ECT, combined with risperidone, produce a rapid and effective elimination of aggressive behaviors in schizophrenic patients. In addition, there was a resolution of aggression in four patients with no positive symptoms. This suggests that aggression in some schizophrenic patients develops as a primary symptom of schizophrenia and is not related to other positive symptoms of the disease or the patient's personality traits. PMID:11281510

  10. [Multicomponent antithrombotic effect of the neuroprotective prolyl dipeptide GVS-111 and its major metabolite cyclo-L-prolylglycine].

    PubMed

    Ostrovskaia, R U; Liapina, L A; Pastorova, V E; Mirzoev, T Kh; Gudasheva, T A; Seredenin, S B; Ashmarin, I P

    2002-01-01

    The experiments in vivo showed that the new nootropic prolyl-containing GVS-111 produces an antithrombotic effect, influencing various stages of the blood coagulation process. GVS-111 exhibits anticoagulant and fibrinolytic properties and enhances fibrin destabilization by reducing the XIIIa factor activity. These effects are manifested upon both intraperitoneal (1 mg/kg) and peroral (10 mg/kg) administration of GVS-111 (in both cases, a single daily treatment over a period of 10 days). The same effects (anticoagulant, fibrinolytic, antifibrin-stabilizing) were observed in in vitro experiments with both GVS-111 (10(-3)-10(-6) M) and its main metabolite cyclo-L-prolylglycine (up to 10(-10) M). In addition, the latter metabolite exhibited an antiaggregant effect. The antithrombotic activity of GVS-111, together with previously established neuroprotector properties, low toxicity, and the absence of complications, makes this compound a promising antistroke drug. PMID:12109290