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Sample records for aggressive antithrombotic therapy

  1. 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

  2. Antithrombotic therapy for pregnancy loss.

    PubMed

    de Jong, Paulien G; Goddijn, Mariëtte; Middeldorp, Saskia

    2013-01-01

    BACKGROUND Although an association between thrombophilia and pregnancy loss has been observed in many studies, little is known about the pathophysiological mechanisms behind this association. Considering the association between thrombophilia and pregnancy loss, the efficacy of antithrombotic therapy for women with pregnancy loss (with or without thrombophilia) has been studied for the past 30 years. METHODS We performed a comprehensive review of the literature on the strength of the association between thrombophilia and pregnancy loss, the pathophysiological mechanisms and the efficacy of antithrombotic therapy to increase the chance of live birth. RESULTS The association between pregnancy loss and thrombophilia varies according to the type of thrombophilia (e.g. antiphospholipid syndrome versus forms of inherited thrombophilia) and according to the type of pregnancy loss (single versus recurrent pregnancy loss and early versus late pregnancy loss). Thrombophilia may induce thrombosis in decidual vessels or impair placentation through hypercoagulability and inflammation, but these hypotheses need further verification. For women with antiphospholipid syndrome, evidence from small-sized trials suggests a beneficial effect of antithrombotic therapy but additional randomized controlled trials are essential to confirm this. Whether antithrombotic therapy increases the chance of live birth in women with inherited thrombophilia is unknown. Recent randomized controlled trials have consistently shown that antithrombotic therapy does not increase the chance of live birth in women with unexplained recurrent miscarriage. CONCLUSIONS There are large gaps in knowledge and a lack of evidence for treatment of women with pregnancy loss with thrombophilia. To provide a solid base for clinical practice, further studies on the role of coagulation in reproduction, as well as international collaborations in randomized controlled trials of antithrombotic therapy in women with pregnancy

  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. VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy

    PubMed Central

    Greer, Ian A.; Middeldorp, Saskia; Veenstra, David L.; Prabulos, Anne-Marie; Vandvik, Per Olav

    2012-01-01

    Background: The use of anticoagulant therapy during pregnancy is challenging because of the potential for both fetal and maternal complications. This guideline focuses on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. Methods: The methods of this guideline follow 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 in this supplement. Results: We recommend low-molecular-weight heparin for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). For pregnant women with acute VTE, we suggest that anticoagulants be continued for at least 6 weeks postpartum (for a minimum duration of therapy of 3 months) compared with shorter durations of treatment (Grade 2C). For women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses, we recommend antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin (75-100 mg/d) over no treatment (Grade 1B). For women with inherited thrombophilia and a history of pregnancy complications, we suggest not to use antithrombotic prophylaxis (Grade 2C). For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B). Conclusions: Most recommendations in this guideline are based on observational studies and extrapolation from other populations. There is an urgent need for appropriately designed studies in this population. PMID:22315276

  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 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

  8. Antithrombotic therapy for pregnant women.

    PubMed

    Toyoda, Kazunori

    2013-01-01

    Coagulability increases during pregnancy, and thromboembolism can easily occur. Venous thromboembolism is a cause of death in pregnant women, but arterial thrombosis such as ischemic stroke in pregnancy is also not uncommon. In pharmacotherapy for thromboembolism in pregnant women, fetal toxicity and teratogenicity must be carefully considered. As anticoagulants in pregnant women, unfractionated heparin and low-molecular-weight heparin are recommended, but warfarin is not recommended since it has a low molecular weight and crosses the placenta. Various types of new oral anticoagulant drugs have been available in Japan since 2011. However, the Japanese package inserts for these anticoagulants advise quite cautious administration in pregnant women. The guidelines on pregnant women include less information about antiplatelet drugs than anticoagulant drugs. Aspirin may cause teratogenicity and fetal toxicity, and perinatal mortality is increased. However, when low doses of aspirin are administered as antiplatelet therapy, the US Food and Drug Administration has assigned pregnancy category C, and treatment is relatively safe. Neurosurgeons and neurologists commonly encounter pregnant women with thromboembolism, such as ischemic stroke. Up-to-date information and correct selection of drugs are necessary in consultation with specialists in perinatal care.

  9. [Antithrombotic therapy in atrial arrhythmia].

    PubMed

    Cohen, Ariel

    2004-02-15

    The principal complication of the atrial arrythmias is the thrombo-embolic accident, notably the cerebro-vascular accident. The efficacity of the oral anticoagulants in reducing cerebro-vascular accidents has been demonstrated in numerous studies. This is significantly superior to that obtained with the anti-platelet drugs. However, the anti-vitamin K drugs (warfarin) carry a risk of serious haemorrhage of around 5% per year. This restricts the proposal of this treatment to patients with an elevated risk of vascular accidents: age, diabetes, previous cerebro-vascular accidents, and cardiac failure are the risk factors. Nevertheless, the risk of haemorrhage is responsible for an under prescription of the anticoagulants in the elderly. This explains the interest aroused by alternative therapeutics: the results of trials on ximelagatran, a direct anti-thrombin, are promising. In patients with an arrythmia, cardioversion carries a thrombo-embolic risk of around 1%. This risk is reduced by prior anticoagulant treatment. The procedure for this treatment is orientated by a trans-oesophageal echocardiogram. The incertitude of the duration of anticoagulant therapy without cardioversion calls for respect of the arrythmia. The treatment of this is limited to control of the cardiac rhythm and anticoagulant treatment.

  10. Antithrombotic Therapy in Peripheral Artery Disease

    PubMed Central

    Alonso-Coello, Pablo; Bellmunt, Sergi; McGorrian, Catherine; Anand, Sonia S.; Guzman, Randolph; Criqui, Michael H.; Akl, Elie A.; Olav Vandvik, Per; Lansberg, Maarten G.; Guyatt, Gordon H.

    2012-01-01

    Background: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD). 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: The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B). Conclusions: Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of

  11. 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

  12. 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

  13. Venous thromboembolism and antithrombotic therapy in pregnancy.

    PubMed

    Chan, Wee-Shian; Rey, Evelyne; Kent, Nancy E; Chan, Wee-Shian; Kent, Nancy E; Rey, Evelyne; Corbett, Thomas; David, Michèle; Douglas, M Joanne; Gibson, Paul S; Magee, Laura; Rodger, Marc; Smith, Reginald E

    2014-06-01

    To present an approach, based on current evidence, for the diagnosis, treatment, and thromboprophylaxis of venous thromboembolism in pregnancy and postpartum. Published literature was retrieved through searches of PubMed, Medline, CINAHL, and The Cochrane Library from November 2011 to July 2013 using appropriate controlled vocabulary (e.g. pregnancy, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pulmonary thrombosis) and key words (e.g., maternal morbidity, pregnancy complications, thromboprophylaxis, antithrombotic therapy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English or French. There were no date restrictions. Grey (unpublished) literature was identified through searching the websites of clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1).

  14. Antithrombotic therapy for secondary stroke prevention.

    PubMed

    Alberts, Mark J

    2011-12-01

    : Antithrombotic therapy is a key component of any strategy for the secondary prevention of ischemic stroke. A better understanding of the various therapeutic options will lead to improved stroke prevention, better medication adherence, and fewer complications. : Antiplatelet agents and anticoagulants are the two major classes of antithrombotic therapy used for stroke prevention. The etiology and mechanism of the stroke must be considered in order to make the best decision regarding which agent(s) to use for secondary stroke prevention. The recent Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study showed that clopidogrel and aspirin plus extended-release dipyridamole had similar event rates in terms of recurrent stroke, but clopidogrel was better tolerated, with fewer bleeding events. Several new anticoagulants are poised to replace warfarin for stroke prevention in the setting of atrial fibrillation. These include dabigatran (a new oral direct thrombin inhibitor) and possibly apixaban (a new oral factor Xa inhibitor). These new medications are much easier to use than warfarin and may be more effective and safer, with fewer drug and food interactions and no need for routine blood monitoring. Thus, these new medications may improve adherence as well as clinicians' inclination to treat with anticoagulation. : Because each antiplatelet agent or anticoagulant has certain advantages and disadvantages, clinicians must choose an agent that the patient can afford and tolerate in terms of side effects and adherence. The hope and expectation is that the proper use of these medications in accordance with current guidelines will reduce the risk of a recurrent stroke.

  15. Antithrombotic therapy in patients with cerebral microbleeds.

    PubMed

    Wilson, Duncan; Werring, David J

    2017-02-01

    Cerebral microbleeds (CMBs) are a radiological marker of cerebral small vessel disease corresponding to small haemosiderin foci identified by blood-sensitive MRI. CMBs are common in older community populations, and in individuals with ischaemic stroke or transient ischaemic attack (TIA), and intracerebral haemorrhage (ICH). We summarize how CMBs might contribute to assessing the future risk of ischaemic stroke and ICH to inform antithrombotic (antiplatelet or anticoagulant) decisions. CMBs are a risk factor for future ischaemic stroke and ICH in all community and hospital populations studied. Following ischaemic stroke/TIA treated with antithrombotics, increasing CMB burden increases the risk of ICH more steeply than that of ischaemic stroke. In ICH populations the risk of recurrent ICH increases with CMB burden, and is highest in those with strictly lobar CMBs or other haemorrhagic findings (e.g. cortical superficial siderosis) suggesting cerebral amyloid angiopathy (CAA). In ischaemic stroke or patients with TIA less than five CMBs should not affect antithrombotic decisions, although with more than five CMBs the risks of future ICH and ischaemic stroke are finely balanced, and antithrombotics might cause net harm. In lobar ICH populations, a high burden of strictly lobar CMBs is associated with CAA and high ICH risk; antithrombotics should be avoided unless there is a compelling indication.

  16. Antithrombotic stewardship: a multidisciplinary team approach towards improving antithrombotic therapy outcomes during and after hospitalisation: a study protocol

    PubMed Central

    Dreijer, Albert R; Kruip, Marieke J H A; Diepstraten, Jeroen; Polinder, Suzanne; Brouwer, Rolf; Leebeek, Frank W G; Vulto, Arnold G; van den Bemt, Patricia M L A

    2016-01-01

    Introduction Antithrombotic therapy carries high risks for patient safety. Antithrombotics belong to the top 5 medications involved in potentially preventable hospital admissions related to medication. To provide a standard for antithrombotic therapy and stress the importance of providing optimal care to patients on antithrombotic therapy, the Landelijke Standaard Ketenzorg Antistolling (LSKA; Dutch guideline on integrated antithrombotic care) was drafted. However, the mere publication of this guideline does not guarantee its implementation. This may require a multidisciplinary team effort. Therefore, we designed a study aiming to determine the influence of hospital-based antithrombotic stewardship on the effect and safety of antithrombotic therapy outcomes during and after hospitalisation. Methods and analysis In this study, the effect of the implementation of a multidisciplinary antithrombotic team is compared with usual care using a pre-post study design. The study is performed at the Erasmus University Medical Center Rotterdam and the Reinier de Graaf Hospital Delft. Patients who are or will be treated with antithrombotics are included in the study. We aim to include 1900 patients, 950 in each hospital. Primary outcome is the proportion of patients with a composite end point consisting of ≥1 bleeding or ≥1 thrombotic event from the beginning of antithrombotic therapy (or hospitalisation) until 3 months after hospitalisation. Bleeding is defined according to the International Society of Thrombosis and Haemostasis (ISTH) classification. A thrombotic event is defined as any objectively confirmed arterial or venous thrombosis, including acute myocardial infarction or stroke for arterial thrombosis and deep venous thrombosis or pulmonary embolism or venous thrombosis. An economic evaluation is performed to determine whether the implementation of the multidisciplinary antithrombotic team will be cost-effective. Ethics and dissemination This protocol was

  17. A systematic review of anti-thrombotic therapy in epistaxis.

    PubMed

    Musgrave, K M; Powell, J

    2016-12-01

    There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

  18. [Dental treatment and anti-thrombotic therapy. Part II: the era of new anti-thrombotic drugs].

    PubMed

    Chackartchi, T; Sachar Helft, S; Findler, M

    2014-01-01

    Surgical intra-oral treatment for patients under antithrombotic therapy presents a challenge for the dental team. Within the last few years evidence based systematic reviews established new clinical guidelines for wide groups of patients which need to use antithrombotic treatment. The expected increase in use of antithrombotic treatment forced the pharmaceutical industry to provide new treatments. The former anticoagulant and anti-platelets aggregation groups of drugs were limited to small variety of medication. The search for the new treatments with ideal properties led to newly invented groups of drugs. In this article we will describe the new advancements in anti-thrombotic treatments. The article will summarize the limited knowledge of surgical management of patients under the new anti-thrombotic medications and the recommended approach for oral surgical procedures.

  19. Timing of Platelet Rich Plasma Injections During Antithrombotic Therapy.

    PubMed

    Ramsook, Ryan Ravi; Danesh, Houman

    2016-01-01

    The use of platelet rich plasma (PRP) spans across many fields owing to its role in healing and as a natural alternative to surgery. PRP continues to grow however much of the literature is anecdotal or case report based and there is a lack of controlled trials to evaluate standards for PRP. The International Cellular Medical Society (ICMS) has developed guidelines to help with the safe advancement of PRP; however there remains a gap in literature concerning the timing of PRP injections in patients who are on antithrombotic therapy. The importance of an intact platelet surface membrane allows for the appropriate release of the healing bioproteins and growth factors granting PRP therapy its efficacy. This along with the proliferation of differentiated cells, enhancement of collagen synthesis, early angiogenesis and revascularization help promote the benefits of regeneration. The intrinsic and extrinsic pathways of the coagulation cascade are valuable in that disruption of this mechanism or prematurely activated platelets may result in limited efficacy. Anticoagulants and antiplatelet drugs are commonly used in patients who are candidates for PRP. As antithrombotic agents affect platelet stability, they will have an effect on PRP efficacy and must be discontinued at an appropriate time frame prior to injection therapy. Understanding the pharmacokinetics and platelet effects can help guide discussion on the proper timing of discontinuation and resumption of a particular antithrombotic agent. With future research, the establishment of clinical practice guidelines concerning PRP and antithrombotic therapy can help structure safe and efficacious means in which to promote healing and regeneration in a growing patient population. Platelet rich plasma, antithrombotic therapy, coagulation, platelet activation, regenerative medicine, growth factors.

  20. Implementing genotype-guided antithrombotic therapy.

    PubMed

    Seip, Richard L; Duconge, Jorge; Ruaño, Gualberto

    2010-05-01

    Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1-10 mg/day. The VKORC1 -1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C19*2 and *3 alleles (cumulative frequency: 20-50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel.

  1. Management of antithrombotic therapy in patients undergoing electrophysiological device surgery.

    PubMed

    Zacà, Valerio; Marcucci, Rossella; Parodi, Guido; Limbruno, Ugo; Notarstefano, Pasquale; Pieragnoli, Paolo; Di Cori, Andrea; Bongiorni, Maria Grazia; Casolo, Giancarlo

    2015-06-01

    The aim of this review is to formulate practical recommendations for the management of antithrombotic therapy in patients undergoing cardiac implantable electronic device (CIED) surgery by providing indications for a systematic approach to the problem integrating general technical considerations with patient-specific elements based on a careful evaluation of the balance between haemorrhagic and thromboembolic risk. Hundreds of thousands patients undergo implantation or replacement of CIEDs annually in Europe, and up to 50% of these subjects receive antiplatelet agents or oral anticoagulants. The rate of CIED-related complications, mainly infective, has also significantly increased so that transvenous lead extraction procedures are, consequently, often required. Cardiac implantable electronic device surgery is peculiar and portends specific intrinsic risks of developing potentially fatal haemorrhagic complications; on the other hand, the periprocedural suspension of antithrombotic therapy in patients with high thromboembolic risk cardiac conditions may have catastrophic consequences. Accordingly, the management of the candidate to CIED surgery receiving concomitant antithrombotic therapy is a topic of great clinical relevance yet controversial and only partially, if at all, adequately addressed in evidence-based current guidelines. In spite of the fact that in many procedures it seems reasonably safe to proceed with aspirin only or without interruption of anticoagulants, restricting to selected cases the use of bridging therapy with parenteral heparins, there are lots of variables that may make the therapeutic choices challenging. The decision-making process applied in this document relies on the development of a stratification of the procedural haemorrhagic risk and of the risk deriving from the suspension of antiplatelet or anticoagulant therapy combined to generate different clinical scenarios with specific indications for optimal management of periprocedural

  2. Implementing genotype-guided antithrombotic therapy

    PubMed Central

    Seip, Richard L; Duconge, Jorge; Ruaño, Gualberto

    2010-01-01

    Genotyping has the potential to improve the efficacy and safety of major antithrombotic drugs. For warfarin, the stable maintenance dose varies from 1–10 mg/day. The VKORC1 −1639G>A allele and the CYP2C9*2 and *3 alleles (cumulative frequency: 90% in Asians, 65% in Europeans and 20% in Africans), explain 45% of response variability in European and 30% in African populations. The large clinical trials COAG and EU-PACT will define the extent to which pharmacogenetic dosing affects the safety and efficacy of warfarin and coumarin derivatives. The platelet inhibitor clopidogrel requires activation by the CYP2C19 enzyme. CYP2C19*2 and *3 alleles (cumulative frequency: 20–50%) produce null enzyme activity, and their presence attenuates platelet inhibition and increases cardiovascular events. The US FDA-mandated drug labeling recognizes the relevance of genotyping in the selection and dosing of both warfarin and clopidogrel. PMID:20462345

  3. 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

  4. [Antithrombotic therapy in patients with mechanical valve prostheses].

    PubMed

    Roudaut, R; Lorient-Roudaut, M F

    1996-11-01

    Mechanical valvular prostheses have the advantage of longevity but carry a risk of thrombosis which is itself dependent on many haemodynamic, haemostatic and parietal factors. Antithrombotic therapy in patients with mechanical valvular prostheses is based on vitamin-K antagonists, the optimal dosage of which should reflect the type and location of the prosthesis and the underlying pathology. The patient with a mechanical valvular prosthesis treated by oral anticoagulation must be fully informed and regularly followed up. Special situations: extracardiac surgery, dental extraction, gastrointestinal endoscopy, require specific, well established management.

  5. Antithrombotic therapy for heart failure in sinus rhythm.

    PubMed

    Subramaniam, Veeran; Davis, Russell C; Shantsila, Eduard; Lip, Gregory Y H

    2009-12-01

    Although the risk of thromboembolism in chronic heart failure is high even in the absence of atrial fibrillation, the risk to benefit ratio of anticoagulation vs. antiplatelet therapy or no antithrombotic therapy is poorly defined in this population. Post hoc analysis of large therapeutic heart failure trials has estimated the risk of thromboembolism to be between 1 and 4.5%. However, most of these studies have included some patients with atrial fibrillation, and thromboembolism was not a predefined endpoint. At present, the evidence for either anticoagulation or antiplatelet therapy is limited and the results from current large-scale randomized studies are awaited. From the randomized studies carried out thus far, there is a beneficial trend in favour of anticoagulation therapy, with less hospitalization for heart failure compared with patients taking aspirin.

  6. Factor XI and contact activation as targets for antithrombotic therapy.

    PubMed

    Gailani, D; Bane, C E; Gruber, A

    2015-08-01

    The most commonly used anticoagulants produce therapeutic antithrombotic effects either by inhibiting thrombin or factor Xa (FXa) or by lowering the plasma levels of the precursors of these key enzymes, prothrombin and FX. 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 FXII, the zymogen of a protease (FXIIa) that initiates contact activation when blood is exposed to foreign surfaces, and FXI, the zymogen of the protease FXIa, which links contact activation to the thrombin generation mechanism. In the case of FXI, 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 FXI 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 FXI and FXII in thrombosis and results of preclinical and human trials for therapies targeting these proteins.

  7. 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

  8. Anithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy

    PubMed Central

    Altman, Raul

    2007-01-01

    A tendency toward bleeding often undercuts the beneficial preventive effect of higher doses of a single antithrombotic drug or combined antithrombotic therapy. Although high doses of antithrombotic drugs may be necessary for optimal prevention, such therapy can also elicit more frequent bleeding. Although major bleeding could be a reversible event is likely to lead clinicians to discontinue antithrombotic therapy which in turn could increase the risk of myocardial infarction, stroke, and cardiovascular death. Thus, to prevent thrombotic events without frequent bleeding complications, the preferred approach might be to use anti-inflammatory drugs in addition to the first-line antithrombotic drugs to reduce inflammation and thrombin formation in atheroma. Although some preliminary data have been already published, to confirm the potential benefit of anti-inflammatory drugs in acute coronary syndromes large prospective double-bind randomized trials are necessary. PMID:17727726

  9. 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

  10. Clinical problems with antithrombotic therapy for endoscopic submucosal dissection for gastric neoplasms

    PubMed Central

    Yoshio, Toshiyuki; Nishida, Tsutomu; Hayashi, Yoshito; Iijima, Hideki; Tsujii, Masahiko; Fujisaki, Junko; Takehara, Tetsuo

    2016-01-01

    Endoscopic submucosal dissection (ESD) is minimally invasive and thus has become a widely accepted treatment for gastric neoplasms, particularly for patients with comorbidities. Antithrombotic agents are used to prevent thrombotic events in patients with comorbidities such as cardio-cerebrovascular diseases and atrial fibrillation. With appropriate cessation, antithrombotic therapy does not increase delayed bleeding in low thrombosis-risk patients. However, high thrombosis-risk patients are often treated with combination therapy with antithrombotic agents and occasionally require the continuation of antithrombotic agents or heparin bridge therapy (HBT) in the perioperative period. Dual antiplatelet therapy (DAPT), a representative combination therapy, is frequently used after placement of drug-eluting stents and has a high risk of delayed bleeding. In patients receiving DAPT, gastric ESD may be postponed until DAPT is no longer required. HBT is often required for patients treated with anticoagulants and has an extremely high bleeding risk. The continuous use of warfarin or direct oral anticoagulants may be possible alternatives. Here, we show that some antithrombotic therapies in high thrombosis-risk patients increase delayed bleeding after gastric ESD, whereas most antithrombotic therapies do not. The management of high thrombosis-risk patients is crucial for improved outcomes. PMID:28042389

  11. Understanding risk communication through patient narratives about complex antithrombotic therapies.

    PubMed

    Andreas, Dorothy C; Abraham, Neena S; Naik, Aanand D; Street, Richard L; Sharf, Barbara F

    2010-08-01

    The purpose of this study was to explore how patients use narratives to create coherent understandings of risks associated with complex antithrombotic therapies. We led four focus groups consisting of patients older than 65 years of age who had a diagnosis of cardiovascular disease and were using a prescription for cardioprotective agents, such as aspirin, anticoagulants, and/or antiplatelets. The participants' stories were retrospective accounts about physician and patient interactions and adverse events organized in the plot structure of a trial-and-error story. The trial-and-error narrative structure emphasizes patients' idiosyncrasies and reasons why they expect to experience adverse events from changes in treatment. Any fears that they might have had about these risks were mitigated by physician expertise, patient responsibility, and medical technology. Patients who expressed concern about not having sufficient access to medical expertise (e.g., physicians, laboratory tests) seemed less willing to accept risks. The trial-and-error risk narratives helped patients deal with ambiguity and uncertainty about the outcomes of their therapies, and revealed patients' orientations to the risks they faced.

  12. The efficacy of laparoscopic cholecystectomy without discontinuation in patients on antithrombotic therapy

    PubMed Central

    Yun, Jong Hyuk; Jung, Hae Il; Lee, Hyoung Uk; Baek, Moo-Jun

    2017-01-01

    Purpose Laparoscopic cholecystectomy (LC) is one of the most commonly performed surgeries in the world today. However, there is no consensus regarding whether LC can be performed in patients with acute cholecystitis while on antithrombotic therapy. The objective of our study was to describe postoperative outcomes of patients who underwent emergent LC without interruption to antithrombotic therapy. Methods We performed a retrospective review of patients who underwent LC for acute cholecystitis while on antithrombotic therapy from 2010 to 2015 at Soonchunhyang Universtiy Cheonan Hospital. Patients were divided into 2 groups as underwent emergent LC and elective LC. Results A total of 67 patients (emergent group, 22; elective group, 45) were included in the analysis. Elective group had significantly longer duration between the admission and operation (8 [7–10] days vs. 2 [1–3] days, P < 0.001) and longer duration of antithrombotic drugs discontinuation (7 days vs. 1 [0–3] days, P < 0.001). Emergent group had significantly more postoperative anemia (6 patients vs. 0 patient, P = 0.001) and 3 of 6 patients received packed RBC transfusion in postoperative period. However, there was no significant difference in length of postoperative stays, length of intensive care unit stays and mortality rates. Conclusion Emergent LC without interruption to antithrombotic therapy was relatively safe and useful. A well-designed multicenter study is needed to confirm the safety and efficacy of LC without suspension of antithrombotic therapy and to provide a simple guideline. PMID:28289668

  13. Cerebral Microbleeds and Macrobleeds: Should They Influence Our Recommendations for Antithrombotic Therapies?

    PubMed Central

    Haley, Kellen E.; Greenberg, Steven M.; Gurol, M. Edip

    2014-01-01

    Intracerebral hemorrhage (ICH, or macrobleeds) and cerebral microbleeds—smaller foci of hemosiderin deposits commonly detected by magnetic resonance imaging (MRI) of older adults with or without ICH—are both associated with an increased risk of future ICH. These hemorrhagic pathologies also share risk factors with ischemic thromboembolic conditions that may require antithrombotic therapy, requiring specialists in cardiology, internal medicine and neurology to weigh the benefits versus hemorrhagic risks of antithrombotics in individual patients. This paper will review recent advances in our understanding of hemorrhage prone cerebrovascular pathologies with a particular emphasis on use of these markers in decision making for antithrombotic use. PMID:24122195

  14. Perioperative management of antithrombotic therapy in cardiovascular patients.

    PubMed

    Nuttall, Marc T; Rodgers, George M

    2011-01-01

    Many patients with underlying cardiovascular disease require long-term anticoagulation. The perioperative or periprocedural management of patients who require temporary interruption of anticoagulant or antiplatelet medications is a common and often challenging clinical problem. It requires a fine balance between the risk of thromboembolic events during anticoagulant interruption and the risk of bleeding in the setting of antithrombotic therapy administered around the time of surgery. Interruption of anticoagulation is associated with an increased risk of thromboembolic events. Stratifying patients into thromboembolic risk groups may be helpful in directing anticoagulation management in the perioperative setting. Bridging anticoagulation, generally with low-molecular-weight heparin (LMWH), is often an integral part of perioperative thrombosis risk reduction. Perioperative anticoagulation management varies depending on the indication for anticoagulation and the anticoagulant or antiplatelet agent being used by the patient. In this article, we review some of the general principles involved with perioperative anticoagulation and discuss the perioperative management of patients taking vitamin K antagonists (VKAs), bridging regimens for anticoagulants and antiplatelet agents, and strategies for managing patients on the newer oral anticoagulants.

  15. Pathophysiological basis for anticoagulant and antithrombotic therapy in pulmonary hypertension.

    PubMed

    Lopes, Antonio Augusto

    2006-01-01

    In pulmonary hypertension (PH), thrombosis and thromboembolism may occur as primary events associated with inherited or acquired thrombophilia. Alternatively, in situ thrombosis may develop as a complication of pre-existing vasculopathy as in the case of idiopathic PH and related disorders (so called pulmonary arterial hypertension). In these disorders, a number of abnormalities has been described involving endothelial cells, platelets and other circulating cellular and soluble elements. These abnormalities are suggestive of a shift of pulmonary vascular microenvironment toward a procoagulant, prothrombotic and antifibrinolytic pattern. The abnormalities described so far include circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P-selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and cytokines. Also, decreased endothelial production of natural anticoagulants (thrombomodulin) and platelet antiaggregating substances (nitric oxide, prostacyclin) have been demonstrated. The present review is focused on the procoagulant, prothrombotic and antifibrinolytic mechanisms so far identified in PH, in both clinical setting and animal models. Understanding of these mechanisms is crucial for a proper selection of anticoagulant and antithrombotic therapies and provides the rationale for development of novel therapeutic options.

  16. Antithrombotic therapy in acute coronary syndromes: guidelines translated for the clinician.

    PubMed

    Gharacholou, S Michael; Lopes, Renato D; Washam, Jeffrey B; Newby, L Kristin; James, Stefan K; Alexander, John H

    2010-05-01

    The use of anticoagulant and antiplatelet therapy during the management of acute coronary syndromes (ACS) has been associated with improvements in short- and long-term clinical outcomes, regardless of whether patients are managed conservatively or with acute coronary revascularization. Translating the existing evidence for selection of the most appropriate antithrombotic strategy has been summarized in available guideline recommendations. Given the breadth of antithrombotic recommendations across existing U.S. and European guidelines, synthesis of these recommendations for practicing clinicians who treat patients with ACS are increasingly desired. Providing a summary of the similarities across guidelines while noting the areas where divergence exists becomes an important facet in translating optimal antithrombotic management in ACS for the treating clinician. This review highlights the important aspects of clinical practice guidelines that practicing physicians should consider when selecting antithrombotic therapies to reduce ischemic risk while minimizing hemorrhagic risk across all ACS subtypes.

  17. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

    PubMed

    Bates, Shannon M; Greer, Ian A; Middeldorp, Saskia; Veenstra, David L; Prabulos, Anne-Marie; Vandvik, Per Olav

    2012-02-01

    The use of anticoagulant therapy during pregnancy is challenging because of the potential for both fetal and maternal complications. This guideline focuses on the management of VTE and thrombophilia as well as the use of antithrombotic agents during pregnancy. The methods of this guideline follow 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 in this supplement. We recommend low-molecular-weight heparin for the prevention and treatment of VTE in pregnant women instead of unfractionated heparin (Grade 1B). For pregnant women with acute VTE, we suggest that anticoagulants be continued for at least 6 weeks postpartum (for a minimum duration of therapy of 3 months) compared with shorter durations of treatment (Grade 2C). For women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses, we recommend antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin (75-100 mg/d) over no treatment (Grade 1B). For women with inherited thrombophilia and a history of pregnancy complications, we suggest not to use antithrombotic prophylaxis (Grade 2C). For women with two or more miscarriages but without APLA or thrombophilia, we recommend against antithrombotic prophylaxis (Grade 1B). Most recommendations in this guideline are based on observational studies and extrapolation from other populations. There is an urgent need for appropriately designed studies in this population.

  18. Antithrombotic Therapy in a Prospective Trial of a Pediatric Ventricular Assist Device

    PubMed Central

    Bomgaars, Lisa R.; Massicotte, M. Patricia

    2016-01-01

    Efficacious ventricular assist device (VAD) support in pediatric patients depends on successful antithrombotic management. The experience with antithrombotic management for the EXCOR Pediatric VAD Investigational Device Exemption (IDE) study is described. All 68 children in North America enrolled in the IDE study from May 9, 2007 to December 10, 2010 are included. The Edmonton Anticoagulation and Platelet Inhibition Protocol was provided for management guidance. Monitoring parameters, drug dosing, targeted serious adverse events, and pump changes were reviewed. Major bleeding occurred in 43% of all subjects with most events occurring within 14 days of implantation. Bleeding events were probably/definitely related in 24% to antithrombotic management. Neurologic events occurred in 28% of subjects and were probably/definitely related in 9% to antithrombotic therapy intensity. Most neurologic events occurred between 4 and 30 days postimplantation and sporadically thereafter. Pump change occurred in 56% of subjects. Use of an antithrombotic protocol for enrolled subjects was possible in this multicenter study. Incidence of significant bleeding and thromboembolic events was acceptable when balanced against life-saving benefits of VADs. Further studies are needed to optimize the antithrombotic management of this patient population. PMID:27556152

  19. [Astronauts, asteroids and the universe of antithrombotic therapies in primary percutaneous coronary intervention].

    PubMed

    De Luca, Leonardo; Granatelli, Antonino

    2017-06-01

    A sensation of self-awareness on the relativity of our certainties comes over looking to the huge amount of data on antithrombotic therapies assessed in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This sensation can be compared to the so-called "overview effect", a cognitive shift in awareness reported by some astronauts during spaceflight, often while viewing the Earth from orbit. In this review we will mention drugs floated like meteors in the Universe of STEMI treatment and we will discuss the body of evidence on oral and intravenous antithrombotic therapies for patients undergoing pPCI.

  20. [What physicians think and know about antithrombotic therapy in atrial fibrillation].

    PubMed

    Linchak, R M; Kompaniets, O G; Nedbaĭkin, A M; Komkov, D S; Iusova, I A

    2014-01-01

    We conducted an anonymous survey among 382 physicians (58% internists, 42% cardiologists) in order to obtain information on their opinion on various aspects of antithrombotic therapy in atrial fibrillation. The survey revealed low level of awareness about algorithms of stratification of risks of stroke, systemic embolism, and bleeding. Reported rates of clinical use of recommended antithrombotic agents were: warfarin--30, aspirin monotherapy--19, dabigatran--10, rivaroxaban--8, and combination of aspirin and clopidogrel--8%. Rate of use of drugs without sufficient evidence base in AF was 25%. When asked to designate antithrombotic drug of choice 85% of physicians indicated warfarin and 12%--novel anticoagulants (NOAC). The following factors were considered as limiting wide application of NOAC: high cost (59%), lack of data on these drugs (14%), and impossibility to control safety of their administration (9%).

  1. Management of antithrombotic therapy for acute coronary syndromes and atrial fibrillation in patients with hemophilia.

    PubMed

    Mannucci, Pier Mannuccio

    2012-03-01

    Patients with hemophilia now have a life expectancy very close to that of the unaffected male population and, hence, are at risk of developing the classic age-related morbidities, i.e., cardiovascular diseases. The peculiarity of the management of these diseases in hemophilia is that antithrombotic drugs impinge on the already compromised hemostasis of these lifelong bleeders. This opinion article outlines the strategies we have developed, based on our clinical experience, for the antithrombotic treatment of two common cardiovascular diseases - acute coronary syndromes and chronic atrial fibrillation - in patients with hemophilia A and B. In the absence of specific evidence-based guidelines for patients with coagulation defects, antithrombotic treatment is currently based on expertise and adaptation of the guidelines developed for non-hemophilic patients. Replacement therapy should be tailored with the deficient coagulation factor so as to control the increased risk of bleeding inherent in the use of antiplatelet and anticoagulant drugs.

  2. Gene Therapy Shows Promise for Aggressive Lymphoma

    MedlinePlus

    ... fullstory_163824.html Gene Therapy Shows Promise for Aggressive Lymphoma Over one-third of patients appeared disease- ... 2017 (HealthDay News) -- An experimental gene therapy for aggressive non-Hodgkin lymphoma beat back more than a ...

  3. Antithrombotic Therapy for Secondary Prevention in Patients With Diabetes Mellitus and Coronary Artery Disease.

    PubMed

    Park, Yongwhi; Franchi, Francesco; Rollini, Fabiana; Angiolillo, Dominick J

    2016-01-01

    Diabetes mellitus (DM) is a key risk factor for recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). The prothrombotic milieu that characterizes patients with DM underscores the importance of oral antithrombotic therapy for secondary prevention of recurrent events in these patients. Indeed, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12inhibitor clopidogrel, which has represented the mainstay of treatment for many years, has significantly reduced the incidence of recurrent atherothrombotic events. However, recurrence rates in DM patients still remain high despite this treatment regimen, which may be partly related to inadequate platelet inhibition induced by standard DAPT with aspirin and clopidogrel. This underpins the need for more potent antithrombotic treatment regimens for secondary prevention of atherothrombotic events in DM patients following ACS or PCI. The development of antiplatelet therapies associated with more potent oral platelet P2Y12receptor inhibition, including prasugrel and ticagrelor, as well as platelet inhibitors blocking alternative pathways, such as thrombin-mediated platelet inhibition with vorapaxar, may represent potential treatment options in DM patients. Moreover, with the introduction of the target-specific oral anticoagulants, there has been a reappraisal of the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. This review provides an update on the recent advances and limitations of oral antithrombotic agents used for secondary prevention in DM patients following ACS or PCI.

  4. Patient values and preferences for antithrombotic therapy in atrial fibrillation. A Narrative Systematic Review.

    PubMed

    Loewen, Peter S; Ji, Angela Tianshu; Kapanen, Anita; McClean, Alison

    2017-06-02

    Guidelines recommend that patients' values and preferences should be considered when selecting stroke prevention therapy for atrial fibrillation (SPAF). However, doing so is difficult, and tools to assist clinicians are sparse. We performed a narrative systematic review to provide clinicians with insights into the values and preferences of AF patients for SPAF antithrombotic therapy. Narrative systematic review of published literature from database inception. 1) What are patients' AF and SPAF therapy values and preferences? 2) How are SPAF therapy values and preferences affected by patient factors? 3) How does conveying risk information affect SPAF therapy preferences? and 4) What is known about patient values and preferences regarding novel oral anticoagulants (NOACs) for SPAF? Twenty-five studies were included. Overall study quality was moderate. Severe stroke was associated with the greatest disutility among AF outcomes and most patients value the stroke prevention efficacy of therapy more than other attributes. Utilities, values, and preferences about other outcomes and attributes of therapy are heterogeneous and unpredictable. Patients' therapy preferences usually align with their values when individualised risk information is presented, although divergence from this is common. Patients value the attributes of NOACs but frequently do not prefer NOACs over warfarin when all therapy-related attributes are considered. In conclusion, patients' values and preferences for SPAF antithrombotic therapy are heterogeneous and there is no substitute for directly clarifying patients' individual values and preferences. Research using choice modelling and tools to help clinicians and patients clarify their SPAF therapy values and preferences are needed.

  5. 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

  6. 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

  7. Antithrombotic therapy for the CardioWest temporary total artificial heart.

    PubMed

    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.

  8. Management of antithrombotic therapy before full-mouth extraction.

    PubMed

    Powless, R Andrew; Omar, Hesham R; Mangar, Devanand; Camporesi, Enrico M

    2013-06-01

    The management of antiplatelet and anticoagulant therapy before full-mouth extraction is a major concern for dentists. Approach should vary depending on the risk of bleeding and adverse cardiac events. We have adapted a more conservative approach with continuation of antiplatelet therapy in the majority of patients while implementing local hemostatic measures with good outcomes. Specific recommendations are provided for antiplatelet therapy before mouth extraction.

  9. Selecting antithrombotic therapy for patients with atrial fibrillation

    PubMed Central

    TANAKA-ESPOSITO, CHRISTINE; CHUNG, MINA K.

    2015-01-01

    When considering anticoagulant therapy for patients with atrial fibrillation, one must balance the reduction in risk of thromboembolism that this therapy offers against the risk of bleeding that it poses. The American Heart Association, American College of Cardiology, and Heart Rhythm Society updated their atrial fibrillation guidelines in 2014. This review outlines a rationale for clinical decision-making based on the new guidelines and summarizes the currently approved drugs. PMID:25552627

  10. [Antithrombotic therapy in patients with atrial flutter before planned cardioversion].

    PubMed

    М'якінькова, Людмила О; Тесленко, Юрій В; Пустовойт, Ганна Л; Ярмола, Тетяна І; Циганенко, Ірина В

    atrium flutter and fibrillation are the heart rhythm disorders that increase the risk of life-dangerous complications, e.g. cardioembolic stroke, pulmonary embolism. Recommendations for managing patients with atrial fibrillation - atrial flutter, with paroxysm duration over 48 hours, demand anticoagulant therapy. Oral anticoagulants, which are the antagonists of K vitamin (Varpharin) and the new oral anticoagulants (Rivaroxaban), are used during the per-manipulative procedure of patients with atrial flutter before restoring the sinus rhythm with transesophageal cardiac pacing. the present investigation aims to compare efficiency and safety of Varpharin and Rivaaroxaban in treatment patients with atrial flutter before planned cardioversion with transesophageal heart pacing. Varpharin (control group) - in doses equivalent for reaching the target МНВ - or Rivaroxaban (research group), 20 mg., were prescribed to 42 patients with coronary heart disease, concomitant arterial hypertension, and non-valvular paroxysm of atrial flutter with more than 48-hour duration, divided into two groups. There was held the general clinical, echocardioscopy examination. Thrombotic Risk Factor Assessment was made according to the CHA2DS2-VASc scale, Hemorrhagic Risk Factor Assessment was performed according to the HAS-BLED scale, and clinical symptoms assessment was made according to the EHRA scale. The heart rhythm was restored with the transesophageal heart pacing. the per-manipulative procedure of the patients of research group (21 days were suggested according to the guidelines) shortened, unlike the patients of control group (the period of target МНВ selection had made 30,76±0,62days), the reduction of the symptoms severity by EHRA was considered in dynamics. According to the results of transesophageal heart pacing, the heart rhythm of 15 research group patients restored, and 6 research group patients had atrial fibrillation. Among the patients of the control group, 6 had

  11. Antithrombotic therapy in atrial fibrillation: aspirin is rarely the right choice

    PubMed Central

    Sabir, Ian N; Matthews, Gareth D K; Huang, Christopher L-H

    2013-01-01

    Atrial fibrillation, the commonest cardiac arrhythmia, predisposes to thrombus formation and consequently increases risk of ischaemic stroke. Recent years have seen approval of a number of novel oral anticoagulants. Nevertheless, warfarin and aspirin remain the mainstays of therapy. It is widely appreciated that both these agents increase the likelihood of bleeding: there is a popular conception that this risk is greater with warfarin. In fact, well-managed warfarin therapy (INR 2-3) has little effect on bleeding risk and is twice as effective as aspirin at preventing stroke. Patients with atrial fibrillation and a further risk factor for stroke (CHA2DS2-VASc >0) should therefore either receive warfarin or a novel oral agent. The remainder who are at the very lowest risk of stroke are better not prescribed antithrombotic therapy. For stroke prevention in atrial fibrillation; aspirin is rarely the right choice. PMID:23404744

  12. Aggressive adolescents benefit from massage therapy.

    PubMed

    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 randomly 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 parents as being less aggressive. Significant differences were not found for the adolescents who were assigned to the relaxation group.

  13. Antidote-controlled antithrombotic therapy targeting factor IXa and von Willebrand factor.

    PubMed

    Becker, Richard C; Oney, Sabah; Becker, Kristian C D; Sullenger, Bruce

    2009-09-01

    Thrombotic disorders and their common clinical phenotypes of acute myocardial infarction, ischemic stroke, and venous thromboembolism are the proximate cause of substantial morbidity, mortality, and health care expenditures worldwide. Accordingly, therapies designed to attenuate thrombus initiation and propagation, reflecting integrated platelet-mediated and coagulation protease-mediated events, respectively, represent a standard of care. Unfortunately, there are numerous inherent limitations of existing therapies that include target nonselectivity, variable onset and offset of pharmacodynamic effects, a narrow efficacy-safety profile, and the absence of a safe and reliable platform for either accurate titration, based on existing patient-specific, disease-specific, and clinical conditions, or active reversibility. Herein, we summarize our experience with oligonucleotide antithrombotic agents and their complementary antidotes, targeting the platelet adhesive protein von Willebrand factor and the pivotal coagulation protease factor IXa.

  14. Severe bleeding after antithrombotic therapy in urosepsis masquerading as myocardial infarction.

    PubMed

    Cheng, Kuo-Wei; Shih, Hsin-Chin; How, Chorng-Kuang; Lin, Yang-Ying; Hung-Tsang Yen, David; Huang, Mu-Shun

    2011-01-01

    Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.

  15. 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.

  16. Effect of a combined anti-thrombotic therapy of thrombosis on prosthetic heart valves

    PubMed Central

    Wei, Wei; Zheng, Zhichao; Huang, Shuping

    2015-01-01

    Objective To evaluate the curative effects and risks of a medical therapy with combined anti-thrombotic agents for thrombosis on prosthetic heart valves. Methods Twenty-two patients who suffered from thrombosis on prosthetic valves with stable hemodynamics were divided into the inpatient group and the outpatient group. Thrombosis on the valves were demonstrated by transesophageal echocardiographies (TEE). A combined anti-thrombotic therapy with clopidogrel and warfarin were prescribed for all the patients during the whole treatment. Low molecular weight heparin (LMWH) was given twice daily during the first 5 days for the inpatients. The patients accepted regular follow-ups for observation of the functions of prosthetic valves, changes of thrombi, coagulation status and general clinical status. Results There were 5 men and 17 women. Thirteen patients suffered from thrombosis on the mechanical mitral valves (MVs), five on the mechanical tricuspid valves (TVs), one on the mechanical aortic valve and tricuspid bio-prosthetic valve, one on the mechanical aortic valve, one on the mitral bio-prosthetic valve, and one on the tricuspid bio-prosthetic valve. After an average of 36.4±23.1 days’ observation, 16 (73%) patients’ valvular function recovered normal without TTE detectable thrombi, 6 (27%) patients’ valvular function remained abnormal including three patients without TTE detectable thrombi during follow-ups. No significant differences of thrombi changes and period of thrombi disappearance were observed between the inpatient group and the outpatient group. For patients with mitral thrombosis, sizes of the left atriums (LAs) decreased an average of 4.1 mm after treatment (95% CI, 1.2-6.9 mm). No significant changes of other chambers and left ventricular ejection fractions (LVEF) were observed. For patients with tricuspid thrombosis, LVEF improved an average of 10.5% after treatment (95% CI, 0.1-17.9%). No significant changes of chambers were observed. None

  17. Effect of a combined anti-thrombotic therapy of thrombosis on prosthetic heart valves.

    PubMed

    Wei, Wei; Dong, Taiming; Zheng, Zhichao; Huang, Shuping

    2015-03-01

    To evaluate the curative effects and risks of a medical therapy with combined anti-thrombotic agents for thrombosis on prosthetic heart valves. Twenty-two patients who suffered from thrombosis on prosthetic valves with stable hemodynamics were divided into the inpatient group and the outpatient group. Thrombosis on the valves were demonstrated by transesophageal echocardiographies (TEE). A combined anti-thrombotic therapy with clopidogrel and warfarin were prescribed for all the patients during the whole treatment. Low molecular weight heparin (LMWH) was given twice daily during the first 5 days for the inpatients. The patients accepted regular follow-ups for observation of the functions of prosthetic valves, changes of thrombi, coagulation status and general clinical status. There were 5 men and 17 women. Thirteen patients suffered from thrombosis on the mechanical mitral valves (MVs), five on the mechanical tricuspid valves (TVs), one on the mechanical aortic valve and tricuspid bio-prosthetic valve, one on the mechanical aortic valve, one on the mitral bio-prosthetic valve, and one on the tricuspid bio-prosthetic valve. After an average of 36.4±23.1 days' observation, 16 (73%) patients' valvular function recovered normal without TTE detectable thrombi, 6 (27%) patients' valvular function remained abnormal including three patients without TTE detectable thrombi during follow-ups. No significant differences of thrombi changes and period of thrombi disappearance were observed between the inpatient group and the outpatient group. For patients with mitral thrombosis, sizes of the left atriums (LAs) decreased an average of 4.1 mm after treatment (95% CI, 1.2-6.9 mm). No significant changes of other chambers and left ventricular ejection fractions (LVEF) were observed. For patients with tricuspid thrombosis, LVEF improved an average of 10.5% after treatment (95% CI, 0.1-17.9%). No significant changes of chambers were observed. None experienced major bleedings except

  18. 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…

  19. 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…

  20. Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines

    PubMed Central

    Norris, Susan L.; Schulman, Sam; Hirsh, Jack; Eckman, Mark H.; Akl, Elie A.; Crowther, Mark; Vandvik, Per Olav; Eikelboom, John W.; McDonagh, Marian S.; Lewis, Sandra Zelman; Gutterman, David D.; Cook, Deborah J.; Schünemann, Holger J.

    2012-01-01

    Background: To develop the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines (AT9), the American College of Chest Physicians (ACCP) assembled a panel of clinical experts, information scientists, decision scientists, and systematic review and guideline methodologists. Methods: Clinical areas were designated as articles, and a methodologist without important intellectual or financial conflicts of interest led a panel for each article. Only panel members without significant conflicts of interest participated in making recommendations. Panelists specified the population, intervention and alternative, and outcomes for each clinical question and defined criteria for eligible studies. Panelists and an independent evidence-based practice center executed systematic searches for relevant studies and evaluated the evidence, and where resources and evidence permitted, they created standardized tables that present the quality of the evidence and key results in a transparent fashion. Results: One or more recommendations relate to each specific clinical question, and each recommendation is clearly linked to the underlying body of evidence. Judgments regarding the quality of evidence and strength of recommendations were based on approaches developed by the Grades of Recommendations, Assessment, Development, and Evaluation Working Group. Panel members constructed scenarios describing relevant health states and rated the disutility associated with these states based on an additional systematic review of evidence regarding patient values and preferences for antithrombotic therapy. These ratings guided value and preference decisions underlying the recommendations. Each topic panel identified questions in which resource allocation issues were particularly important and, for these issues, experts in economic analysis provided additional searches and guidance. Conclusions: AT9 methodology reflects the current science of evidence

  1. The Korean Heart Rhythm Society's 2014 Statement on Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation: Korean Heart Rhythm Society

    PubMed Central

    Kim, Nam Ho; Nam, Gi Byung; Park, Hyung Wook; On, Young Keun; Lee, Young Soo; Lim, Hong Euy; Joung, Boyoung; Cha, Tae Joon; Hwang, Gyo Seung; Oh, Seil; Kim, June Soo

    2015-01-01

    In patients with nonvalvular atrial fibrillation (AF), the risk of stroke varies considerably according to individual clinical status. The CHA2DS2-VASc score is better than the CHADS2 score for identifying truly lower risk patients with AF. With the advent of novel oral anticoagulants (NOACs), the strategy for antithrombotic therapy has undergone significant changes due to its superior efficacy, safety and convenience compared with warfarin. Furthermore, new aspects of antithrombotic therapy and risk assessment of stroke have been revealed: the efficacy of stroke prevention with aspirin is weak, while the risk of major bleeding is not significantly different from that of oral anticoagulant (OAC) therapy, especially in the elderly. Reflecting these pivotal aspects, previous guidelines have been updated in recent years by overseas societies and associations. The Korean Heart Rhythm Society has summarized the new evidence and updated recommendations for stroke prevention of patients with nonvalvular AF. First of all, antithrombotic therapy must be considered carefully and incorporate the clinical characteristics and circumstances of each individual patient, especially with regards to balancing the benefits of stroke prevention with the risk of bleeding, recommending the CHA2DS2-VASc score rather than the CHADS2 score for assessing the risk of stroke, and employing the HAS-BLED score to validate bleeding risk. In patients with truly low risk (lone AF, CHA2DS2-VASc score of 0), no antithrombotic therapy is recommended, whereas OAC therapy, including warfarin (international normalized ratio 2-3) or NOACs, is recommended for patients with a CHA2DS2-VASc score ≥2 unless contraindicated. In patients with a CHA2DS2-VASc score of 1, OAC therapy should be preferentially considered, but depending on bleeding risk or patient preferences, antiplatelet therapy or no therapy could be permitted. PMID:25653698

  2. Antiplatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair.

    PubMed

    Paparella, Domenico; Di Mauro, Michele; Bitton Worms, Keren; Bolotin, Gil; Russo, Claudio; Trunfio, Salvatore; Scrofani, Roberto; Antona, Carlo; Actis Dato, Guglielmo; Casabona, Riccardo; Colli, Andrea; Gerosa, Gino; Renzulli, Attilio; Serraino, Filiberto; Scrascia, Giuseppe; Zaccaria, Salvatore; De Bonis, Michele; Taramasso, Maurizio; Delgado, Luis; Tritto, Francesco; Marmo, Joseph; Parolari, Alessandro; Myaseodova, Veronika; Villa, Emmanuel; Troise, Giovanni; Nicolini, Francesco; Gherli, Tiziano; Whitlock, Richard; Conte, Manuela; Barili, Fabio; Gelsomino, Sandro; Lorusso, Roberto; Sciatti, Edoardo; Marinelli, Daniele; Di Giammarco, Gabriele; Calafiore, Antonio Maria; Sheikh, Azmat; Alfonso, Juan Jaime; Glauber, Mattia; Miceli, Antonio

    2016-05-01

    To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 ± 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Health literacy and decision making styles for complex antithrombotic therapy among older multimorbid adults.

    PubMed

    Naik, Aanand D; Street, Richard L; Castillo, Diana; Abraham, Neena S

    2011-12-01

    To evaluate the effect of functional health literacy (FHL) on preferences for decision-making; and among those initially preferring a passive decision-making role, to explore how preferences change if their physician actively encourages their involvement. Consecutive older adults with cardiovascular disease receiving complex antithrombotic therapy completed a comprehensive assessment including measures of FHL and preferences for shared decision making. Half of all participants had inadequate or marginal FHL. Those with inadequate FHL were more likely (P=0.01) to prefer passive rather than active decision making styles even after controlling for age, education, and numeracy. However, 40% of patients preferring passive styles had adequate FHL and these patients were significantly more likely to change their preference to more active styles (odds ratio=7.17, P<.01) if their physician "was more supportive or encouraged participation". Screening FHL can provide insight into patients' preferences for active participation in decision making. Clinicians' encouragement of participation can increase engagement by patients with adequate FHL. We propose an algorithm for screening FHL and preferences for participating in decisions about complex medication regimens. Published by Elsevier Ireland Ltd.

  4. Applying antithrombotic therapies to improve outcomes in patients with atrial fibrillation.

    PubMed

    Cannon, Chris; Ezekowitz, Michael D; Granger, Christopher

    2013-08-15

    Approximately 15% to 25% or 75,000 ischemic strokes are attributed to atrial fibrillation annually within the United States. Atrial fibrillation is the most frequently diagnosed cardiac arrhythmia and affects more than 2.66 million Americans. Moreover, atrial fibrillation is associated with a 1.5 to 1.9-fold higher risk of death due to its strong correlation with thromboembolic events. Because of the attributed increased morbidity and mortality, challenges that concern identification of patients at risk for thromboembolic events from atrial fibrillation must be addressed. These challenges include compliance to performance measures, adherence to guidelines, adequate prevention and early control of co-morbidities that affect the progression of atrial fibrillation and associated risks, early initiation of treatment, and successful evaluation of associated risks of bleeding, primary or recurrent stroke, and patient awareness and compliance. This multimedia educational webcast will discuss the state of affairs with respect to antithrombotic therapies and new anticoagulants. The webcast will also review factors influencing physician use of anticoagulation in atrial fibrillation. Clinical decision making and lessons learned from the expert faculty is also included.

  5. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.

    PubMed Central

    Sandercock, P A; van den Belt, A G; Lindley, R I; Slattery, J

    1993-01-01

    A formal statistical overview of all truly randomised trials was undertaken to determine whether antithrombotic therapy is effective and safe in the early treatment of patients with acute stroke. There were 15 completed randomised controlled trials of the value of early antithrombotic treatment in patients with acute stroke. The regimes tested in acute presumed or confirmed ischaemic stroke were: heparin, 10 trials with 1047 patients: oral anticoagulants, one trial with 51 patients: antiplatelet therapy, three trials with 103 patients. Heparin was tested in one trial with 46 patients with acute haemorrhagic stroke. Outcome measures were deep venous thrombosis (confirmed by I125 scanning or venography), pulmonary embolism, death from all causes, haemorrhagic transformation of cerebral infarction, level of disability in survivors. In patients with acute ischaemic stroke, allocation to heparin was associated with a highly significant 81% (SD 8, 2p < 0.00001) reduction in deep venous thrombosis detected by I125 fibrinogen scanning or venogram. Only three trials systematically identified pulmonary emboli, which occurred in 6/106 (5.7%) allocated control vs 3/132 (2.3%) allocated heparin, a non-significant 58% reduction (SD 45.7, 2p > 0.1). There were relatively few deaths in the trials in patients with presumed ischaemic stroke: 94/485 (19.4%) among patients allocated to the control group vs 79/497 (15.9%) among patients who were allocated heparin. The observed 18% (SD 16) reduction in the odds of death was not statistically significant. The least biased estimated of the effect of treatment on haemorrhagic transformation of the cerebral infarct (HTI) comes from trials where all patients were scanned at the end of treatment, irrespective of clinical deterioration; using this analysis, haemorrhagic transformation occurred in 7/102 (6.9%) control vs 8/106 (7.5%) treated, a non-significant 12% increase (SD 56, 2p > 0.1). These data cannot exclude the possibility that

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

    PubMed

    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

    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. 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. 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. By working through trade-offs, patients actively clarified their preferences, learning about CAT risks, benefits, and

  7. 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

  8. Role of emerging antithrombotic therapy in the prevention of cardioembolic complications in patients with atrial fibrillation.

    PubMed

    Deedwania, Prakash C; Huang, Grace W

    2011-08-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS(2) or CHA(2)DS(2)-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the

  9. Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study).

    PubMed

    Jia, Haibo; Dai, Jiannan; Hou, Jingbo; Xing, Lei; Ma, Lijia; Liu, Huimin; Xu, Maoen; Yao, Yuan; Hu, Sining; Yamamoto, Erika; Lee, Hang; Zhang, Shaosong; Yu, Bo; Jang, Ik-Kyung

    2017-03-14

    Plaque erosion, compared with plaque rupture, has distinctly different underlying pathology and therefore may merit tailored therapy. In this study, we aimed to assess whether patients with acute coronary syndrome (ACS) caused by plaque erosion might be stabilized by anti-thrombotic therapy without stent implantation. This was a single-centre, uncontrolled, prospective, proof-of concept study. Patients with ACS including ST-segment elevation myocardial infarction were prospectively enrolled. If needed, aspiration thrombectomy was performed. Patients diagnosed with plaque erosion by optical coherence tomography (OCT) and residual diameter stenosis <70% on coronary angiogram were treated with anti-thrombotic therapy without stenting. OCT was repeated at 1 month and thrombus volume was measured. The primary endpoint was >50% reduction of thrombus volume at 1 month compared with baseline. The secondary endpoint was a composite of cardiac death, recurrent ischaemia requiring revascularization, stroke, and major bleeding. Among 405 ACS patients with analysable OCT images, plaque erosion was identified in 103 (25.4%) patients. Sixty patients enrolled and 55 patients completed the 1-month follow-up. Forty-seven patients (47/60, 78.3%; 95% confidence interval: 65.8-87.9%) met the primary endpoint, and 22 patients had no visible thrombus at 1 month. Thrombus volume decreased from 3.7 (1.3, 10.9) mm3 to 0.2 (0.0, 2.0) mm3. Minimal flow area increased from 1.7 (1.4, 2.4) mm2 to 2.1 (1.5, 3.8) mm2. One patient died of gastrointestinal bleeding, and another patient required repeat percutaneous coronary intervention. The rest of the patients remained asymptomatic. For patients with ACS caused by plaque erosion, conservative treatment with anti-thrombotic therapy without stenting may be an option.

  10. Evaluating the Primary Prevention of Ischemic Stroke of Oral Antithrombotic Therapy in Head and Neck Cancer Patients with Radiation Therapy

    PubMed Central

    Hsu, Chin-Wei

    2016-01-01

    Although previous studies demonstrated the risk of ischemic stroke (IS) in patients with head and neck cancer (HNC), the impact of oral antithrombotic therapy (OAT) on this risk has not yet been assessed. We aimed to evaluate the effectiveness and safety of OAT in patients with HNC treated with RT. This retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. A total of 37,638 patients diagnosed with HNC included in the study were classified as users and nonusers of OAT. Primary outcome was IS or transient ischemic attack (TIA), and secondary outcomes were death and major bleeding. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). There was no significant difference in the risk of IS or TIA between patients on continuous OAT and nonusers (adjusted HR, 0.812; 95% CI, 0.199–3.309). The risk of major bleeding was not significantly different between the groups. From a national population database, we did not find an association between OAT and decreasing risk of ischemic stroke/TIA or increasing hazard of major bleeding. PMID:27990433

  11. Opportunities for improvement in anti-thrombotic therapy and other strategies for the management of acute coronary syndromes: Insights from EPICOR, an international study of current practice patterns.

    PubMed

    Bueno, Héctor; Sinnaeve, Peter; Annemans, Lieven; Danchin, Nicolas; Licour, Muriel; Medina, Jesús; Pocock, Stuart; Sánchez-Covisa, Joaquín; Storey, Robert F; Jukema, J Wouter; Zeymer, Uwe; Van de Werf, Frans

    2016-02-01

    To describe international patterns and opportunities for improvement of pre- and in-hospital care of patients hospitalized for acute coronary syndromes (ACS), with special focus on anti-thrombotic therapy. EPICOR (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary syndrome patients), an international, cohort study, which enrolled 10,568 consecutive ACS survivors from 555 hospitals in 20 countries across Europe and Latin America (September 2010 to March 2011), prospectively registered detailed information on pre- and in-hospital management. Globally, 4738 (44.8%) were attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944 patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel, single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of ACS patients were medically managed. A significant decreasing gradient was found between Northern, Southern and Eastern Europe and Latin America in use of more potent patterns of anti-platelet therapy, reperfusion therapy and invasive strategy. This large international study shows room for improvement in use of anti-thrombotic drugs and other strategies for optimal management of ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice differences not based on evidence or conditioned by economic constraints should be reduced. © The European Society of Cardiology 2015.

  12. 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

  13. 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

  14. Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

    PubMed

    Braun, Oscar Ö; Bico, Besim; Chaudhry, Uzma; Wagner, Henrik; Koul, Sasha; Tydén, Patrik; Scherstén, Fredrik; Jovinge, Stefan; Svensson, Peter J; Gustav Smith, J; van der Pals, Jesper

    2015-01-01

    Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS). We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months. In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT). Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Comparison of Graft Patency, Limb Salvage, and Antithrombotic Therapy Between Prosthetic and Autogenous Below-Knee Bypass for Critical Limb Ischemia

    PubMed Central

    Suckow, Bjoern D.; Kraiss, Larry W.; Stone, David H.; Schanzer, Andres; Bertges, Daniel J.; Baril, Donald T.; Cronenwett, Jack L.; Goodney, Philip P.

    2014-01-01

    Background The autogenous vein is the preferred conduit in below-knee vascular reconstructions. However, many argue that prosthetic grafts can perform well in crural bypass with adjunctive antithrombotic therapy. We therefore compared outcomes of below-knee prosthetic versus autologous vein bypass grafts for critical limb ischemia and the use of adjunctive antithrombotic therapy in both settings. Methods Utilizing the registry of the Vascular Study Group of New England (2003–2009), we studied 1227 patients who underwent below-knee bypass for critical limb ischemia, 223 of whom received a prosthetic graft to the below-knee popliteal artery (70%) or more distal target (30%). We used propensity matching to identify a patient cohort receiving single-segment saphenous vein yet had remained similar to the prosthetic cohort in terms of characteristics, graft origin/target, and antithrombotic regimen. Main outcome measures were graft patency and major limb amputation within 1 year. Secondary outcomes were bleeding complications (reoperation or transfusion) and mortality. We performed comparisons by conduit type and by antithrombotic therapy. Results Patients receiving prosthetic conduit were more likely to be treated with warfarin than those with greater saphenous vein (57% vs. 24%, P < 0.001). After propensity score matching, we found no significant difference in primary graft patency (72% vs. 73%, P = 0.81) or major amputation rates (17% vs. 13%, P = 0.31) between prosthetic and single-segment saphenous vein grafts. In a subanalysis of grafts to tibial versus popliteal targets, we noted equivalent primary patency and amputation rates between prosthetic and venous conduits. Whereas overall 1-year prosthetic graft patency rates varied from 51% (aspirin + clopidogrel) to 78% (aspirin + warfarin), no significant differences were seen in primary patency or major amputation rates by antithrombotic therapy (P = 0.32 and 0.17, respectively). Further, the incidence of bleeding

  16. 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

  17. What you should know about the 2008 American College of Chest Physicians evidence-based clinical practice guidelines (8th) on antithrombotic and thrombolytic therapy.

    PubMed

    Kaatz, Scott

    2010-02-01

    The American College of Chest Physicians published their first consensus conference guidelines on antithrombotic therapy in 1986 and has updated these guidelines approximately every 3 years as a supplement to the journal Chest. These guidelines are widely accepted as an authoritative source of information and considered by many to be the textbook for antithrombotic therapy. The most recent guidelines are from the 8th consensus conference, published in 2008, and this article will highlight new recommendations that have evolved since the 2004 Chest supplement. Examples from the literature that support the evolution these guidelines will focus on changes that are most germane to the majority of attendees at the 10th National Conference on Anticoagulant Therapy and members of the AC Forum. The objective of this article is to help answer ten common clinical questions frequently faced by anticoagulation management services.

  18. 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

  19. [What are the criteria for choosing a model for evaluating arterial antithrombotic therapy?].

    PubMed

    André, P; Bal dit Sollier, C; Bonneau, M; Pignaud, G; Hainaud, P; Azzam, K; Drouet, L

    1996-11-01

    The use of models of experimental arterial thrombosis both in vivo and ex vivo in animals and ex vivo in humans is an obligatory step to the understanding of mechanisms involved in thrombogenesis as well as in the evaluation of anti-thrombotic therapeutics. Arterial thrombogenesis is a complex phenomenon which involves multiple systems, mechanisms and parameters. Therefore studies of thrombogenesis from a pathological as well as a therapeutic point are necessary for understanding this problem in its entirety. For these reasons, it is necessary to use models as representative as possible of the human pathological condition. Besides these theoretical requirements, practical needs have also to be fulfilled (accessibility of the models, adaptation to the type of the technique to different animal model and/or of the size of the animal to the amount of molecule available, cost ...) which necessary lead to some promises. In this review we have tried to underline the criteria for the choice, characteristics, advantages and disadvantages of the major models commonly accepted and used, in such a form that the reader who may not be an expert in the field would be led either to choose a particular model for a specific purpose or to appreciate a paper or a report based on an experimental model of arterial thrombosis. In vitro models of arterial thrombosis are so far removed from reality and due to their nature can generate so much artifacts thus we have omitted their discussion from this paper.

  20. Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review.

    PubMed

    Fanari, Zaher; Weiss, Sandra; Weintraub, William S

    2015-12-01

    Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.

  1. Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy

    PubMed Central

    Lefkou, Eleftheria; Mamopoulos, Apostolos; Dagklis, Themistoklis; Vosnakis, Christos; Rousso, David

    2016-01-01

    BACKGROUND. Administration of conventional antithrombotic treatment (low-dose aspirin plus low–molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency–associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes. METHODS. We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated. RESULTS. In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients. CONCLUSION. The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy. PMID:27454295

  2. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

    PubMed

    Ansell, Jack; Hirsh, Jack; Poller, Leon; Bussey, Henry; Jacobson, Alan; Hylek, Elaine

    2004-09-01

    This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. The article describes the antithrombotic effect of VKAs, the monitoring of anticoagulation intensity, the clinical applications of VKA therapy, and the optimal therapeutic range of VKAs, and provides specific management recommendations. Grade 1 recommendations are strong, and indicate that the benefits do, or do not, outweigh the risks, burdens, and costs. Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this article are the following: for dosing of VKAs, we suggest the initiation of oral anticoagulation therapy with doses between 5 and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 2B). In the elderly and in other patient subgroups with an elevated bleeding risk, we suggest a starting dose at < or = 5 mg (Grade 2C). We recommend basing subsequent doses after the initial two or three doses on the results of INR monitoring (Grade 1C). The article also includes several specific recommendations for the management of patients with INRs above the therapeutic range and for patients requiring invasive procedures. For example, in patients with mild to moderately elevated INRs without major bleeding, we suggest that when vitamin K is to be given it be administered orally rather than subcutaneously (Grade 1A). For the management of patients with a low risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before they undergo surgery (Grade 2C). For patients with a high risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before surgery, to

  3. Cerebrovascular disease, associated risk factors and antithrombotic therapy in a population screening cohort: Insights from the Belgian Heart Rhythm Week programme.

    PubMed

    Proietti, Marco; Mairesse, Georges H; Goethals, Peter; Scavee, Christophe; Vijgen, Johan; Blankoff, Ivan; Vandekerckhove, Yves; Lip, Gregory Yh

    2017-02-01

    Background Cerebrovascular disease confers a major healthcare burden worldwide and is a major cause of death and disability. Several well-established risk factors, such as atrial fibrillation (AF), are associated with cerebrovascular disease and antithrombotic therapy reduces risk. Design This study was a subgroup analysis from the Belgian Heart Rhythm Week, a nationwide AF awareness programme. Methods We studied subjects screened between 2012 and 2014 with available data on clinical risk factors and antithrombotic treatment. Results Of the 38,034 subjects eligible for this analysis, 1513 (4.0%) reported a positive clinical history for cerebrovascular disease. Logistic regression analysis found that age, hypertension, diabetes mellitus, history of vascular disease, history of heart failure and history of AF (all p < 0.001) were independently associated with cerebrovascular disease. Among subjects with history of cerebrovascular disease and AF, 1.7% were taking oral anticoagulant drugs only, while both oral anticoagulant drugs and aspirin were used in 61.5% of subjects, aspirin in 4.3% of patients and no antithrombotic therapy in 32.5% of subjects. Among those subjects without AF, the corresponding figures were 0.8, 9.5, 2.0 and 87.6%, respectively. Conclusions The prevalence of cerebrovascular disease in this contemporary population screening project was higher than that reported in the general population and was associated with the major known stroke risk factors. Sub-optimal antithrombotic therapy management was evident, with a low use of oral anticoagulant drugs among patients with AF and a low use of aspirin among subjects without AF.

  4. Adherence to Guidelines for Antithrombotic Therapy in Patients with Atrial Fibrillation According to CHADS2 Score before and after Stroke: A Multicenter Observational Study from Korea

    PubMed Central

    Kim, Wook-Joo; Park, Jong-Moo; Kang, Kyusik; Cho, Yong-Jin; Hong, Keun-Sik; Lee, Soo Joo; Ko, Youngchai; Lee, Kyung Bok; Park, Tai Hwan; Lee, Jun; Cha, Jae-Kwan; Kim, Dae-Hyun; Yu, Kyung-Ho; Lee, Byung-Chul; Oh, Mi-Sun; Lee, Juneyoung; Lee, JiSung; Jang, Myung Suk; Han, Moon-Ku

    2016-01-01

    Background and Purpose A substantial proportion of patients with atrial fibrillation (AF) are not treated optimally; however, the inappropriateness of drug therapy has never been evaluated before or after a stroke event. We investigated the adherence to guidelines for therapy in AF patients hospitalized with acute ischemic stroke (AIS) before stroke onset and at discharge, with the aim of identifying the factors associated with inappropriate therapy. Methods AIS patients with AF hospitalized within 7 days of onset were identified from a prospective nine-center stroke registry database. Two cohorts were defined: patients diagnosed with AF prior to the stroke event (admission cohort) and patients diagnosed with AF at discharge from hospital (discharge cohort). Any of the following conditions were regarded as nonadherence to guidelines in this study: use of anticoagulant or nonuse of antithrombotics with CHADS2 score=0, nonuse of antithrombotics with CHADS2 score=1, or nonuse of anticoagulant with CHADS2 score ≥2. Results Overall, 406 patients were enrolled in the admission cohort and 518 in the discharge cohort. The rates of nonadherence before a stroke event and at discharge were 77.8% and 33.3%, respectively. These rates varied widely for both cohorts, with interhospital differences being statistically significant. Multivariable analysis revealed that old age, stroke history, and congestive heart failure were associated with nonadherence before stroke. At discharge, males, coronary heart disease, inappropriate antithrombotic use before stroke, and functional disability at discharge were associated with nonadherence. Conclusions This study shows that antithrombotic use in AIS patients with AF might be not optimal before and after stroke in Korea. PMID:26541495

  5. [Fine-tuning of antithrombotic therapy in patients with non-valvular atrial fibrillation. The AFINVA register].

    PubMed

    Dubois Marques, Daniela; Mora Llabata, Vicente; Pacheco Arroyo, Julián; Gasull Insertis, Salvador; Vicente Cañizares, Manuela; Roldán Torres, Ildefonso

    2017-08-31

    To determine whether antithrombotic treatment (ATT) in patients with non-valvular atrial fibrillation in a health area complies with the recommendations of current clinical guidelines. Prospective observational study. Primary Health Care Centres and Cardiology Department of a Health Department of the Valencian Community, Spain. A total of 505 patients with nonvalvular atrial fibrillation were included in the study. ATT was deemed to be inappropriate in patients with a CHA2DS2-VASc score ≥1 and who were not under oral anticoagulation, in patients treated with antivitaminK drugs, and poor control of oral anticoagulation, or with antiplatelet therapy inappropriately associated with anticoagulation, and in patients on ATT with a CHA2DS2-VASc score=0. The median age was 77.4±10years. The ATT was considered inadequate in 58% of cases. Factors independently associated with inadequate ATT were age (OR: 1.02 [1-1.04]; P=.029), hypothyroidism (OR: 1.98 [1.14-3.43]; P=.015), ischaemic heart disease (OR: 1.3 [1.15-2.59]; P=.008) and paroxysmal non-valvular AF (OR: 2.11 [1.41-3.17]; P<.0001). These data underline the high prevalence of inadequate ATT in daily practice, as well its different causes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  6. Review And Insights Into The Bleeding Mechanism Incited By Antithrombotic Therapy: Mechanistic Nuances Of Dual Pro-Hemorrhagic Substrate Incorporating Drug-Induced Microvascular Leakage.

    PubMed

    Stirbys Md PhD, Petras

    2015-01-01

    In patients with atrial fibrillation antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. Cerebrovascular risk-benefit ratio for oral anticoagulation therapies continues to be debated. Macro and/or microhematomas as well as visible or cryptic ones may appear unexpectedly in any anatomic region. The diagnostic and prognostic value of subcutaneous hematomas (petechia, ecchymosis, bruise) potentially predisposing intracerebral micro- or macrobleeding might be reconsidered. Hypothetically, subcutaneous hemorrhagic events are "transparent" signs and reflect the coexistence of remote vulnerable sites that are potential bleeding sources. Obviously vigilance is needed for early signs of drug-related petechiae evaluation to determine whether it is a local/superficial subtlety or a systemic problem. Any bleeding complication, regardless of its scale and anatomical location, might be treated as a worrisome clinical symptom requiring subtle correction of antithrombotic regimen. The focus of this article is to review the current knowledge of drug-related hemorrhage with special emphasis on underlying mechanisms and links between the visible bleeding (predominantly subcutaneous) and remote (such as cerebral) hemorrhagic sources. To mitigate inappropriate therapy, we should consider new conceptual insights and more individualized approaches to achieve an optimal balance of efficacy and safety. We hypothesize that bleeding complications occur as a result of two factors - impact of antithrombotic drugs and related detrimental effect on microvascular network. Most likely the microvasculature undergoes pro-hemorrhagic medication stress leading to unfavorable vascular wall "fenestration" with ensuing consequences. If so, it suggests the presence of dual substrate responsible for hemorrhagic events.

  7. Dual antiplatelet compared to triple antithrombotic therapy in anterior wall acute myocardial infarction complicated by depressed left ventricular ejection fraction.

    PubMed

    Oyetayo, Ola O; Slicker, Kipp; De La Rosa, Lisa; Lane, Wesley; Langsjoen, Dane; Patel, Chhaya; Brough, Kevin; Michel, Jeffrey; Chiles, Christopher

    2015-10-01

    Current guidelines recommend triple antithrombotic therapy (TT) consisting of warfarin, aspirin, and a P2Y12 inhibitor following an anterior ST elevation myocardial infarction (STEMI) complicated by extensive wall motion abnormalities. This recommendation, however, is based on data collected before percutaneous coronary intervention (PCI) became the standard of care for the treatment of STEMI. We designed a retrospective study of patients who received PCI for anterior STEMI over an 8-year period to compare rates of thromboembolic and bleeding events between patients receiving dual antiplatelet therapy (DAPT) and those receiving TT, including warfarin. Patients were included if the predischarge echocardiogram showed extensive wall motion abnormality and an ejection fraction ≤35%. Patients with known left ventricular thrombus were excluded. A total of 124 patients met the criteria, with 80 patients in the DAPT group and 44 in the TT group. The median age was 58 years in the TT group and 64 years in the DAPT group (P < 0.04), with an average ejection fraction of 31%. Thromboembolic events occurred in 4 patients (5%) in the DAPT group compared with 3 patients (6.8%) in the TT group (P = 0.70). Bleeding occurred in 2 patients in the DAPT group and 4 patients in the TT group (2.5% in DAPT vs. 9.1% in TT group, P = 0.18). No differences in rates of clinical embolism or left ventricular thrombus were found. Our data support recent findings that warfarin may not be indicated for patients following PCI for anterior STEMI, even when significant wall motion abnormalities and reduced ejection fraction ≤35% are present.

  8. Dual antiplatelet compared to triple antithrombotic therapy in anterior wall acute myocardial infarction complicated by depressed left ventricular ejection fraction

    PubMed Central

    Oyetayo, Ola O.; Slicker, Kipp; De La Rosa, Lisa; Lane, Wesley; Langsjoen, Dane; Patel, Chhaya; Brough, Kevin; Chiles, Christopher

    2015-01-01

    Current guidelines recommend triple antithrombotic therapy (TT) consisting of warfarin, aspirin, and a P2Y12 inhibitor following an anterior ST elevation myocardial infarction (STEMI) complicated by extensive wall motion abnormalities. This recommendation, however, is based on data collected before percutaneous coronary intervention (PCI) became the standard of care for the treatment of STEMI. We designed a retrospective study of patients who received PCI for anterior STEMI over an 8-year period to compare rates of thromboembolic and bleeding events between patients receiving dual antiplatelet therapy (DAPT) and those receiving TT, including warfarin. Patients were included if the predischarge echocardiogram showed extensive wall motion abnormality and an ejection fraction ≤35%. Patients with known left ventricular thrombus were excluded. A total of 124 patients met the criteria, with 80 patients in the DAPT group and 44 in the TT group. The median age was 58 years in the TT group and 64 years in the DAPT group (P < 0.04), with an average ejection fraction of 31%. Thromboembolic events occurred in 4 patients (5%) in the DAPT group compared with 3 patients (6.8%) in the TT group (P = 0.70). Bleeding occurred in 2 patients in the DAPT group and 4 patients in the TT group (2.5% in DAPT vs. 9.1% in TT group, P = 0.18). No differences in rates of clinical embolism or left ventricular thrombus were found. Our data support recent findings that warfarin may not be indicated for patients following PCI for anterior STEMI, even when significant wall motion abnormalities and reduced ejection fraction ≤35% are present. PMID:26424937

  9. 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.

  10. The effect of a dual or a triple antithrombotic therapy with apixaban on thrombus formation in vivo and in an ex vivo perfusion chamber model

    PubMed Central

    Weisshaar, Stefan; Litschauer, Brigitte; Bucher, Sebastian; Riesenhuber, Martin; Kapiotis, Stylianos; Kyrle, Paul Alexander; Wolzt, Michael

    2016-01-01

    Abstract Background: There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. Methods and Results: Shed blood platelet activation (β-thromboglobulin [β-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions. A triple or dual therapy induced a comparable decrease in shed blood β-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. Conclusion: Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration. PMID:27399131

  11. Acute antithrombotic treatment of ischemic stroke.

    PubMed

    Alderazi, Yazan J; Grotta, James C

    2014-05-01

    Antithrombotic medication is a cornerstone of acute ischemic stroke treatment and secondary prevention. The efficacy of thrombolysis with alteplase in acute stroke has been demonstrated in several clinical trials. This safe and costeffective therapy has transformed the practice of stroke care and has led to subsequent trials of other antithrombotic medications for treatment of ischemic stroke in the acute phase. These antithrombotics include thrombolytic, antiplatelet and anticoagulant agents. While, no other medication has yet demonstrated adequate efficacy, our current and evolving understanding of infarct expansion, ischemic penumbra, collateral circulation and the blood brain barrier is allowing testing of antithrombotic medications tailored to individual patient pathophysiology in clinical trials. This understanding accompanies developments in neuroimaging and organization of stroke care that allow for wide-spread recruitment in these trials. Alteplase remains the mainstay treatment of arterial acute ischemic stroke; however, anticoagulation is the standard therapy for cerebral venous sinus thrombosis. Antithrombotic use in acute stroke, arterial and venous, has demonstrated efficacy but leaves many questions unanswered. This patient population is a fertile ground for novel research, especially as it relates to; combination antithrombotic therapy, combination of pharmacological and mechanical thrombolysis, and the transition to secondary prevention. Here we review the current antithrombotics in the acute phase of ischemic stroke highlighting the evidence-base and areas of uncertainty.

  12. Impact of treatment algorithms on the prescribing of antithrombotic therapy in patients with suspected acute coronary syndrome – a prospective audit

    PubMed Central

    Cameron, Alan C; McCallum, Linsay; Gardiner, Thomas; Darroch, Claire; Walters, Matthew R; Oldroyd, Keith G

    2015-01-01

    Aims Chest pain presentations are common although most patients do not have an acute coronary syndrome (ACS). We hypothesized that our local therapeutic guideline was leading to many low risk patients being inappropriately treated with potent anti-thrombotic therapy for ACS. Methods We conducted a prospective analysis of patients presenting with suspected ACS to the Western Infirmary Glasgow over a 2 month period between 6/10/13–3/11/13 and 5/4/14–2/5/14. We collated data on demographics, investigation, initial management and final diagnosis. Patients taking warfarin were excluded. We calculated sensitivity, specificity and receiver operating characteristic (ROC) curves for our local guideline, the SIGN guideline and a new guideline proposal. Results We studied 202 patients of whom 112 (55%) were male with mean (SD) age 60 (15) years. Full anti-thrombotic therapy for ACS was recommended in 91 patients (45%) according to the NHS GG&C guideline, 37 (18%) by the SIGN guideline and 30 (15%) by our new guideline proposal. The final diagnosis was ACS in 39 patients (19%). The current NHS GG&C guideline had a sensitivity of 80%, specificity 63% and AUROC 0.71 (95% CI 0.63, 0.80). The respective values were 62%, 92% and 0.77 (95% CI 0.67, 0.86) for the SIGN guideline and 54%, 94% and 0.74 (95% CI 0.64, 0.84) for our new proposed guideline. Conclusions Only one-fifth of patients who present with chest pain or suspected ACS have ACS as their final diagnosis. Our new guideline proposal is highly specific and would minimize unnecessary administration of potent anti-thrombotic therapy to low risk patients. PMID:26147691

  13. Recurrent Acute Myocardial Infarction in a Patient with Severe Coronary Artery Ectasia: Implication of Antithrombotic Therapy.

    PubMed

    Tomioka, Tomoko; Takeuchi, Satoshi; Ito, Yoshitaka; Shioiri, Hiroki; Koyama, Jiro; Inoue, Kanichi

    2016-12-12

    BACKGROUND Acute myocardial infarction (AMI) can be caused not only by plaque rupture/erosion, but also by many other mechanisms. Thromboembolism due to atrial fibrillation and coronary thrombosis due to coronary artery ectasia are among the causes. Here we report on a case of recurrent myocardial infarction with coronary artery ectasia. CASE REPORT Our case was a 78-year-old woman with hypertension. Within a one-month interval, she developed AMI twice at the distal portion of her right coronary artery along with coronary artery ectasia. On both events, emergent coronary angiography showed no obvious organic stenosis or trace of plaque rupture at the culprit segment after thrombus aspiration. After the second acute event, we started anticoagulation therapy with warfarin to prevent thrombus formation. In the chronic phase, we confirmed, by using coronary angiography, optimal coherence tomography and intravascular ultrasound, that there was no plaque rupture and no obvious thrombus formation along the coronary artery ectasia segment of the distal right coronary artery, which suggested effectiveness of anticoagulant. Furthermore, by Doppler velocimetry we found sluggish blood flow only in the coronary artery ectasia lesion but not in the left atrium which is generally the main site of systemic thromboembolism revealed by transesophageal echocardiography. CONCLUSIONS These results suggest that the two AMI events at the same coronary artery ectasia segment were caused by local thrombus formation due to local stagnant blood flow. Although it has not yet been generally established, anticoagulation therapy may be effective to prevent thrombus formation in patients with coronary artery ectasia regardless of the prevalence of atrial fibrillation.

  14. Recurrent Acute Myocardial Infarction in a Patient with Severe Coronary Artery Ectasia: Implication of Antithrombotic Therapy

    PubMed Central

    Tomioka, Tomoko; Takeuchi, Satoshi; Ito, Yoshitaka; Shioiri, Hiroki; Koyama, Jiro; Inoue, Kanichi

    2016-01-01

    Patient: Female, 78 Final Diagnosis: Acute myocardial infarction Symptoms: Chest discomfort Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Acute myocardial infarction (AMI) can be caused not only by plaque rupture/erosion, but also by many other mechanisms. Thromboembolism due to atrial fibrillation and coronary thrombosis due to coronary artery ectasia are among the causes. Here we report on a case of recurrent myocardial infarction with coronary artery ectasia. Case Report: Our case was a 78-year-old woman with hypertension. Within a one-month interval, she developed AMI twice at the distal portion of her right coronary artery along with coronary artery ectasia. On both events, emergent coronary angiography showed no obvious organic stenosis or trace of plaque rupture at the culprit segment after thrombus aspiration. After the second acute event, we started anticoagulation therapy with warfarin to prevent thrombus formation. In the chronic phase, we confirmed, by using coronary angiography, optimal coherence tomography and intravascular ultrasound, that there was no plaque rupture and no obvious thrombus formation along the coronary artery ectasia segment of the distal right coronary artery, which suggested effectiveness of anticoagulant. Furthermore, by Doppler velocimetry we found sluggish blood flow only in the coronary artery ectasia lesion but not in the left atrium which is generally the main site of systemic thromboembolism revealed by transesophageal echocardiography. Conclusions: These results suggest that the two AMI events at the same coronary artery ectasia segment were caused by local thrombus formation due to local stagnant blood flow. Although it has not yet been generally established, anticoagulation therapy may be effective to prevent thrombus formation in patients with coronary artery ectasia regardless of the prevalence of atrial fibrillation. PMID:27941711

  15. Aggressive thyroid cancer: targeted therapy with sorafenib.

    PubMed

    Corrado, Alda; Ferrari, Silvia M; Politti, Ugo; Mazzi, Valeria; Miccoli, Mario; Materazzi, Gabriele; Antonelli, Alessandro; Ulisse, Salvatore; Fallahi, Poupak; Miccoli, Paolo

    2017-03-01

    Sorafenib (Nexavar), is a multikinase inhibitor, which has demonstrated both antiproliferative and antiangiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumoral cells (c-RAF [proto-oncogene serine/threonine-protein kinase], BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3) and in tumor vessels (c-RAF, vascular endothelial growth factor receptor [VEGFR]-2, VEGFR-3, and platelet-derived growth factor receptor β). Sorafenib was initially approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. Experimental studies have demonstrated that sorafenib has both antiproliferative and antiangiogenic properties in vitro and in vivo, against thyroid cancer cells. Furthermore, several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary, follicular and medullary aggressive thyroid cancer. The results of the different studies showed good clinical responses and stabilization of the disease and suggested that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies (such as radioiodine). Currently, USA Food and Drug Administration has approved the use of sorafenib for metastatic differentiated thyroid cancer.

  16. The challenges of autologous cell therapy: systemic anti-thrombotic therapies interfering with serum coagulation may disable autologous serum-containing cell products for therapeutical use.

    PubMed

    Seeger, Florian H; Rasper, Tina; Bönig, Halvard; Assmus, Birgit; Zeiher, Andreas M; Dimmeler, Stefanie

    2014-10-01

    Cell therapy of acute myocardial infarction (AMI) with bone marrow-derived mononuclear cells (BMC) resulted in a modest improvement of cardiac function, but clinical trial results were heterogeneous. After isolation, BMC are maintained in medium supplemented with complements such as autologous serum to maintain optimal cell viability until administration. In the REPAIR-AMI trial, serum was prepared using tubes containing coagulation accelerators, but the regulatory agency recommended using additive-free tubes for the pivotal BAMI trial. Here, we show that serum obtained from patients with anti-thrombotic therapy in tubes without coagulation accelerators induces clotting, thereby rendering the cell product unsuitable for intra-coronary application. Specifically, systemic treatment of patients with low doses of heparin prevented efficient coagulation ex vivo, and the resulting partially clotted plasma induced cell aggregation within 1-18 h in the cell product. Utmost care has to be taken to test autologous components of cell products before clinical use. The development of media including the appropriate recombinant growth factors for maintaining cell functionality ex vivo may be warranted.

  17. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

    PubMed

    Douketis, James D; Berger, Peter B; Dunn, Andrew S; Jaffer, Amir K; Spyropoulos, Alex C; Becker, Richard C; Ansell, Jack

    2008-06-01

    This article discusses the perioperative management of antithrombotic therapy and is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). The primary objectives of this article are the following: (1) to address the perioperative management of patients who are receiving vitamin K antagonists (VKAs) or antiplatelet drugs, such as aspirin and clopidogrel, and require an elective surgical or other invasive procedures; and (2) to address the perioperative use of bridging anticoagulation, typically with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). A secondary objective is to address the perioperative management of such patients who require urgent surgery. The recommendations in this article incorporate the grading system that is discussed in this supplement (Guyatt G et al, CHEST 2008; 133:123S-131S). Briefly, Grade 1 recommendations are considered strong and indicate that the benefits do (or do not) outweigh risks, burden, and costs, whereas Grade 2 recommendations are referred to as suggestions and imply that individual patient values may lead to different management choices. The key recommendations in this article include the following: in patients with a mechanical heart valve or atrial fibrillation or venous thromboembolism (VTE) at high risk for thromboembolism, we recommend bridging anticoagulation with therapeutic-dose subcutaneous (SC) LMWH or IV UFH over no bridging during temporary interruption of VKA therapy (Grade 1C); in patients with a mechanical heart valve or atrial fibrillation or VTE at moderate risk for thromboembolism, we suggest bridging anticoagulation with therapeutic-dose SC LMWH, therapeutic-dose IV UFH, or low-dose SC LMWH over no bridging during temporary interruption of VKA therapy (Grade 2C); in patients with a mechanical heart valve or atrial fibrillation or VTE at low risk for thromboembolism, we suggest low-dose SC LMWH or no bridging over bridging with

  18. The outcome of prostaglandin-E1 and dextran-40 compared to no antithrombotic therapy in head and neck free tissue transfer: analysis of 1,351 cases in a single center.

    PubMed

    Riva, Francesco M G; Chen, Yen-Chou; Tan, Ngian-Chye; Lin, Pao-Yuan; Tsai, Yun-Ta; Chang, Hsueh-Wen; Kuo, Yur-Ren

    2012-07-01

    Free tissue transfer has become a popular technique for soft tissue defect reconstruction in head and neck cancer ablation. Although high success rates and good reliability of free flaps are proven, microvascular thrombosis is still the most critical issue for microsurgeons. Pharmacological antithrombotic agents are widely used but their efficacy is still debated. In this study, we analyzed whether prostaglandin-E1 (PGE1) and dextran-40 can improve the outcomes compared to no antithrombotic therapy at all. We retrospectively reviewed 1,351 free flaps performed for head and neck reconstruction after cancer ablation. Three groups defined were 232 flaps received PGE1, 283 flaps received dextran-40, and 836 received no antithrombotic therapy. The demographics of these three groups indicated no statistical differences. The results showed that flap survival revealed no significant difference among PGE1, dextran-40, and control group (P = 0.734). There was a tendency to hematomas in PGE1 group (P = 0.056) when compared with other two groups. Dextran-40 significantly increased flap failure rate in high-risk patients with diabetes mellitus (P = 0.006) or hypertension (P = 0.003), when compared with PGE1 and control group. These results revealed antithrombotic therapy with PGE1 and dextran-40 do not determine a significant improvement in flap survival.

  19. Alternative pharmacologic therapy for aggressive central giant cell granuloma: denosumab.

    PubMed

    Schreuder, Willem H; Coumou, Annet W; Kessler, Peter A H W; de Lange, Jan

    2014-07-01

    In the search for new pharmacologic therapies for central giant cell granuloma (CGCG), proteins that are essential to osteoclastogenesis are intriguing potential targets. In the present case report, we describe a 25-year-old patient with an aggressive CGCG of the maxilla, who was successfully treated with the antiresorptive agent denosumab, after other pharmacologic treatment had failed to achieve regression or stabilization of the tumor. Denosumab could be a promising alternative to potentially mutilating surgery for CGCG. However, more research is needed before definite conclusions can be drawn about the potential role of this agent in the treatment of CGCG.

  20. Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in Patients with Indication for Oral Anticoagulation: Data from a Single Center Registry

    PubMed Central

    Staudacher, Dawid L.; Kaiser, Michael; Hehrlein, Christoph; Bode, Christoph; Ahrens, Ingo

    2015-01-01

    Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention. PMID:26439131

  1. 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

  2. Stenting versus aggressive medical therapy for intracranial arterial stenosis.

    PubMed

    Chimowitz, Marc I; Lynn, Michael J; Derdeyn, Colin P; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, L Scott; Lutsep, Helmi L; Barnwell, Stanley L; Waters, Michael F; Hoh, Brian L; Hourihane, J Maurice; Levy, Elad I; Alexandrov, Andrei V; Harrigan, Mark R; Chiu, David; Klucznik, Richard P; Clark, Joni M; McDougall, Cameron G; Johnson, Mark D; Pride, G Lee; Torbey, Michel T; Zaidat, Osama O; Rumboldt, Zoran; Cloft, Harry J

    2011-09-15

    Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).

  3. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

    PubMed

    Losa, Marco; Bogazzi, Fausto; Cannavo, Salvo; Ceccato, Filippo; Curtò, Lorenzo; De Marinis, Laura; Iacovazzo, Donato; Lombardi, Giuseppe; Mantovani, Giovanna; Mazza, Elena; Minniti, Giuseppe; Nizzoli, Maurizio; Reni, Michele; Scaroni, Carla

    2016-02-01

    Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

  4. Impact of the PI3-kinase/Akt pathway on ITAM and hemITAM receptors: haemostasis, platelet activation and antithrombotic therapy.

    PubMed

    Moroi, Alyssa J; Watson, Steve P

    2015-04-01

    Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that are activated in response to various stimulants, and they regulate many processes including inflammation; the stress response; gene transcription; and cell proliferation, differentiation, and death. Increasing reports have shown that the PI3Ks and their downstream effector Akt are activated by several platelet receptors that regulate platelet activation and haemostasis. Platelets express two immunoreceptor tyrosine based activation motif (ITAM) receptors, collagen receptor glycoprotein VI (GPVI) and Fcγ receptor IIA (FcγRIIA), which are characterized by two YxxL sequences separated by 6-12 amino acids. Activation of an ITAM receptor initiates a reaction cascade via its YxxL sequence in which signaling molecules such as spleen tyrosine kinase (Syk), linker for activation of T cells (LAT) and phospholipase C γ2 (PLCγ2) become activated, leading to platelet activation. Platelets also express another receptor, C-type lectin 2 (CLEC-2), which has a single YxxL sequence, so it is appropriately called a hemITAM receptor. ITAM receptors and the hemITAM receptor share many signaling features. Here we will summarize our current knowledge about how the PI3K/Akt pathway regulates (hem)ITAM receptor-mediated platelet activation and haemostasis and discuss the possible benefits of targeting PI3K/Akt as an antithrombotic therapy.

  5. Antithrombotic Strategies in Endovascular Interventions: Current Status and Future Directions.

    PubMed

    Shishehbor, Mehdi H; Katzen, Barry T

    2013-10-01

    Despite increasing numbers of endovascular interventions to treat arterial and venous disease, scant level 1 evidence is available regarding the role of antithrombotic and antiplatelet therapy in patients undergoing these procedures. The current practice in this regard is heterogeneous and has mainly been driven by data from coronary artery disease and percutaneous coronary intervention. This article discusses the role of antithrombotic and antiplatelet agents for endovascular intervention. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

    PubMed

    Kearon, Clive; Kahn, Susan R; Agnelli, Giancarlo; Goldhaber, Samuel; Raskob, Gary E; Comerota, Anthony J

    2008-06-01

    This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see "Grades of Recommendation" chapter). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE), we recommend anticoagulant therapy with subcutaneous (SC) low-molecular-weight heparin (LMWH), monitored IV, or SC unfractionated heparin (UFH), unmonitored weight-based SC UFH, or SC fondaparinux (all Grade 1A). For patients with a high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). For patients with confirmed PE, we recommend early evaluation of the risks to benefits of thrombolytic therapy (Grade 1C); for those with hemodynamic compromise, we recommend short-course thrombolytic therapy (Grade 1B); and for those with nonmassive PE, we recommend against the use of thrombolytic therapy (Grade 1B). In acute DVT or PE, we recommend initial treatment with LMWH, UFH or fondaparinux for at least 5 days rather than a shorter period (Grade 1C); and initiation of vitamin K antagonists (VKAs) together with LMWH, UFH, or fondaparinux on the first treatment day, and discontinuation of these heparin preparations when the international normalized ratio (INR) is > or = 2.0 for at least 24 h (Grade 1A). For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all

  7. A Structured Review of Antithrombotic Therapy in Peripheral Artery Disease With a Focus on Revascularization: A TASC (InterSociety Consensus for the Management of Peripheral Artery Disease) Initiative.

    PubMed

    Hess, Connie N; Norgren, Lars; Ansel, Gary M; Capell, Warren H; Fletcher, John P; Fowkes, F Gerry R; Gottsäter, Anders; Hitos, Kerry; Jaff, Michael R; Nordanstig, Joakim; Hiatt, William R

    2017-06-20

    Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to support use of these therapies after peripheral artery disease revascularization exist, and much of the rationale for the use of antiplatelet agents after endovascular peripheral revascularization is extrapolated from percutaneous coronary intervention literature. Consequently, guideline recommendations for antithrombotic therapy after lower limb revascularization are inconsistent and not always evidence-based. In this context, the purpose of this structured review is to assess the available randomized data for antithrombotic therapy after peripheral arterial revascularization, with a focus on clinical trial design issues that may affect interpretation of study results, and highlight areas that require further investigation. © 2017 American Heart Association, Inc.

  8. [The effect of group-based psychodrama therapy on decreasing the level of aggression in adolescents].

    PubMed

    Karataş, Zeynep; Gökçakan, Dan Zafer

    2009-01-01

    This study aimed to examine the effect of group-based psychodrama therapy on the level aggression in adolescents. The study included 23 students from Nezihe Yalvac Anatolian Vocational High School of Hotel Management and Tourism that had high aggression scores. Eleven of the participants (6 female, 5 male) constituted the experimental group and 12 (6 male, 6 female) were in the control group. The 34-item Aggression Scale was used to measure level of aggression. We utilized mixed pattern design including experiment-control, pre-test and post test and follow up. The experimental group participated in group-based psychodrama therapy once a week for 90 minutes, for 14 weeks in total. The Aggression Scale was administered to the experimental and control groups before and after treatment; it was additionally administered to the experimental group 16 weeks after treatment. Data were analyzed using ANCOVA and dependent samples t tests. Our analysis shows that group-based psychodrama had an effect on the experimental group in terms of total aggression, anger, hostility, and indirect aggression scores (F=65.109, F=20.175, F=18.593, F=40.987, respectively, P<.001). There was no effect of the group-based treatment on verbal or physical aggression scores. Follow-up indicated that the effect of the therapy was still measureable 16 weeks after the cessation of the therapy. Results of the present study indicate that group-based psychodrama therapy decreased the level of aggression in the experimental group. Current findings are discussed with reference to the literature. Recommendations for further research and for psychiatric counselors are provided.

  9. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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. This study highlighted the importance of teaching reinforcement behavior therapy by kindergarten teachers in decreasing verbal and physical aggression in preschoolers. IRCT2014042617436N1.

  11. Circulating Tumor DNA to Monitor Therapy for Aggressive B-Cell Lymphomas.

    PubMed

    Kwok, Mary; Wu, S Peter; Mo, Clifton; Summers, Thomas; Roschewski, Mark

    2016-09-01

    The goal of therapy for aggressive B-cell lymphomas such as diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) is to achieve cure. Combination chemotherapy with rituximab cures most patients, but those with recurrent disease have a poor prognosis. Medical imaging scans such as computed tomography (CT) and positron emission tomography (PET) are the principal methods to assess response and monitor for disease relapse after therapy but are fundamentally limited by risks of radiation, cost, and a lack of tumor specificity. Novel sequencing-based DNA monitoring methods are capable of quantifying small amounts of circulating tumor DNA (ctDNA) before, during, and after therapy for mature B-cell lymphomas. Detection of ctDNA encoding clonal rearranged variable-diversity-joining (VDJ) receptor gene sequences has demonstrated improved analytical sensitivity and enhanced tumor specificity compared to imaging scans in DLBCL, offering broad clinical applicability across a range of aggressive B-cell lymphomas. Molecular monitoring of ctDNA has vaulted into the spotlight as a promising non-invasive tool with immediate clinical impact on monitoring for recurrence after therapy prior to clinical symptoms. As these clinical observations are validated, ctDNA monitoring needs to be investigated as a tool for response-adapted therapy and as a marker of minimal residual disease upon completion of therapy in aggressive B-cell lymphomas. Molecular monitoring of ctDNA holds tremendous promise that may ultimately transform our ability to monitor disease in aggressive B-cell lymphomas.

  12. Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

    PubMed

    Guyatt, Gordon H; Eikelboom, John W; Gould, Michael K; Garcia, David A; Crowther, Mark; Murad, M Hassan; Kahn, Susan R; Falck-Ytter, Yngve; Francis, Charles W; Lansberg, Maarten G; Akl, Elie A; Hirsh, Jack

    2012-02-01

    This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.

  13. Spontaneous coronary artery dissection: aggressive vs. conservative therapy.

    PubMed

    Shamloo, Behrooz K; Chintala, Rajesh S; Nasur, Ali; Ghazvini, Mohammad; Shariat, Parastoo; Diggs, James A; Singh, Steven N

    2010-05-01

    Spontaneous coronary artery dissection (SCAD) is a rare condition that commonly presents as an acute coronary event in the younger population, especially in females of childbearing age. Generally, there is no consensus on the etiology, prognosis, and treatment of SCAD. The Medline database was searched for "spontaneous coronary artery dissection" between 1931 and 2008. A total of 440 cases of SCAD were identified. Demographic data were analyzed with either the Student's t-test or the chi-square test for categorical and nominal variables, respectively. Kaplan-Meier outcome analysis was used to assess the outcome of a given treatment for all patients after 1990. SCAD was found more commonly in females with 308 (70%) cases. Pregnancy was associated with SCAD in 80 (26.1%) cases. Among pregnant patients, 67 (83.8%) developed SCAD in the postpartum period and 13 (16.2%) patients in the prepartum period. Analysis of treatment modalities showed that 21.2% of the patients who were conservatively managed after the initial diagnosis eventually required surgical or catheter-based intervention compared to 2.5% of patients who were initially treated with an aggressive strategy. Kaplan-Meier analysis showed that patients with an isolated single lesion in left or right coronary artery had a statistically significant better outcome when treated with an early aggressive strategy, including coronary artery bypass grafting (CABG) or stent placement as compared to a conservative strategy (p = 0.023, p = 0.006, respectively). Early intervention with either CABG or percutaneous coronary intervention following the diagnosis of SCAD leads to a better outcome and less need for further intervention.

  14. 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. © The Author(s) 2015.

  15. The Role of Aggressive Corticosteroid Therapy in Patients With Juvenile Dermatomyositis: A Propensity Score Analysis

    PubMed Central

    Seshadri, Roopa; Feldman, Brian M.; Ilowite, Norman; Cawkwell, Gail; Pachman, Lauren M.

    2010-01-01

    Objective To compare outcomes at 36 months in patients newly diagnosed with juvenile dermatomyositis (DM) treated with aggressive versus standard therapy. Methods At diagnosis, 139 untreated juvenile DM patients were given aggressive therapy (intravenous methylprednisolone or oral prednisone 5–30 mg/kg/day; n = 76) or standard therapy (1–2 mg/kg/day; n = 63) by the treating physician. Aggressive therapy patients were more ill at diagnosis. Matching was based on the propensity for aggressive therapy because propensity scoring can reduce confounding by indication. Logistic regression of the matched data determined predictors of outcomes, controlling for clinical confounders and propensity score. Outcomes comprised Disease Activity Score (DAS) for skin and muscle, range of motion (ROM), and calcification. Results Sex, race, and age were similar between groups, and initial DAS weakness and ROM significantly predicted the therapy chosen. Based on propensity scores, 42 patients from each group were well matched. In the matched pairs, there were no significant differences in outcomes. Methotrexate use (odds ratio [OR] 3.6, 95% confidence interval [95% CI] 1.15–11.5) and duration of untreated disease (OR 1.2, 95% CI 1–1.38) were associated with ROM loss, hydroxychloroquine use (OR 11.2, 95% CI 3.7–33) and calcification (OR 6.8, 95% CI 1.8–25.4) with persistent rash, abnormal baseline lactate dehydrogenase (OR 11.2, 95% CI 1.4–92) and age at onset (OR 1.3, 95% CI 1–1.4) with weakness, and duration of untreated disease (OR 1.2, 95% CI 1–1.39) with calcification. Conclusion Using a retrospective, nonrandomized design with propensity score matching, there was little difference in efficacy outcomes between aggressive and standard therapy; however, the sickest patients were treated with aggressive therapy and were not included in the matched analysis. Comprehensive clinical studies are needed to determine therapeutic pathways to the best outcome. PMID:18576304

  16. Safety and utility of acute electroconvulsive therapy for agitation and aggression in dementia.

    PubMed

    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

    2015-03-01

    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. Twenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), 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-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. Regression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory (F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory (F(4,31) = 14.6; p < 0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression 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 because of recurrence of agitation and for three participants because of adverse events. Electroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Prevalence of Atrial Fibrillation and Antithrombotic Therapy in Hemodialysis Patients: Cross-Sectional Results of the Vienna InVestigation of AtriaL Fibrillation and Thromboembolism in Patients on HemoDIalysis (VIVALDI)

    PubMed Central

    Königsbrügge, Oliver; Posch, Florian; Antlanger, Marlies; Kovarik, Josef; Klauser-Braun, Renate; Kletzmayr, Josef; Schmaldienst, Sabine; Auinger, Martin; Zuntner, Günther; Lorenz, Matthias; Grilz, Ella; Stampfel, Gerald; Steiner, Stefan; Pabinger, Ingrid; Säemann, Marcus; Ay, Cihan

    2017-01-01

    Background Atrial fibrillation (AF) adds significant risk of stroke and thromboembolism in patients on hemodialysis (HD). The aim of this study was to investigate the prevalence of AF in a population-based cohort of HD patients and practice patterns of antithrombotic therapy for stroke prevention in AF. Methods The Vienna InVestigation of AtriaL fibrillation and thromboembolism in patients on hemodialysis (VIVALDI), an ongoing prospective observational cohort study, investigates the prevalence of AF and the risk of thromboembolic events in HD patients in Vienna, Austria. We analyzed cross-sectional data of 626 patients (63.4% men, median age 66 years, approx. 73% of HD patients in Vienna), who provided informed consent. A structured interview with each patient was performed, recent and archived ECGs were viewed and medical histories were verified with electronic records. Results The overall prevalence of AF was 26.5% (166 patients, 71.1% men, median age 72 years) of which 57.8% had paroxysmal AF, 3.0% persistent AF, 32.5% permanent AF, and 6.6% of patients had newly diagnosed AF. The median CHA2DS2-VASc Score was 4 [25th-75th percentile 3–5]. In multivariable analysis, AF was independently associated with age (odds ratio: 1.05 per year increase, 95% confidence interval: 1.03–1.07), male sex (1.7, 1.1–2.6), history of venous thromboembolism (2.0, 1.1–3.6), congestive heart failure (1.7, 1.1–2.5), history of or active cancer (1.5, 1.0–2.4) and time on HD (1.08 per year on HD, 1.03–1.13). Antithrombotic treatment was applied in 84.4% of AF patients (anticoagulant agents in 29.5%, antiplatelet agents in 33.7%, and both in 21.1%). In AF patients, vitamin-K-antagonists were used more often than low-molecular-weight heparins (30.1% and 19.9%). Conclusions The prevalence of AF is high amongst HD patients and is associated with age, sex, and distinct comorbidities. Practice patterns of antithrombotic treatment indicate a lack of consensus for stroke prevention

  18. Aggressive therapy improves cirrhosis in glycogen storage disease type IX.

    PubMed

    Tsilianidis, Laurie A; Fiske, Laurie M; Siegel, Sara; Lumpkin, Chris; Hoyt, Kate; Wasserstein, Melissa; Weinstein, David A

    2013-06-01

    Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.

  19. De-escalating therapy in gastric aggressive lymphoma

    PubMed Central

    Cuccurullo, Rosanna; Govi, Silvia; Ferreri, Andrés JM

    2014-01-01

    The treatment of primary gastric diffuse large B-cell lymphoma (DLBCL) has changed radically over the last 10–15 years, with the abandonment of routine gastrectomy in favor of more conservative therapies. Low-level evidence suggests that consolidation radiotherapy could be avoided in patients with limited-stage DLBCL of the stomach who achieve complete remission after rituximab-CHOP combination. Small, recent prospective trials suggest that selected patients with limited-stage Helicobacter pylori (H. pylori)-positive DLBCL of the stomach and favorable prognostic factors can be managed with antibiotics alone, with excellent disease control and cure rates, keeping chemo-radiotherapy for unresponsive patients. This recommendation should equally regard patients with mucosa-associated lymphoid tissue-related or de novo DLBCL. Future studies should be focused on the establishment of reliable variables able to distinguish the best candidates for exclusive treatment with H. pylori eradication from those who need for conventional chemo-immunotherapy. PMID:25083073

  20. Antithrombotic agents: implications in dentistry.

    PubMed

    Little, James W; Miller, Craig S; Henry, Robert G; McIntosh, Bruce A

    2002-05-01

    Thrombosis and the complicating emboli that can result are important causes of illness and death. Thrombosis is of greater overall clinical importance in terms of morbidity and mortality than all of the hemorrhagic disorders combined. Agents such as heparin, low-molecular weight heparin, warfarin, aspirin, ticlopidine, clopidogrel, and tirofiban are used to prevent venous or arterial thrombosis. Patients taking these antithrombotic agents may be at risk for excessive bleeding after invasive dental procedures. The current antithrombotic agents used in medicine are reviewed, and the dental management of patients taking these agents is discussed.

  1. Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases.

    PubMed

    Losa, Marco; Mazza, Elena; Terreni, Maria Rosa; McCormack, Ann; Gill, Anthony J; Motta, Micaela; Cangi, Maria Giulia; Talarico, Anna; Mortini, Pietro; Reni, Michele

    2010-12-01

    The prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas. This was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150-200 mg/m(2) per day for 5 days every 4 weeks for a maximum of 12 cycles. Response assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels. Four patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O(6)-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response. Temozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.

  2. Maintenance electroconvulsive therapy for aggression and self-injurious behavior in two adolescents with autism and catatonia.

    PubMed

    Haq, Aazaz U; Ghaziuddin, Neera

    2014-01-01

    Frequent aggression toward others and repetitive self-injurious behaviors (SIB) can be features of catatonia in patients with autism. Similar to catatonia secondary to other etiologies, catatonia associated with autism responds well to treatment with benzodiazepines and/or electroconvulsive therapy (ECT). The authors report here on two adolescent patients with autism who presented with severe aggression, one of whom also engaged in repetitive SIB. With ongoing treatment with maintenance ECT, dramatic reduction in aggression and SIB were noted, allowing both patients a reasonable quality of life in their own homes. Attempts to taper off ECT coincided with return of aggression symptoms, although not SIB.

  3. Transcatheter left atrial appendage occlusion in patients with atrial fibrillation and a high bleeding risk using aspirin alone for post-implant antithrombotic therapy.

    PubMed

    Korsholm, Kasper; Nielsen, Kirsten Melgaard; Jensen, Jesper Møller; Jensen, Henrik Kjærulf; Andersen, Grethe; Nielsen-Kudsk, Jens Erik

    2017-04-20

    The aim of the study was to evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) with the AMPLATZER Cardiac Plug (ACP) or Amulet using aspirin alone (ASA) as post-implantation antithrombotic treatment. This was a single-centre, prospective, non-randomised study on LAAO with the ACP or Amulet in a consecutive cohort (n=110) treated by ASA alone post implantation. The primary outcome was device-related thrombosis, while secondary outcomes were ischaemic stroke or major bleeding. Clinical follow-up was conducted after six weeks and 12 months with TEE and cardiac CT. One hundred and seven patients were included in the analysis. Three patients were excluded due to a mechanical valve prosthesis. CHA2DS2-VASc score was 4.4±1.6 and HAS-BLED 4.1±1.1. Successful implantation was obtained in all patients with a periprocedural complication rate of 4.6%. Median follow-up was 2.3 years, with a total of 265 patient-years. Device-related thrombosis was detected in 2/107 (1.9%) cases. Stroke occurred in 6/107 patients, with an annualised rate of 2.3%, which is a 61% risk reduction compared to the predicted rate. Annual risk of major bleeding was reduced by 57%. LAAO with the ACP or Amulet was safely performed with ASA monotherapy after implantation without an increased risk of device-related thrombosis or stroke.

  4. Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer.

    PubMed

    Loeb, Stacy; Folkvaljon, Yasin; Damber, Jan-Erik; Alukal, Joseph; Lambe, Mats; Stattin, Pär

    2017-05-01

    Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.

  5. Antithrombotic and antiplatelet activities of Soshiho-tang extract

    PubMed Central

    2013-01-01

    Background Soshiho-tang (SH; Chinese name, Xiao-Chai-Hu-Tang; Japanese name, Shosaiko-to) is a traditional Korean, Chinese, and Japanese medicine, which has been used to treat various conditions, including hepatitis, liver cirrhosis, and chronic and acute liver disease. SH consists of seven herbal components, of which Scutellaria baicalensis Georgi and Zingiber officinale Roscoe, are reported to have antithrombotic and antiplatelet activities. We investigated the antithrombotic activity of SH, including S. baicalensis and Z. officinale, as an integrative therapy. Methods To identify the antithrombotic activity of SH, we used a FeCl3-induced thrombus formation model. The mechanism of SH-mediated antithrombotic activity was assessed by determining platelet aggregation and coagulation times ex vivo, washed platelet aggregation, serotonin secretion, and thromboxane B2 formation. Results SH prolonged the occlusion time of thrombus formation when applied in a FeCl3-induced thrombus formation model. SH also inhibited collagen-induced platelet aggregation ex vivo in a concentration-dependent manner; however, it did not affect coagulation. Hence, to identify the antiplatelet effect of SH, we investigated washed platelet aggregations in vitro. SH significantly inhibited various agonist-induced platelet aggregations, and it completely inhibited serotonin secretion and thromboxane B2 formation. Conclusions The findings suggest that SH inhibited FeCl3-induced thrombus formation through antiplatelet activity, including inhibition of platelet aggregation, and serotonin and TXB2 production. Thus, SH may be useful as an integrative herbal formula for the treatment of thrombosis. PMID:23773779

  6. Dexa-BEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma.

    PubMed

    Atta, Johannes; Chow, Kai U; Weidmann, Eckhart; Mitrou, Paris S; Hoelzer, Dieter; Martin, Hans

    2007-02-01

    Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.

  7. Successful surgical drainage and aggressive medical therapy in a preterm neonate with Bacillus cereus meningitis.

    PubMed

    Drazin, Doniel; Lehman, Deborah; Danielpour, Moise

    2010-01-01

    Bacillus cereus meningitis is a rare disease with a very high mortality rate in neonates. The authors present the rare case of a premature infant with B. cereus bacteremia and subsequent intracranial abscesses. In addition to aggressive medical therapy, surgical drainage was performed via a left frontal mini-craniotomy. At 15 months of age, the patient had mild developmental delay, cortical blindness, and sensorineural hearing loss. The clinical case is described and difficulties in the management of B. cereus meningoencephalitis in infants are discussed.

  8. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.

    PubMed

    Misir Krpan, Ana; Dusek, Tina; Rakusic, Zoran; Solak, Mirsala; Kraljevic, Ivana; Bisof, Vesna; Ozretic, David; Kastelan, Darko

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

  9. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma

    PubMed Central

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma. PMID:28357143

  10. Multiple relapses in high-grade osteosarcoma: when to stop aggressive therapy?

    PubMed

    Tamamyan, Gevorg; Dominkus, Martin; Lang, Susanna; Diakos, Christopher; Mittheisz, Edda; Horcher, Ernst; Holter, Wolfgang; Zoubek, Andreas; Bielack, Stefan; Kager, Leo

    2015-03-01

    The prognosis after relapse of high-grade osteosarcoma is poor and complete resection of all tumors is essential for survival. A 6-year old was diagnosed with high-grade osteosarcoma and treated according to the COSS-96 protocol. Within 5 years from initial diagnosis, five osteosarcoma relapses occurred and every time it was possible to achieve complete surgical remission. Additional treatments included chemotherapy and dendritic cell-based cancer immune therapy. Since the end of therapy of the 5th relapse, he is alive for 11½ years. Our experience further supports that aggressive surgery can help to achieve long-term survival even in patients with multiple osteosarcoma relapses. © 2014 Wiley Periodicals, Inc.

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

    PubMed

    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.

  12. Multifocal aggressive squamous cell carcinomas induced by prolonged voriconazole therapy: a case report.

    PubMed

    Morice, C; Acher, A; Soufir, N; Michel, M; Comoz, F; Leroy, D; Verneuil, L

    2010-01-01

    Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.

  13. 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

  14. Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments.

    PubMed

    Mega, Jessica L; Simon, Tabassome

    2015-07-18

    Antithrombotic drugs, which include antiplatelet and anticoagulant therapies, prevent and treat many cardiovascular disorders and, as such, are some of the most commonly prescribed drugs worldwide. The first drugs designed to inhibit platelets or coagulation factors, such as the antiplatelet clopidogrel and the anticoagulant warfarin, significantly reduced the risk of thrombotic events at the cost of increased bleeding in patients. However, both clopidogrel and warfarin have some pharmacological limitations including interpatient variability in antithrombotic effects in part due to the metabolism, interactions (eg, drug, environment, and genetic), or targets of the drugs. Increased knowledge of the pharmacology of antithrombotic drugs and the mechanisms underlying thrombosis has led to the development of newer drugs with faster onset of action, fewer interactions, and less interpatient variability in their antithrombotic effects than previous antithrombotic drugs. Treatment options now include the next-generation antiplatelet drugs prasugrel and ticagrelor, and, in terms of anticoagulants, inhibitors that directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, edoxaban) are available. In this Series paper we review the pharmacological properties of these most commonly used oral antithrombotic drugs, and explore the development of antiplatelet and anticoagulant therapies.

  15. Perioperative complications following preoperative cessation of antithrombotic agents for total knee arthroplasty

    PubMed Central

    Hwang, Jin-Young; Oh, Sohee; Kim, Chong-Soo; Chang, Jee-Eun; Min, Seong-Won

    2016-01-01

    Abstract The number of elderly patients undergoing total knee arthroplasty (TKA) has steadily increased. Elderly patients undergoing TKA usually have underlying diseases, and some of them take antithrombotic agents for the prevention or treatment of these co-morbidities, including cardiovascular, cerebrovascular, or thromboembolic diseases. When these patients are scheduled to undergo TKA, preoperative cessation of antithrombotic agents is considered on the basis of its risks and benefits. This study was aimed to evaluate the impact of discontinuing antithrombotic agents for primary total knee arthroplasty (TKA) on perioperative complications. Patients who underwent primary TKA between 2008 and 2012 were identified, and classified into two groups: group A, in whom antithrombotic agents were ceased preoperatively, and group B, in which patients did not receive antithrombotic therapy. Patient characteristics, history of antithrombotic therapy, intraoperative blood loss, perioperative blood transfusion, postoperative 30-day complications, and postoperative hospital stay were recorded. Of 885 patients undergoing primary TKA, 218 (24.6%) patients were included in group A, and 667 (75.4%) in group B. Group A received transfusion more frequently than group B (P < 0.001). However, there was no difference between the two groups in terms of intraoperative blood loss, postoperative 30-day complications, and postoperative hospital stay. Patients who discontinued antithrombotic drugs before primary TKA do not have a higher incidence of postoperative 30-day complications, including cardiovascular, cerebrovascular, or thromboembolic events. Moreover, the estimated intraoperative blood loss was not different compared with patients not receiving antithrombotic agents preoperatively. Larger prospective studies of this issue are required. PMID:27902607

  16. Antithrombotic management of patients with prosthetic heart valves: current evidence and future trends.

    PubMed

    Sun, Jack C J; Davidson, Michael J; Lamy, Andre; Eikelboom, John W

    2009-08-15

    Over 4 million people worldwide have received a prosthetic heart valve, and an estimated 300,000 valves are being implanted every year. Prosthetic heart valves improve quality of life and survival of patients with severe valvular heart disease, but the need for antithrombotic therapy to prevent thrombotic complications in valve recipients poses challenges for clinicians and patients. Here, we review antithrombotic therapies for patients with prosthetic heart valves and management of thromboembolic complications. Advances in antithrombotic therapy and valve technologies are likely to improve the management of patients with prosthetic heart valves in developed countries, but the most important unmet need and potential for benefit from these new therapies is in developing countries where a massive and rapidly increasing burden of valvular heart disease exists.

  17. Laser prostatectomy: two and a half years' experience with aggressive multifocal therapy.

    PubMed

    Kollmorgen, T A; Malek, R S; Barrett, D M

    1996-08-01

    The aim of this study was to evaluate patient outcome 1 to 2 1/2 years after aggressive neodymium: yttrium-aluminum-garnet (Nd:YAG) laser prostatectomy alone or combined with potassium titanyl phosphate (KTP/532) laser therapy. In 32 men with symptomatic bladder outlet obstruction caused by benign prostatic hyperplasia, Nd:YAG laser energy (40 W) was delivered to six or more locations on the prostatic lateral lobes and one or more on the median lobe. In a subgroup of 15 of these patients, the prostate was also incised and sculpted with KTP/532 laser to create a better channel. In the 32 men, voiding parameters improved: mean peak flow rate increased from 10 to 21 mL/s (110%), residual volume decreased from 167 to 64 mL (62%), and American Urological Association (AUA) symptom score decreased from 24 to 9 (63%). Catheters were removed after 3 days. Of the 17 patients treated with the Nd:YAG laser alone, 12 (70.5%) required recatheterization, whereas only 5 of the 15 (33%) who received KTP/532 laser therapy after Nd:YAG treatment required recatheterization (P < 0.001). In the entire group of 32 patients, complications included predictably prolonged retention (14 to 60 days) in 4 patients (12.5%) with hypotonic bladders, prolonged dysuria in 4 (12.5%), vesical neck contracture in 2 (6%), and significant hematuria in 1; none had incontinence. All 25 sexually active men remained potent (100%), but among these patients retrograde ejaculation developed in 5 (20%). Aggressive Nd:YAG laser prostatectomy is safe and effective for obstructive prostates up to 70 mL in volume and produces good results that are sustained for up to 2 1/2 years. Adjunctive KTP/532 laser therapy apparently creates an unobstructed channel more quickly and reduces the rate of postoperative retention, but it does not alter other voiding parameters.

  18. 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

  19. Amniotic membrane transplantation ineffective as additional therapy in patients with aggressive Mooren’s ulcer

    PubMed Central

    2013-01-01

    Background Mooren’s ulcer is a severe ulcerative inflammation of the cornea. The exact pathogenesis remains unclear. Therefore many therapies of Mooren’s ulcer are recommended in literature. To shed more light on the ongoing question of optimal treatment of severe progressive Mooren’s ulcer, we here report on a retrospective case series of patients treated with systemic immunosuppressive therapy and additional amniotic membrane transplantation. Methods Medical records from seven patients (eleven eyes), 4 male and 3 female, with severe progressive Mooren’s ulcer were analysed retrospectively. The mean follow up was 88.4 ± 80.8 months (range 12–232 month). A HLA-typing was performed in all patients. A systemic immunosuppressive therapy was administered in all patients. The amniotic membrane was transplanted after the base of the ulcer was resected. Results Multiple amniotic membrane transplantations were necessary in six patients. The visual outcome of all patients was poor. No patient achieved a visual acuity better than 20/630 Snellen chart. Five patients were positive for HLA-DQ2 and four patients were positive for HLA-DR17(3). Conclusions The aggressive and highly inflammatory form of Mooren’s ulcer is difficult to treat and the progression of the disease is hard to influence positively even under systemic immunosuppressive therapy. Therefore, the main intention of therapy is to achieve a stable epithelialized corneal surface without the risk of perforation. Amniotic membrane transplantation is not able to cure severe forms of Mooren’s ulcer. However it supports the immunosuppressive therapy in acute situations as in critical corneal thinning. PMID:24345289

  20. 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. PMID:27630854

  1. Prior Antithrombotic Use Is Associated With Favorable Mortality and Functional Outcomes in Acute Ischemic Stroke.

    PubMed

    Myint, Phyo K; Hellkamp, Anne S; Fonarow, Gregg C; Reeves, Matthew J; Schwamm, Lee H; Schulte, Phillip J; Xian, Ying; Suter, Robert E; Bhatt, Deepak L; Saver, Jeffrey L; Peterson, Eric D; Smith, Eric E

    2016-08-01

    Antithrombotics are the mainstay of treatment in primary and secondary prevention of stroke, and their use before an acute event may be associated with better outcomes. Using data from Get With The Guidelines-Stroke with over half a million acute ischemic strokes recorded between October 2011 and March 2014 (n=540 993) from 1661 hospitals across the United States, we examined the unadjusted and adjusted associations between previous antithrombotic use and clinical outcomes. There were 250 104 (46%) stroke patients not receiving any antithrombotic before stroke; of whom approximately one third had a documented previous vascular indication. After controlling for clinical and hospital factors, patients who were receiving antithrombotics before stroke had better outcomes than those who did not, regardless of whether a previous vascular indication was present or not: adjusted odds ratio (95% confidence intervals) were 0.82 (0.80-0.84) for in-hospital mortality, 1.18 (1.16-1.19) for home as the discharge destination, 1.15 (1.13-1.16) for independent ambulatory status at discharge, and 1.15 (1.12-1.17) for discharge modified Rankin Scale score of 0 or 1. Previous antithrombotic therapy was independently associated with improved clinical outcomes after acute ischemic stroke. Ensuring the use of antithrombotics in appropriate patient populations may be associated with benefits beyond stroke prevention. © 2016 American Heart Association, Inc.

  2. Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer.

    PubMed

    Menderes, Gulden; Clark, Mitchell; Santin, Alessandro D

    2016-04-01

    Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer. Although it represents only 10% of all endometrial cancer cases, USC accounts for up to 40% of all endometrial cancer-related recurrences and subsequent deaths. With such a dismal prognosis, there is an expanding role for novel targeted approaches in the treatment of 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. The results emphasize the relevance of these novel therapeutic targets for biologic therapy of USC, which will be reviewed in this article.

  3. Patient-related risk factors for tooth loss in aggressive periodontitis after active periodontal therapy.

    PubMed

    Bäumer, Amelie; El Sayed, Nihad; Kim, Ti-Sun; Reitmeir, Peter; Eickholz, Peter; Pretzl, Bernadette

    2011-04-01

    Evaluation of patient-related risk factors contributing to tooth loss and recurrence of periodontitis 10.5 years after initial therapy in patients with aggressive periodontitis (AgP). Eighty-four of 174 patients were included. Re-examination consisted of patient's history, clinical examination and test for interleukin (IL)-1 composite genotype. Patients' charts were searched for regularity of maintenance and initial diagnosis. Statistical analysis was performed using Poisson and logistical regression analysis. The responder rate was 48%. Thirteen of 84 patients presented a localized AgP, 68 were females and 29 smoked. One hundred and thirteen teeth out of 2154 were lost after therapy (1.34 teeth/patient). Age (p=0.0018), absence of IL-1 composite genotype (p=0.0091) and educational status (p=0.0085) were identified as statistically significant risk factors for tooth loss. Twenty patients exhibited recurrence of periodontitis at re-examination. Smoking (p=0.0034) and mean Gingival Bleeding Index (GBI) (p=0.0239) contributed significantly to recurrence of disease. No patient participating regularly in supportive periodontal therapy (SPT) showed disease recurrence. Age, absence of IL-1 composite genotype and low social status are detected as risk factors for tooth loss. Smoking and high mean GBI are associated with an increased risk for recurrence of periodontitis, whereas regular SPT acts as a protective factor. © 2011 John Wiley & Sons A/S.

  4. Antithrombotic treatment in anticoagulated atrial fibrillation patients undergoing percutaneous coronary intervention.

    PubMed

    Dézsi, Csaba András; Dézsi, Balázs Bence; Dézsi, Döme András

    2017-01-05

    Coronary artery disease coexists in a clinically relevant number of patients with atrial fibrillation and it often requires percutaneous coronary intervention. These patients represent a particular challenge for clinicians in terms of antithrombotic management. They require combined antiplatelet-anticoagulant therapy to reduce the risk of recurrent ischemic cardiac events and stroke; however, this antithrombotic strategy is associated with an increased risk of bleeding complications. In the absence of randomized, controlled clinical trials, the majority of current recommendations rely on the results of cohort studies, meta-analyses, post-hoc analyses and subgroup analyses of large, phase III studies. Based on the available evidence, the present review discusses the optimal antithrombotic strategy for patients receiving chronic anticoagulant therapy due to atrial fibrillation who require antiplatelet treatment after acute coronary syndrome and/or percutaneous coronary intervention, and discusses the issue of dental procedures. The correct planning of therapy significantly reduces the risk of bleeding complications and thromboembolic events.

  5. Non-Surgical Therapy Reduces Presence of JP2 Clone in Localized Aggressive Periodontitis.

    PubMed

    Burgess, Danielle K; Huang, Hong; Harrison, Peter; Kompotiati, Theodora; Aukhil, Ikramuddin; Shaddox, Luciana M

    2017-08-18

    Previous studies have provided substantial evidence on the association of Aggregatibacter actinomycetemcomitans (Aa), and its highly leukotoxic JP2 genotype, with localized aggressive periodontitis (LAP). The present study aims to evaluate the presence of JP2 in LAP individuals following periodontal treatment. Sixty African American LAP patients between ages 5 and 25 years were examined. At baseline, pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BoP) and plaque index were measured and subgingival plaque was collected from both LAP diseased sites and healthy sites for each participant. Patients received whole-mouth ultrasonic debridement, scaling and root planning and a 7-day prescription of amoxicillin and metronidazole. Participants were re-evaluated, re-sampled and received regular maintenance therapy at 3, 6 and 12-months post-treatment. PCR technique was used detect presence of the JP2 genotype before and after treatment. At baseline, the JP2 sequence was identified in 75% of LAP diseased sites and in 56.67% of healthy sites. At 3, 6 and 12-months post-treatment, patient compliance was 40, 31 and 31, respectively, and JP2 detection decreased to 17.5%, 6.45% and 3.23% respectively, in diseased sites (P<0.001) and to 2.5%, 3.23% and 0% respectively, in healthy sites (P<0.001). Clinical parameters of disease were also significantly reduced after therapy (p<0001). Additionally, significant correlations were observed between JP2 presence and mean PD (p < 0.002) and CAL (p < 0.001), post-therapy. Periodontal therapy was successful in reducing clinical parameters of LAP and the subgingival presence of JP2 in diseased and healthy sites.

  6. 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

  7. 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

  8. The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

    PubMed Central

    van Haelst, Paul L.; Wobbes, Martgriet H.; Gans, Rijk O.; Zijlstra, Felix; May, Johan F.; Smit, Andries J.; Tervaert, Jan Willem Cohen; van Doormaal, Jasper J.

    2007-01-01

    Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy. PMID:17342417

  9. [Antithrombotic treatment in patients with stable coronary artery disease. Which drugs and for how long?].

    PubMed

    Gitt, A K; Zahn, R

    2014-11-01

    Stable chronic coronary artery disease (SCAD) encompasses several groups of patients including those with stable angina pectoris or other symptoms thought to be linked to CAD as well as patients with known prior acute coronary syndrome or prior coronary interventions, who have become asymptomatic with treatment and need regular follow-up. Patients with SCAD have an elevated risk for subsequent ischemic events and significantly benefit not only from lipid-lowering therapy with statins but also in particular from long-term antithrombotic treatment. These patients therefore need lifelong antithrombotic treatment with 100 mg acetylsalicylic acid (ASA) daily whereby clopidogrel 75 mg daily is indicated as an alternative in cases of aspirin intolerance. As chronic CAD may present with very different developmental phases spanning from chronic stable phases to acute coronary syndromes, antithrombotic treatment in SCAD patients needs continuous evaluation and adaptation. In addition, new concomitant diseases, such as atrial fibrillation may necessitate further adaptation of antithrombotic therapy. The current overview focuses on the description of the long-term antithrombotic treatment of SCAD as well as on the need for adaptation in the setting of elective percutaneous coronary interventions (PCI).

  10. Structure-activity relationship studies for multitarget antithrombotic drugs.

    PubMed

    Neves, Ana R; Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena

    2016-12-01

    Thrombosis is a complex process involving multiple pathways. Currently, therapy relies on the combination of two or more antithrombotic drugs, showing that inhibiting more than one target provides benefits in the prevention and treatment of thrombosis. This review focuses on structure-activity relationship studies of molecules possessing multiple actions against thrombosis, namely, dual inhibitors of coagulation, dual inhibitors of coagulation and platelet aggregation, and also dual inhibitors of platelet aggregation. EP217609 has just entered clinical trials, which raise the expectations on the multitarget strategy to prevent or treat thrombosis.

  11. 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.

  12. Generalization and Behavior Covariation of Aggression in Children Receiving Stress Inoculation Therapy.

    ERIC Educational Resources Information Center

    Maag, John W.; And Others

    1988-01-01

    Examines the effects of a stress inoculation program on the aggressive behavior of four behaviorally disordered preadolescent males. Finds that three of the four boys exhibited decreases in aggressive behavior and increases in coping behavior that generalized to nontreatment day school setting. (FMW)

  13. Traumatic Intracranial Hemorrhage Correlates with Preinjury Brain Atrophy, but Not with Antithrombotic Agent Use: A Retrospective Study

    PubMed Central

    Dunham, C. Michael; Hoffman, David A.; Huang, Gregory S.; Omert, Laurel A.; Gemmel, David J.; Merrell, Renee

    2014-01-01

    of preinjury brain atrophy with acute intracranial hemorrhage is a novel finding. Contrary to antithrombotic agent status, admission neurologic abnormality is a predictor of adverse post-admission outcomes. Study findings indicate that effective hemostasis is maintained with antithrombotic therapy. PMID:25279785

  14. Novel 2-Aminobenzamides as Potential Orally Active Antithrombotic Agents

    PubMed Central

    2012-01-01

    In an effort to develop potent antithrombotic agents, a series of novel 2-aminobenzamide derivatives were synthesized and screened for their in vivo antithrombotic activity. Among the 23 compounds tested, compound (8g) showed the most promising antithrombotic activity, which was comparable with clinically used aspirin or warfarin, but at variance with these standard drugs, 8g did not exhibit the increased bleeding time, suggesting its potential as a novel antithrombotic agent. PMID:24900559

  15. 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.

  16. Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiation therapy

    PubMed Central

    Allott, Emma H.; Howard, Lauren E.; Song, Hai-Jun; Sourbeer, Katharine N.; Koontz, Bridget F.; Salama, Joseph K.; Freedland, Stephen J.

    2014-01-01

    Background While elevated body mass index (BMI) has been associated with increased risk of aggressive prostate cancer (PC), the importance of adipose tissue distribution is not well understood. We examined associations between overall and visceral obesity and aggressive PC risk. Moreover, given racial differences in adipose tissue distribution, we examined whether race modified these associations. Methods We conducted a cross-sectional analysis of 308 radiation-treated PC patients within the Durham VA from 2005–2011. Multivariable logistic regression examined the association between BMI categories and tertiles of waist circumference (WC), visceral fat area (VFA) and periprostatic adipose tissue area (PPAT) with high-grade PC risk (Gleason score ≥7 vs. ≤6). Models stratified by race examined whether these associations differed between black and non-black men. Results Both elevated BMI (p-trend=0.054) and WC (p-trend=0.040) were associated with increased high-grade PC risk, with similar results between races, although the association with BMI was not statistically significant. In contrast, elevated VFA was associated with increased aggressive PC risk in black men (p-trend=0.002) but not non-black men (p-trend=0.831), with a significant interaction between race and VFA (p-interaction=0.035). Though similar patterns were observed for PPAT, none were statistically significant. Conclusions Among men undergoing radiation therapy for PC, visceral obesity is associated with increased aggressive PC risk, particularly among black men. If confirmed in future studies, these results suggest adipose tissue distribution differences may contribute to PC racial disparity. Impact These findings highlight the need to elucidate mechanisms contributing to racial differences in the association between visceral obesity and aggressive PC. PMID:25146088

  17. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial.

    PubMed

    Moreland, Larry W; O'Dell, James R; Paulus, Harold E; Curtis, Jeffrey R; Bathon, Joan M; St Clair, E William; Bridges, S Louis; Zhang, Jie; McVie, Theresa; Howard, George; van der Heijde, Désirée; Cofield, Stacey S

    2012-09-01

    To assess whether it is better to intensively treat all patients with early rheumatoid arthritis (RA) using combinations of drugs or to reserve this approach for patients who do not have an appropriate response (as determined by a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] of ≥ 3.2 at week 24) to methotrexate (MTX) monotherapy, and to assess whether combination therapy with MTX plus etanercept is superior to the combination of MTX plus sulfasalazine plus hydroxychloroquine. The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) study is a 2-year, randomized, double-blind trial. A 2 × 2 factorial design was used to randomly assign subjects to 1 of 4 treatment arms: immediate treatment with MTX plus etanercept, immediate oral triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or step-up from MTX monotherapy to one of the combination therapies (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine) at week 24 if the DAS28-ESR was ≥ 3.2. All treatment arms included matching placebos. The primary outcome was an observed-group analysis of DAS28-ESR values from week 48 to week 102. At week 24 (beginning of the step-up period), subjects in the 2 immediate-treatment groups demonstrated a greater reduction in the DAS28-ESR compared with those in the 2 step-up groups (3.6 versus 4.2; P < 0.0001); no differences between the combination-therapy regimens were observed. Between week 48 and week 102, subjects randomized to the step-up arms had a DAS28-ESR clinical response that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm. There was no significant difference in the DAS28-ESR between subjects randomized to oral triple therapy and those randomized to receive MTX plus etanercept. By week 102, there was a statistically significant difference in the change in radiographic measurements from baseline between the group receiving MTX

  18. Fludarabine, cyclophosphamide, doxorubicin (FCD), and rituximab: a remission induction therapy for aggressive pediatric post-transplant lymphoproliferative disease (PTLD).

    PubMed

    Giraldi, Eugenia; Provenzi, Massimo; Fiocchi, Roberto; Colledan, Michele; Cornelli, Pieremilio; Torre, Giuliano; Rambaldi, Alessandro; Conter, Valentino

    2011-08-01

    Management of aggressive, usually late-occurring, post-transplant lymphoproliferative disorders (PTLDs), a life-threatening complication after solid organ transplants, remains controversial. Four children affected by aggressive CD20+ PTLDs received a chemo-immunotherapy regimen for remission induction based on fludarabine, cyclophosphamide, doxorubicin, and rituximab, associated with a rapid discontinuation of immunosuppression (IS). Subsequent consolidation chemotherapy consisted of Berlin-Frankfurt-Münster-modified blocks. All patients achieved a complete remission, which persisted for 25, 68+, 80+, and 103+ months after diagnosis. Therapy was well tolerated. No patients developed allograft rejection during PTLD treatment. Our experience suggests that this chemo-immunotherapeutic approach may be an effective treatment strategy while allowing for a concomitant discontinuation of IS.

  19. 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

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

    PubMed

    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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. Search For The Ideal Antithrombotic Drug: Utopian Task Likely Is Implemented Already.

    PubMed

    Stirbys Md PhD, Petras

    2016-01-01

    Atrial fibrillation is the most prevalent cardiac arrhythmia with a high risk of ischemic stroke. Thromboprophylaxis plays a key role in prevention of cardioembolic and non-cardioembolic events. Oral antithrombotic drugs are most often used to reduce hypercoagulable state. Patients may suffer from both under- and overtreatment compromising the outcomes. Medication peculiarities at large are well-known and widely debated. Non-adherence to antithrombotic drug regimen poses a significant risk of stroke. There is a pressing need for more detailed delineation of risk factors, namely by incorporation of the letter "N" (meaning "Non-adherence to drug therapy") into the well-known risk score alphanumeric display: CHA2DS2N-VASc. Better delineation of risk factors related to antithrombotic treatment as well as those related to treatment for congestive heart failure, hypertension, diabetes are desirable. Similarly, the bleeding risk score formula HAS-BLED might be improved by an additional risk factor, marked as the symbol "E", meaning "Excessive antithrombotic dosing" i.e. HAS-BLEDE. Improved formulas would help raise the predictive scores value and awareness for clinicians facing the problem of non-adherence to treatment regimen. If patients properly followed the prescribed drug therapy regimen it would potentially reveal that we already have ideal or near ideal antithrombotic drug(s). These drugs, herein non-specified, are widely used, but due to non-adherence they are not categorized as the best ones. That is why considerable efforts are focused on continued research and new developments.

  7. Electroconvulsive therapy in adolescents with intellectual disability and severe self-injurious behavior and aggression: a retrospective study.

    PubMed

    Consoli, Angele; Cohen, Johan; Bodeau, Nicolas; Guinchat, Vincent; Wachtel, Lee; Cohen, David

    2013-01-01

    Efficacious intervention for severe, treatment-refractory self-injurious behavior and aggression (SIB/AGG) in children and adolescents with intellectual disability and concomitant psychiatric disorders remains a complex and urgent issue. The aim of this study is to assess the efficacy of electroconvulsive therapy (ECT) on severe and treatment-resistant SIB/AGG in young people with intellectual disability and current psychiatric disorder. We reviewed the charts of all patients (N = 4) who received ECT in the context of SIB/AGG with resistance to behavioral interventions, milieu therapy and pharmacotherapy from 2007 to 2011. We scored the daily rate of SIB/AGG per patient for each hospital day. Inter rater reliability was good (intraclass correlations = 0.91). We used a mixed generalized linear model to assess whether the following explanatory variables (time, ECT) influenced the course of SIB/AGG over time, the dependant variable. The sample included two girls and two boys. The mean age at admission was 13.8 years old [range 12-14]. The patients had on average 19 ECT sessions [range 16-26] and one patient received maintenance ECT. There was no effect of time before and after ECT start. ECT was associated with a significant decrease in SIB/AGG scores (p < 0.001): mean aggression score post-ECT was half the pre-ECT value. ECT appears beneficial in severe, treatment-resistant SHBA in adolescents with intellectual disability.

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

    PubMed

    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.

  9. Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation. Intracoronary Stenting and Antithrombotic Regimen: CAUTION in Discontinuing Clopidogrel Therapy--ISAR-CAUTION.

    PubMed

    Fiedler, K Anette; Mehilli, Julinda; Kufner, Sebastian; Schlichting, Anna; Ibrahim, Tareq; Sibbing, Dirk; Ott, Ilka; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Schulz, Stefanie

    2014-06-01

    There is little evidence on the optimal mode of clopidogrel discontinuation. Epidemiological studies observed clustering of thrombotic events after cessation of chronic clopidogrel therapy. The underlying mechanism has been ascribed to transient platelet hyper-reactivity. Gradual tapering of clopidogrel may have the potential to attenuate this phenomenon. The objective of the present study was to assess whether in patients with drug-eluting stents (DES) gradual discontinuation of clopidogrel maintenance therapy is superior to conventional, abrupt discontinuation. Patients with planned discontinuation of chronic clopidogrel therapy after DES implantation were randomised in a double-blinded fashion to either gradual discontinuation (according to a tapering schema over four weeks) or abrupt discontinuation (after continued clopidogrel therapy for additional four weeks). The primary endpoint was the composite of cardiac death, myocardial infarction, stroke, stent thrombosis, major bleeding or rehospitalisation due to an acute coronary syndrome at 90 days. Enrollment of 3,000 patients was planned. The study was stopped prematurely due to slow recruitment after enrollment of 782 patients. At 90 days, nine of 392 patients (2.3%) with tapered cessation reached the primary endpoint compared to five of 390 patients (1.3%) with abrupt cessation (p=0.284). The composite of death or myocardial infarction occurred in three patients with tapered and three patients with abrupt discontinuation (p=0.764). In conclusion, tapered discontinuation of chronic clopidogrel therapy is not superior to abrupt discontinuation regarding the primary endpoint in this study. However, the results must be interpreted in view of the premature termination of the trial and low event rates.

  10. 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

  11. The impact of preinjury antithrombotic medication on hemostatic interventions in trauma patients.

    PubMed

    Kudo, Daisuke; Kushimoto, Shigeki; Shiraishi, Atsushi; Ogura, Hiroshi; Hagiwara, Akiyoshi; Saitoh, Daizoh

    2017-01-01

    The purpose of this study was to determine whether preinjury medication with antithrombotic agents was related to an increase in hemostatic interventions in patients with severe trauma without traumatic brain injury. Consecutive trauma patients who were admitted to the emergency departments of the study hospitals with an injury severity score ≥16 were enrolled in this retrospective, observational, multicenter study of coagulation in the acute phase of severe trauma. Patients without a traumatic brain injury with an abbreviated injury scale ≥3 were evaluated. Patients were divided into those with and those without preinjury medication with antithrombotic agents. The impact of preinjury antithrombotic medication on the composite primary outcome, defined as administration of fresh frozen plasma ≥10 U and/or hemostatic treatment (surgery and/or interventional radiology) within 24 hours, was analyzed. The preinjury medication group consisted of 20 (6.4%) of the total 312 patients. Preinjury medication was one of the independent risk factors for the composite outcome (odds ratio, 3.16; 95% confidence interval, 1.08-9.10; P < .05) adjusting for age, sex, and injury severity score on multivariate analysis. Preinjury antithrombotic therapy was also associated with hemostatic treatments within 24 hours (odds ratio, 3.40; 95% confidence interval, 1.16-9.85; P = .026). Survival time was not different between the 2 groups on Cox regression analysis. Preinjury antithrombotic medication in severe trauma patients without traumatic brain injury may be associated with a higher risk of hemostatic interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 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

  13. Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy.

    PubMed

    Pauli, Chantal; Fuchs, Bruno; Pfirrmann, Christian; Bridge, Julia A; Hofer, Silvia; Bode, Beata

    2014-01-20

    Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the bony containment, mostly located intracortically in the proximal radius. The diagnosis of a periosteal ABC was confirmed by FISH demonstrating USP6 gene rearrangement on the initial biopsy. Function conserving surgery could be performed, enabling reconstruction of the affected bone. Inhibition of RANKL with denosumab may offer therapeutic option for patients not only with giant cell tumors but also with ABCs.

  14. 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

  15. Cost-Effectiveness of Triple Therapy Versus Etanercept Plus Methotrexate in Early Aggressive Rheumatoid Arthritis.

    PubMed

    Jalal, Hawre; O'Dell, James R; Bridges, S Louis; Cofield, Stacey; Curtis, Jeffrey R; Mikuls, Ted R; Moreland, Larry W; Michaud, Kaleb

    2016-12-01

    To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started with methotrexate and added either etanercept or sulfasalazine plus hydroxychloroquine to patients with persistent disease activity. We built a Markov cohort model that uses individual-level data from the TEAR trial, published literature, and supplemental clinical data. Costs were in US dollars, benefits in quality-adjusted life years (QALYs), perspective was societal, and the time horizon was 5 years. The immediate strategies were more efficacious than step-up strategies. SE and IE were more costly than ST and IT, primarily due to treatment cost differences. In addition, IT was the least expensive and most effective strategy when the time horizon was 1 and 2 years. When the time horizon was 5 years, IE was marginally more effective than IT (3.483 versus 3.476 QALYs), but IE was substantially more expensive than IT ($148,800 versus $52,600), producing an incremental cost-effectiveness ratio of $12.5 million per QALY. These results were robust to both one-way deterministic and joint probabilistic sensitivity analyses. IT was highly cost-effective in the majority of scenarios. Although IE was more effective in 5 years, a substantial reduction in the cost of biologic agents was required in order for IE to become cost-effective in early aggressive RA under willingness-to-pay thresholds that most health care settings may find acceptable. © 2016, American College of Rheumatology.

  16. The Rosenzweig Picture-Frustration Study "extra-aggression" score as an indicator in cognitive restructuring therapy for male perpetrators of domestic violence.

    PubMed

    Norman, Michael; Ryan, Lawrence J

    2008-04-01

    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 Rosenzweig instrument. The resulting responses were rated by trained scorers. Chi-square calculations revealed that batterers in the first quarter of treatment manifested Rosenzweig responses indicative of extra-aggressiveness, whereas in the fourth quarter, batterers manifested Rosenzweig responses indicative of im-aggression. The data are discussed relative to implications for domestic violence treatment and the use of the Rosenzweig instrument as an index of treatment progress.

  17. Cardiac surgery in patients on antiplatelet and antithrombotic agents.

    PubMed

    Woo, Y Joseph

    2005-01-01

    The widespread application of antithrombotic agents carries significant potential for inducing excessive peri-operative hemorrhage during cardiac surgery. Specific surgical and medical strategies can be employed to attenuate this bleeding. These antithrombotic agents and anti-hemorrhagic measures will be reviewed in depth.

  18. Critique of "Stenting versus aggressive medical therapy for intracranial arterial stenosis" by Chimowitz et al in the new England Journal of Medicine.

    PubMed

    Abou-Chebl, Alex; Steinmetz, Helmuth

    2012-02-01

    Symptomatic intracranial stenoses are an important cause of stroke and have a high risk of recurrent stroke with medical therapy. The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Arterial Stenosis (SAMMPRIS) trial unexpectedly showed a higher-than-expected rate of complications with intracranial stenting and a lower-than-expected recurrence rate with medical therapy. In this commentary, the authors review possible explanations for these findings and suggest future strategies for study.

  19. 'Real-world' antithrombotic treatment in atrial fibrillation: The EORP-AF pilot survey.

    PubMed

    Lip, Gregory Y H; Laroche, Cécile; Dan, Gheorghe-Andrei; Santini, Massimo; Kalarus, Zbigniew; Rasmussen, Lars Hvilsted; Ioachim, Popescu Mircea; Tica, Otilia; Boriani, Giuseppe; Cimaglia, Paolo; Diemberger, Igor; Hellum, Camilla Fragtrup; Mortensen, Bettina; Maggioni, Aldo P

    2014-06-01

    Current guidelines strongly recommend that oral anticoagulation should be offered to patients with atrial fibrillation and ≥1 stroke risk factors. The guidelines also recommend that oral anticoagulation still should be used in the presence of stroke risk factors irrespective of rate or rhythm control. In an analysis from the dataset of the EURObservational Research Programme on Atrial Fibrillation Pilot Survey (n = 3119), we examined antithrombotic therapy prescribing, with particular focus on the risk factors determining oral anticoagulation or antiplatelet therapy use. When oral anticoagulation was used among admitted patients in whom no pharmacologic cardioversion, electrical cardioversion, or catheter ablation was performed or planned, vitamin K antagonist therapy was prescribed in the majority (72.2%), whereas novel oral anticoagulants were used in the minority (7.7%). There was no significant difference in bleeding risk factors among the patients treated with the different types of antithrombotic therapies, except for those with chronic kidney disease, in whom oral anticoagulation was less commonly used (P = .0318). Antiplatelet therapy was more commonly used in patients with a high Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly score (≥2) (P < .0001). More oral anticoagulation use was associated with female gender (P = .0245). Less novel oral anticoagulant use was associated with valvular heart disease (P < .0001), chronic heart failure (P = .0010), coronary artery disease (P < .0001), and peripheral artery disease (P = .0092). Coronary artery disease was the strongest reason for combination therapy with oral anticoagulation plus antiplatelet drug (odds ratio, 8.54; P < .0001). When the Congestive heart failure, Hypertension, Age ≥75 [Doubled], Diabetes, Stroke [Doubled]-Vascular disease, Age 65-74, and Sex category [female

  20. Novel Therapies Against Aggressive and Recurrent Epithelial Cancers by Molecular Targeting Tumor- and Metastasis-Initiating Cells and Their Progenies

    PubMed Central

    Mimeault, Murielle; Batra, Surinder K.

    2010-01-01

    A growing body of experimental evidence has revealed that the highly tumorigenic cancer stem/progenitor cells endowed with stem cell-like properties might be responsible for initiation and progression of numerous aggressive epithelial cancers into locally invasive, metastatic and incurable disease states. The malignant transformation of tissue-resident adult stem/progenitor cells or their progenies into tumorigenic and migrating cancer stem/progenitor cells and their resistance to current cancer therapies have been associated with their high expression levels of specific oncogenic products and drug resistance-associated molecules. In this regard, we describe the tumorigenic cascades that are frequently activated in cancer stem/progenitor cells versus their differentiated progenies during the early and late stages of the epithelial cancer progression. The emphasis is on the growth factor signaling pathways involved in the malignant behavior of prostate and pancreatic cancer stem/progenitor cells and their progenies. Of clinical interest, the potential molecular therapeutic targets to eradicate the tumor- and metastasis-initiating cells and their progenies and develop new effective combination therapies against locally advanced and metastatic epithelial cancers are also described. PMID:20184544

  1. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study.

    PubMed

    Le Page, Emmanuelle; Deburghgraeve, Véronique; Lester, Marie-Antoinette; Cardiet, Isabelle; Leray, Emmanuelle; Edan, Gilles

    2015-01-01

    Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (± 3) and 8.3 (± 4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2-30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave's disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.

  2. Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.

    PubMed

    Ferrara, Fortunato; Staquicini, Daniela I; Driessen, Wouter H P; D'Angelo, Sara; Dobroff, Andrey S; Barry, Marc; Lomo, Lesley C; Staquicini, Fernanda I; Cardó-Vila, Marina; Soghomonyan, Suren; Alauddin, Mian M; Flores, Leo G; Arap, Marco A; Lauer, Richard C; Mathew, Paul; Efstathiou, Eleni; Aparicio, Ana M; Troncoso, Patricia; Navone, Nora M; Logothetis, Christopher J; Marchiò, Serena; Gelovani, Juri G; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih

    2016-10-24

    Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.

  3. Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer

    PubMed Central

    Ferrara, Fortunato; Staquicini, Daniela I.; Driessen, Wouter H. P.; D’Angelo, Sara; Dobroff, Andrey S.; Barry, Marc; Lomo, Lesley C.; Staquicini, Fernanda I.; Cardó-Vila, Marina; Soghomonyan, Suren; Alauddin, Mian M.; Flores, Leo G.; Arap, Marco A.; Lauer, Richard C.; Mathew, Paul; Efstathiou, Eleni; Aparicio, Ana M.; Troncoso, Patricia; Navone, Nora M.; Logothetis, Christopher J.; Marchiò, Serena; Gelovani, Juri G.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih

    2016-01-01

    Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC. PMID:27791181

  4. Generalized aggressive periodontitis: microbiological composition and clinical parameters in non-surgical therapy.

    PubMed

    Usin, María M; Tabares, Sandra M; Menso, Julieta; de Albera, Estela R; Sembaj, Adela

    2016-12-01

    The aim of this study was to determine the variations in periodontal parameters and microbiological composition in periodontal pockets at the baseline and 3 and 6 months post treatmentin patients with Generalized Aggressive Periodontitis(GAP) undergoing non surgical periodontal treatment combined with chlorhexidine and systemic antibiotics. Medical and dental history was taken from 10 subjects, average age 30.6±2.7 years, diagnosed with GAP. A non surgical periodontal treatment combined with 0.12% chlorhexidine, 875 mg amoxicillin and 500 mg metronidazole every 12 hours for ten days was conducted. At each visit, the following measurements wererecorded: bacterial plaque (BP), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), hypermobility, and furcation lesions, and a sample of subgingivalplaque was taken from the site of the deepest probing depth of each sextant to identify Porphyromonas gingivalis, Treponemadenticola, Tannerella forsythia, Prevotella intermedia and Aggregatibacter actinomycetemcomitans using molecular biology techniques. After 6 months, the Wilcoxon test showed an increase of 0.97 mm in CAL (p=0.0047) and 2.54 mm in PD(p=0.009). A healthy site was defined as having a PD <5 mm, negative BOP and no pathogenic bacteria detected at 6 months, indicating significant improvement (p=0.008), with OR (95%CI) =4.7 (1.102220.11).With the treatment protocol used in this study, 6 months after treatment, patients had an approximately 4- fold higher possibility of presenting PD <5 mm and periodontal pockets without periodontal pathogenic bacteria.

  5. The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

    PubMed

    Carty, F; Mahon, B P; English, K

    2017-04-01

    Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross-talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange.

  6. Early detection, aggressive therapy: optimizing the management of feline mammary masses.

    PubMed

    Giménez, Fernanda; Hecht, Silke; Craig, Linden E; Legendre, Alfred M

    2010-03-01

    This article reviews the incidence, etiology, diagnosis, treatment and prognosis of mammary tumors in cats. Approximately 80% of feline mammary masses are malignant, with adenocarcinoma being the most common tumor type. Early diagnosis is, therefore, essential to improve the prognosis and quality of life of affected cats. Surgery is the most widely used treatment for malignant tumors. However, as mammary tumors are often advanced and metastasis has already occurred by the time of diagnosis, surgery routinely does not provide a cure. Ovariohysterectomy or hormonal therapy are the treatments of choice for fibroadenomatous hyperplasia (the most common benign mass) and usually lead to a successful outcome. Copyright 2010. Published by Elsevier Ltd.

  7. Advancement in antithrombotics for stroke prevention in atrial fibrillation.

    PubMed

    Umer Usman, Mohammed Haris; Raza, Sabreen; Raza, Shariq; Ezekowitz, Michael

    2008-08-01

    The focus of this review is the evolving field of antithrombotic drug therapy for stroke prevention in patients with atrial fibrillation (AF). The current standard of therapy includes warfarin, acenocoumarol and phenprocoumon which have proven efficacy by reducing stroke by 68% against placebo. However, a narrow therapeutic index, wide variation in metabolism, and numerous food and drug interactions have limited their clinical application to only 50% of the indicated population. Newer agents such as direct thrombin inhibitors, factor Xa inhibitors, factor IX inhibitors, tissue factor inhibitors and a novel vitamin K antagonist are being developed to overcome the limitations of current agents. The direct thrombin inhibitor dabigatran is farthest along in development. Further clinical trial testing, and eventual incorporation into clinical practice will depend on safety, efficacy and cost. Development of a novel vitamin K antagonist with better INR control will challenge the newer mechanistic agents in their quest to replace the existing vitamin K antagonists. Till then, the large unfilled gap to replace conventional agents remains open. This review will assess all these agents, and compare their mechanism of action, stage of development and pharmacologic profile.

  8. Effects of aggressive statin therapy on patients with coronary saphenous vein bypass grafts: a systematic review and meta-analysis of randomized, controlled trials.

    PubMed

    Kang, Sheng; Liu, Yong; Liu, Xue-bo

    2013-08-01

    The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs) in randomized, controlled trials (RCTs). We searched MEDLINE (1980-June 2012), the Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PubMed (to June 2012), and found 10 relevant RCTs, including 7 substudy analyses from a Post-CABG trial, and 1 pooled analysis of the PROVE-IT TIMI 22 trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators) and A to Z trial. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes; phase Z of the A to Z trial. A total of 6645 of participants, ages ranging from 21 to 75 years old, were treated with coronary artery bypass graft (CABG) and were followed for 2 to 5 years. Eight studies showed that aggressive statin therapy had lower LDL-C levels and a decrease of 39% in graft atherosclerotic progression, 12% in new occlusions, and 19% in new lesions more than moderate statin therapy. Three reports indicated that aggressive statin therapy lowered the risk of repeated myocardial infarction more than moderate statin therapy for coronary revascularization (95% CI, 0.66-0.95; risk ratio [RR] = 0.80; and 95% CI, 0.66-0.85; RR = 0.75) and lowered the risk of cardiac death as well (95% CI, 0.64-1.08; RR = 0.83). Aggressive statin therapy had safety similar to that of moderate statin therapy except for a slight increase in myopathic events and aminotransferase levels. Seventy percent to 90% of patients took statin treatment as prescribed in long-term. Compared with moderate statin therapy, long-term aggressive statin lowered the LDL-C level significantly, further decreased the atherosclerotic progression of SVG, reduced the risks of repeated myocardial infarction and coronary revascularization after CABG, and revealed similar patient compliance

  9. 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

  10. 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).

  11. Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

    PubMed Central

    Pereira, Rebeca Cristina Costa; Lourenço, André Luiz; Terra, Luciana; Abreu, Paula Alvarez; Laneuville Teixeira, Valéria; Castro, Helena Carla

    2017-01-01

    Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents. PMID:28335516

  12. Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic.

    PubMed

    Pereira, Rebeca Cristina Costa; Lourenço, André Luiz; Terra, Luciana; Abreu, Paula Alvarez; Laneuville Teixeira, Valéria; Castro, Helena Carla

    2017-03-20

    Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60), which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.

  13. Cardiovascular pharmacogenetics of anti-thrombotic agents and non-steroidal anti-inflammatory drugs.

    PubMed

    Stitham, J; Vanichakarn, P; Ying, L; Hwa, J

    2014-01-01

    The use of antithrombotic agents, particularly antiplatelet drugs like aspirin and clopidogrel, has been instrumental in decreasing the risk for adverse cardiovascular events across a wide range of patients. However, despite the established benefits, the use of these medications remains suboptimal. There is a high degree of inter-individual variation in response to these treatments, whereby patients experience occlusive thromboembolic events, in spite of maintaining an appropriate treatment regimen. This has lead to the notion of antithrombotic "resistance" or "poor responders", which has been a growing concern amongst clinicians and other healthcare providers. Compounding this matter even further, reports of increased cardiovascular risk associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, have revealed additional and unforeseen contributors to myocardial infarction and stroke. With all medications, striking a balance between the potential risks and benefits seems more art than science at times. However, given their widespread use and critical cardiovascular implications, further emphasis has been placed on understanding factors influencing antithrombotic and NSAID therapies. A major aim in cardiovascular pharmacogenetics is the discovery of genetic biomarkers that will allow for prospective screening and individualized prediction of drug efficacy and adverse reactions for these medications (both alone and together) within the context of cardiovascular disease.

  14. Animal-assisted therapy with chronic psychiatric inpatients: equine-assisted psychotherapy and aggressive behavior.

    PubMed

    Nurenberg, Jeffry R; Schleifer, Steven J; Shaffer, Thomas M; Yellin, Mary; Desai, Prital J; Amin, Ruchi; Bouchard, Axel; Montalvo, Cristina

    2015-01-01

    Animal-assisted therapy (AAT), most frequently used with dogs, is being used increasingly as an adjunctive alternative treatment for psychiatric patients. AAT with larger animals, such as horses, may have unique benefits. In this randomized controlled study, equine and canine forms of AAT were compared with standard treatments for hospitalized psychiatric patients to determine AAT effects on violent behavior and related measures. The study included 90 patients with recent in-hospital violent behavior or highly regressed behavior. Hospitalization at the 500-bed state psychiatric hospital was two months or longer (mean 5.4 years). Participants were randomly selected to receive ten weekly group therapy sessions of standardized equine-assisted psychotherapy (EAP), canine-assisted psychotherapy (CAP), enhanced social skills psychotherapy, or regular hospital care. Participants' mean age was 44, 37% were female, 76% had diagnoses of schizophrenia or schizoaffective disorder, and 56% had been committed involuntarily for civil or forensic reasons. Violence-related incident reports filed by staff in the three months after study intake were compared with reports two months preintake. Interventions were well tolerated. Analyses revealed an intervention group effect (F=3.00, df=3 and 86, p=.035); post hoc tests showed specific benefits of EAP (p<.05). Similar AAT effects were found for the incidence of 1:1 clinical observation (F=2.70, df=3 and 86, p=.051); post hoc tests suggested benefits of CAP (p=.058) as well as EAP (p=.082). Covariance analyses indicated that staff can predict which patients are likely to benefit from EAP (p=.01). AAT, and perhaps EAP uniquely, may be an effective therapeutic modality for long-term psychiatric patients at risk of violence.

  15. Aggressive management of shunt infection: combined intravenous and intraventricular antibiotic therapy for twelve or less days.

    PubMed

    James, Hector E; Bradley, John S

    2008-01-01

    This report is limited to patients with a single cerebrospinal fluid (CSF) shunt infected by a single organism, and compares two treatment protocols. In the initial protocol (1975-1991), patients underwent removal of the shunt system and received intravenous and intraventricular antibiotics. Intraventricular antibiotics were administered twice daily to those with external ventricular drainage. When CSF was cultured 48 h off all antibiotics and found to be sterile at 24 h of incubation, a new shunt was inserted. Follow-up CSF cultures were obtained in all patients between 1-6 months following placement of the new shunt. There were 25 patients (ages 1 month to 16 years; mean +/- SD: 23 +/- 4.0 months). CSF obtained from the shunt yielded the following: Staphylococcus epidermidis (19), Staphylococcus aureus (2), Streptococcus species (2), Serratia marcescens (1), and Propionebacterium species (1). The duration of intravenous antibiotics was 7-12 days (mean +/- SD: 9.7 +/- 1.3 days), and intraventricular antibiotic therapy was 6.2 +/- 1.7 days. Total hospital stay was 15.2 +/- 2.3 days. The follow-up period was 7.7 +/- 3.6 years. Following the initial protocol in another 15 patients (1992-2004), the treatment regime was modified in that intraventricular antibiotics were administered once daily in patients with external ventricular drainage, and the CSF was cultured at 24 h off antibiotics, instead of 48 h. Results were similar to the initial protocol with respect to days of antibiotic therapy and hospital stay. Based on our retrospective nonrandomized series, we believe patients with a single shunt and noncompartmentalized hydrocephalus can be successfully treated without a prolonged antibiotic course and lengthy hospital stay.

  16. Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies

    PubMed Central

    Subbiah, Vivek; Hess, Kenneth R.; Khawaja, Muhammad Rizwan; Wagner, Michael J.; Tang, Chad; Naing, Aung; Fu, Siqing; Janku, Filip; Piha-Paul, Sarina; Tsimberidou, Apostolia M.; Herzog, Cynthia E.; Ludwig, Joseph A.; Patel, Shreyaskumar; Ravi, Vinod; Benjamin, Robert S.; Meric-Bernstam, Funda; Hong, David S.

    2016-01-01

    Prognosis of patients with advanced sarcoma after progression from FDA approved therapies remains grim. In this study, clinical outcomes of 100 patients with advanced sarcoma who received treatment on novel targeted therapy trials were evaluated. Outcomes of interest included best response, clinical benefit rate, progression-free survival (PFS) and overall survival (OS). Median patient age was 48 years (range 14–80). Patients had received a median of 2 prior lines of systemic treatment. Phase I treatments were anti-VEGF–based (n = 45), mTOR inhibitor–based (n = 15), and anti-VEGF + mTOR inhibitor–based (n = 17) or involved other targets (n = 23). Best responses included partial response (n = 4) and stable disease (n = 57). Clinical benefit rate was 36% (95% confidence interval 27–46%). Median OS was 9.6 months (95% Confidence Interval 8.1–14.2); median PFS was 3.5 months (95% Confidence Interval 2.4–4.7). RMH prognostic score of 2 or 3 was associated with lower median OS (log-rank p-value < 0.0001) and PFS (log-rank p-value 0.0081). Receiving cytotoxic chemotherapy as part of phase I trial was also associated with shorter median OS (log-rank p-value 0.039). Patients with advanced sarcoma treated on phase I clinical trials had a clinical benefit rate of 36% and RMH score predicted survival. PMID:27748430

  17. 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

  18. Safety of reduced anti-thrombotic strategies in HeartMate II patients: A one-year analysis of the US-TRACE Study.

    PubMed

    Katz, Jason N; Adamson, Robert M; John, Ranjit; Tatooles, Antone; Sundareswaran, Kartik; Kallel, Faouzi; Farrar, David J; Jorde, Ulrich P

    2015-12-01

    Patients with bleeding complications during left ventricular assist device (LVAD) support often require a reduction in the recommended warfarin plus aspirin regimen. To characterize those who can be safely managed with a reduced anti-thrombotic strategy, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelEt Therapy in Patients with the HeartMate II LVAS) study was initiated in the United States (U.S.) and Europe. The TRACE U.S. arm enrolled HeartMate II (HMII; Thoratec) outpatients on a regimen of reduced anti-thrombotic therapy (RT), defined as vitamin K antagonist (warfarin) only, aspirin only, or no anti-thrombotic agent. The indication for RT, changes in anti-thrombotic therapies, and patient outcomes after RT were documented. Results for patients reaching 12 months or outcome are presented here. Between April 2012 and June 2013, 100 HMII outpatients (85% men) on RT (median age 64.5 [interquartile range, 32, 82] years, 61% with ischemic etiology, 69% destination therapy) were enrolled from 9 U.S. sites. The primary reason for RT initiation was in response to a bleeding event (82%). Pharmacotherapy at RT initiation included warfarin only (38%), aspirin only (28%), or no anti-thrombotic agent (34%). Freedom from ischemic stroke at 1 year was 93.8% ± 2.5%, and freedom from device thrombosis was 92.7% ± 2.7%. Despite RT, a subsequent bleeding event occurred in 52%. Reducing anti-thrombotic therapies in response to bleeding among HMII patients was achievable but may be associated with a higher risk for device thrombosis. Furthermore, despite an RT strategy, bleeding often will persist in those prone to such events. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Aggressive Trimodality Therapy for T1N2M1 Nonsmall Cell Lung Cancer with Synchronous Solitary Brain Metastasis: Case Report and Rationale

    PubMed Central

    Showalter, Timothy N.; Lin, Alexander

    2009-01-01

    Aggressive treatment, including resection of both metastasis and primary tumor, has been studied for non-small cell lung cancer patients with synchronous solitary brain metastasis. Involvement of mediastinal lymph nodes is considered a poor prognostic factor and a contraindication to surgical resection of the primary lung tumor after treatment for brain metastasis. Here we present the case of a patient who presented with a Stage IV T1N2M1 non-small cell lung cancer with synchronous solitary brain metastasis. He is alive and without evidence of disease two years after aggressive, multimodality treatment that included craniotomy, whole-brain radiation therapy, thoracic surgery, chemotherapy, and mediastinal radiation therapy. PMID:20169130

  20. 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

  1. Antithrombotic treatment in patients undergoing transcatheter aortic valve implantation (TAVI).

    PubMed

    Nijenhuis, Vincent J; Bennaghmouch, Naoual; van Kuijk, Jan-Peter; Capodanno, Davide; ten Berg, Jurriën M

    2015-04-01

    Transcatheter aortic valve implantation (TAVI) is an established treatment option for symptomatic patients with severe aortic valvular disease who are not suitable for conventional surgical aortic valve replacement. Despite improving experience and techniques, ischaemic and bleeding complications after TAVI remain prevalent and impair survival in this generally old and comorbid-rich population. Due to changing aetiology of complications over time, antiplatelet and anticoagulant therapy after TAVI should be carefully balanced. Empirically, a dual antiplatelet strategy is generally used after TAVI for patients without an indication for oral anticoagulation (OAC; e. g. atrial fibrillation, mechanical mitral valve prosthesis), including aspirin and a thienopyridine. For patients on OAC, a combination of OAC and aspirin or thienopyridine is generally used. This review shows that current registries are unfit to directly compare antithrombotic regimens. Small exploring studies suggest that additional clopidogrel after TAVI only affects bleeding and not ischemic complications. However, these studies are lack in quality in terms of Cochrane criteria. Currently, three randomised controlled trials are recruiting to gather more knowledge about the effects of clopidogrel after TAVI.

  2. 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

  3. 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.

  4. Systemic antimicrobials adjunctive to a repeated mechanical and antiseptic therapy for aggressive periodontitis: a 6-month randomized controlled trial.

    PubMed

    Varela, Victor M; Heller, Débora; Silva-Senem, Mayra X; Torres, Maria Cynésia M B; Colombo, Ana Paula V; Feres-Filho, Eduardo J

    2011-08-01

    The purpose of this study is to compare the additional benefit of systemic antimicrobials versus placebos to a repeated mechanical instrumentation combined with comprehensive local chemical plaque control for the periodontal treatment of generalized aggressive periodontitis (GAgP). This was a 6-month randomized, double-masked, placebo-controlled clinical trial. All GAgP patients received full-mouth disinfection followed by staged scaling and root planing without (placebo group; n = 17) or with (test group; n = 18) systemic antimicrobials (500 mg amoxicillin [AMX] + 250 mg metronidazole [MET]; three times a day for 10 days). Clinical parameters were measured at baseline and 3 and 6 months post-therapy. Significant differences between groups at baseline were sought by using the Mann-Whitney U test, whereas comparisons over time were examined by using a general linear model repeated measures procedure. Both groups demonstrated similar improvements in most parameters over time. The test group presented a greater mean probing depth (PD) reduction and clinical attachment level (CAL) gain at sites with initially moderate PD at 6 months (P <0.03). No differences were seen between groups regarding mean reductions and mean gains, respectively, for PD and CAL initially ≥7 mm. The test group presented a higher percentage of sites that improved ≥2 mm and ended up with PD ≤4 mm or a lower percentage of sites that worsened ≥2 mm and remained with PD >4 mm at 3 months (P <0.01). No differences were noticed between groups for these parameters at 6 months. AMX + MET brought additional clinical effects to the repeated mechanical and antiseptic treatment of GAgP in a very short time (3 months), which tended to fade away over time (6 months).

  5. Good response of an aggressive rare variant of signet ring cell carcinoma of prostate with hormonal therapy.

    PubMed

    Tiwari, Deviprasad; Nayak, Brusabhanu; Seth, Amlesh

    2017-03-08

    Primary signet ring cell carcinoma (SRCC) of the prostate is a rare entity, characterised by its aggressive nature and dismal prognosis. We report a case of an advanced SRCC of the prostate presenting as a large pelvic mass with obstructive uropathy and rectal involvement managed by complete androgen blockade. At 24 months follow-up, the patient has no evidence of progression or metastasis. Aggressive management with multimodality approach combining surgery, radiation and hormonal ablation can result in long disease-free survival in some patients, despite the aggressive nature of this disease.

  6. Antithrombotic treatment of atrial fibrillation: new insights.

    PubMed

    Le Heuzey, J Y

    2012-10-01

    The incidence and prevalence of atrial fibrillation are quickly increasing, mainly due to the ageing of the population. Atrial fibrillation is, to date, a problem of public health. Atrial fibrillation is associated to a five-fold risk of stroke, which may be identified by score risks, such as CHADS(2) score. The classical antithrombotic treatment of atrial fibrillation is based on vitamin K antagonists. Trials made in the 90's have clearly shown that vitamin K antagonists were able to decrease stroke risk by about 60%. New oral anticoagulants are now available on the market to treat patients with atrial fibrillation. These drugs are dabigatran which has demonstrated an interest in the RE-LY trial. Two doses may be prescribed, 110 mg bid and 150 mg bid. Anti Xa have also demonstrated an interest : rivaroxaban in the ROCKET AF trial and apixaban in the AVERROES (versus aspirin) and ARISTOTLE trials. In the future these drugs will have a major place in the armamentarium used to treat patients with atrial fibrillation. In all these trials a decrease in intra cranial haemorrhages has been demonstrated. In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys.

  7. Temporal trends in the use of antithrombotics at admission

    PubMed Central

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

    2016-01-01

    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

  8. The Effect of Nonsurgical Periodontal Therapy on the Level of Human Neutrophil Peptides 1-3 in Patients with Aggressive Periodontitis.

    PubMed

    Dolińska, Ewa; Skurska, Anna; Dymicka-Piekarska, Violetta; Milewski, Robert; Pietruski, Jan; Pietruska, Małgorzata; Sculean, Anton

    2017-09-21

    To assess the presence of HNP1-3 in the gingival crevicular fluid (GCF) of patients suffering from aggressive periodontitis before and after nonsurgical periodontal therapy. Twenty patients, each with generalised aggressive periodontitis (GAP) were included in the study. After periodontal examination, one site with a probing depth (PD) ≥ 4 mm was selected. Patients received nonsurgical treatment (scaling and root planing [SRP]) with additional administration of systemic antibiotic therapy (amoxicillin 375 mg three times daily + metronidazole 250 mg three times daily for 7 days). Prior to therapy and 3 and 6 months after, the following parameters were evaluated from the same site: PD, gingival recession (GR), clinical attachment level (CAL), plaque index (PI), bleeding on probing (BOP), sulcus fluid flow rate (SFFR). The level of HNP1-3 in GCF was determined by means of a commercially available ELISA kit. Compared to baseline, the level of HNP 1-3 did not show statistically significant differences at 3 and 6 months. The evaluated clinical parameters and SFFR showed statistically significant decreases compared to baseline. At 6 months, PD (median) decreased from 7 to 3.5 and CAL (median) decreased from 7 to 4. In patients with GAP, nonsurgical periodontal therapy in conjunction with systemic administration of amoxicillin and metronidazole had no effect on the level of HNP1-3 in GCF.

  9. Experimental antithrombotic effects of sesame seed whole grains and extracts.

    PubMed

    Kinugasa, Chifumi; Naemura, Aki; Hyodo, Kanae; Nakai, Yoshiki; Katsuta, Masumi; Yamamoto, Junichiro

    2011-09-01

    Prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet is known to enhance the risks for acute thrombotic events, and nutritional products experimentally shown to be antithrombotic, might contribute beneficial effects. The present study forms part of a series of investigations into the antithrombotic effect of various foods and vegetables. Roasted and crushed whole grains from six varieties of sesame seeds were added to the diet of mice. Antithrombotic activity was measured in the carotid artery in vivo, using a He-Ne laser-induced thrombosis technique after 12 weeks. Col/Chichibu/Maruteru-2/1995 and T016 varieties showed significant antithrombotic activity, whilst 00037803 was prothrombotic. The acute effects of purified ingredients, sesamin, sesamolin and sesamol, given orally or intra-arterially, were also examined after a single dose. The most effective ingredient was sesamol, followed by sesamolin and sesamin. Daily intake of specific antithrombotic sesame whole grains or purified active ingredients might help to prevent atherothrombotic diseases.

  10. Compliance with antithrombotic guidelines in surgery patients in German hospitals: a multicenter study involving pharmacy interns.

    PubMed

    Hohmann, Carina; Eickhoff, Christiane; Kaemmerer, Wolfgang; Schulz, Martin

    2012-06-01

    Despite the existence of antithrombotic guidelines, there is low compliance with these guidelines in clinical practice. Until now pharmacy interns (PIs) have not been involved in this process. The objectives were to involve PIs to evaluate compliance with antithrombotic guidelines for VTE prophylaxis in surgery patients, and in cases of noncompliance to carry out pharmaceutical interventions. The study was conducted in 7 hospitals in Germany involving 27 PIs within the project "Pharmacy interns on the ward" (P-STAT 2). Pharmacy interns determined the thromboembolic risk, documented antithrombotic medication, and checked the compliance with current antithrombotic guidelines. A total of 6491 patients were enrolled; 5695 patients received antithrombotic prophylaxis. Antithrombotic guideline was followed in 77.5% patients. Many patients are not receiving appropriate VTE prophylaxis or heparin bridging regimen despite the fact that evidence-based antithrombotic guidelines are available. Pharmacy interns may play an important role in antithrombotic management.

  11. 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

  12. Aurora A inhibitor (MLN8237) plus Vincristine plus Rituximab is synthetic lethal and a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma

    PubMed Central

    Mahadevan, Daruka; Stejskal, Amy; Cooke, Laurence S.; Manziello, Ann; Morales, Carla; Persky, Daniel O.; Fisher, Richard I.; Miller, Thomas P.; Qi, Wenqing

    2015-01-01

    Purpose Aurora A and B are oncogenic serine/threonine kinases that regulate mitosis. Over-expression of Auroras promotes resistance to microtubule targeted agents. We investigated mechanistic synergy by inhibiting the mitotic spindle apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either vincristine [MV] or docetaxel [MD] in aggressive B-NHL. The addition of rituximab [R] to MV or MD was evaluated for synthetic lethality. Experimental Design Aggressive B-NHL cell subtypes were evaluated in vitro and in vivo for target modulation and anti-NHL activity with single agents, doublets and triplets by analyzing cell proliferation, apoptosis, tumor growth, survival and mechanisms of response/relapse by gene expression profiling with protein validation. Results MV is synergistic while MD is additive for cell proliferation inhibition in B-NHL cell culture models. Addition of R to MV is superior to MD but both significantly induce apoptosis compared to doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest single agent activity for M, R, D and V with tumor growth inhibition (TGI) of ~10–15%. Of the doublets, MV caused tumor regression, while TGI was observed with MD (~55–60%) and MR (~25–50%) respectively. Although MV caused tumor regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was curative, while MDR led to TGI of ~85%. PCNA, Aurora B, cyclin B1, cyclin D1 and Bcl-2 proteins of harvested tumors confirmed response and resistance to therapy. Conclusions Addition of R to MV is a novel therapeutic strategy for aggressive B-NHL and warrants clinical trial evaluation. PMID:22374334

  13. Aurora A inhibitor (MLN8237) plus vincristine plus rituximab is synthetic lethal and a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma.

    PubMed

    Mahadevan, Daruka; Stejskal, Amy; Cooke, Laurence S; Manziello, Ann; Morales, Carla; Persky, Daniel O; Fisher, Richard I; Miller, Thomas P; Qi, Wenqing

    2012-04-15

    Aurora A and B are oncogenic serine/threonine kinases that regulate mitosis. Overexpression of Auroras promotes resistance to microtubule-targeted agents. We investigated mechanistic synergy by inhibiting the mitotic spindle apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either vincristine [MV] or docetaxel [MD] in aggressive B-cell non-Hodgkin lymphoma (B-NHL). The addition of rituximab [R] to MV or MD was evaluated for synthetic lethality. Aggressive B-NHL cell subtypes were evaluated in vitro and in vivo for target modulation and anti-NHL activity with single agents, doublets, and triplets by analyzing cell proliferation, apoptosis, tumor growth, survival, and mechanisms of response/relapse by gene expression profiling with protein validation. MV is synergistic whereas MD is additive for cell proliferation inhibition in B-NHL cell culture models. Addition of rituximab to MV is superior to MD, but both significantly induce apoptosis compared with doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest single-agent activity for MLN8237, rituximab, docetaxel, and vincristine with tumor growth inhibition (TGI) of approximately 10% to 15%. Of the doublets, MV caused tumor regression, whereas TGI was observed with MD (approximately 55%-60%) and MR (approximately 25%-50%), respectively. Although MV caused tumor regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was curative, whereas MDR led to TGI of approximately 85%. Proliferation cell nuclear antigen, Aurora B, cyclin B1, cyclin D1, and Bcl-2 proteins of harvested tumors confirmed response and resistance to therapy. Addition of rituximab to MV is a novel therapeutic strategy for aggressive B-NHL and warrants clinical trial evaluation. ©2012 AACR.

  14. Direct thrombin inhibition with bivalirudin as an antithrombotic strategy in general and interventional cardiology.

    PubMed

    Ahrens, Ingo; Smith, Belinda K; Bode, Christoph; Peter, Karlheinz

    2007-08-01

    Antithrombotic therapy is a crucial component of interventional cardiology and currently involves the administration of both anticoagulant and antiplatelet agents. The implementation of standard dual or triple antiplatelet therapies has allowed percutaneous coronary intervention (PCI) with stent implantation to become the treatment of choice in most patients with acute coronary syndromes (ACS), particularly in patients with ST-segment elevation myocardial infarction. However, the combined use of antithrombotic agents increases the bleeding risk associated with coronary intervention, which is a concern due to the increasing evidence that bleeding complications are associated with a higher risk of ischaemic events and death. The shortcomings of currently available anticoagulant drugs have promoted the ongoing development of new, powerful anticoagulant agents that have both efficacy in the setting of PCI and a reduced risk of bleeding; one of these classes of agents targets the thrombin molecule, a key factor in the coagulation cascade, and belongs to the class of anticoagulants known as direct thrombin inhibitors (DTIs). Bivalirudin, a synthetic peptide, is a DTI with unique, favourable pharmacological properties that include predictable linear pharmacokinetics. Bivalirudin was approved as an anticoagulant in patients undergoing routine PCI in 2000 by the FDA (in 2004 in Europe and Australia) and more recently in patients with ACS undergoing PCI. The pharmacological properties of bivalirudin, along with current indications for its use, are discussed in this review, with a focus on the major completed and ongoing clinical trials with bivalirudin.

  15. 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

  16. Antithrombotic potency of ticagrelor versus clopidogrel in type-2 diabetic patients with cardiovascular disease.

    PubMed

    Zafar, M Urooj; Baber, Usman; Smith, Donald A; Sartori, Samantha; Contreras, Johanna; Rey-Mendoza, Juan; Linares-Koloffon, Carlos A; Escolar, Gines; Mehran, Roxana; Fuster, Valentin; Badimon, Juan J

    2017-08-24

    Type-2 Diabetes Mellitus [T2DM] is associated with increased platelet reactivity and hypo-response to antiplatelet drugs. Ticagrelor, with its faster and more potent antiplatelet effects, was shown to reduce adverse events more than clopidogrel in the overall CAD patient population of PLATO trial, but the benefits did not reach statistical significance in the T2DM subgroup. To better understand these findings, we compared the antithrombotic effects of ticagrelor versus with clopidogrel in T2DM patients with cardiovascular disease. In a randomized, 2 treatment-sequence, crossover-design, T2DM patients (n=20, 57±8 years, 60 % male) received a loading-dose [LD] plus one week of daily-therapy [DT] of clopidogrel or ticagrelor. Treatment effects were assessed by measuring thrombus formation (Badimon Chamber) and platelet aggregation (Multiple Electrode Aggregometry (MEA) Analyzer and VerifyNow®) at 2- and 6-hour post-LD and on Day-7 of DT, in comparison with pre-treatment baseline. After 2 weeks of washout, patients switched to the second treatment under identical testing conditions. Ticagrelor significantly reduced thrombus formation versus baseline at 2- and 6-hour post-LD and Day-7 of DT (33 %, 40 % and 31 %, respectively, p<0.01 for all) whereas thrombus reductions with clopidogrel were much lower and significant only at 6-hour post-LD (16 %, 20 % and 17 %, respectively). Antithrombotic effect of ticagrelor at 6-hour was significantly stronger than clopidogrel (p<0.05). Platelet aggregation (MEA and VerifyNow®) was inhibited by both treatments but effects of ticagrelor were significantly stronger at each time-point. Ticagrelor exhibits a faster and more potent antithrombotic effect than clopidogrel in T2DM patients with cardiovascular disease, supporting its use in this population.

  17. Aggressive Behavior

    MedlinePlus

    ... Listen Español Text Size Email Print Share Aggressive Behavior Page Content Article Body My child is sometimes very aggressive. What is the best ... once they are quiet and still reinforces this behavior, so your child learns that time out means “quiet and still.” ...

  18. Signaling aggression.

    PubMed

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds.

  19. Rapid Improvement of thyroid storm-related hemodynamic collapse by aggressive anti-thyroid therapy including steroid pulse: A case report.

    PubMed

    Kiriyama, Hiroyuki; Amiya, Eisuke; Hatano, Masaru; Hosoya, Yumiko; Maki, Hisataka; Nitta, Daisuke; Saito, Akihito; Shiraishi, Yasuyuki; Minatsuki, Shun; Sato, Tatsuyuki; Murakami, Haruka; Uehara, Masae; Manaka, Katsunori; Makita, Noriko; Watanabe, Masafumi; Komuro, Issei

    2017-06-01

    Heart failure is relatively common in patients with hyperthyroidism, but thyrotoxic cardiomyopathy with poor left ventricular (LV) systolic function is very rare. We experienced a representative case of a patient who presented with severe LV dysfunction related to thyroid storm and needed extracorporeal membrane oxygenation (ECMO) temporally. Thyrotoxic cardiomyopathy. Aggressive antithyroid therapy, including steroid pulse to hyperthyroidism, leads to the dramatic improvement of cardiac function and she was successfully weaned from ECMO. The most outstanding feature of the current case was the rapid decrease of cardiac injury and improvement of cardiac function by strengthening antithyroid therapy, including steroid pulse, without thyroid hormone level normalization. In thyroid storm, various systemic inflammatory reactions have different time courses and among them, the cardiac phenotype emerges in most striking and critical ways.

  20. 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

  1. Antithrombotic medication and incident open-angle glaucoma.

    PubMed

    Marcus, Michael W; Müskens, Rogier P H M; Ramdas, Wishal D; Wolfs, Roger C W; de Jong, Paulus T V M; Vingerling, Johannes R; Hofman, Albert; Stricker, Bruno H C; Jansonius, Nomdo M

    2012-06-20

    To determine the associations between the use of antithrombotic drugs and incident open-angle glaucoma (OAG). Ophthalmic examinations including measurements of the IOP and perimetry were performed at baseline and follow-up in 3939 participants of the prospective population-based Rotterdam Study who did not have OAG at baseline. The use of antithrombotic drugs was monitored continuously during follow-up. Antithrombotic drugs were stratified into anticoagulants and platelet aggregation inhibitors. Associations between incident OAG and the use of antithrombotic drugs were assessed using Cox regression; the model was adjusted for age, sex, baseline IOP and IOP-lowering treatment, family history of glaucoma, and myopia. Associations between antithrombotic drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 participants (2.7%) developed OAG. The hazard ratio for anticoagulant use was 0.90 (95% confidence interval [CI], 0.55-1.48; P = 0.69) and for platelet aggregation inhibitors 0.80 (0.53-1.21; P = 0.28). There was no trend towards a reduced or increased risk of incident OAG with prolonged anticoagulant use (P value for trend 0.84) or platelet aggregation inhibitor use (0.59). There was a significant IOP-lowering effect of anticoagulants (-0.31 mm Hg; 95% CI, -0.58 to -0.04 mm Hg; P = 0.025) but not of platelet aggregation inhibitors (P = 0.06). The IOP-lowering effect of anticoagulants disappeared after additional adjustment for the use of systemic beta-blockers. Use of anticoagulants or platelet aggregation inhibitors appears not to be associated with incident OAG.

  2. Treating Comorbid Anxiety and Aggression in Children

    ERIC Educational Resources Information Center

    Levy, Karyn; Hunt, Caroline; Heriot, Sandra

    2007-01-01

    Objective: The aim of the study was to evaluate the effectiveness of an intervention that targeted both anxious and aggressive behaviors in children with anxiety disorders and comorbid aggression by parent report. Method: The effects of a cognitive-behavioral therapy intervention targeting comorbid anxiety and aggression problems were compared…

  3. Treating Comorbid Anxiety and Aggression in Children

    ERIC Educational Resources Information Center

    Levy, Karyn; Hunt, Caroline; Heriot, Sandra

    2007-01-01

    Objective: The aim of the study was to evaluate the effectiveness of an intervention that targeted both anxious and aggressive behaviors in children with anxiety disorders and comorbid aggression by parent report. Method: The effects of a cognitive-behavioral therapy intervention targeting comorbid anxiety and aggression problems were compared…

  4. Comparison between full-mouth scaling and root planing and quadrant-wise basic therapy of aggressive periodontitis: 6-month clinical results.

    PubMed

    Moreira, Rafael M; Feres-Filho, Eduardo J

    2007-09-01

    The aim of this study was to test the hypothesis that there are no differences in clinical parameters in generalized aggressive periodontitis patients after full-mouth scaling and root planing (FRP) or quadrant-wise basic periodontal therapy (BPT) when combined with an antibiotic regimen. Patients were allocated randomly to BPT (N = 15; mean age: 29.5 +/- 5.7 years) or FRP (N = 15; mean age: 28.4 +/- 5.7 years). All subjects received oral hygiene instructions including the use of a 0.12% chlorhexidine mouthrinse solution twice a day for 2 months. Patients also received amoxicillin, 500 mg, and metronidazole, 250 mg, three times a day for 7 days. Probing depth (PD), clinical attachment level, visible plaque, and bleeding on probing were recorded at baseline and at 2, 4, and 6 months post-therapy. Statistically significant changes within and between groups were determined using the general linear model repeated measures procedure. Both groups showed a significant improvement in all clinical parameters post-therapy, which was particularly evident at 2 months in the sites that had been deepest at baseline. For instance, the mean PD at sites with mean PD > or =7 mm at baseline had decreased 3.9 mm in the BPT group and 3.6 mm in the FRP group. At 6 months, the percentage of sites with PD > or =7 mm decreased from 13.2% +/- 3.2% to 0% in the BPT group and from 13.3% +/- 3.5% to 0.2% +/- 0.1% in the FRP group. No statistically significant differences were observed between groups for most clinical parameters. Within the limits of the present investigation, FRP and BPT caused comparable clinical effects in aggressive periodontitis patients when an adjunctive combined antibiotic regimen was included.

  5. Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers.

    PubMed

    Mimeault, M; Batra, S K

    2008-03-01

    The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devastating diseases associated with a high rate of recurrence after treatment with the conventional clinical therapies including surgery, ionizing radiation, hormonal therapy and systemic chemotherapy, which generally lead to the death of patients. Therefore, the establishment of the molecular events underlying cancer initiation and progression into locally invasive and metastatic diseases is of major interest in basic cancer research as well as for the development of new effective clinical therapeutic options against the recurrent and lethal cancers. Recent advances have led to the identification of specific oncogenic products that are implicated in the malignant transformation of adult stem/progenitor cells into leukemic or tumorigenic and migrating cancer stem/progenitor cells during cancer progression. Of therapeutic interest, the molecular targeting of deregulated signaling elements in cancer stem/progenitor cells and their local microenvironment represents a new potential strategy for the development of more effective clinical treatments against aggressive cancers. Particularly, the combined use of chemotherapeutic drugs to eradicate cancer-initiating cells with hematopoietic stem cell or genetically-modified stem cell transplant is emerging as potential cancer treatments that hold great promise in the area of clinical cancer research. These targeting and stem cell-based therapies may offer the ultimate hope for treating and even curing the patients diagnosed with locally advanced cancers at high risk of recurrence, metastatic and/or relapsed cancers in the clinics.

  6. Targeting of cancer stem/progenitor cells plus stem cell-based therapies: the ultimate hope for treating and curing aggressive and recurrent cancers

    PubMed Central

    MIMEAULT, M.; BATRA, S.K.

    2013-01-01

    The rapid progression from aggressive primary cancers into locally advanced and invasive and/or metastatic diseases remains a big obstacle for an early diagnosis and curative therapeutic intervention for cancer patients. The late-stage leukemias and disseminated and metastatic sarcomas, melanomas, brain tumors and epithelial cancers are the devastating diseases associated with a high rate of recurrence after treatment with the conventional clinical therapies including surgery, ionizing radiation, hormonal therapy and systemic chemotherapy, which generally lead to the death of patients. Therefore, the establishment of the molecular events underlying cancer initiation and progression into locally invasive and metastatic diseases is of major interest in basic cancer research as well as for the development of new effective clinical therapeutic options against the recurrent and lethal cancers. Recent advances have led to the identification of specific oncogenic products that are implicated in the malignant transformation of adult stem/progenitor cells into leukemic or tumorigenic and migrating cancer stem/progenitor cells during cancer progression. Of therapeutic interest, the molecular targeting of deregulated signaling elements in cancer stem/progenitor cells and their local microenvironment represents a new potential strategy for the development of more effective clinical treatments against aggressive cancers. Particularly, the combined use of chemotherapeutic drugs to eradicate cancer-initiating cells with hematopoietic stem cell or genetically-modified stem cell transplant is emerging as potential cancer treatments that hold great promise in the area of clinical cancer research. These targeting and stem cell-based therapies may offer the ultimate hope for treating and even curing the patients diagnosed with locally advanced cancers at high risk of recurrence, metastatic and/or relapsed cancers in the clinics. PMID:18427384

  7. 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

  8. Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two-Year Followup in the Treatment of Early Aggressive Rheumatoid Arthritis Trial.

    PubMed

    Charles-Schoeman, Christina; Wang, Xiaoyan; Lee, Yuen Yin; Shahbazian, Ani; Navarro-Millán, Iris; Yang, Shuo; Chen, Lang; Cofield, Stacey S; Moreland, Larry W; O'Dell, James; Bathon, Joan M; Paulus, Harold; Bridges, S Louis; Curtis, Jeffrey R

    2016-03-01

    To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time. Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P < 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P < 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup. Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept

  9. 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

  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.

  11. 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.

  12. Antiplatelets and antithrombotics in patients with liver insufficiency. From pathophysiology to clinical practice.

    PubMed

    Deutsch, Melanie; Koskinas, John

    2016-12-05

    The liver represents the site of synthesis of most procoagulant and anticoagulant factors, fibrinolytic proteins and thrombopoetin while being also involved in the clearance of hemostatic and fibrinolyic proteins. Therefore in patients with liver insufficiency a great variety of disturbances can be documented resulting however in a new "rebalanced" hemostatic system with a labile equilibrium between thromboses or bleeding. Interestingly patients with liver insufficiency may present with arterial or venous thrombotic episodes requiring antiplatelet and/or antithrombotic therapy despite low platelet count or prolonged INR. The aim of this review is to point on the current knowledge regarding hemostasis in patients with liver insufficiency underlining practical recommendations of the use of antiplatelet and anticoagulant drugs in this setting.

  13. Antithrombotic treatment and characteristics of elderly patients with non-valvular atrial fibrillation hospitalized at Internal Medicine departments. NONAVASC registry.

    PubMed

    Gullón, Alejandra; Suárez, Carmen; Díez-Manglano, Jesús; Formiga, Francesc; Cepeda, José María; Pose, Antonio; Camafort, Miguel; Castiella, Jesús; Rovira, Eduardo; Mostaza, José María

    2017-03-03

    The prevalence of non-valvular atrial fibrillation (NVAF) increases with the patient's age and is associated with high morbi-mortality rates. The main goal of this study was to describe the characteristics of hospitalized elderly patients with NVAF and to identify the clinical and functional factors which determine the use of different antithrombotic strategies. Observational, prospective, multicentre study carried out on patients with NVAF over the age of 75, who had been admitted for any medical condition to Internal Medicine departments. We evaluated 804 patients with a mean age of 85 years (range 75-101), of which 53.9% were females. The prevalence of risk factors and cardiovascular disease was high: hypertension (87.6%), heart failure (65.4%), ischemic cardiomyopathy (24.4%), cerebrovascular disease (22.4%) and chronic kidney disease (45%). Among those cases with previous diagnoses of NVAF, antithrombotic treatment was prescribed in 86.2% of patients: anticoagulants (59.7%), antiplatelet medication (17.8%) and double therapy (8.7%). The factors associated with the use of antithrombotic treatment were history of acute coronary syndrome and atrial fibrillation progression longer than one year. Older age, atrial fibrillation for less than one year, higher HAS-BLED scores and severe cognitive impairment were associated with the use of anti-platelet drugs. Permanent atrial fibrillation favoured the use of anticoagulants. Hospitalized patients older than 75 years old with NVAF showed numerous comorbidities. The percentage of anticoagulation was small and 18% received only anti-platelet therapy. The patient's age, atrial fibrillation's progression time and the severity of the cognitive impairment influenced this therapy choice. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Understanding Aggression.

    ERIC Educational Resources Information Center

    Scott, J. P.

    Research in many fields of the social and biological sciences indicates that there are ecological, cultural, social, psychological, physiological, and genetic causes of aggression. The agonistic behavior system, which adapts to situations of social conflict, includes several patterns of conduct ranging from overt fighting to complete passivity. In…

  15. Dental treatment in the era of new anti-thrombotic agents.

    PubMed

    Sahar-Helft, Sharonit; Chackartchi, Tali; Polak, David; Findler, Mordechai

    2017-09-17

    In recent years, there have been dramatic changes in anti-thrombotic treatment as a result of new anti-thrombotic agents, as well as changes in the indications for their use. As a consequence, dentists are encountering larger numbers of patients who are undergoing anti-thrombotic treatment and who have increased risk for bleeding. The current paper aims to review the literature regarding up-to-date anti-thrombotic treatment and provide information regarding their implications on dentistry. An online search was performed of the literature published between 2000 and 2016. Articles dealing with evidence-based clinical guidelines for anti-thrombotic treatments, as well as literature reporting the use of anti-thrombotic medications were included. The manuscripts were screened according to their relevance to dentistry as well as their treatment protocol guidelines. In total, 5,539 publications were identified: 56 of 554 evidence-based clinical guidelines were found that dealt with treatment protocols with anti-thrombotic agents; and 132 of 5,539 articles describe direct anti-thrombotic medications. Dental treatment includes a risk for bleeding. As a result of the increasing number of patients taking new-generation anti-thrombotic drugs, dentists must be up to date regarding the implications of such drugs on dental treatment as well as the practical means to achieve haemostasis. © 2017 FDI World Dental Federation.

  16. 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

  17. Factor XI and XII as antithrombotic targets

    PubMed Central

    Müller, Felicitas; Gailani, David; Renné, Thomas

    2015-01-01

    Purpose of review Arterial and venous thrombosis are major causes of morbidity and mortality, and the incidence of thromboembolic diseases increases as a population ages. Thrombi are formed by activated platelets and fibrin. The latter is a product of the plasma coagulation system. Currently available anticoagulants such as heparins, vitamin K antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for terminating blood loss at sites of vascular injury. As a result, anticoagulants currently in clinical use increase the risk of bleeding, partially offsetting the benefits of reduced thrombosis. This review focuses on new targets for anticoagulation that are associated with minimal or no therapy-associated increased bleeding. Recent findings Data from experimental models using mice and clinical studies of patients with hereditary deficiencies of coagulation factors XI or XII have shown that both of these clotting factors are important for thrombosis, while having minor or no apparent roles in processes that terminate blood loss (hemostasis). Summary Hereditary deficiency of factor XII (Hageman factor) or factor XI, plasma proteases that initiate the intrinsic pathway of coagulation, impairs thrombus formation and provides protection from vascular occlusive events, while having a minimal impact on hemostasis. As the factor XII–factor XI pathway contributes to thrombus formation to a greater extent than to normal hemostasis, pharmacological inhibition of these coagulation factors may offer the exciting possibility of anticoagulation therapies with minimal or no bleeding risk. PMID:21730835

  18. The microbial community shifts of subgingival plaque in patients with generalized aggressive periodontitis following non-surgical periodontal therapy: a pilot study.

    PubMed

    Han, Jing; Wang, Peng; Ge, Shaohua

    2017-02-07

    The object of this study is to characterize the bacterial community of subgingival plaque of two subjects with generalized aggressive periodontitis (GAgP) pre- and post-treatment. We picked two patients with GAgP and used high-throughput 16S rDNA sequencing. V4 hypervariable region was picked for PCR amplification of subgingival samples. Then, the PCR products were sequenced through Illumina MiSeq platform. One month after therapy, both the clinical features and periodontal parameters improved obviously. Moreover, the composition and structure of subgingival bacterial community changed after initial periodontal therapy. Also, the composition of the subgingival microbiota was highly individualized among different patients. Bacteroidetes, Spirochaetes and Fusobacteria were related to pathogenicity of GAgP while Actinobacteria and Proteobacteria seemed associated with clinical symptoms resolution. In this study, we found the subgingival bacterial community was high in species richness but dominated by a few species or phylotypes, with significant shifts of microbiota that occurred after treatment. This study demonstrated the shift of the subgingival bacterial community before and after treatment by high-throughput 16S rDNA sequencing, and provided a concise method for analysis of microbial community for periodontal diseases.

  19. Prospective evaluation of aggressive medical therapy for atherosclerotic renal artery stenosis, with renal artery stenting reserved for previously injured heart, brain, or kidney.

    PubMed

    Hanzel, George; Balon, Helena; Wong, Oliver; Soffer, Daniel; Lee, Daniel Taehee; Safian, Robert David

    2005-11-01

    Sixty-six patients with atherosclerotic renal artery stenosis (RAS) and serum creatinine < or =2.0 mg/dl were treated with antihypertensive therapy, a statin, and aspirin. Renal stenting was reserved for patients with injuries to the heart, brain, or kidneys. The primary end point was stenotic kidney glomerular filtration rate (GFR) at 21 months; secondary end points included major adverse clinical events, serum creatinine, total GFR, and blood pressure (BP). After baseline evaluation, 26 of 66 patients underwent renal stenting because of injuries to the heart, brain, or kidneys. After 21 months, 6 medical patients required renal stenting, and 5 patients experienced late clinical events (2 medical patients, 3 stent patients). There was no difference in final BP between groups. Whereas medical patients experienced 6% and 8% decreases in total and stenotic kidney GFR, stent patients experienced 7% and 11% increases in total kidney (p = 0.006) and stenotic kidney (p = 0.02) GFR. There was no difference in final serum creatinine. In conclusion, patients with atherosclerotic RAS and baseline creatinine < or =2.0 mg/dl can be safely managed with aggressive medical therapy, with a small decrease in GFR. For patients who develop injuries to the heart, brain, or kidneys, renal artery stenting may further reduce hypertension and improve renal function.

  20. The microbial community shifts of subgingival plaque in patients with generalized aggressive periodontitis following non-surgical periodontal therapy: a pilot study

    PubMed Central

    Han, Jing; Wang, Peng; Ge, Shaohua

    2017-01-01

    The object of this study is to characterize the bacterial community of subgingival plaque of two subjects with generalized aggressive periodontitis (GAgP) pre- and post-treatment. We picked two patients with GAgP and used high-throughput 16S rDNA sequencing. V4 hypervariable region was picked for PCR amplification of subgingival samples. Then, the PCR products were sequenced through Illumina MiSeq platform. One month after therapy, both the clinical features and periodontal parameters improved obviously. Moreover, the composition and structure of subgingival bacterial community changed after initial periodontal therapy. Also, the composition of the subgingival microbiota was highly individualized among different patients. Bacteroidetes, Spirochaetes and Fusobacteria were related to pathogenicity of GAgP while Actinobacteria and Proteobacteria seemed associated with clinical symptoms resolution. In this study, we found the subgingival bacterial community was high in species richness but dominated by a few species or phylotypes, with significant shifts of microbiota that occurred after treatment. This study demonstrated the shift of the subgingival bacterial community before and after treatment by high-throughput 16S rDNA sequencing, and provided a concise method for analysis of microbial community for periodontal diseases. PMID:27732961

  1. Neural Mechanisms of Cognitive-Behavioral Therapy for Aggression in Children and Adolescents: Design of a Randomized Controlled Trial Within the National Institute for Mental Health Research Domain Criteria Construct of Frustrative Non-Reward

    PubMed Central

    Wyk, Brent C. Vander; Eilbott, Jeffrey A.; McCauley, Spencer A.; Ibrahim, Karim; Crowley, Michael J.; Pelphrey, Kevin A.

    2016-01-01

    Abstract Objective: We present the rationale and design of a randomized controlled trial of cognitive-behavioral therapy (CBT) for aggression in children and adolescents, which is conducted in response to the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) approach initiative. Specifically, the study is focused on the brain-behavior associations within the RDoC construct of frustrative non-reward. On the behavioral level, this construct is defined by reactions elicited in response to withdrawal or prevention of reward, most notably reactive aggression. This study is designed to test the functional magnetic resonance (fMRI) and electrophysiological (EEG) correlates of aggression and its reduction after CBT. Methods: Eighty children and adolescents with high levels of aggression across multiple traditional diagnostic categories, ages 8–16, will be randomly assigned to receive 12 sessions of CBT or 12 sessions of supportive psychotherapy. Clinical outcomes will be measured by the ratings of aggressive behavior collected at baseline, midpoint, and endpoint evaluations, and by the Improvement Score of the Clinical Global Impressions Scale assigned by an independent evaluator (blinded rater). Subjects will also perform a frustration-induction Go-NoGo task and a task of emotional face perception during fMRI scanning and EEG recording at baseline and endpoint. Results: Consistent with the NIMH strategic research priorities, if functional neuroimaging and EEG variables can identify subjects who respond to CBT for aggression, this can provide a neuroscience-based classification scheme that will improve treatment outcomes for children and adolescents with aggressive behavior. Conclusions: Demonstrating that a change in the key nodes of the emotion regulation circuitry is associated with a reduction of reactive aggression will provide evidence to support the validity of the frustrative non-reward construct. PMID:26784537

  2. Neural Mechanisms of Cognitive-Behavioral Therapy for Aggression in Children and Adolescents: Design of a Randomized Controlled Trial Within the National Institute for Mental Health Research Domain Criteria Construct of Frustrative Non-Reward.

    PubMed

    Sukhodolsky, Denis G; Vander Wyk, Brent C; Eilbott, Jeffrey A; McCauley, Spencer A; Ibrahim, Karim; Crowley, Michael J; Pelphrey, Kevin A

    2016-02-01

    We present the rationale and design of a randomized controlled trial of cognitive-behavioral therapy (CBT) for aggression in children and adolescents, which is conducted in response to the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) approach initiative. Specifically, the study is focused on the brain-behavior associations within the RDoC construct of frustrative non-reward. On the behavioral level, this construct is defined by reactions elicited in response to withdrawal or prevention of reward, most notably reactive aggression. This study is designed to test the functional magnetic resonance (fMRI) and electrophysiological (EEG) correlates of aggression and its reduction after CBT. Eighty children and adolescents with high levels of aggression across multiple traditional diagnostic categories, ages 8-16, will be randomly assigned to receive 12 sessions of CBT or 12 sessions of supportive psychotherapy. Clinical outcomes will be measured by the ratings of aggressive behavior collected at baseline, midpoint, and endpoint evaluations, and by the Improvement Score of the Clinical Global Impressions Scale assigned by an independent evaluator (blinded rater). Subjects will also perform a frustration-induction Go-NoGo task and a task of emotional face perception during fMRI scanning and EEG recording at baseline and endpoint. Consistent with the NIMH strategic research priorities, if functional neuroimaging and EEG variables can identify subjects who respond to CBT for aggression, this can provide a neuroscience-based classification scheme that will improve treatment outcomes for children and adolescents with aggressive behavior. Demonstrating that a change in the key nodes of the emotion regulation circuitry is associated with a reduction of reactive aggression will provide evidence to support the validity of the frustrative non-reward construct.

  3. Infusional etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone +/- rituximab as first-line therapy for aggressive non-Hodgkin lymphoma

    PubMed Central

    Lamar, Zanetta S.; Fino, Nora; Palmer, Jodi; Gruber, Lindsey; Morris, Bonny B.; RaetskayaSolntseva, Olga; Kennedy, LeAnne; Vaidya, Rakhee; Hurd, David; Zamkoff, Kenneth

    2015-01-01

    Introduction Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and to compensate for increased drug clearance. The goal of this study was to examine risk factors and outcomes in patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. Patients and Methods We report 136 patients with previously untreated aNHL treated with infusional DA-EPOCH chemotherapy +/- rituximab from 2005-2013. Overall survival was estimated by Kaplan Meier methods. Univariate and multivariate logistic regression was used to determine factors associated with experiencing death, progression, or relapse at two years. Results The overall response rate was 82%. Relapse-free survival at 1, 3, and 5 years was 68%, 63%, and 52% with 95% CIs [0.59,0.85], [0.54,0.70], and [0.31,0.70], respectively. Patients with T-cell aNHL had increased risk of death, progression or relapse [OR:3.5, 95% CI: 1.4, 8.8] compared to those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow and number of cycles completed were independent predictors of death or relapse. Conclusion Our data suggests EPOCH+/-R is active in both B and T-cell aNHL. Toxicity did not significantly delay treatment or negatively impact outcomes. Dose adjustment by hematopoietic nadir had no impact on outcomes. The impact of smoking during chemotherapy should be further evaluated. PMID:26725264

  4. 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

    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

    2013-03-01

    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.

  5. Antithrombotic activity of argan oil: an in vivo experimental study.

    PubMed

    Mekhfi, Hassane; Belmekki, Fatima; Ziyyat, Abderrahim; Legssyer, Abdelkhaleq; Bnouham, Mohamed; Aziz, Mohammed

    2012-09-01

    Argan oil has been shown to inhibit in vitro and ex vivo platelet aggregation without extending bleeding time. In this report, we examined in vivo the antithrombotic activity of argan oil in an experimental thrombosis model in mice: acute pulmonary thromboembolism and in vitro its effect in a coagulation assay. Acute pulmonary thromboembolism was induced, after argan oil treatment, by an intravenous injection of a collagen and epinephrine mixture. The paralyzed and dead mice in each group were numbered and the percentage of protection against acute pulmonary thromboembolism was calculated. The histologic study was conducted in lung tissue to estimate the percentage of opened and occluded vessels by platelet thrombi. The coagulation assay was monitored in platelet-poor plasma from normal rats by measuring the clotting parameters (activated partial thromboplastin time, prothrombin time, and thrombin time) in the presence and absence of argan oil. Argan oil (1 mL/100 g/day), administered orally, showed an antithrombotic activity preventing the paralysis or death (50%) induced by the collagen-epinephrine intravenous injection. This observation was confirmed by the lung histologic examination, in which the density of occluded blood vessels was significantly decreased (62.16 ± 3.95%). However, the argan oil remained inactive for the coagulation parameters of activated partial thromboplastin time, prothrombin time, and thrombin time at variance with heparin, an anticoagulant reference drug. The antithrombotic activity of argan oil seemed unrelated to the anticoagulant activity. We suggest that argan oil might be an interesting natural dietary source for the nutritional prevention of hemostasis and cardiovascular disorders. Clinical trials would be necessary and relevant to confirm this hypothesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. 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.

  7. In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste

    PubMed Central

    Suleria, Hafiz Ansar Rasul; Hines, Barney M.; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A.

    2016-01-01

    Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin. PMID:28042854

  8. In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste.

    PubMed

    Suleria, Hafiz Ansar Rasul; Hines, Barney M; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A

    2016-12-31

    Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin.

  9. 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

  10. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation

    PubMed Central

    Camm, A John; Accetta, Gabriele; Ambrosio, Giuseppe; Atar, Dan; Bassand, Jean-Pierre; Berge, Eivind; Cools, Frank; Fitzmaurice, David A; Goldhaber, Samuel Z; Goto, Shinya; Haas, Sylvia; Kayani, Gloria; Koretsune, Yukihiro; Mantovani, Lorenzo G; Misselwitz, Frank; Oh, Seil; Turpie, Alexander G G; Verheugt, Freek W A; Kakkar, Ajay K

    2017-01-01

    Objective We studied evolving antithrombotic therapy patterns in patients with newly diagnosed non-valvular atrial fibrillation (AF) and ≥1 additional stroke risk factor between 2010 and 2015. Methods 39 670 patients were prospectively enrolled in four sequential cohorts in the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF): cohort C1 (2010–2011), n=5500; C2 (2011–2013), n=11 662; C3 (2013–2014), n=11 462; C4 (2014–2015), n=11 046. Baseline characteristics and antithrombotic therapy initiated at diagnosis were analysed by cohort. Results Baseline characteristics were similar across cohorts. Median CHA2DS2-VASc (cardiac failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female)) score was 3 in all four cohorts. From C1 to C4, the proportion of patients on anticoagulant (AC) therapy increased by almost 15% (C1 57.4%; C4 71.1%). Use of vitamin K antagonist (VKA)±antiplatelet (AP) (C1 53.2%; C4 34.0%) and AP monotherapy (C1 30.2%; C4 16.6%) declined, while use of non-VKA oral ACs (NOACs)±AP increased (C1 4.2%; C4 37.0%). Most CHA2DS2-VASc ≥2 patients received AC, and this proportion increased over time, largely driven by NOAC prescribing. NOACs were more frequently prescribed than VKAs in men, the elderly, patients of Asian ethnicity, those with dementia, or those using non-steroidal anti-inflammatory drugs, and current smokers. VKA use was more common in patients with cardiac, vascular, or renal comorbidities. Conclusions Since NOACs were introduced, there has been an increase in newly diagnosed patients with AF at risk of stroke receiving guideline-recommended therapy, predominantly driven by increased use of NOACs and reduced use of VKA±AP or AP alone. Trial registration number NCT01090362; Pre-results. PMID:27647168

  11. Effects of antithrombotic agents evaluated in a nonhuman primate vascular shunt model.

    PubMed Central

    Mason, R. G.; Wolf, R. H.; Zucker, W. H.; Shinoda, B. A.; Mohammad, S. F.

    1976-01-01

    The effects of aspirin, cyproheptadine, dextran, dipyridamole, and sulfinpyrazone on thrombus deposition were determined. These antithrombotic agents were evaluated in a nonhuman primate model for thrombus generation that employed test devices exposed to blood in an arteriovenous shunt. Thrombus deposition on test devices was quantitated gravimetrically. Of the antithrombotic agents tested, cyproheptadine was found to be the most effective, and aspirin, dextran, and dipyridamole were each somewhat less effective. Sulfinpyrazone had only a slight antithrombotic effect. Ultrastructual studies of thrombus deposited in test devices showed that the various antithrombotic agents tested did not prevent completely the formation of fibrin, aggregation of platelets, or adhesion and spreading of platelets and leukocytes. This model for thrombus generation is felt to be a more efficient means for evaluating antithrombotic agents than previously described nonhuman primate models. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:820202

  12. [Peculiarities of antithrombotic treatment in exacerbation of coronary heart disease and transcutaneous coronary interventions in patients suffering from atrial fibrillation and taking vitamin K antagonists (literature review)].

    PubMed

    Iavelov, I S

    2010-01-01

    The review analyses various approaches to management of patients presenting with atrial fibrillation and having to take vitamin K agonists in order to prevent arterial thromboembolic complications in cases they develop exacerbations of their coronary hear disease and/or require transcutaneous coronary interventions. With the problem being insufficiently studied as yet, the majority of therapeutic decisions as to the most efficient and safe methods of administering antithrombotic agents in the clinical situations involved are made based on the results of follow up of the patients, the data regarding peculiarities of the action of therapeutic agents, and common sense. Presented herein are contemporary recommendations on long-term antithrombotic therapy in patients suffering from atrial fibrillation and taking vitamin K antagonists and subjected to coronary stenting.

  13. Suicide plus immune gene therapy prevents post-surgical local relapse and increases overall survival in an aggressive mouse melanoma setting.

    PubMed

    Villaverde, Marcela S; Combe, Kristell; Duchene, Adriana G; Wei, Ming X; Glikin, Gerardo C; Finocchiaro, Liliana M E

    2014-09-01

    In an aggressive B16-F10 murine melanoma model, we evaluated the effectiveness and antitumor mechanisms triggered by a surgery adjuvant treatment that combined a local suicide gene therapy (SG) with a subcutaneous genetic vaccine (Vx) composed of B16-F10 cell extracts and lipoplexes carrying the genes of human interleukin-2 and murine granulocyte and macrophage colony stimulating factor. Pre-surgical SG treatment, neither alone nor combined with Vx was able to slow down the fast evolution of this tumor. After surgery, both SG and SG + Vx treatments, significantly prevented (in 50% of mice) or delayed (in the remaining 50%) post-surgical recurrence, as well as significantly prolonged recurrence-free (SG and SG + Vx) and overall median survival (SG + Vx). The treatment induced the generation of a pseudocapsule wrapping and separating the tumor from surrounding host tissue. Both, SG and the subcutaneous Vx, induced this envelope that was absent in the control group. On the other hand, PET scan imaging of the SG + Vx group suggested the development of an effective systemic immunostimulation that enhanced (18)FDG accrual in the thymus, spleen and vertebral column. When combined with surgery, direct intralesional injection of suicide gene plus distal subcutaneous genetic vaccine displayed efficacy and systemic antitumor immune response without host toxicity. This suggests the potential value of the assayed approach for clinical purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Development and Internal Validation of a Prediction Model to Estimate the Probability of Needing Aggressive Immunosuppressive Therapy With Cytostatics in de Novo Lupus Nephritis Patients.

    PubMed

    Restrepo-Escobar, Mauricio; Granda-Carvajal, Paula Andrea; Jaimes, Fabián

    2017-07-18

    To develop a multivariable clinical prediction model for the requirement of aggressive immunosuppression with cytostatics, based on simple clinical record data and lab tests. The model is defined in accordance with the result of the kidney biopsies. Retrospective study conducted with data from patients 16 years and older, with SLE and nephritis with less than 6 months of evolution. An initial bivariate analysis was conducted to select the variables to be included in a multiple logistic regression model. Goodness of fit was evaluated using a Hosmer-Lemeshow test (H-L) and the discrimination capacity of the model by means of the area under the ROC (AUC) curve. Data from 242 patients was gathered; of these, 18.2% (n=44) did not need an addition of cytostatics according to the findings of their kidney biopsies. The variables included in the final model were 24-h proteinuria, diastolic blood pressure, creatinine, C3 complement and the interaction of hematuria with leukocyturia in urinary sediment. The model showed excellent discrimination (AUC=0.929; 95% CI=0.894-0.963) and adequate calibration (H-L, P=.959). In recent-onset LN patients, the decision to use or not to use intensive immunosuppressive therapy could be performed based on our prediction model as an alternative to kidney biopsies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  15. [Search for the "optimal" dose of antithrombotic agents].

    PubMed

    Mismetti, P; Laporte-Simitsidis, S; Decousus, H

    1996-11-01

    The determination of the "optimal" dose is an essential step in the development of a molecule. In the case of anti-thrombotic agents, the search for this "optimal" dose is based on dose-effect relationships on biological criteria in phase I, and, often, radiological criteria in phase II trials. The main objective of these dose studies is not to directly evaluate the benefit-risk ratio of the molecule under development, but to find the dose which will be tested in phase II to estimate the benefit-risk ratio. Errors of choice of dosage observed at the end of phase III trials may be due to problems of extrapolability of the results of the dose studies due to too strict a selection of subjects included and therefore not representative of the target population of the new treatment or to the use of intermediary criteria for the evaluation of the antithrombotic effect. However, these dosage errors are still mainly due to an inadequate search for the "optimal" dose despite the fact that the ethnical and economic consequences are not negligible.

  16. 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.

  17. Antithrombotic effect and mechanism of Rubus spp. Blackberry.

    PubMed

    Xie, Pingyao; Zhang, Yong; Wang, Xuebiao; Wei, Jinfeng; Kang, Wenyi

    2017-05-24

    The compounds of Rubus spp. Blackberry (RSB) were isolated and identified by a bioassay-guided method, and their antithrombotic effects and mechanism were investigated with the acute blood stasis rat model. The RSB extract was evaluated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) assays in vitro. Results indicated that RSB extract exhibited anticoagulant activity. In addition to compounds 1 and 6, the other compounds also exhibited anticoagulant activity in vitro. Therefore, the in vivo antithrombosis effects of RSB extract were investigated by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of thromboxane B2 (TXB2), 6-keto prostaglandin F1α (6-keto-PGF1α), endothelial nitric oxide synthase (eNOS) and ET-1 (endothelin-1) were measured. Results suggested that RSB extract had inhibitory effects on thrombus formation, and its antithrombotic effects were associated with the regulation of vascular endothelium active substance, activation of blood flow and an anticoagulation effect.

  18. Antithrombotic Effect and Mechanism of Radix Paeoniae Rubra

    PubMed Central

    Xie, Pingyao; Cui, Lili; Shan, Yuan

    2017-01-01

    The compounds of Radix Paeoniae Rubra (RPR) were isolated and identified by bioassay-guided method, and antithrombotic effects and mechanism were investigated by the acute blood stasis rat model. The RPR extract was evaluated by APTT, TT, PT, and FIB assays in vitro. Results indicated that RPR extract exhibited the anticoagulant activity. In order to find active compounds, six compounds were isolated and identified, and four compounds, paeoniflorin (Pae), pentagalloylglucose (Pen), albiflorin (Ali), and protocatechuic acid (Pro), exhibited the anticoagulant activity in vitro. Therefore, the antithrombosis effects of RPR extract and four active compounds were investigated in vivo by measuring whole blood viscosity (WBV), plasma viscosity (PV), APTT, PT, TT, and FIB. Meanwhile, the levels of TXB2, 6-Keto-PGF1α, eNOS, and ET-1 were detected. Results suggested that RPR extract and four active compounds had the inhibition effect on thrombus formation, and the antithrombotic effects were associated with the regulation of vascular endothelium active substance, activating blood flow and anticoagulation effect. PMID:28299338

  19. Development of Antithrombotic Aptamers: From Recognizing Elements to Drugs.

    PubMed

    Zavyalova, Elena; Golovin, Andrey; Pavlova, Galina; Kopylov, Alexey

    2016-01-01

    Blood hemostasis is attained with two sophisticated interconnected network systems, a coagulation cascade and a platelet activation system. Multiple inhibitors were developed to various components of both systems to prevent thrombosis-related morbid events that are of extremely high frequency in the human population. Antithrombotic inhibitors possess both positive and negative aspects. One of the essential modern requirements is a controllable mode of action for both anticoagulants and antiplatelets that could be achieved due to the high affinity and specificity of the inhibitor, as well as a possibility to apply an antidote, which quickly annihilates activity of the inhibitor and restores the proper hemostasis. Aptamers are DNA or RNA oligonucleotides with particular tertiary structure, such as DNA guanine quadruplex. Besides antibodies and other peptides/proteins, aptamers are one more example of the molecular recognizing elements that specifically bind to the target. Therefore, aptamers could be developed into a promising novel class of the drugs with high affinity, specificity, innate low toxicity, and rational antidote. Several aptamers with prospective antithrombotic activity have been reviewed; some of them are in preclinical and clinical trials.

  20. 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

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

    PubMed

    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.

  2. Impact of Implementing a Protocol on the Perioperative Management in Patients Treated with Antithrombotics Admitted for Hip Fracture Surgery: an Observational Study.

    PubMed

    Iavecchia, Luján; Safiya, Ahmad; Salat, David; Sabaté, Mònica; Bosch, Montse; Biarnés, Alfons; Camps, Angels; Castellà, Dolors; Lalueza, Pilar; Pons, Verònica; Teixidor, Jordi; Villar, Maria M; Agustí, Antònia

    2016-11-01

    This study aimed to describe the impact of implementing a protocol on the perioperative management of patients admitted for hip fracture treated with antithrombotics. A protocol was designed based on the recommendations from the American College of Chest Physicians (ACCP). After its implementation (May 2012), information on antithrombotic management was collected from admission to 3 months after surgery in retrospective (October 2011-March 2012) and prospective (October 2012-March 2013) cohorts. Patients' thromboembolic risk was classified into high, moderate or low according to the ACCP categories. A total of 113 and 101 cases were included in the retrospective and prospective cohorts, respectively. No differences in age, gender, American Society of Anaesthesiology score or thrombotic risk categories were observed between cohorts. Most patients were treated with aspirin or triflusal (55.1% and 48.1% in each cohort, respectively), clopidogrel (24.5% and 26.6%) or acenocoumarol (16.3% and 20.2%). In moderate to high thromboembolic risk patients, a higher rate of bridging therapy with full doses of enoxaparin (18.5% and 50%, p = 0.04 before and 9.1% and 43.7%, p = 0.02 after surgery) and a lower rate of aspirin discontinuation (76% and 55.3%, p = 0.03) were observed in the prospective cohort. Both cohorts had a similar percentage of cases with bleeding (68.1% and 68.3%) and thrombotic events (11.5% and 13%). No differences in the timing between surgery and the discontinuation or resumption of antithrombotics were noted. After the protocol implementation, aspirin was less often stopped and bridging therapy with therapeutic doses of enoxaparin was used more often. However, interruption and resumption times of antithrombotics remained almost unchanged. In order to achieve these goals, more efforts should be made to implement the protocol in clinical practice. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. A comparative study of antithrombotic and antiplatelet activities of different fucoidans from Laminaria japonica.

    PubMed

    Zhao, Xue; Dong, Shizhu; Wang, Jingfeng; Li, Fang; Chen, Anjin; Li, Bafang

    2012-06-01

    Fucoidans extracted from brown algae represent an intriguing group of natural fucose-enriched sulfated polysaccharide, with excellent anticoagulant, antimetastatic, antiangiogenic and anti-inflammatory activities. In the present study, we compared antithrombotic activities of four fucoidan fractions with different molecular weight and sulfated ester content from Laminaria japonica in an electrical induced arterial thrombosis and their potential mechanism underlying such activity. In vivo middle molecular weight (MMW) fucoidan fractions with molecular weight about 28000 and 35000 exhibited better antithrombotic activity in electrical induced arterial thrombosis than low molecular weight (LMW) fucoidan LF1 and LF2 (Mw 7600 and 3900). Inhibition of arterial thrombosis occurred at dose of 0.1-0.25mg/kg for MMW fucoidans, accompanied with moderate anticoagulant activity and significant decrease of whole blood viscosity and hematocrit. The antithrombotic effects of MMW Fucoidans might be related with promotion of TFPI content and decrease of TXB2 content, without affecting platelet aggregation and 6-keto-PGF1α content in vivo. In contrast, LMW fucoidans showed a correlation among anticoagulant, antiplatelet and antithrombotic effects in vivo. Antithrombotic action of LF1 and LF2 required high dose of 2.5-10mg/kg, concomitantly with anticoagulant activity and specific inhibition of platelet aggregation in vivo. Their antithrombotic effect might be related to their promotion of TFPI and 6-keto-PGF1α, down regulation of TXB2, without affecting hemorheology. These findings suggested that fucoidan fractions with different molecular weight acted on the antithrombotic action by different mechanism. By comparison, highly sulfated fucoidan LF2 with molecular weight of 3900 seemed to be a more suitable choice of antithrombotic drug for its antithrombotic activity accompanied with specific inhibitory activity on platelet aggregation, low anticoagulant activity and low hemorrhagic

  4. Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis

    PubMed Central

    Li, Dianhe; Wang, Haofei; Qiu, Min; Li, Na

    2017-01-01

    Background We performed a meta-analysis to compare overall survival (OS) outcomes in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) who underwent aggressive thoracic therapy (ATT) with those who did not. Methods A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted. Hazard ratio (HR) for the main endpoint OS was pooled using a fixed-effects model. Subgroup analysis was performed in patients with single organ metastases, or with different numbers of brain metastases, or with different stages of thoracic disease. Pooled survival curves of OS were constructed. Results Seven eligible retrospective observational cohort studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. For patients with synchronous oligometastatic NSCLC, ATT was associated with a significant improvement of OS (HR, 0.48; 95% CI, 0.39–0.60; P<0.00001). In subgroup analysis, the association with OS was similar or even strengthened, with a HR of 0.42 (95% CI, 0.31–0.56) in single organ metastases group, 0.49 (95% CI, 0.31–0.75) in solitary brain metastasis group, and 0.38 (95% CI, 0.20–0.73) in thoracic stage I–II group, respectively. The pooled cumulative survival rates for patients received ATT were 74.9% at 1 year, 52.1% at 2 years, 23.0% at 3 years, and 12.6% at 4 years. The corresponding pooled survival for patients who did not receive ATT were 32.3%, 13.7%, 3.7%, and 2.0%, respectively. Conclusions Survival benefit from ATT is common in synchronous oligometastatic patients. Selected patients with synchronous oligometastatic NSCLC could also achieve long-term survival with ATT. PMID:28275479

  5. The in vitro and vivo effects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target.

    PubMed

    Zheng, Hua-Chuan; Liu, Jia-Jie; Li, Jing; Wu, Ji-Cheng; Yang, Lei; Zhao, Gui-Feng; Zhao, Xin; Jiang, Hua-Mao; Huang, Ke-Qiang; Li, Zhi-Jie

    2017-02-16

    Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0.05) of cancer cells. WT parafibromin transfectants showed the overexpression of Cyclin B1, Cyclin D1, Cyclin E, p38, p53, and AIF in HCT-15 and HCT-116 cells, while MT parafibromin only up-regulated p38 expression. There was lower mRNA expression of bcl-2 in parafibromin transfectants than the control and mock, while higher expression of c-myc, Cyclin D1, mTOR, and Raptor. According to transcriptomic analysis, WT parafibromin suppressed PI3K-Akt and FoxO signaling pathways, while MT one promoted PI3K-Akt pathway, focal adhesion, and regulation of actin cytoskeleton. Parafibromin was less expressed in colorectal cancer than paired mucosa (p<0.05), and inversely correlated with its differentiation at both mRNA and protein levels (p<0.05). These findings indicated that WT parafibromin might reverse the aggressive phenotypes of colorectal cancer cells and be employed as a target for gene therapy. Down-regulated parafibromin expression might be closely linked to colorectal carcinogenesis and cancer differentiation.

  6. Enhanced aggressiveness of bystander cells in an anti-tumor photodynamic therapy model: Role of nitric oxide produced by targeted cells.

    PubMed

    Bazak, Jerzy; Fahey, Jonathan M; Wawak, Katarzyna; Korytowski, Witold; Girotti, Albert W

    2017-01-01

    The bystander effects of anti-cancer ionizing radiation have been widely studied, but far less is known about such effects in the case of non-ionizing photodynamic therapy (PDT). In the present study, we tested the hypothesis that photodynamically-stressed prostate cancer PC3 cells can elicit nitric oxide (NO)-mediated pro-growth/migration responses in non-stressed bystander cells. A novel approach was used whereby both cell populations existed on a culture dish, but made no physical contact with one other. Visible light irradiation of target cells sensitized with 5-aminolevulinic acid-induced protoporphyrin IX resulted in a striking upregulation of inducible nitric oxide synthase (iNOS) along with NO, the level of which increased after irradiation. Slower and less pronounced iNOS/NO upregulation was also observed in bystander cells. Activation of transcription factor NF-κB was implicated in iNOS induction in both targeted and bystander cells. Like surviving targeted cells, bystanders exhibited a significant increase in growth and migration rate, both responses being strongly attenuated by an iNOS inhibitor (1400W), a NO scavenger (cPTIO), or iNOS knockdown. Incubating bystander cells with conditioned medium from targeted cells failed to stimulate growth/migration, ruling out involvement of relatively long-lived stimulants. The following post-irradiation changes in pro-survival/pro-growth proteins were observed in bystander cells: upregulation of COX-2 and activation of protein kinases Akt and ERK1/2, NO again playing a key role. This is the first reported evidence for NO-enhanced bystander aggressiveness in the context of PDT. In the clinical setting, such effects could be averted through pharmacologic use of iNOS inhibitors as PDT adjuvants. Copyright © 2016. Published by Elsevier Inc.

  7. Considerations for analgosedation and antithrombotic management during extracorporeal life support

    PubMed Central

    Burcham, Pamela K.; Rozycki, Alan J.

    2017-01-01

    Despite the immense growth in extracorporeal life support (ECLS) technology and experience, opportunity remains to better characterize the pharmacotherapeutic considerations during ECLS. Analgosedation can be particularly challenging in the ECLS population due to in drug-circuit interactions that may lead to decreased systemic concentrations and pharmacodynamic effect. ECLS also requires the use of antithrombotic agents to mitigate the prothrombotic state created by the artificial surface in the ECLS circuit. There are a number of coagulation monitoring tests available. However, optimal monitoring and management in ECLS has not been established. Heparin continues to be the anticoagulant of choice for most ECLS centers, however, there is growing interest in the use of parenteral direct thrombin inhibitors (DTI) in this population. Advances in understanding pharmacotherapeutic management have not kept up with the technological advances in this population. More investigation is warranted to gain a greater understanding of the pharmacotherapeutic implications, facilitate standardized evidence-based practices, and improve patient centered outcomes. PMID:28275614

  8. 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. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  9. 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

  10. The aggression questionnaire.

    PubMed

    Buss, A H; Perry, M

    1992-09-01

    A new questionnaire on aggression was constructed. Replicated factor analyses yielded 4 scales: Physical Aggression, Verbal Aggression, Anger, and Hostility. Correlational analysis revealed that anger is the bridge between both physical and verbal aggression and hostility. The scales showed internal consistency and stability over time. Men scored slightly higher on Verbal Aggression and Hostility and much higher on Physical Aggression. There was no sex difference for Anger. The various scales correlated differently with various personality traits. Scale scores correlated with peer nominations of the various kinds of aggression. These findings suggest the need to assess not only overall aggression but also its individual components.

  11. 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

  12. Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi.

    PubMed

    Di Renzo, Nicola; Brugiatelli, Maura; Montanini, Antonella; Vigliotti, Maria Luigia; Cervetti, Giulia; Liberati, Anna Marina; Luminari, Stefano; Spedini, Pierangelo; Giglio, Gianfranco; Federico, Massimo

    2006-03-01

    Patients with aggressive NHL who fail initial treatment or subsequently relapse have a very poor outcome and less than 20-25% achieve a prolonged disease-free interval with salvage therapies. To improve the outcome of patients with refractory aggressive NHL not suitable for High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT), the efficacy of a combination of gemcitabine, vinorelbine, procarbazine and prednisone (ViGePP) were tested. Between November 1999 and September 2002, 69 patients with relapsed or refractory aggressive NHL were treated with ViGePP regimen, every 4 weeks up to six courses. At the end of planned chemotherapy patients could receive additional radiotherapy on residual masses or on sites of previously bulky disease. Sixty-six patients were available for evaluation of study end-points. Thirty patients were refractory to therapy and 36 patients had relapsed after remission obtained with previous therapy. At the end of therapy, complete remission (CR) rate was 23%, 3-year relapse free survival rate was 40% and 3-year overall survival rate was 25% for the whole series (29% and 20% for relapsed and refractory patients, respectively). Patients achieving CR with ViGePP had a significantly better survival as compared with the remaining ones (p = 0.0003). ViGePP as used in the present setting has demonstrated a promising activity, comparable to other conventional dose regimens. Although CR was achieved only in a minority of patients, this was durable in a significant proportion of them. This regimen should be tested in less heavily pre-treated patients and probably in combination with new active agents such Rituximab. Further developments of this combination are warranted.

  13. 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.…

  14. 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.…

  15. 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.

  16. Antithrombotic management in patients with percutaneous coronary intervention requiring oral anticoagulation

    PubMed Central

    Undas, Anetta

    2016-01-01

    The dynamic evolution of therapeutic options including the use of vitamin K antagonists (VKA), non-vitamin K oral anticoagulants (NOAC), more potent antiplatelet drugs as well as new generation drug-eluting stents could lead to the view that the current recommendations on the management of patients with percutaneous coronary intervention (PCI) requiring oral anticoagulation do not keep up with the results of several clinical studies published within the last 5 years. In the present overview, we summarize the recent advances in antithrombotic management used in atrial fibrillation patients undergoing PCI for stable coronary artery disease or acute coronary syndrome (ACS). The safety and efficacy of prasugrel and ticagrelor taken with oral anticoagulants also remain to be established in randomized trials; therefore the P2Y12 inhibitor clopidogrel on top of aspirin or without is now recommended to be used together with a VKA or NOAC. It is still unclear which dose of a NOAC in combination with antiplatelet agents and different stents should be used in this clinical setting and whether indeed NOAC are safer compared with VKA in such cardiovascular patients. Moreover, we discuss the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. To minimize bleeding risk in anticoagulated patients following PCI or ACS, the right agent should be prescribed to the right patient at the right dose and supported by regular clinical evaluation and laboratory testing, especially assessment of renal function when a NOAC is used. PMID:27980542

  17. Anticoagulant Therapy

    PubMed Central

    Teitel, Jerome M.

    1984-01-01

    Venous thromboembolic diseases are among the most important causes of morbidity and mortality in Canada. Agents which interfere with the coagulation mechanism are highly effective in treating these disorders, but at the potentially high cost of serious hemorrhagic complications. The optimal prevention of both serious outcomes and complications of therapy can be achieved by prophylactic treatment of high risk patients. Heparin and vitamin K antagonists remain the mainstays of antithrombotic therapy. The pharmacology of these agents is reviewed, and a rational approach to their clinical use is presented. PMID:21279098

  18. Atrial fibrillation, CHA2DS2-VASc score, antithrombotics and risk of traffic accidents: A population-based cohort study.

    PubMed

    Lai, Hui-Chin; Chien, Wu-Chien; Chung, Chi-Hsiang; Lee, Wen-Lieng; Wang, Kuo-Yang; Wu, Tsu-Juey; Liu, Chia-Ning; Liu, Tsun-Jui

    2015-10-15

    Traffic accidents account for a substantial proportion of premature disabilities and deaths. Whether atrial fibrillation (AF) provokes while antithrombotics prevent from such events remains un-investigated. All patients ≥40years with newly diagnosed AF in 2005 were scrutinized from the "Longitudinal Health Insurance Database 2005" (1 million beneficiaries) of Taiwan's National Health Insurance Institute as the AF group. Four-fold number of age-, gender-, and comorbidity-matched patients but without AF served as the Non-AF controls. Patients were followed till occurrence of hospitalization-requiring traffic injury, death, withdrawal from insurance, or the end of 2010. Cumulative incidence of traffic accidents was compared between groups, and predictors and preventive role of antithrombotics for these accidents were identified by Cox regression analysis. Within a mean follow-up of 4.3years, traffic injury occurred significantly more often in patients with AF (N=1724) than those without it (N=6896) (5.4 vs. 4.9 per 1000 person-years, log-rank p=0.012, HR 1.110, 95% CI 1.013-1.572). Cox models identified age ≧65years, hypertension, coronary artery disease, stroke, liver cirrhosis and CHADS2VASC score≧1 as risk factors for traffic injury in AF patients, whereas oral anticoagulants (HR 0.576, 95% CI 0.285-0.791, p=0.002) used in patients with CHADS2VASC score ≧1 but not antiplatelet therapy (p=0.197) as negative predictors. Patients with AF are more vulnerable to traffic accidents especially when with higher CHADS2VASC scores and other comorbidities. This tendency to traffic accidents, however, could be ameliorated by oral anticoagulation in specialized cases but not by antiplatelet therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Antithrombotic effects of magnesium sulfate in in vivo experiments.

    PubMed

    Sheu, Joen R; Hsiao, George; Shen, Ming Y; Lee, Yen M; Yen, Mao H

    2003-05-01

    In this study, magnesium sulfate was effective in reducing the mortality of adenosine diphosphate-induced acute pulmonary thromboembolism in mice, when it was administered intravenously at doses of 100 and 200 microg/g body weight. In addition, intravenous injections of magnesium sulfate (100 and 200 microg/g) significantly prolonged bleeding time in the severed mesenteric arteries of rats by approximately 1.7- and 1.9-fold, respectively, compared with normal saline. Continuous infusion of magnesium sulfate (20 microg/g per minute) for 10 minutes also significantly increased the bleeding time by approximately 1.7-fold, and the bleeding time returned to baseline within 60 minutes of cessation of magnesium sulfate infusion. On the other hand, platelet thrombi formation was induced by irradiating mesenteric venules with filtered light in mice pretreated with intravenous fluorescein sodium. When magnesium sulfate was administered at 300 microg/g during induction of platelet plug formation with 10 microg/kg fluorescein sodium, occlusion time was not significantly prolonged, but a dose of 600 microg/g did significantly prolong the occlusion time. Furthermore, aspirin (250 microg/g) also showed a similar activity in this experiment in prolonging the occlusion time. In conclusion, these results suggest that magnesium sulfate has an effective antithrombotic activity in vivo, and treatment with magnesium sulfate may lower the risk of thromboembolic-related disorders.

  20. Identification of the platelet ADP receptor targeted by antithrombotic drugs.

    PubMed

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B

    2001-01-11

    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

  1. Antithrombotic activity of oral administered low molecular weight fucoidan from Laminaria Japonica.

    PubMed

    Zhao, Xue; Guo, Fengjun; Hu, Jing; Zhang, Lijuan; Xue, Changhu; Zhang, Zhaohui; Li, Bafang

    2016-08-01

    Fucoidans extracted from brown algae have been documented to have excellent antithrombotic activity when administered by either intravenous or subcutaneous route in animal models. However, it is unknown if the fucoidans also have antithrombotic activity when administered orally, a highly desirable feature of oral antithrombotic agents. In the present study, we compared the oral absorption, bioavailability and antithrombotic activity of two fucoidan fractions from Laminaria japonica with different molecular weight by oral administration in an electricity induced arterial thrombosis model and the underlying molecular mechanisms. After a single dose of oral administration, the fucoidan content in plasma and urine in rats was assessed using the reverse-phased HPLC analysis of 1-phenyl-3-methyl-5-pyrazolone (PMP)-labeled fucose. The fucose content in the low molecular weight (LMW) fucoidan-treated rats increased up to 2-fold and peaked at 15h, indicating that the LMW fucoidan had much better absorption and bioavailability than the MMW fucoidan in vivo. Oral administration of the LMW fucoidan at 400 and 800mg/kg for 30days inhibited the arterial thrombosis formation effectively induced by electrical shock in rats, accompanied by moderate anticoagulation activity, regulation on TXB2 and 6-keto-PGF1α, significant antiplatelet activity and effective fibrinolysis. The LMW fucoidan showed better oral absorption and antithrombotic activity in addition to different antithrombotic mechanisms compared to those of the medium molecular weight (MMW) fucoidan. Thus, the LMW fucoidan has a potential to become an oral antithrombotic agent. Copyright © 2016. Published by Elsevier Ltd.

  2. AGGRESSIVE TREATMENT OF SPONTANEOUS PNEUMOTHORAX

    PubMed Central

    Hecker, Sydney P.; Jamplis, Robert W.; Mitchell, Sidney P.

    1962-01-01

    In analysis of the results of treatment of 48 episodes of spontaneous pneumothorax, aggressive treatment by means of closed intercostal drainage with constant suction was found to achieve the aims of therapy more effectively than conservative measures of bed rest with or without needle aspiration. In general, full expansion of the lung was more quickly restored, recurrence was of lesser incidence, the period in hospital was shorter and the time away from work was reduced. ImagesFigure 1. PMID:13905846

  3. Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study.

    PubMed

    Fiedler, K Anette; Byrne, Robert A; Schulz, Stefanie; Sibbing, Dirk; Mehilli, Julinda; Ibrahim, Tareq; Maeng, Michael; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Sarafoff, Nikolaus

    2014-04-01

    An increasing number of patients undergoing coronary stenting need lifelong anticoagulation and therefore require a triple therapy typically consisting of aspirin, clopidogrel, and a vitamin K antagonist. Triple therapy confers an elevated bleeding risk as compared with dual therapy; however, omission of either antiplatelet or anticoagulation therapy might increase the risk of stent thrombosis or thrombembolic events. Although guidelines recommend a duration of dual antiplatelet therapy of 6 to 12months after drug-eluting stent (DES) implantation, the optimal duration of dual antiplatelet therapy in patients receiving oral anticoagulation is not known. We postulate that 6-week clopidogrel therapy after DES implantation as compared with 6-month therapy is associated with improved clinical outcomes in patients undergoing DES implantation receiving concomitant aspirin and vitamin K antagonists. The ISAR-TRIPLE is a randomized, open-label trial that examines the restriction of clopidogrel therapy from 6 months to 6 weeks after DES implantation in the setting of concomitant aspirin and oral anticoagulant. Patients are randomized in a 1:1 fashion to either 6-week or 6-month clopidogrel therapy. The primary end point is a composite of death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding. The secondary end point comprises ischemic and bleeding complications. According to sample size calculations, a total of 600 patients are required to be enrolled. Clinical follow-up is scheduled at 6 weeks and at 6 and 9 months after randomization. There is clinical equipoise regarding the optimal duration of triple therapy after DES implantation in patients who need vitamin K antagonist therapy. The ISAR-TRIPLE trial aims to test the hypothesis that a 6-week triple therapy compared with a 6-month triple therapy improves net clinical outcomes. Copyright © 2014 Mosby, Inc. All rights reserved.

  4. 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)

  5. [A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].

    PubMed

    Ozawa, Hikaru; Abiko, Yasushi; Akimoto, Takeshi

    2003-01-01

    The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and

  6. Aggression in Huntington's disease: a systematic review of rates of aggression and treatment methods.

    PubMed

    Fisher, Caroline A; Sewell, Katherine; Brown, Anahita; Churchyard, Andrew

    2014-01-01

    Aggression is commonly reported in individuals with Huntington's disease (HD). While correlating factors for aggression are often speculated about, features that are associated with, and contribute to, aggression in this population have not been clearly determined. This systematic review investigates rates of aggression and treatment options for aggression in HD. A number of key findings were revealed. Studies reporting on rates of aggression revealed that its prevalence is high, falling between 22 and 66 percent in the majority of studies. Aggression may be more common in males with HD, and is also found in higher rates in individuals who experience frequent falls, have obsessive-compulsive symptoms and suicidal ideation. There is little research investigating antecedents for aggression in HD. A wide variety of psychotropic medications have been reported in the literature to treat individuals with HD and aggressive behaviour. However, due to methodological limitations, no treatment recommendations can be made, based on the current literature. Two non-medication therapies have been investigated, behaviour support and sensory modulation intervention. However, again, due to methodological limitations with these studies, further research is needed before they can be recommended as frontline interventions. This review highlights the need for further methodologically rigorous studies investigating the treatment of aggression in HD.

  7. Recent clinical management of antithrombotic agents for gastrointestinal endoscopy after revision of guidelines in Japan.

    PubMed

    Ono, Satoshi; Fujishiro, Mitsuhiro; Ikeda, Yuichi; Komuro, Issei; Koike, Kazuhiko

    2015-09-01

    In 2012, the Japan Gastroenterological Endoscopy Society (JGES) revised guidelines for the management of gastrointestinal endoscopy for patients using antithrombotic agents. The conventional guidelines emphasized reducing the bleeding risk that accompanies gastrointestinal endoscopy, but the present guidelines prioritize reduction of thromboembolism risk during discontinuation of antithrombotic agents, which is consistent with Western guidelines. When the advantages outweigh the disadvantages, the guidelines permit endoscopic biopsy and high-bleeding-risk procedures without discontinuation of selected antithrombotic agents. These guidelines created a paradigm shift that has slowly, but surely, changed clinical daily practice in Japan. As a result, endoscopic biopsy without discontinuation of antithrombotic agents has been widely accepted, although solid evidence for its support is still lacking. Additionally, feasibility of high-bleeding-risk procedures without discontinuation of selected antithrombotic agents is also controversial because evidence newly acquired after publication of the present guidelines is low in evidence level. Consequently, clinical studies with a high evidence level, including randomized controlled studies, are mandatory to establish reliable upcoming guidelines. At the same time, under the present guidelines, the accomplishment of such studies in Japan is expected.

  8. Rhythms, rhythmicity and aggression.

    PubMed

    Bronsard, Guillaume; Bartolomei, Fabrice

    2013-09-01

    The relationships between biological rhythms and human aggressive behavior are addressed and discussed in this article: First, circadian rhythms and aggression are considered. Studies of sleep/waking cycle disturbances in aggression are reported. Severe aggression is associated with profound changes in sleep architecture. Causal link is difficult to establish given that sleep disturbance and aggressive behavior could be the symptoms of the same disorder. Specific aggressive behavior developed during sleep is also described. In addition, hormonal circadian rhythm studies are reported. Thus, low cortisol levels, in particular low cortisol variability, are associated with aggressive behavior, suggesting an inhibitory role of cortisol. Testosterone has daily and seasonal fluctuations, but no link with aggression has been established. Neurophysiological underlying mechanisms are discussed in the last part of this article, with a focus on the relationship between brain rhythm and aggression. Increase of slow-wave EEG activities is observed in individuals with aggressive behavior. Epilepsy, as a disease of brain rhythm could be associated with aggressive behavior, in pre, post and inter ictal periodes. Incidence of aggression is not likely more prevalent in epileptic individuals compared to those with other neurological conditions. Ictal changes take the form of profound behavioral changes, including aggressive behavior which has been interpreted as the emergence of "archeical" or innate motor patterns. In this multidisciplinary approach, the main difficulty is the categorization of the differents types of aggression. Finally, taken together, these studies suggest that biological rhythms, especially circadian rhythms, could provide therapeutic benefits to human aggressive behavior. Biological rhythymicity seems to be a necessary permanent training offering interesting perspectives for the adaptation to changes in the field of aggression. Copyright © 2013 Elsevier Ltd

  9. Long-term follow-up of tandem high-dose therapy with autologous stem cell support for adults with high-risk age-adjusted international prognostic index aggressive non-Hodgkin Lymphomas: a GOELAMS pilot study.

    PubMed

    Monjanel, Hélène; Deconinck, Eric; Perrodeau, Elodie; Gastinne, Thomas; Delwail, Vincent; Moreau, Anne; François, Sylvie; Berthou, Christian; Gyan, Emmanuel; Milpied, Noël

    2011-06-01

    Single high-dose therapy (HDT) followed by autologous peripheral blood stem cell (PBSC) support improves complete response and overall survival (OS) in untreated aggressive non-Hodgkin's lymphoma (NHL). However, patients with a high age-adjusted international prognostic index (aa-IPI equal to 3) still have poor clinical outcome despite high dose intensity regimen. To improve complete response in this subgroup, the French Groupe Ouest-Est des Leucémies et Autres Maladies du Sang (GOELAMS) conducted a pilot phase II trial (073) evaluating tandem HDT with PBSC support in a series of 45 patients with aa-IPI equal to 3 untreated aggressive non-Hodgkin's lymphoma. After induction with an anthracyclin-containing regimen, responders underwent tandem HDT conditioned by high-dose mitoxantrone plus cytarabine for the first HDT and total-body irradiation (TBI), carmustine, etoposide, and cyclophosphamide for the second HDT. Thirty-one patients out of 41 evaluable patients completed the program. There were 4 toxic deaths. The complete response rate was 49%. With a median follow-up of 114 months for surviving patients, the OS was 51%, and 19 out of the 22 patients (86%) who reached a complete response are alive and relapse-free. Recent prospective evaluation of quality of life and comorbidities of surviving patients does not reveal long-term toxicities of the procedure. In the era of monoclonal antibodies and response-adapted therapy, the role of tandem HDT still need to be determined.

  10. Alcohol and Aggression.

    ERIC Educational Resources Information Center

    Gustafson, Roland

    1994-01-01

    Reviews the acute effects of alcohol on aggressive responding. From experimental studies that use human subjects, it is concluded that a moderate dose of alcohol does not increase aggression if subjects are unprovoked. Under provocative situations, aggression is increased as a function of alcohol intoxication, provided that subjects are restricted…

  11. [Antithrombotic and hemorrhagic activities of fucoidan isolated from Fucus evanescens brown algae].

    PubMed

    Drozd, N N; Miftakhova, N T; Savchik, E Iu; Kalinina, T B; Makarov, V A; Imbs, T I; Zviagintseva, T N; Kuznetsova, T A; Besednova, N N

    2011-01-01

    The antithrombotic and hemorrhagic activities of fucoidan with molecular weight within 20 - 40 kD isolation from Fucus evanescens seaweed have been investigated. The antithrombin activity of fucoidan is 41 +/- 9 aIIa IU/mg and the anti-factor Oà activity is 38 +/- 8 aOà IU/mg. The antithrombin and anti-factor Oà activities of plasma, antithrombotic activity (100% prevention of formation of a blood clot observed at a dose of 10 mg/kg), and hemorrhagic activity (to a lesser degree, than that of unfractionated heparin in comparable antithrombotic activity doses) increase as the doses of fucoidan increases from 2.5 to 10 mg/kg at intravenous injection in rats.

  12. Antiplatelet therapy in patients undergoing coronary stenting

    PubMed Central

    ten Berg, J.M.; van Werkum, J.W.; Heestermans, A.A.C.M.; Jaarsma, W.; Hautvast, R.M.A.; den Heijer, P.; de Boer, M.J.

    2006-01-01

    Background Anticoagulation after coronary stenting is essential to prevent stent thrombosis. Drug-eluting stents, which are the preferred therapy, may be associated with a higher tendency for stent thrombosis. Methods Patients who underwent coronary stent placement and presented with late stent thrombosis are described. Results Eight patients with stent thrombosis are presented. Early discontinuation of the antithrombotic medication is associated with the occurrence of these complications. Conclusion Long-term antithrombotic therapy seems essential to prevent stent thrombosis, especially for patients treated with drug-eluting stents. PMID:25696663

  13. 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

  14. Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

    PubMed

    Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

    2015-12-01

    This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

  15. Pharmacists' role in handling problems with prescriptions for antithrombotic medication in Belgian community pharmacies.

    PubMed

    Desmaele, S; De Wulf, I; Dupont, A G; Steurbaut, S

    2015-08-01

    Community pharmacists have an important task in the follow-up of patients treated with antithrombotics. When delivering these medicines, pharmacists can encounter drug-related problems (DRPs) with substantial clinical and economic impact. To investigate the amount and type of antithrombotic related DRPs as well as how community pharmacists handled these DRPs. Belgian community pharmacies. MSc pharmacy students of six Belgian universities collected data about all DRPs encountered by a pharmacist during ten half days of their pharmacy internship. Data were registered about DRPs detected at delivery and in an a posteriori setting, when consulting the medical history of the patient. Classification of the DRP, cause of the DRP, intervention and result of the intervention were registered. Amount and type of antotrombitocs related DRPs occurring in community pharmacies, as well as how community pharmacists handled these DRPs. 3.1 % of the 15,952 registered DRPs concerned antithrombotics. 79.3 % of these DRPs were detected at delivery and 20.7 % were detected a posteriori. Most antithrombotic-related DRPs concerned problems with the choice of the drug (mainly because of drug-drug interactions) or concerned logistic problems. Almost 80 % of the antithrombotic-related DRPs were followed by an intervention of the pharmacist, mainly at the patient's level, resulting in 90.1 % of these DRPs partially or totally solved. Different DRPs with antithrombotic medication occurred in Belgian community pharmacies. About 20 % was detected in an a posteriori setting, showing the benefit of medication review. Many of the encountered DRPs were of technical nature (60.7 %). These DRPs were time-consuming for the pharmacist to resolve and should be prevented. Most of the DRPs could be solved, demonstrating the added value of the community pharmacist as first line healthcare provider.

  16. 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.

  17. Hearing regulates Drosophila aggression

    PubMed Central

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C.; Heinrich, Ralf; Callaerts, Patrick

    2017-01-01

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly’s auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level. PMID:28115690

  18. Hearing regulates Drosophila aggression.

    PubMed

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

    2017-02-21

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

  19. An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial.

    PubMed

    Hanberg, Jennifer S; Tang, W H Wilson; Wilson, F Perry; Coca, Steven G; Ahmad, Tariq; Brisco, Meredith A; Testani, Jeffrey M

    2017-08-15

    Effective decongestion of heart failure patients predicts improved outcomes, but high dose loop diuretics (HDLD) used to achieve diuresis predict adverse outcomes. In the DOSE trial, randomization to a HDLD intensification strategy (HDLD-strategy) improved diuresis but not outcomes. Our objective was to determine if potential beneficial effects of more aggressive decongestion may have been offset by adverse effects of the HDLD used to achieve diuresis. A post hoc analysis of the DOSE trial (n=308) was conducted to determine the influence of post-randomization diuretic dose and fluid output on the rate of death, rehospitalization or emergency department visitation associated with the HDLD-strategy. Net fluid output was used as a surrogate for beneficial decongestive effects and cumulative loop diuretic dose for the dose-related adverse effects of the HDLD-strategy. Randomization to the HDLD-strategy resulted in increased fluid output, even after adjusting for cumulative diuretic dose (p=0.006). Unadjusted, the HDLD-strategy did not improve outcomes (p=0.28). However, following adjustment for cumulative diuretic dose, significant benefit emerged (HR=0.64, 95% CI 0.43-0.95, p=0.028). Adjusting for net fluid balance eliminated the benefit (HR=0.95, 95% CI 0.67-1.4, p=0.79). A clinically meaningful benefit from a randomized aggressive decongestion strategy became apparent after accounting for the quantity of loop diuretic administered. Adjusting for the diuresis resulting from this strategy eliminated the benefit. These hypothesis-generating observations may suggest a role for aggressive decongestion in improved outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Antithrombotic Potential of Tormentil Extract in Animal Models

    PubMed Central

    Marcinczyk, Natalia; Jarmoc, Dominika; Leszczynska, Agnieszka; Zakrzeska, Agnieszka; Kramkowski, Karol; Strawa, Jakub; Gromotowicz-Poplawska, Anna; Chabielska, Ewa; Tomczyk, Michal

    2017-01-01

    Potentilla species that have been investigated so far display pharmacological activity mainly due to the presence of polyphenols. Recently, it was shown that polyphenol-rich extract from rhizome of Potentilla erecta (tormentil extract) affects the metabolism of arachidonic acid and exerts both anti-inflammatory and anti-oxidant activities, suggesting a possible effect on thrombosis. Accordingly, the aim of the study was to evaluate the effect of tormentil extract on haemostasis in a rat model of thrombosis. Lyophilized water-methanol extract from P. erecta rhizome was administrated per os for 14 days in doses of 100, 200, and 400 mg/kg in a volume of 2 mL/kg in a 5% water solution of gummi arabici (VEH). In the in vivo experiment an electrically induced carotid artery thrombosis model with blood flow monitoring was used in Wistar rats. Collected blood samples were analyzed ex vivo functionally and biochemically for changes in haemostasis. Tormentil extract (400 mg/kg) significantly decreased thrombus weight and prolonged the time to carotid artery occlusion and bleeding time without changes in the blood pressure. In the ex vivo experiment tormentil extract (400 mg/kg) reduced thromboxane production and decreased t-PA activity, while total t-PA concentration, as well as total PAI-1 concentration and PAI-1 activity remained unchanged. Furthermore, tormentil extract (400 mg/kg) decreased bradykinin concentration and shortened the time to reach maximal optical density during fibrin generation. Prothrombin time, activated partial thromboplastin time, QUICK index, fibrinogen level, and collagen-induced aggregation remained unchanged. To investigate the involvement of platelets in the antithrombotic effect of tormentil, the extract was administrated per os for 2 days to mice and irreversible platelets activation after ferric chloride induced thrombosis was evaluated under intravital conditions using confocal microscopy system. In this model tormentil extract (400 mg

  1. Orthodontic Management in Aggressive Periodontitis

    PubMed Central

    Bhattarai, Bhagabat

    2017-01-01

    Aggressive periodontitis is a type of periodontitis with early onset and rapid progression and mostly affecting young adults who occupy a large percentage of orthodontic patients. The role of the orthodontist is important in screening the disease, making a provisional diagnosis, and referring it to a periodontist for immediate treatment. The orthodontist should be aware of the disease not only before starting the appliance therapy, but also during and after the active mechanotherapy. The orthodontic treatment plan, biomechanics, and appliance system may need to be modified to deal with the teeth having reduced periodontal support. With proper force application and oral hygiene maintenance, orthodontic tooth movement is possible without any deleterious effect in the tooth with reduced bone support. With proper motivation and interdisciplinary approach, orthodontic treatment is possible in patients with controlled aggressive periodontitis. PMID:28299350

  2. Orthodontic Management in Aggressive Periodontitis.

    PubMed

    Gyawali, Rajesh; Bhattarai, Bhagabat

    2017-01-01

    Aggressive periodontitis is a type of periodontitis with early onset and rapid progression and mostly affecting young adults who occupy a large percentage of orthodontic patients. The role of the orthodontist is important in screening the disease, making a provisional diagnosis, and referring it to a periodontist for immediate treatment. The orthodontist should be aware of the disease not only before starting the appliance therapy, but also during and after the active mechanotherapy. The orthodontic treatment plan, biomechanics, and appliance system may need to be modified to deal with the teeth having reduced periodontal support. With proper force application and oral hygiene maintenance, orthodontic tooth movement is possible without any deleterious effect in the tooth with reduced bone support. With proper motivation and interdisciplinary approach, orthodontic treatment is possible in patients with controlled aggressive periodontitis.

  3. 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…

  4. Bipolar disorder and aggression.

    PubMed

    Látalová, K

    2009-06-01

    In clinical practice, overt aggressive behaviour is frequently observed in patients diagnosed with bipolar disorder. It can be dangerous and complicates patient care. Nevertheless, it has not been adequately studied as a phenomenon that is separate from other symptoms such as agitation. The aim of this review is to provide information on the prevalence, clinical context, and clinical management of aggression in patients with bipolar disorder. MEDLINE and PsycInfo data bases were searched for articles published between 1966 and November 2008 using the combination of key words 'aggression' or 'violence' with 'bipolar disorder'. For the treatment searches, generic names of mood stabilisers and antipsychotics were used in combination with key words 'bipolar disorder' and 'aggression'. No language constraint was applied. Articles dealing with children and adolescents were not included. Acutely ill hospitalised bipolar patients have a higher risk for aggression than other inpatients. In a population survey, the prevalence of aggressive behaviour after age 15 years was 0.66% in persons without lifetime psychiatric disorder, but 25.34% in bipolar I disorder. Comorbidity with personality disorders and substance use disorders is frequent, and it elevates the risk of aggression in bipolar patients. Impulsive aggression appears to be the most frequent subtype observed in bipolar patients. Clinical management of aggression combines pharmacological and non-pharmacological approaches. A major problem with the evidence is that aggression is frequently reported only as one of the items contributing to the total score on a scale or a subscale. This makes it impossible to ascertain specifically aggressive behaviour. Large controlled head-to-head randomised controlled studies comparing treatments for aggressive behaviour in bipolar disorder are not yet available. There is some evidence favouring divalproex, but it is not particularly strong .We do not know if there are any efficacy

  5. Current practice of antithrombotic treatment in ischemic stroke: a survey among Hungarian neurologists.

    PubMed

    Sztriha, Lśzló K; Vécsei, László

    2008-05-30

    Large multicenter trials have already evaluated the relative benefit of various types of antithrombotic medication in ischemic stroke. However, the application of the trial results still remains uncertain in some clinical situations. We set out to evaluate the various aspects of antithrombotic treatment use among clinical practitioners. A virtually nationwide survey was performed among Hungarian neurologists involved in stroke care, who responded to a questionnaire concerning the use of antiplatelet agents and anticoagulation in acute ischemic stroke and for secondary prevention. The response rate was 65%. Most (69%) practitioners always wait for brain imaging before initiating antithrombotic treatment in acute stroke. Aspirin (100 mg/day) is the most frequently prescribed antiplatelet agent after a first ischemic episode. Common reasons for the prescription of alternative agents instead of aspirin after a first attack include high-risk cases and intolerance or allergy to aspirin. The results of in vitro platelet aggregation studies frequently influence drug selection. If an event recurs during a given antiplatelet treatment, most neurologists change the medication. Some participants reported the administration of anticoagulation, or of the combination of aspirin plus clopidogrel in certain situations that are not cardiological indications. This study provides information on the use of antithrombotic treatment in general neurological practice, including everyday clinical situations where no help is available from guidelines.

  6. Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7).

    PubMed

    Kucharewicz, Iwona; Pawlak, Robert; Matys, Tomasz; Pawlak, Dariusz; Buczko, Wlodzimierz

    2002-11-01

    It is well established that renin-angiotensin system blockers exert NO/prostacyclin-dependent antithrombotic effects. Because some beneficial effects of these drugs are mediated by angiotensin (Ang)-(1-7), in the present study we examined if their antithrombotic action could be mediated by Ang-(1-7). Intravenous infusion of Ang-(1-7) (1, 10, or 100 pmol/kg per minute for 2 hours) into rats developing venous thrombosis caused 50% to 70% reduction of the thrombus weight. This effect was dose-dependently reversed by cotreatment with A-779 (selective Ang-[1-7] receptor antagonist) or EXP 3174 (angiotensin type 1 receptor antagonist) but not by PD 123,319 (angiotensin type 2 receptor antagonist). Similarly, the antithrombotic effects of captopril (ACE inhibitor) and losartan (angiotensin type 1 receptor blocker) were attenuated by A-779 in a dose-dependent manner. The effect of Ang-(1-7) was completely abolished by concomitant administration of NO synthase inhibitor (N(G)-nitro-L-arginine methyl ester) and prostacyclin synthesis inhibitor (indomethacin), as has been shown previously for captopril and losartan. Thus, the antithrombotic effect of renin-angiotensin system blockers involves Ang-(1-7)-evoked release of NO and prostacyclin.

  7. Manual ventilation therapy and aggressive potassium supplementation in the management of respiratory failure secondary to severe hypokalaemia in a cat with exocrine pancreatic insufficiency.

    PubMed

    Daste, Thomas; Dossin, Olivier; Reynolds, Brice S; Aumann, Marcel

    2014-04-01

    A domestic shorthair cat was referred for progressive muscle weakness and dyspnoea. The cat had a 2-month history of severe weight loss, small intestinal diarrhoea, polyphagia and polyuria/polydipsia. Biochemical analysis and venous blood gas evaluation revealed severe hypokalaemia [1.7 mmol/l; reference interval (RI): 3.5-5.1 mmol/l] and hypoventilation (partial pressure of carbon dioxide = 68 mmHg; RI: 34-38 mmHg). Aggressive potassium supplementation was initiated. The cat was manually ventilated until serum potassium increased to 3 mmol/l. A diagnosis of exocrine pancreatic insufficiency (EPI) was made based on clinical signs and serum feline trypsin-like immunoreactivity (0.1 μg/l; RI: 12-82 μg/l). Medical management of the EPI resulted in clinical recovery.

  8. Antithrombotic potential of GW813893: a novel, orally active, active-site directed factor Xa inhibitor.

    PubMed

    Abboud, Melanie A; Needle, Saul J; Burns-Kurtis, Cynthia L; Valocik, Richard E; Koster, Paul F; Amour, Augustin J; Chan, Chuen; Brown, David; Chaudry, Laiq; Zhou, Ping; Patikis, Angela; Patel, Champa; Pateman, Anthony J; Young, Rob J; Watson, Nigel S; Toomey, John R

    2008-07-01

    Factor Xa (FXa) has been a target of considerable interest for drug development efforts aimed at suppressing thrombosis. In this report, a new orally active, small molecule, active-site directed FXa inhibitor, GW813893, has been profiled in a succession of in vitro and in vivo assays involved in its preclinical characterization as a potential antithrombotic therapeutic. In vitro profiling of GW813893 consisted of assessing its inhibitory potential against FXa and a broad panel of related and unrelated enzymes and receptors. Additionally, the FXa inhibition potential of GW813893 was assessed in prothrombinase and plasma-based clotting assays. In vivo characterization of GW813893 consisted of thrombosis studies in a rat inferior vena cava model, a rat carotid artery thrombosis model, and a rabbit jugular thrombosis model. Bleeding studies were conducted in a rat tail transection model. Ex vivo determinations of compound effects on FX and clotting activity were also undertaken. GW813893 was more than 90-fold selective over all enzymes tested, and it inhibited FXa and prothrombinase activity with a Ki of 4.0 nM and 9.7 nM, respectively. In vivo, GW813893 concentration-dependently suppressed thrombotic activity in all models tested. The antithrombotic activity correlated with the suppression of plasma-based clotting activity and the inhibition of plasma FX activity (P < 0.02). Over the antithrombotic dose-range, an increased bleeding diathesis was not observed. These experiments demonstrate that GW813893 is a potent, selective, orally active inhibitor of FXa. The data suggest that GW813893 has robust antithrombotic potential at doses that have no detectable hemostasis liability. Collectively, the profile suggests that GW813893 has the preclinical pharmacology underpinnings of an oral antithrombotic therapeutic.

  9. Evaluation of safety of endoscopic biopsy without cessation of antithrombotic agents in Japan.

    PubMed

    Ono, Satoshi; Fujishiro, Mitsuhiro; Kodashima, Shinya; Takahashi, Yu; Minatsuki, Chihiro; Mikami-Matsuda, Rie; Asada-Hirayama, Itsuko; Konno-Shimizu, Maki; Tsuji, Yosuke; Mochizuki, Satoshi; Niimi, Keiko; Yamamichi, Nobutake; Kaneko, Makoto; Yatomi, Yutaka; Koike, Kazuhiko

    2012-07-01

    Although guidelines in Japan recommend the cessation of antithrombotic agents before endoscopic biopsy, the safety of biopsy without the cessation of these agents has not been evaluated to date in this country. Therefore, we aimed to assess the feasibility of biopsy without cessation of antithrombotic agents in Japan. This was a prospective single-arm study from a single institution. From May 2010 to November 2011, 112 outpatients who were receiving antithrombotic agents because of their high-risk status for a thromboembolic event (after implantation of coronary stent, after valve replacement, or a previous history of thromboembolic event or heart failure due to atrial fibrillation) were enrolled. We evaluated the rate of severe bleeding complications within 2 weeks after endoscopy and the endoscopic bleeding time (EBT) after biopsy in patients who underwent biopsy for endoscopic findings requiring pathology assessment. Among the 112 participants, 101 biopsies were performed for 48 and 12 outpatients who had had esophagogastroduodenoscopy and colonoscopy, respectively. All the biopsies provided enough specimens to evaluate pathologically. Hemostasis after biopsy was confirmed for all biopsies during endoscopic observation. No patients complained of any bleeding symptoms in the 2-week observation period after biopsy (0/101; 95% confidence interval [CI] 0-3.6%). Concerning the EBT (median 2.2 ± 1.8 min, range 0.5-9 min), there were no significant differences between patients receiving single antithrombotic agents and those receiving multiple agents (2.4 ± 1.4 vs. 2.1 ± 2.1 min), nor were there any significant differences between patients not receiving and receiving warfarin (2.3 ± 1.8 vs. 2.2 ± 1.8 min). Biopsy without cessation of antithrombotic agents, as recommended in Western guidelines, can also be acceptable for Japanese people if performed carefully.

  10. [The incidence and clinical implications of left ventricular thrombosis in 769 patients with acute myocardial infarct treated with antithrombotics and fibrinolytics].

    PubMed

    Boccardi, L; Natale, E; Minardi, G; Tubaro, M; Pucci, E; Ricci, R; Di Segni, M; Di Marcotullio, G; Malinconico, U; Giovannini, E

    1991-10-01

    Seven hundred sixty-nine patients (pts) admitted to the Coronary Care Unit (CCU) between January 1987 and January 1990 suffering from first acute myocardial infarction (AMI) were studied. The presence of left ventricular thrombosis (LVT) was evaluated by two-dimensional echocardiography (2D-echo). The relation of LVT to site, size and intra-CCU clinical outcome of AMI, in terms of systemic embolic events, Killip class and mortality, was also assessed. AMI was transmural in 707 pts (92%), anterior in 446 pts (58%) and inferior in 261 pts (34%), non-Q in 62 pts (8%). Two hundred sixty-one pts (34%) were treated with IV thrombolytic therapy followed by IV heparin 1000 IU/h over 12 hrs and then calcium heparin (CH) 12500 IU s.c. bid; 508 pts (66%) were given only antithrombotic therapy (CH 12500 IU s.c. bid). 2D-Echo was performed within 48 hours and on day 5-7 from the onset of AMI. In 41 pts (5.3%) LVT was observed: 39 had anterior AMI (8.7% of all anterior AMI pts), one had inferior AMI (0.4% of all inferior AMI pts), and one had non-Q AMI (1.6% of all non-Q AMI pts) [p less than 0.001 for anterior AMI vs inferior and non-Q AMI]. Pts with LVT had a greater infarct size (number of akinetic plus dyskinetic segments/total number of segments x 100) compared to pts without LVT (32.3 +/- 12.6% vs 16.4 +/- 5.7%, p less than 0.001). In pts treated with thrombolytic therapy, LVT incidence was not significantly different from that of pts treated with antithrombotic therapy (4.2% vs 5.9%) alone.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Production of platelet-rich plasma gel from elderly patients under antithrombotic drugs: Perspectives in chronic wounds care.

    PubMed

    Velier, M; Magalon, J; Daumas, A; Cassar, M; Francois, P; Ghazouane, A; Philandrianos, C; Bertrand, B; Frere, C; Bernot, D; Villani, P; Dignat George, F; Sabatier, F

    2017-08-14

    Platelet-Rich Plasma (PRP) is an autologous biological therapy obtained by centrifuging the patient's own blood to concentrate platelets. The addition of autologous thrombin and calcium chloride to PRP allows the production of a semi-solid form called PRP gel. PRP gel is increasingly used in a variety of tissue defects and predominantly in the management of non-healing chronic wounds. The topical application of PRP gel seems promising due to the capability of platelets to store and secrete growth factors (GF), fibrin and cytokines, which are essentials for wound healing. Most patients who suffered from chronic wounds are elderly patients with co-morbidities and polypharmacy including antithrombotic drugs such as antiplatelet agents (AP) or anticoagulants (AC), which could hamper the feasibility of this autologous platelet-derived therapy. To date, no study has investigated PRP gel formation in patients with AP or AC. The aim of this study was to evaluate the influence of AP or AC drugs on the production of PRP gel formation from elderly patients. Different biological characteristics were determined to qualify the production of PRP gel from such patients (Interquartile range (IQR) = 75-92 years) compared to healthy volunteers (IQR = 23-37 years). No significant difference was observed in the volume, composition (quantity of platelets, leukocytes and red blood cells) and functionality of platelets from PRP except a higher ADP-induced P-selectin expression in healthy donors compared with elderly patients. Autologous thrombin characteristics were similar in the two groups. Gel time formation (IQR: 120-195 seconds for controls and 135-210 seconds for elderly patients) and final composition of PRP gel were not significantly modified. Concentrations of theoretical thrombin generated in the serum and in the gel were inversely correlated with the time of formation of PRP gel (r(2) = 0.57, p = 0.012). Altogether these data indicate that PRP gel preparation is not

  12. Humor, Aggression, and Aging.

    ERIC Educational Resources Information Center

    Barrick, Ann Louise; And Others

    Although humor is an important phenomenon in human interactions, it has rarely been studied in the elderly. An understanding of responses to humor in aggressive cartoons as a function of advancing age would provide information regarding both the development of humor and the negative (aggressive) emotional experiences of the elderly. This study was…

  13. Serotonin and Aggression.

    ERIC Educational Resources Information Center

    Brown, Serena-Lynn; And Others

    1994-01-01

    Decreased serotonin function has consistently been shown to be highly correlated with impulsive aggression across a number of different experimental paradigms. Such lowered serotonergic indices appear to correlate with the dimension of aggression dyscontrol and/or impulsivity rather than with psychiatric diagnostic categories per se. Implications…

  14. 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

  15. 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…

  16. 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…

  17. 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…

  18. 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.

  19. 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…

  20. 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…

  1. Addressing canine and feline aggression in the veterinary clinic.

    PubMed

    Moffat, Kelly

    2008-09-01

    Handling aggressive dogs and cats in the veterinary clinic can be frustrating, time consuming, and injurious for both employee and animal. This article discusses the etiology of the aggressive dog and cat patient and how best to approach these cases. A variety of handling techniques, safety products, and drug therapy are reviewed.

  2. 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

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

    2015-09-01

    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.

  3. Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphoma.

    PubMed

    Lehmann, C; Wyen, C; Hoffmann, C; Fätkenheuer, G

    2005-01-01

    Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients.

  4. Training Aggressive Adolescents in Prosocial Behavior

    ERIC Educational Resources Information Center

    Goldstein, Arnold P.; And Others

    1978-01-01

    Structured Learning Therapy (SLT) teaches aggressive adolescents prosocial skills (negotiation, self-relaxation, and anger control) by modeling, role playing, social reinforcement, and transfer of training. This article summarizes initial application of SLT with psychiatric clients, includes guidelines for improving trainee-trainer-treatment…

  5. Effects of ozone therapy on haemostatic and oxidative stress index in coronary artery disease.

    PubMed

    Martínez-Sánchez, Gregorio; Delgado-Roche, Livan; Díaz-Batista, Arquímides; Pérez-Davison, Gema; Re, Lamberto

    2012-09-15

    Coronary artery disease (CAD) is the most common cause of sudden death, and death of people over 20 years of age. Because ozone therapy can activate the antioxidant system and improve blood circulation and oxygen delivery to tissue, the aim of this study was to investigate the therapeutic efficacy of ozone in patients with CAD, treated with antithrombotic therapy, Aspirin and policosanol. A randomized controlled clinical trial was performed with 53 patients divided into two groups: one (n=27) treated with antithrombotic therapy and other (n=26) treated with antithrombotic therapy plus rectal insufflation of O(3). A parallel group (n=50) age and gender matched was used as reference for the experimental variables. The efficacy of the treatments was evaluated by comparing hemostatic indexes and biochemical markers of oxidative stress in both groups after 20 day of treatment. Ozone treatment significantly (P<0.001) improved prothrombin time when compared to the antithrombotic therapy only group, without modifying bleeding time. Combination antithrombotic therapy+O(3) improved the antioxidant status of patients reducing biomarkers of protein and lipid oxidation, enhancing total antioxidant status and modulating the level of superoxide dismutase and catalase with a 57% and 32% reduction in superoxide dismutase and catalase activities respectively, moving the redox environment to a status of low production of O(2)(•-) with an increase in H(2)O(2) detoxification. No side effects were observed. These results show that medical ozone treatment could be a complementary therapy in the treatment of CAD and its complications.

  6. Brief Report: Comparative Effects of Antecedent Exercise and Lorazepam on the Aggressive Behavior of an Autistic Man.

    ERIC Educational Resources Information Center

    Allison, David B.; And Others

    1991-01-01

    This case study of a 24-year-old man with autistic disorder and mental retardation who exhibited aggression found that antecedent exercise significantly decreased aggression; drug therapy with an anxiolytic (lorazepam) alone had no significant effect on aggression; and exercise plus medication decreased aggression to a somewhat lesser degree than…

  7. Shifts of subgingival bacterial population after nonsurgical and pharmacological therapy of localized aggressive periodontitis, followed for 1 year by Ion Torrent PGM platform.

    PubMed

    Campisciano, Giuseppina; Toschetti, Annamaria; Comar, Manola; Taranto, Rosanna Di; Berton, Federico; Stacchi, Claudio

    2017-01-01

    The possibility of targeting the hypervariable region V3 of the 16S rRNA gene using Ion Torrent Personal Genome Machine (PGM) could provide a complete analysis of subgingival plaque samples, potentially able to identify microbiological species missed by culture-based methods. A 16-year-old female smoker patient, affected by localized aggressive periodontitis, underwent a full-mouth disinfection protocol and was inserted in a 3-month recall program. Microbiological samples were collected at baseline and at 30, 100, 365 days follow-up and analyzed by Ion Torrent PGM. Capnocytophaga, Fusobacterium, Prevotella, and Treponema were the most represented pathogens at baseline. Nonsurgical treatment and systemic antibiotics drastically lowered the anaerobic species, and their presence remained limited after 100 days, while a consistent recolonization by anaerobic bacteria was detected at 365 days. The patient showed a general improvement of periodontal conditions. Differently from polymerase chain reaction and other microarray techniques, Ion Torrent performs a quantitative analysis of the microbiota, irrespective of the searched species. An accurate definition of the shifts of the bacterial community might help periodontal researchers for a better understanding of the impact of different treatment approaches or in intercepting nonresponsive conditions.

  8. Anti-thrombotic activity of DT-13, a saponin isolated from the root tuber of Liriope muscari.

    PubMed

    Tian, Youqing; Ma, Shengtang; Lin, Biqi; Kou, Junping; Yu, Boyang

    2013-01-01

    To investigate the anti-thrombotic activity of DT-13 in experimental animal models. The anti-thrombotic activity of DT-13 was evaluated by measuring the thrombus induced by inferior vena cava (IVC) ligation in mice and rats. The anti-thrombotic mechanism of DT-13 was investigated by assessing the mRNA expression levels of interleukin-6 (IL-6) and tissue factor (TF) in rat IVC tissue around thrombus. DT-13 markedly inhibited thrombosis induced by IVC ligation for 6 h in mice (2.0 and 4.0 mg/kg, p.o.) and for 18 h in rats (1.4 mg/kg, p.o.). Furthermore, DT-13 down-regulated the increased mRNA expression levels of IL-6 and TF in rats. DT-13 has an anti-thrombotic activity due to down-regulation of the increased mRNA expression levels of IL-6 and TF.

  9. 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.

  10. Aggression and sport.

    PubMed

    Burton, Robert W

    2005-10-01

    Viewing aggression in its healthy form, in contrast to its extreme and inappropriate versions, and sport as a health-promoting exercise in psychological development and maturation may allow participants and spectators alike to retain an interest in aggression and sport and derive further enjoyment from them. In addition, it will benefit all involved with sport to have a broader understanding of human aggression. Physicians, mental health professionals, and other health care providers can be influential in this process, and should be willing to get involved and speak out when issues and problems arise.

  11. The Effects of Diode Laser Therapy as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis: A 1-Year Randomized Controlled Clinical Trial.

    PubMed

    Matarese, Giovanni; Ramaglia, Luca; Cicciù, Marco; Cordasco, Giancarlo; Isola, Gaetano

    2017-09-14

    The aim of this study was to investigate and compare the clinical, microbial, and inflammatory effects of a diode laser as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of generalized aggressive periodontitis (GAgP). Using a split-mouth design, 31 patients with GAgP were enrolled in the study. The maxillary right and left quadrants were randomly assigned to SRP+diode laser or SRP alone. Patients were examined on a regular basis for clinical, microbiological, and inflammatory mediator changes over a 1-year period. Clinical attachment level (CAL) was the primary outcome variable chosen. In addition, subgingival biofilm samples and gingival crevicular fluid (GCF) inflammatory mediators were analyzed at each follow-up session. Compared to baseline, both treatments demonstrated an improvement in periodontal parameters at 1 year. However, SRP+diode laser produced a significant improvement in probing depth (PD; 2.56 ± 0.44 vs. 3.36 ± 0.51 mm, p < 0.05) and CAL (3.47 ± 0.25 vs. 4.11 ± 0.26 mm, p < 0.05) values compared to SRP alone. Similarly, in the SRP+diode laser group, the bacteria of orange complex group were significantly reduced at 30 and 60 days compared to SRP alone. Moreover, SRP+diode laser determined a reduction in mean GCF level of interleukin (IL)-1β and IL-1β/IL-10 ratio at 15 and 30 days compared to SRP alone (p < 0.05). At 1 year, SRP+diode laser yielded a significant reduction in some clinical parameters, while microbial and inflammatory mediator changes were not significantly reduced compared to SRP alone.

  12. 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

  13. 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.

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

    PubMed Central

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

    2015-01-01

    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 over twenty-five 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 was associated with migration and accumulation of activated polymorphonuclear neutrophils (PMN) from spleens into tumors, which was not observed 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

  15. Rationale and design of the carotid plaque in human for all evaluations with aggressive rosuvastatin therapy (CHALLENGER trial): evaluation by magnetic resonance imaging.

    PubMed

    Miyauchi, Katsumi; Takaya, Norihide; Hirose, Takahisa; Ikeda, Fuki; Kawamori, Ryuzo; Ohishi, Hidenori; Yoshida, Kensaku; Yamamoto, Munetaka; Arai, Hajime; Urabe, Takao; Hattori, Nobutaka; Suzuki, Michimasa; Maehara, Tadayuki; Sase, Kazuhiro; Hatsukami, Thomas S; Yuan, Chun; Daida, Hiroyuki

    2009-01-01

    Intensive lipid-lowering therapy with statins reduces levels of low-density lipoprotein (LDL)-cholesterol (C) and improves plaque volume and composition in patients with cardiovascular disease. Furthermore, rosuvastatin ameliorated carotid stenosis in the ASTEROID study, and altered the composition of plaques in a predominantly Caucasian study population in the ORION study. However, it is not known whether statin therapy achieves similar quantitative improvement in carotid artery plaque in other ethnic groups. Fifty patients with hypercholesterolemia (LDL-C >or=120 mg/dl) and a maximum carotid intima-media thickness >or=1.8 mm will be enrolled and treated with rosuvastatin at a dose of 5 mg/day for 96 weeks. The primary endpoints will be the percent change of carotid plaque volume and the change in plaque composition after 96 weeks of treatment, as evaluated by magnetic resonance imaging. The CHALLENGER study will provide a noninvasive assessment of the changes in carotid plaque volume and composition achieved by reduction of LDL levels in Japanese patients with carotid stenosis on long-term rosuvastatin therapy.

  16. Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery?

    PubMed

    Butwick, A J; Carvalho, B

    2011-02-01

    Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

  17. Purification and characterization of a novel antithrombotic peptide from Scolopendra subspinipes mutilans.

    PubMed

    Kong, Yi; Huang, Shi-Long; Shao, Yu; Li, Shuai; Wei, Ji-Fu

    2013-01-09

    The centipede has been prescribed for the treatment of cardiovascular diseases in Korea, China and other Far Eastern Asian countries for several hundred years. A novel antithrombotic peptide was isolated from Scolopendra subspinipes mutilans using a combination of ultrafiltration, Sephadex G-50 column, Source 15Q anion exchange column and RP-HPLC C18 column. The molecular mass of the purified peptide is 346Da measured by Electrospray Ionization Mass Spectrometry (ESI-MS). The primary structure of the peptide is Ser-Gln-Leu (SQL) determined by Edman degradation. SQL potently prolonged the activated partial thromboplastin time (aPTT), and inhibited platelet aggregation. These results help to clarify the mechanism of the antithrombotic activity of the centipede for effective treatment of cardiovascular and cerebrovascular diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Antithrombotic and thrombolytic effects of antithrombin: comparison with either heparin or defibrase

    NASA Astrophysics Data System (ADS)

    Tomaru, Takanobu; Nakamura, Fumitaka; Miwa, Atsuko; Fujimori, Yoshiharu; Uchida, Yasumi

    1993-05-01

    Anti-thrombotic and thrombolytic effects of anti-thrombin agent (Argatroban;Arg 0.5 mg/kg) was evaluated by angioscopy and compared with heparin (250 U/kg). Occlusive thrombus was produced in canine iliac artery by balloon injury. At another side, balloon denudation was attempted at 20 minutes after the administration of the agent. One hour thrombus was control. Angioscopic percent luminal obstruction with thrombus reduced by Arg (from 69 to 32%, P < 0.0001), but not by heparin (from 53% to 59%). Both agents had antithrombotic effects and prevented thrombus formation. The activated partial thromboplastin time (APTT) prolonged to 190% with argatroban and 1253% with heparin (P < 0.0001). Thus, antithrombin agent has both preventive effect of thrombosis and thrombolytic effect without marked prolongation of the APTT.

  19. Antithrombotic treatment in patients with atrial fibrillation as a risk factor of stroke.

    PubMed

    Yaghy, Momen; Murin, J; Pernicky, M; Pekarovicova, Z; Mikes, P

    2008-01-01

    For over two decades, valuable insights have been accumulated from epidemiologic studies and randomized trials about the risks and prevention of atrial fibrillation. Atrial fibrillation (AF) substantially raises the risk of stroke, most likely through an atrio-embolic mechanism. Warfarin and other members of its class of oral anticoagulants targeted at an international normalized ratio (INR) of 2.5 can abrogate the risk of stroke attributable to AF effectively and fairly safely. High-quality management of anticoagulation can be achieved in usual clinical care. These insights have important implications for the care of individual patients and more generally for public health. Future research is needed to specify the risk of stroke and hemorrhage among patients with AF better, particularly among older individuals, to optimize use of antithrombotic agents, and to define the role of recently developed antithrombotic drugs and invasive nondrug approaches (Tab. 3, Ref. 20). Full Text (Free, PDF) www.bmj.sk.

  20. Chemical characteristics and antithrombotic effect of chondroitin sulfates from sturgeon skull and sturgeon backbone.

    PubMed

    Gui, Meng; Song, Juyi; Zhang, Lu; Wang, Shun; Wu, Ruiyun; Ma, Changwei; Li, Pinglan

    2015-06-05

    Chondroitin sulfates (CSs) were extracted from sturgeon skull and backbone, and their chemical composition, anticoagulant, anti-platelet and thrombolysis activities were evaluated. The average molecular weights of CS from sturgeon skull and backbone were 38.5kDa and 49.2kDa, respectively. Disaccharide analysis indicated that the sturgeon backbone CS was primarily composed of disaccharide monosulfated in position four of the GalNAc (37.8%) and disaccharide monosulfated in position six of the GalNAc (59.6%) while sturgeon skull CS was primarily composed of nonsulfated disaccharide (74.2%). Sturgeon backbone CS showed stronger antithrombotic effect than sturgeon skull CS. Sturgeon backbone CS could significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT), inhibited ADP-induced platelet aggregation and dissolved platelet plasma clots in vitro. The results suggested that sturgeon backbone CS can be explored as a functional food with antithrombotic function.

  1. 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…

  2. School Aggression and Dispositional Aggression among Middle School Boys

    ERIC Educational Resources Information Center

    Ballard, Mary E.; Rattley, Kelvin T.; Fleming, Willie C.; Kidder-Ashley, Pamela

    2004-01-01

    We examined the relationship between dispositional (trait) aggression and administrative reports of school aggression among 100 adolescent male participants from an urban middle school. Aggression was fairly common among the sample; 58 boys had a record of school aggression, and many of those were repeat offenders. Our hypothesis that those higher…

  3. Aggressive Angiomyxoma in Males.

    PubMed

    Dehuri, Priyadarshini; Gochhait, Debasis; Srinivas, B H; Sistla, Sarath Chandra

    2017-06-01

    Paratesticular aggressive angiomyxoma is a very rare tumour in males. Most of documented cases of aggressive angiomyxomas have been seen in genital, perineal and pelvic regions in women of child bearing age. We report two cases of aggressive angiomyxomas in males who presented with inguinal swellings. A globular mass with greyish white, glistening cut surface was received after excision of the mass. Microscopic examination revealed a paucicellular tumour comprising of spindle shaped cells along with vessels of varying calibre. The accompanying stroma was myxocollagenous. In addition there was evidence of fat infiltration in one of the cases. Immunohistochemical staining showed CD34, desmin, vimetin positivity and negative staining for S100, actin, Estrogen Receptors (ER) and Progesterone Receptors (PR). The microscopic and immunohistochemical features favoured the diagnosis of aggressive angiomyxoma. This report of angiomyxoma in two cases of males assumes great significance in view of the extreme rarity of the tumour in males and its locally infiltrative nature.

  4. Aggressive Angiomyxoma in Males

    PubMed Central

    Dehuri, Priyadarshini; Srinivas, BH; Sistla, Sarath Chandra

    2017-01-01

    Paratesticular aggressive angiomyxoma is a very rare tumour in males. Most of documented cases of aggressive angiomyxomas have been seen in genital, perineal and pelvic regions in women of child bearing age. We report two cases of aggressive angiomyxomas in males who presented with inguinal swellings. A globular mass with greyish white, glistening cut surface was received after excision of the mass. Microscopic examination revealed a paucicellular tumour comprising of spindle shaped cells along with vessels of varying calibre. The accompanying stroma was myxocollagenous. In addition there was evidence of fat infiltration in one of the cases. Immunohistochemical staining showed CD34, desmin, vimetin positivity and negative staining for S100, actin, Estrogen Receptors (ER) and Progesterone Receptors (PR). The microscopic and immunohistochemical features favoured the diagnosis of aggressive angiomyxoma. This report of angiomyxoma in two cases of males assumes great significance in view of the extreme rarity of the tumour in males and its locally infiltrative nature. PMID:28764175

  5. Management of dental patients receiving antiplatelet therapy or chronic oral anticoagulation: A review of the latest evidence.

    PubMed

    Dézsi, Csaba András; Dézsi, Balázs Bence; Dézsi, András Döme

    2017-12-01

    The perioperative management of patients treated with antithrombotic medications who undergo surgical procedures represents a common clinical problem. Dental interventions are usually associated with a low risk of bleeding; however, the dental implications of new antithrombotic agents are not yet fully understood. The present review is based on the latest evidence and recommendations published on the periprocedural management of dental patients treated with single or dual antiplatelet therapy, vitamin K antagonists, or direct oral anticoagulants for a variety of indications.

  6. Inducing heat shock protein 70 expression provides a robust antithrombotic effect with minimal bleeding risk.

    PubMed

    Allende, Mikel; Molina, Eva; Lecumberri, Ramón; Sanchez-Arias, Juan Antonio; Ugarte, Ana; Guruceaga, Elizabeth; Oyarzabal, Julen; Hermida, José

    2017-08-30

    Antithrombotic medications target coagulation factors. Their use is associated with an increased bleeding risk. Safer drugs are needed. The heat shock protein 70 (Hsp70) exhibits antithrombotic properties that do not influence bleeding. By using murine models, we aimed to test the hypothesis that overexpressing Hsp70 with CM-695, a first in class dual inhibitor of HDAC6 and phosphodiesterase 9, protects against thrombosis while leaves bleeding tendency unaltered. CM-695 was used to induce Hsp70 overexpression. Hsp70 overexpressing mice were submitted to three thrombosis-triggering procedures. The ferric chloride carotid artery model was used to compare the antithrombotic role of CM-695 and rivaroxaban, a direct oral anticoagulant. The mouse tail transection model was used to compare the bleeding tendency upon CM-695 or rivaroxaban administration. Intraperitoneal (i. p.) 20 mg/kg CM-695 increased Hsp70 expression markedly in the murine aortic tissue. This treatment delayed thrombosis in the collagen/epinephrine [p=0.04 (Log-Rank test), n=10], Rose Bengal/laser [median vessel occlusion time (OT): 58.6 vs 39.0 minutes (min) in the control group (CG), p=0.008, n≥10] and ferric chloride (OT: 14.7 vs 9.2 min in the CG, p=0.032, n≥10) models. I.p. 80 mg/kg CM-695 (n≥9) and intravenous 3 mg/kg rivaroxaban (n≥8) significantly delayed thrombosis. CM-695 did not induce bleeding [median bleeding time (BT): 8.5 vs 7.5 min in the CG, n≥10]. However, BT was dramatically increased by rivaroxaban (30.0 vs 13.7 min in the CG, p=0.001, n=10). In conclusion, CM-695 is a new antithrombotic small molecule devoid of bleeding risk that may be envisioned as a useful clinical tool.

  7. Lignans and aromatic glycosides from Piper wallichii and their antithrombotic activities.

    PubMed

    Shi, Yan-Ni; Shi, Yi-Ming; Yang, Lian; Li, Xing-Cong; Zhao, Jin-Hua; Qu, Yan; Zhu, Hong-Tao; Wang, Dong; Cheng, Rong-Rong; Yang, Chong-Ren; Xu, Min; Zhang, Ying-Jun

    2015-03-13

    Piper wallichii (Miq.) Hand.-Mazz. is a medicinal plant used widely for the treatment of rheumatoid arthritis, inflammatory diseases, cerebral infarction and angina in China. Previous study showed that lignans and neolignans from Piper spp. had potential inhibitory activities on platelet aggregation. In the present study, we investigated the chemical constituents of Piper wallichii and their antithrombotic activities, to support its traditional uses. The methanolic extract of the air-dried stems of Piper wallichii was separated and purified using various chromatographic methods, including semi-preparative HPLC. The chemical structures of the isolates were determined by detailed spectroscopic analysis, and acidic hydrolysis in case of the new glycoside 2. Determination of absolute configurations of the new compound 1 was facilitated by calculated electronic circular dichroism using time-dependent density-functional theory. All compounds were tested for their inhibitory effects on platelet aggregation induced by platelet activating factor (PAF) in rabbits׳ blood model, from which the active ones were further evaluated the in vivo antithrombotic activity in zebrafish model. A new neolignan, piperwalliol A (1), and four new aromatic glycosides, piperwalliosides A-D (2-5) were isolated from the stems of Piper wallichii, along with 25 known compounds, including 13 lignans, six aromatic glycosides, two phenylpropyl aldehydes, and four biphenyls. Five known compounds (6-10) showed in vitro antiplatelet aggregation activities. Among them, (-)-syringaresinol (6) was the most active compound with an IC50 value of 0.52 mM. It is noted that in zebrafish model, the known lignan 6 showed good in vivo antithrombotic effect with a value of 37% at a concentration of 30 μM, compared with the positive control aspirin with the inhibitory value of 74% at a concentration of 125μM. This study demonstrated that lignans, phenylpropanoid and biphenyl found in Piper wallichii may be

  8. Evaluation of Two Treatments for Reactive and Proactive Aggression in Preschool

    ERIC Educational Resources Information Center

    Whitaker, Regina Navonne

    2010-01-01

    Previous research has indicated that preschoolers identified for aggressive behavior would benefit from family, group, or individual therapy. However, there remains an important gap in the current literature regarding treatments for aggressive behavior based on the subtype of aggression. The purpose of this pilot study was to examine if 2…

  9. AdCD40L gene therapy counteracts T regulatory cells and cures aggressive tumors in an orthotopic bladder cancer model.

    PubMed

    Loskog, Angelica S I; Fransson, Moa E; Totterman, Thomas T H

    2005-12-15

    The aim of this study was to develop an immunostimulating gene therapy for the treatment of orthotopic bladder carcinoma by transferring the gene for CD40L into the tumor site. CD40L stimulation of dendritic cells induces interleukin-12 expression that drives Th1 type of immune responses with activation of cytotoxic T cells. The gene for murine CD40L was transferred into bladders of tumor-bearing mice using an adenoviral vector construct. To facilitate viral uptake, the bladders were pretreated with Clorpactin. Survival of mice as well as transgene expression and immunologic effect, such as resistance to tumor challenge and presence of T regulatory cells, were monitored. On viral vector instillation, CD40L expression could be detected by reverse transcription-PCR. As a sign of transgene function, interleukin-12 (IL-12) expression was significantly increased. AdCD40L gene therapy cured 60% of mice with preestablished tumors. The cured mice were completely resistant to subcutaneous challenge with MB49 tumor cells, whereas the growth of a syngeneic irrelevant tumor was unaltered. Furthermore, the mRNA expression level of the T regulatory cell transcription factor Foxp3 was evaluated both in tumor biopsies and lymph nodes. There were no differences within the tumors of the different treatment groups. However, Foxp3 mRNA levels were down-regulated in the lymph nodes of AdCD40L-treated mice. Correspondingly, T cells from AdCD40L-treated mice were not able to inhibit proliferation of naive T cells as opposed to T cells from control-treated, tumor-bearing mice. AdCD40L gene therapy evokes Th1 cytokine responses and counteracts T regulatory cell development and/or function.

  10. 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.

  11. Purified polysaccharides of Geoffroea spinosa barks have anticoagulant and antithrombotic activities devoid of hemorrhagic risks.

    PubMed

    Souza, Racquel O S; Assreuy, Ana M S; Madeira, Juliana C; Chagas, Francisco D S; Parreiras, Luane A; Santos, Gustavo R C; Mourão, Paulo A S; Pereira, Maria G

    2015-06-25

    Polysaccharides were extracted from the barks of Geoffroea spinosa, purified using anion exchange chromatography and characterized by chemical and methylation analysis, complemented by infrared and NMR spectroscopies. These polysaccharides were tested for their anticoagulant, antithrombotic and antiplatelet activities and also for their effects on bleeding. Unfractionated polysaccharide contains low levels of protein and high levels of carbohydrate (including hexuronic acid). The purified polysaccharides (fractions FII and FIII) are composed of arabinose (Ara), rhamnose (Rha), hexuronic acid, small amounts of galactose, but no sulfate ester. They have highly complex structure, which was partially characterized. NMR and methylation analysis indicate that the polysaccharides have a core of α-Rhap and branches of 5-linked α-Araf. Residues of 4-linked α-GalpA are also found in the structure. The unfractionated (TPL) and fraction FIII, but not fractions FI and FII, prolonged the activated partial thromboplastin time (aPTT). TPL, FII and FIII inhibited the platelet aggregation induced by ADP. More significantly, both unfractionated and purified fractions exhibited potent antithrombotic effect (31-60%) and the fractions did not modify the bleeding tendency. These plant polysaccharides could be alternative source of new anticoagulant, antiplatelet and antithrombotic compounds devoid of the undesirable risk of hemorrhage.

  12. Antithrombotic effect of a polysaccharide fraction from Laminaria japonica from the South China Sea.

    PubMed

    Xie, Lu; Chen, Meng-Hua; Li, Jing; Yang, Xiao-Mei; Huang, Qiao-Juan

    2011-09-01

    Some in vitro studies have identified an antithrombotic effect of polysaccharides from Laminaria japonica, but this activity remains to be confirmed in vivo. In this study a polysaccharide fraction termed PLG was extracted from L. japonica in the Beibu Gulf in Guangxi, China, and its antithrombotic effects explored in rat models of carotid and venous thrombosis. Its anticoagulation and antiplatelet properties were assessed by measuring the prothrombin time (PT), activated partial thromboplastin time (APTT) and ADP-induced platelet aggregation rate (Agg(max)). Its effects on bleeding time were measured using the tail transection method. It was found that pretreatment with an intraperitoneal injection of PLG at 2.5 or 5.0 mg/kg significantly prolonged the occlusion time in the carotid thrombosis model, and a dose of 5.0 mg/kg reduced the thrombus weight in the venous thrombosis model. Pretreatment with PLG (5.0 mg/kg) increased the APTT and decreased the ADP-induced platelet Agg(max). Neither dose of PLG significantly prolonged the bleeding time compared with the control group. In an in vitro anticoagulation assay using human plasma, PLG at 57.14, 28.57 and 28.57 μg/mL inhibited APTT and PT in a concentration-dependent manner. The results show that PLG possesses antithrombotic activity in a rat model, and that it may prove to be clinically useful in humans. Copyright © 2011 John Wiley & Sons, Ltd.

  13. [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.

  14. 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.

  15. Aggressive Angiomyxoma of the Vulva and Bladder.

    PubMed

    Song, Mihae; Glasgow, Michelle; Murugan, Paari; Rivard, Colleen

    2017-10-01

    Aggressive angiomyxoma is a rare, locally infiltrative tumor, frequently occurring in female patients. Although wide local excision is considered standard therapy, radical surgery may be needed. A 49-year-old woman presented with an aggressive angiomyxoma involving the vulva and bladder. Given the hormone receptor status and size of the tumor, the patient was initially treated with fulvestrant and goserelin acetate in an attempt to reduce the size of the mass. She was followed up at 1- to 3-month intervals; after 6 months of treatment, owing to increasing size of the mass and worsening symptoms, the decision was made to proceed with radical surgery. Although a less radical surgical approach is preferred, radical surgery is possible for treatment of aggressive angiomyxoma when needed.

  16. Antithrombotic Regimens for Patients Taking Oral Anticoagulation After Coronary Intervention: A Meta-analysis of 16 Clinical Trials and 9,185 Patients.

    PubMed

    Gao, Xiao-Fei; Chen, Yan; Fan, Zhong-Guo; Jiang, Xiao-Min; Wang, Zhi-Mei; Li, Bing; Mao, Wen-Xing; Zhang, Jun-Jie; Chen, Shao-Liang

    2015-08-01

    The optimal antithrombotic regimen remains controversial in patients taking oral anticoagulation (OAC) undergoing coronary stenting. This study sought to compare efficacy and safety outcomes of triple therapy (OAC, aspirin, and clopidogrel) vs dual therapy (clopidogrel with aspirin or OAC) in these patients. We hypothesize OAC plus clopidogrel could be the optimal regimen for patients with indications for OAC receiving stent implantation. Medline, the Cochrane Library, and other Internet sources were searched for clinical trials comparing the efficacy and safety of triple vs dual therapy for patients taking OAC after coronary stenting. Sixteen eligible trials including 9185 patients were identified. The risks of major adverse cardiac events (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.82-1.39, P = 0.65), all-cause mortality (OR: 0.98, 95% CI: 0.76-1.27, P = 0.89), myocardial infarction (OR: 1.01, 95% CI: 0.77-1.31, P = 0.97), and stent thrombosis (OR: 0.91, 95% CI: 0.49-1.69, P = 0.75) were similar between triple and dual therapy. Compared with dual therapy, triple therapy was associated with a reduced risk of ischemic stroke (OR: 0.57, 95% CI: 0.35-0.94, P = 0.03) but with higher major bleeding (OR: 1.52, 95% CI: 1.11-2.10, P = 0.01) and minor bleeding (OR: 1.59, 95% CI: 1.05-2.42, P = 0.03). Subgroup analysis indicated there were similar ischemic stroke and major bleeding outcomes between triple therapy and therapy with OAC plus clopidogrel. Treatment with OAC and clopidogrel was associated with similar efficacy and safety outcomes compared with triple therapy. Triple therapy could be replaced by OAC plus clopidogrel without any concern about additional risk of thrombotic events. © 2015 Wiley Periodicals, Inc.

  17. Apelin: an antithrombotic factor that inhibits platelet function.

    PubMed

    Adam, Frédéric; Khatib, Abdel-Majid; Lopez, Jose Javier; Vatier, Camille; Turpin, Sabrina; Muscat, Adeline; Soulet, Fabienne; Aries, Anne; Jardin, Isaac; Bobe, Régis; Stepanian, Alain; de Prost, Dominique; Dray, Cédric; Rosado, Juan Antonio; Valet, Philippe; Feve, Bruno; Siegfried, Geraldine

    2016-02-18

    Apelin peptide and its receptor APJ are directly implicated in various physiological processes ranging from cardiovascular homeostasis to immune signaling. Here, we show that apelin is a key player in hemostasis with an ability to inhibit thrombin- and collagen-mediated platelet activation. Mice lacking apelin displayed a shorter bleeding time and a prothrombotic profile. Their platelets exhibited increased adhesion and a reduced occlusion time in venules, and displayed a higher aggregation rate after their activation by thrombin compared with wild-type platelets. Consequently, human and mouse platelets express apelin and its receptor APJ. Apelin directly interferes with thrombin-mediated signaling pathways and platelet activation, secretion, and aggregation, but not with ADP and thromboxane A2-mediated pathways. IV apelin administration induced excessive bleeding and prevented thrombosis in mice. Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful adducts in antiplatelet therapies and may provide a promising perspective for patients who continue to display adverse thrombotic events with current antiplatelet therapies.

  18. Oxytocin and Aggression.

    PubMed

    de Jong, Trynke R; Neumann, Inga D

    2017-09-02

    The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

  19. Adolescents' aggression to parents: longitudinal links with parents' physical aggression.

    PubMed

    Margolin, Gayla; Baucom, Brian R

    2014-11-01

    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) and to investigate whether adolescents' emotion dysregulation and attitudes condoning child-to-parent aggression moderate associations. 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, and 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. 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 the effects. 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 an early signal of aggression into adulthood. Copyright

  20. 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

  1. Aggressive lymphoma in the elderly.

    PubMed

    Lichtman, S M

    2000-02-01

    Persons 65 years of age and older are the fastest growing segment of the United States population. Over the next 30 years they will comprise approximately 20% of the population. There will be a parallel rise in the number of patients with non-Hodgkin's lymphoma. Age has long been known to be an adverse prognostic factor. Clinical trials of older patients are complicated by the effect of comorbid illness, particularly its effect on overall survival. CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) remains the standard therapy for all patients with aggressive non-Hodgkin's lymphoma. There are a number of regimens which may be beneficial for older patients with significant comorbidity and poor performance status. The randomized trials in the elderly has reaffirmed CHOP and emphasize the need for adequate dosing, maintaining schedule and anthracyclines. Relapsed patients have a poor prognosis but selected fit older patients may benefit from aggressive reinduction regimens and possibly bone marrow transplantation. Future research should include defining the role of comorbidity, measurement of organ dysfunction and assessment of performance status with geriatric functional scales. New drug treatments should also be explored.

  2. How to treat splenic marginal zone lymphoma (SMZL) in patients unfit for surgery or more aggressive therapies: experience in 30 cases.

    PubMed

    Cervetti, Giulia; Ghio, Francesco; Cecconi, Nadia; Morganti, Riccardo; Galimberti, Sara; Petrini, Mario

    2017-04-01

    Splenic marginal zone lymphoma (SMZL) is an indolent disease that typically affects elderly patients. Thanks to its outcome, most patients don't need any specific therapy and 'a watch and wait' policy is frequently employed. Treatment is required in symptomatic cases. Splenectomy remains one of the first line options in patients fit for surgery. The best pharmacological strategy has not yet been identified for poor surgical risk cases. Amongst different possible chemotherapeutic approaches, alkylating agents, alone or in association with Rituximab, could employ in 'frail' patients. In the present study, the role of oral cyclophosphamide (100 mg per day for 15 consecutive days, every 30 for a total of six cycles) associated with anti-CD20 monoclonal antibody has been evaluated in 30 newly diagnosed SMZL patients, not fit for splenectomy or more toxic chemotherapic regimens. Overall response rate was 87% (CR 70%; PR 17%). Median PFS was 20 months (range, 1-53), with better outcome for low-risk cases according to IIL score prognostic index. Toxicity profile resulted mild.

  3. A preliminary assessment of factors associated with recurrent disease in a surgical adjuvant clinical trial for patients with breast cancer with special emphasis on the aggressiveness of therapy.

    PubMed

    Ahmann, D L; O'Fallon, J R; Scanlon, P W; Payne, W S; Bisel, H F; Edmonson, J H; Frytak, S; Hahn, R G; Ingle, J N; Rubin, J; Creagan, E T

    1982-08-01

    Two hundred ninety-three patients were randomly assigned to three treatment regimens following mastectomy for operable but prognostically unfavorable breast cancer: L-PAM, CFP, or CFP with radiation therapy. For premenopausal patients an increased risk of recurrence was associated with the presence of unfavorable local signs, large number of lymph nodes involved, greater body weight, younger age, and L-PAM treatment. For the postmenopausal patients only three factors were associated with an increased risk of recurrent disease: large tumor size, large number of lymph nodes involved, and inner/central location of the primary lesion. Specifically, the treatment employed has shown no effect. Of particular importance is the fact that for neither group of patients does our experience presently demonstrate clear association of recurrent disease with the level of drug dose administered. Furthermore, evidence suggests that although patients who experience little or no myelosuppression have significantly worse disease-free intervals than patients who experience moderate or severe myelosuppression, here is no benefit for severe myelosuppression over moderate, myelosuppression.

  4. Systematic review and network meta-analysis comparing antithrombotic agents for the prevention of stroke and major bleeding in patients with atrial fibrillation

    PubMed Central

    Cameron, Chris; Coyle, Doug; Richter, Trevor; Kelly, Shannon; Gauthier, Kasandra; Steiner, Sabine; Carrier, Marc; Coyle, Kathryn; Bai, Annie; Moulton, Kristen; Clifford, Tammy; Wells, George

    2014-01-01

    Objective To examine the comparative efficacy and safety of antithrombotic treatments (apixaban, dabigatran, edoxaban, rivaroxaban and vitamin K antagonists (VKA) at a standard adjusted dose (target international normalised ratio 2.0–3.0), acetylsalicylic acid (ASA), ASA and clopidogrel) for non-valvular atrial fibrillation and among subpopulations. Design Systematic review and network meta-analysis. Data sources A systematic literature search strategy was designed and carried out using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and the grey literature including the websites of regulatory agencies and health technology assessment organisations for trials published in English from 1988 to January 2014. Eligibility criteria for selecting studies Randomised controlled trials were selected for inclusion if they were published in English, included at least one antithrombotic treatment and involved patients with non-valvular atrial fibrillation eligible to receive anticoagulant therapy. Results For stroke or systemic embolism, dabigatran 150 mg and apixaban twice daily were associated with reductions relative to standard adjusted dose VKA, whereas low-dose ASA and the combination of clopidogrel plus low-dose ASA were associated with increases. Absolute risk reductions ranged from 6 fewer events per 1000 patients treated for dabigatran 150 mg twice daily to 15 more events for clopidogrel plus ASA. For major bleeding, edoxaban 30 mg daily, apixaban, edoxaban 60 mg daily and dabigatran 110 mg twice daily were associated with reductions compared to standard adjusted dose VKA. Absolute risk reductions with these agents ranged from 18 fewer per 1000 patients treated each year for edoxaban 30 mg daily to 24 more for medium dose ASA. Conclusions Compared with standard adjusted dose VKA, new oral anticoagulants were associated with modest reductions in the absolute risk of stroke and major bleeding. People on antiplatelet drugs experienced more

  5. Developing a novel antithrombotic in the academic environment.

    PubMed

    Hirsh, J

    2001-04-01

    In recent years, academic research institutions have increasingly sought to commercialize their discoveries, providing the opportunity to raise venture capital and benefit financially from their developments. In the last 6 years, Hamilton Civic Hospitals Research Center, affiliated with McMaster University, Ontario, Canada, has set up two companies, Vascular Therapeutics and Osteokine, to commercialize its discoveries in thrombosis and osteoporosis. Epidemiological evidence shows a continuing socioeconomic burden of both of these disorders, thereby offering opportunities for new drug development. Key areas in the field of thrombosis include novel parenteral anticoagulants to replace heparin as adjunctive therapy in acute coronary syndromes, safer and more practical oral anticoagulants that do not require monitoring to replace coumarins, and oral antiplatelet drugs for use in combination with aspirin. Since their creation, Vascular Therapeutics and Osteokine have attracted major funding and developed several patentable compounds that show clinical and commercial promise. Copyright 2001 by W.B. Saunders Company.

  6. 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

  7. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma.

    PubMed

    Locke, Frederick L; Neelapu, Sattva S; Bartlett, Nancy L; Siddiqi, Tanya; Chavez, Julio C; Hosing, Chitra M; Ghobadi, Armin; Budde, Lihua E; Bot, Adrian; Rossi, John M; Jiang, Yizhou; Xue, Allen X; Elias, Meg; Aycock, Jeff; Wiezorek, Jeff; Go, William Y

    2017-01-04

    Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m(2)) and fludarabine (30 mg/m(2)) for 3 days followed by KTE-C19 at a target dose of 2 × 10(6) CAR T cells/kg. The incidence of dose-limiting toxicity (DLT) was the primary endpoint. Seven patients were treated with KTE-C19 and one patient experienced a DLT of grade 4 cytokine release syndrome (CRS) and neurotoxicity. Grade ≥3 CRS and neurotoxicity were observed in 14% (n = 1/7) and 57% (n = 4/7) of patients, respectively. All other KTE-C19-related grade ≥3 events resolved within 1 month. The overall response rate was 71% (n = 5/7) and complete response (CR) rate was 57% (n = 4/7). Three patients have ongoing CR (all at 12+ months). CAR T cells demonstrated peak expansion within 2 weeks and continued to be detectable at 12+ months in patients with ongoing CR. This regimen of KTE-C19 was safe for further study in phase 2 and induced durable remissions in patients with refractory DLBCL. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Response-adapted therapy for aggressive non-Hodgkin's lymphomas based on early [18F] FDG-PET scanning: ECOG-ACRIN Cancer Research Group study (E3404).

    PubMed

    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

    2015-07-01

    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 three 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 four cycles of R-ICE, PET-negative patients received two 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.

  9. A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

    PubMed

    Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

    2014-06-01

    Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

  10. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

    Saylor, Keith E; Amann, Birgit H

    2016-02-01

    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. 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. 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. 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 aggressive behaviors do not remit with primary ADHD therapy

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. Aggressiveness and Disobedience

    ERIC Educational Resources Information Center

    Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling

    2011-01-01

    This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…

  17. School Interventions for Aggression.

    ERIC Educational Resources Information Center

    Shapiro, Edward S.; Derr, Tami F.

    1987-01-01

    The scope and incidence of school-based aggression, specifically physical and verbal assault, are noted. Interventions discussed include: contingency management (reinforcement, ignoring, response cost, timeout, peer procedures, and aversive consequences) and self-management procedures (social skills training, problem-solving training, and…

  18. Success, Failure, and Aggression.

    ERIC Educational Resources Information Center

    Harris, Mary B.; Fisher, Judith L.

    In order to discover the effects of success and failure on subsequent aggressiveness, 26 male and 55 female college students were randomly assigned to success, failure, and neutral conditions. Those in the success condition were led to feel they were superior to other college students on a task, those in the failure condition were led to feel they…

  19. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  20. Aggressiveness and Disobedience

    ERIC Educational Resources Information Center

    Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling

    2011-01-01

    This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…

  1. 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…

  2. Long-term prognosis in patients continuing taking antithrombotics after peptic ulcer bleeding

    PubMed Central

    Wang, Xi-Xu; Dong, Bo; Hong, Biao; Gong, Yi-Qun; Wang, Wei; Wang, Jue; Zhou, Zhen-Yu; Jiang, Wei-Jun

    2017-01-01

    AIM To investigate the long-term prognosis in peptic ulcer patients continuing taking antithrombotics after ulcer bleeding, and to determine the risk factors that influence the prognosis. METHODS All clinical data of peptic ulcer patients treated from January 1, 2009 to January 1, 2014 were retrospectively collected and analyzed. Patients were divided into either a continuing group to continue taking antithrombotic drugs after ulcer bleeding or a discontinuing group to discontinue antithrombotic drugs. The primary outcome of follow-up in peptic ulcer bleeding patients was recurrent bleeding, and secondary outcome was death or acute cardiovascular disease occurrence. The final date of follow-up was December 31, 2014. Basic demographic data, complications, and disease classifications were analyzed and compared by t- or χ2-test. The number of patients that achieved various outcomes was counted and analyzed statistically. A survival curve was drawn using the Kaplan-Meier method, and the difference was compared using the log-rank test. COX regression multivariate analysis was applied to analyze risk factors for the prognosis of peptic ulcer patients. RESULTS A total of 167 patients were enrolled into this study. As for the baseline information, differences in age, smoking, alcohol abuse, and acute cardiovascular diseases were statistically significant between the continuing and discontinuing groups (70.8 ± 11.4 vs 62.4 ± 12.0, P < 0.001; 8 (8.2%) vs 15 (21.7%), P < 0.05; 65 (66.3%) vs 13 (18.8%), P < 0.001). At the end of the study, 18 patients had recurrent bleeding and three patients died or had acute cardiovascular disease in the continuing group, while four patients had recurrent bleeding and 15 patients died or had acute cardiovascular disease in the discontinuing group. The differences in these results were statistically significant (P = 0.022, P = 0.000). The Kaplan-Meier survival curve indicated that the incidence of recurrent bleeding was higher in patients

  3. Association Between Use of Antithrombotic Medication and Hematuria-Related Complications.

    PubMed

    Wallis, Christopher J D; Juvet, Tristan; Lee, Yuna; Matta, Rano; Herschorn, Sender; Kodama, Ronald; Kulkarni, Girish S; Satkunasivam, Raj; Geerts, William; McLeod, Anne; Narod, Steven A; Nam, Robert K

    2017-10-03

    Antithrombotic medications are among the most commonly prescribed medications. To characterize rates of hematuria-related complications among patients taking antithrombotic medications. Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. Receipt of an oral anticoagulant or antiplatelet medication. Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. Among 2 518 064 patients, 808 897 (mean [SD] age, 72.1 [6.8] years; 428 531 [53%] women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio [IRR], 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. Antithrombotic effects of PAR1 and PAR4 antagonists evaluated under flow and static conditions.

    PubMed

    Hosokawa, Kazuya; Ohnishi, Tomoko; Miura, Naoki; Sameshima, Hisayo; Koide, Takehiko; Tanaka, Kenichi A; Maruyama, Ikuro

    2014-01-01

    Thrombin-mediated activation of human platelets involves the G-protein-coupled protease-activated receptors PAR1 and PAR4. Inhibition of PAR1 and/or PAR4 is thought to modulate platelet activation and subsequent procoagulant reactions. However, the antithrombotic effects of PAR1 and PAR4 antagonism have not been fully elucidated, particularly under flow conditions. A microchip-based flow chamber system was used to evaluate the influence of SCH79797 (PAR1 antagonist) and YD-3 (PAR4 antagonist) on thrombus formation mediated by collagen and tissue thromboplastin at shear rates simulating those experienced in small- to medium-sized arteries (600s(-1)) and large arteries and small veins (240s(-1)). At a shear rate of 600s(-1), SCH79797 (10μM) efficiently reduced fibrin-rich platelet thrombi and significantly delayed occlusion of the flow chamber capillary (1.44 fold of control; P<0.001). The inhibitory activity of SCH79797 was diminished at 240s(-1). YD-3 (20μM) had no significant effect at either shear rate. The antithrombotic effects of SCH79797 were significantly augmented when combined with aspirin and AR-C66096 (P2Y12 antagonist), but not with YD-3. In contrast, no significant inhibition of tissue factor-induced clot formation under static conditions was observed in blood treated with SCH79797 and YD-3, although thrombin generation in platelet-rich plasma was weakly delayed by these antagonists. Our results suggest that the antithrombotic activities of PAR1 and/or PAR4 antagonism is influenced by shear conditions as well as by combined platelet inhibition with aspirin and a P2Y12-antagonist. © 2013.

  9. ANTITHROMBOTIC PROPERTIES OF IXOLARIS, A POTENT INHIBITOR OF THE EXTRINSIC PATHWAY OF THE COAGULATION CASCADE

    PubMed Central

    Nazareth, Rômulo A.; Tomaz, Luana S.; Ortiz-Costa, Susana; Atella, Geórgia C.; Ribeiro, José M. C.; Francischetti, Ivo M. B.; Monteiro, Robson Q.

    2010-01-01

    Summary Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents extensive sequence homology to TFPI. It binds to FXa or FX as scaffolds and inhibits extrinsic Xnase. Differently from TFPI, however, Ixolaris does not bind to the active site cleft of FXa. Instead, complex formation is mediated by the FXa heparin-binding exosite, which may also results in decreased FXa activity into the prothrombinase complex. In this report, we show that recombinant 125I-Ixolaris interacts with rat and human FX in plasma and prolongs the prothrombin time (PT) and activated partial thromboplastin time (aPTT) in vitro. We have also investigated the effects of Ixolaris in vivo, using a venous thrombosis model. Subcutaneous (s.c.) or intravenous (i.v.) administration of Ixolaris in rats causes a dose-dependent reduction in thrombus formation, with complete inhibition attained at 20 μg/kg and 10 μg/kg, respectively. Remarkably, antithrombotic effects were observed 3 h after s.c. administration of Ixolaris and lasted for 24 h thereafter. Ex vivo experiments also showed that Ixolaris (up to 100 μg/kg) did not affect the aPTT, while the PT was increased by ~0.4-fold at the highest Ixolaris concentration. Remarkably, effective antithrombotic doses of Ixolaris (20 μg/Kg) was not associated with bleeding which was significant only at higher doses of the anticoagulant (40 μg/Kg). Our experiments demonstrate that Ixolaris is an effective and possibly safe antithrombotic agent in vivo. PMID:16807644

  10. Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

    PubMed

    Malhotra, Konark; Khunger, Monica; Ouyang, Bichun; Liebeskind, David S; Mohammad, Yousef M

    2016-01-01

    Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS). This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke. Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke. Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke.

  11. Evaluation of antithrombotic activity of thrombin DNA aptamers by a murine thrombosis model.

    PubMed

    Zavyalova, Elena; Samoylenkova, Nadezhda; Revishchin, Alexander; Golovin, Andrey; Pavlova, Galina; Kopylov, Alexey

    2014-01-01

    Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are among them. RA-36, the 31-meric DNA aptamer, consists of two thrombin binding pharmacophores joined with the thymine linker. It has been shown earlier that RA-36 directly inhibits thrombin in the reaction of fibrinogen hydrolysis, and also it inhibits plasma and blood coagulation. Studies of both inhibitory and anticoagulation effects had indicated rather high species specificity of the aptamer. Further R&D of RA-36 requires exploring its efficiency in vivo. Therefore the development of a robust and adequate animal model for effective physiological studies of aptamers is in high current demand. This work is devoted to in vivo study of the antithrombotic effect of RA-36 aptamer. A murine model of thrombosis has been applied to reveal a lag and even prevention of thrombus formation when RA-36 was intravenous bolus injected in high doses of 1.4-7.1 µmol/kg (14-70 mg/kg). A comparative study of RA-36 aptamer and bivalirudin reveals that both direct thrombin inhibitors have similar antithrombotic effects for the murine model of thrombosis; though in vitro bivalirudin has anticoagulation activity several times higher compared to RA-36. The results indicate that both RA-36 aptamer and bivalirudin are direct thrombin inhibitors of different potency, but possible interactions of the thrombin-inhibitor complex with other components of blood coagulation cascade level the physiological effects for both inhibitors.

  12. Evaluation of Antithrombotic Activity of Thrombin DNA Aptamers by a Murine Thrombosis Model

    PubMed Central

    Zavyalova, Elena; Samoylenkova, Nadezhda; Revishchin, Alexander; Golovin, Andrey; Pavlova, Galina; Kopylov, Alexey

    2014-01-01

    Aptamers are nucleic acid based molecular recognition elements with a high potential for the theranostics. Some of the aptamers are under development for therapeutic applications as promising antithrombotic agents; and G-quadruplex DNA aptamers, which directly inhibit the thrombin activity, are among them. RA-36, the 31-meric DNA aptamer, consists of two thrombin binding pharmacophores joined with the thymine linker. It has been shown earlier that RA-36 directly inhibits thrombin in the reaction of fibrinogen hydrolysis, and also it inhibits plasma and blood coagulation. Studies of both inhibitory and anticoagulation effects had indicated rather high species specificity of the aptamer. Further R&D of RA-36 requires exploring its efficiency in vivo. Therefore the development of a robust and adequate animal model for effective physiological studies of aptamers is in high current demand. This work is devoted to in vivo study of the antithrombotic effect of RA-36 aptamer. A murine model of thrombosis has been applied to reveal a lag and even prevention of thrombus formation when RA-36 was intravenous bolus injected in high doses of 1.4–7.1 µmol/kg (14–70 mg/kg). A comparative study of RA-36 aptamer and bivalirudin reveals that both direct thrombin inhibitors have similar antithrombotic effects for the murine model of thrombosis; though in vitro bivalirudin has anticoagulation activity several times higher compared to RA-36. The results indicate that both RA-36 aptamer and bivalirudin are direct thrombin inhibitors of different potency, but possible interactions of the thrombin-inhibitor complex with other components of blood coagulation cascade level the physiological effects for both inhibitors. PMID:25192011

  13. Interaction of incidental microbleeds and prior use of antithrombotics with early hemorrhagic transformation: Causative or protective?

    PubMed Central

    Malhotra, Konark; Khunger, Monica; Ouyang, Bichun; Liebeskind, David S.; Mohammad, Yousef M.

    2016-01-01

    Background: Gradient echo (GRE) sequence of magnetic resonance imaging (MRI) is a sensitive tool to detect hemorrhagic transformation (HT) and old cerebral microbleeds (CMBs). Presence of CMBs and prior use of antithrombotics pose a risk of HT in ischemic stroke. We evaluated the association of CMBs and antithrombotic use with resultant HT in acute ischemic stroke (AIS). Methods: This retrospective study included AIS patients admitted to our center between January 2009 and August 2010 who underwent GRE-weighted MRI within 48 h of admission. Demographic and clinical data including diabetes mellitus, hypertension, hyperlipidemia, prior intake of antiplatelets/anticoagulants/statins, and presence of CMBs at admission were collected and compared between patients who developed HT and those who did not. We did a multivariate analysis using logistic regression to assess the effect of CMBs and prior use of antithrombotic agents on the risk of development for early HT in ischemic stroke. Results: Of 529 AIS patients, 81 (15%) were found to have HT during the initial hospital course. CMBs were found in only 9 of 81 patients (11%) with HT and in 40 out of remaining 448 patients (9%) who did not develop HT. The presence of CMBs was not associated with increased risk of HT (P = 0.53). However, prior use of antiplatelets (33% vs. 47% in the patients without HT, P = 0.02) was associated with decreased risk of HT in ischemic stroke. Conclusion: Presence of incidental CMBs was not associated with increased risk for early HT of an ischemic stroke. Interestingly, the prior intake of antiplatelets was found to be protective against HT of ischemic stroke. PMID:27994355

  14. 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

  15. 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

  16. rt-PA with Antithrombotic Therapies in a Case with Capsular Warning Syndrome

    PubMed Central

    Fuseya, Yasuhiro; Kawamura, Miyuki; Matsuda, Eri; Takada, Kozue; Watanabe, Kiwamu; Fujitake, Junko; Nakaya, Yoshifumi

    2017-01-01

    We herein report a case of capsular warning syndrome (CWS) that was successfully treated with recombinant tissue plasminogen activator (rt-PA). A 70-year-old woman had repeated stereotyped transient ischemic attacks (TIAs) of right hemiparesis and dysarthria. After hospitalization, argatroban, aspirin, and cilostazol were started but were ineffective. Thirteen hours after the first episode of TIAs, severe symptoms occurred. Magnetic resonance imaging showed acute infarctions in the internal capsule to corona radiata, so we used rt-PA. Since then, the TIAs have not occurred, and the symptoms have considerably improved. This case suggests that rt-PA might be effective and safe for use in treating CWS. PMID:28202868

  17. Evaluation of surgery risk factor associated to antithrombotic therapy in patients who underwent colorectal surgery.

    PubMed

    Del Rio, Paolo; Sozzi, Francesco; Bertocchi, Elisa; Dell'Abate, Paolo; Perrone, Gennaro; Arcuri, Maria Francesca; Sianesi, Mario

    2016-01-01

    I trattamenti antipiastrinici sono comuni nel mondo occidentale ed il rischio di sanguinamento correlato a procedure chirurgiche o comunque invasive è di conseguenza elevato e pertanto abbiamo volute analizzare la correlazione tra la chirurgia del colon.retto ,la terapia antipiastrinica e le complicanze chirurgiche postoperatorie. Sono stati studiati 176 pazienti operati per tumori del colon-retto considerando i seguenti dati:tipo di intervento xchirurgico,l’indice di massa corporea (BMI), il valore dell’emoglobina (Hb); PT preoperatorio e le trasfusioni di sangue pre epost-operatorie e durante lo stesso intervento chirurgico. L’analisi si è concentrata su due gruppi :pazienti sottoposti a trattamento antipiastrinico (ATterapia antiaggregante) e pazienti non trattati ( NAT: non terapia antiaggregante piastrinica). Nei gruppi di pazienti sottoposti a emicolectomia destra, i valori di emoglobina erano più bassi neri pazienti che hanno ricevuto la terapia antitrombotica rispetto ai pazienti che non hanno ricevuto questa terapia, con una significatività statistica (p <0,05); dati analoghi sono stati osservati nei pazienti sottoposti a emicolectomia sinistra. I pazienti dipeso normale trattati con terapia antiaggregante avevano valori più bassi di emoglobina senza significatività statistica (valore di p non significativo). I pazienti in sovrappeso sottoposti a trattamento antiaggregante hanno presentato valori di Hb inferiori a quelli non trattati (p < 0,05). La percentuale di emotrasfusioneè risultata maggiore nei pazienti sottoposti a trattamento antiaggregante (AT) a prescindere dal tipo di interveno chirurgico rispetto al secondo gruppo con significatività statistica. Tra i pazienti normopeso si è registrata una diversa incidenza di trasfusione di sangue nei pazienti trattati con AT (50%) e quelli non trattati (29%) con un significato statistico (p <0,05), mentre i pazienti in sovrappeso non hanno presenato questa significativa differenza. È stata analizzata l’incidenza di complicanze post-operatorie in pazienti di peso normale e pazienti in sovrappeso e abbiamo rilevato l’incidenza di complicanze ,sia minori che maggiori, è stata più alta nei pazienti sottoposti terapia antiaggregante rispetto al secondo grippo indipendentemente dal peso. In conclusione, la terapia antiaggregante in pazienti sottoposti ad interventi chirurgici invasivi cambia l’incidenza di alcuni fattori di rischio, cone il sanguinamento e le complicanze post-operatorie.Questo risultato sottolinea l’importanza di una corretta manipolazione e preparazione nei pazienti trattai con agenti antitreombotici che devono subire un intervento chirurgico invasivo.

  18. The Antithrombotic Effect of Angiotensin-(1–7) Involves Mas-Mediated NO Release from Platelets

    PubMed Central

    Fraga-Silva, Rodrigo Araújo; Pinheiro, Sergio Veloso Brant; Gonçalves, Andrey Christian Costa; Alenina, Nathalia; Bader, Michael; Santos, Robson Augusto Souza

    2008-01-01

    The antithrombotic effect of angiotensin(Ang)-(1–7) has been reported, but the mechanism of this effect is not known. We investigated the participation of platelets and receptor Mas-related mechanisms in this action. We used Western blotting to test for the presence of Mas protein in rat platelets and used fluorescent-labeled FAM-Ang-(1–7) to determine the specific binding for Ang-(1–7) and its displacement by the receptor Mas antagonist A-779 in rat platelets and in Mas−/ − and Mas+/+ mice platelets. To test whether Ang-(1–7) induces NO release from platelets, we used the NO indicator DAF-FM. In addition we examined the role of Mas in the Ang-(1–7) antithrombotic effect on induced thrombi in the vena cava of male Mas−/ − and Mas+/+ mice. The functional relevance of Mas in hemostasis was evaluated by determining bleeding time in Mas+/+ and Mas−/ − mice. We observed the presence of Mas protein in platelets, as indicated by Western Blot, and displacement of the binding of fluorescent Ang-(1–7) to rat platelets by A-779. Furthermore, in Mas+/+ mouse platelets we found specific binding for Ang-(1–7), which was absent in Mas−/ − mouse platelets. Ang-(1–7) released NO from rat and Mas+/+ mouse platelets, and A-779 blocked this effect. The NO release stimulated by Ang-(1–7) was abolished in Mas−/ − mouse platelets. Ang-(1–7) inhibited thrombus formation in Mas+/+ mice. Strikingly, this effect was abolished in Mas−/ −mice. Moreover, Mas deficiency resulted in a significant decrease in bleeding time (8.50 ± 1.47 vs. 4.28 ± 0.66 min). This study is the first to show the presence of Mas protein and specific binding for Ang-(1–7) in rat and mouse platelets. Our data also suggest that the Ang-(1–7) antithrombotic effect involves Mas-mediated NO release from platelets. More importantly, we showed that the antithrombotic effect of Ang-(1–7) in vivo is Mas dependent and that Mas is functionally important in hemostasis. PMID

  19. Antithrombotic activity of fractions and components obtained from raspberry leaves (Rubus chingii).

    PubMed

    Han, Na; Gu, Yuhong; Ye, Chun; Cao, Yan; Liu, Zhihui; Yin, Jun

    2012-05-01

    The 70% ethanol fraction from an aqueous extract of raspberry leaves was shown to be the most antithrombotic fraction in in vitro and in vivo tests. The total flavonoids and phenolics in this fraction were 0.286g/g and 0.518g/g by colorimetry. Six compounds, including salicylic acid, kaempferol, quercetin, tiliroside, quercetin 3-O-β-d-glucopyranoside and kaempferol 3-O-β-d-glucopyranoside, were isolated from the active fraction. Among them, kaempferol, quercetin and tiliroside obviously delayed plasma recalcification time (PRT) in blood.

  20. Serotonin and Aggressiveness in Chickens

    USDA-ARS?s Scientific Manuscript database

    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 ...

  1. 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

  2. Regional differences in presentation and antithrombotic treatment of patients with atrial fibrillation: Baseline characteristics from a clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with atrial fibrillation (IMPACT-AF).

    PubMed

    Vinereanu, Dragos; Al-Khalidi, Hussein R; Rao, Meena P; He, Wensheng; Lopes, Renato D; Bahit, Cecilia M; Ciobanu, Andrea O; Fox, Kathleen A; Pokorney, Sean D; Xian, Ying; Jiang, Jie; Kamath, Deepak Y; Berwanger, Otavio; Tajer, Carlos; Huo, Yong; Xavier, Denis; Granger, Christopher B

    2017-10-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there are few contemporary comparative data on AF from middle-income countries. Baseline characteristics of the IMPACT-AF trial were analyzed to assess regional differences in presentation and antithrombotic treatment of AF from 5 middle-income countries (Argentina, Brazil, China, India, and Romania) and factors associated with antithrombotic treatment prescription. IMPACT-AF enrolled 2281 patients (69 ± 11 years, 47% women) at 48 sites. Overall, 66% of patients were on anticoagulation at baseline, ranging from 38% in China to 91% in Brazil. The top 3 reasons for not prescribing an anticoagulant were patient preference/refusal (26%); concomitant antiplatelet therapy (15%); and risks outweighing the benefits, as assessed by the physician (13%). In a multivariable model, the most significant factors associated with prescription of oral anticoagulants were no prior major bleeding (odds ratio [OR] = 4.34; 95% CI = 2.22-8.33), no alcohol abuse (OR = 2.27; 95% CI = 1.12-4.55), and history of rheumatic valvular heart disease (OR = 2.10; 95% CI = 1.36-3.26), with a strong predictive accuracy (c statistic = 0.85), whereas the most significant factors associated with prescription of a combination of oral anticoagulants and antiplatelet drugs were prior coronary revascularization (OR = 5.10; 95% CI = 2.88-9.05), prior myocardial infarction (OR = 2.24; 95% CI = 1.38-3.63), and no alcohol abuse (OR = 2.22; 95% CI = 1.11-4.55), with a good predictive accuracy (c statistic = 0.76). IMPACT-AF provides contemporary data from 5 middle-income countries regarding antithrombotic treatment of AF. Lack of prior major bleeding and coronary revascularization were the most important factors associated with prescription of oral anticoagulants and their combination with antiplatelet drugs, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille.

    PubMed

    Choi, Jun-Hui; Kim, Dae-Won; Park, Se-Eun; Lee, Hyo-Jeong; Kim, Ki-Man; Kim, Kyung-Je; Kim, Myung-Kon; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.

  4. Antiplatelet and Antithrombotic Effects of the Extract of Lindera obtusiloba Leaves

    PubMed Central

    Kim, Jun Ho; Lee, Jaemin; Kang, Soouk; Moon, Hongsik; Chung, Kyung Ho; Kim, Kyoung Rak

    2016-01-01

    Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity. PMID:27302963

  5. Discovery of novel protease activated receptors 1 antagonists with potent antithrombotic activity in vivo.

    PubMed

    Perez, Michel; Lamothe, Marie; Maraval, Catherine; Mirabel, Etienne; Loubat, Chantal; Planty, Bruno; Horn, Clemens; Michaux, Julien; Marrot, Sebastien; Letienne, Robert; Pignier, Christophe; Bocquet, Arnaud; Nadal-Wollbold, Florence; Cussac, Didier; de Vries, Luc; Le Grand, Bruno

    2009-10-08

    Protease activated receptors (PARs) or thrombin receptors constitute a class of G-protein-coupled receptors (GPCRs) implicated in the activation of many physiological mechanisms. Thus, thrombin activates many cell types such as vascular smooth muscle cells, leukocytes, endothelial cells, and platelets via activation of these receptors. In humans, thrombin-induced platelet aggregation is mediated by one subtype of these receptors, termed PAR1. This article describes the discovery of new antagonists of these receptors and more specifically two compounds: 2-[5-oxo-5-(4-pyridin-2-ylpiperazin-1-yl)penta-1,3-dienyl]benzonitrile 36 (F 16618) and 3-(2-chlorophenyl)-1-[4-(4-fluorobenzyl)piperazin-1-yl]propenone 39 (F 16357), obtained after optimization. Both compounds are able to inhibit SFLLR-induced human platelet aggregation and display antithrombotic activity in an arteriovenous shunt model in the rat after iv or oral administration. Furthermore, these compounds are devoid of bleeding side effects often observed with other types of antiplatelet drugs, which constitutes a promising advantage for this new class of antithrombotic agents.

  6. Dragon's Blood extract has antithrombotic properties, affecting platelet aggregation functions and anticoagulation activities.

    PubMed

    Xin, Nian; Li, Yu-Juan; Li, Yan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Schlappi, Michael; Deng, Yu-Lin

    2011-05-17

    Dragon's Blood from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China), as a traditional Chinese medicinal herb, was shown to have certain antithrombotic effects. A new preparation process was used to extract effective components from Dragon's Blood. A 95% ethanol extract A (EA) and a precipitate B (PB) fraction were obtained and compared. Reliability of the preparation process was validated by pharmacodynamic experiments. A rat/mouse thrombosis and blood stasis model was developed for this study, and EA and PB effects on thrombosis, platelet functions and blood coagulation activities were analyzed. It was observed that the EA fraction had significantly better inhibitory effects than the PB fraction on thrombosis (p<0.05), platelet aggregation function (p<0.01) and anticoagulation activity (p<0.05-0.01). The results obtained here showed that EA fraction from Dragon's Blood contained pharmacologically effective compounds with antithrombotic effects, partially improving platelet function and anticoagulation activity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  7. Novel antiplatelet and antithrombotic activities of essential oil from Lavandula hybrida Reverchon "grosso".

    PubMed

    Ballabeni, V; Tognolini, M; Chiavarini, M; Impicciatore, M; Bruni, R; Bianchi, A; Barocelli, E

    2004-11-01

    Lavender extracts are known to produce several mild effects at central and peripheral level. However, no studies are so far available about the potential effects of lavender essential oil on the hemostatic system. In this work, we demonstrated antiplatelet properties of lavender oil towards platelet aggregation induced by arachidonic acid, U46619, collagen and ADP (IC50 = 51, 84, 191 and 640 microg/ml, respectively) on guinea-pig platelet rich plasma (PRP) and its ability to destabilize clot retraction (IC50 = 149 microg/ml) induced by thrombin on rat PRP. Furthermore, antithrombotic properties were studied in an in vivo model of pulmonary thromboembolism induced by intravenous injection of a collagen-epinephrine mixture in mice subacutely treated with lavender oil. In this model, lavender oil (100 mg/kg/day os for 5 days) significantly reduced thrombotic events without inducing prohemorrhagic complications at variance with acetylsalicylic acid used as reference drug. Finally, main components of the oil were studied in vitro in order to assess their antiplatelet effects, but none of them possessed an activity comparable to the oil itself. These results provide the first experimental evidence of lavender oil's antiplatelet/antithrombotic properties which could be due to a synergistic effect of its components.

  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. A newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effects.

    PubMed

    Omura, Kazunobu; Hitosugi, Masahito; Zhu, Xia; Ikeda, Masashi; Maeda, Hiroaki; Tokudome, Shogo

    2005-11-01

    Natto, steamed soybeans fermented by Bacillus subtilis natto, is a traditional Japanese food. We derived a purified protein layer, called NKCP as a trade mark, from B. subtilis natto fermentation. In the present study, we examined the fibrinolytic and antithrombotic effects of NKCP and identified its active component to clarify the fibrinolytic effect of NKCP observed in preliminary clinical trials previously. The active component of NKCP was identified as a 34-kilodalton protein designated bacillopeptidase F. NKCP showed direct degradation of artificial blood clot in saline. The protease activity, accounting for the fibrinolytic effect of NKCP, was examined with a chromogenic substrate for plasmin. Dose-dependent prolongations of both prothrombin time and active partial thromboplastin time were observed in rats with intra-duodenum administration of NKCP. Our in vitro and in vivo studies suggest that NKCP has both a fibrinolytic effect and an antithrombotic effect similar to heparin. Because NKCP is derived from food and has safety data demonstrated by previous animal experiments and preliminary clinical trials, NKCP is considered as safe for clinical use.

  10. 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

  11. 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

  12. 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…

  13. Effects of external incentive and aggressive predisposition on aggression reduction.

    PubMed

    Fitz, D; Kimble, C; Heidenfelder, K

    1979-09-01

    Female undergraduates (N = 40) received four counteraggression strategies (0%, 10%, 50%, and 150% retaliation) in response to their aggression in a complex reaction time task. They either were or were not offered a monetary incentive to beat their opponent and were divided into those low and high in their initial predisposition to aggression. Four major findings resulted: 1) escalation of aggression to 150% retaliation supported reciprocity over contingent punishment theory. 2) Ss low in aggression were unaffected by strategies, rather than being most responsive to pacifism, as predicted. 3) Ss high in aggression reduced their aggression most to the intermediate 10% and 50% retaliation strategies. 4) An external (monetary) incentive for beating the opponent did not parallel the aggressiveness personality factor as expected. The external incentive reduced the difference between low and high aggression participants and resulted in a linear relationship between retaliation strategy and aggression reduction. This is the first study showing minimum (10%) retaliation to be more effective than pacifism (0% retaliation), but the effect occurred only among the 25% most aggressive Ss when there was no monetary incentive.

  14. Improved outcomes with European Society of Cardiology guideline-adherent antithrombotic treatment in high-risk patients with atrial fibrillation: a report from the EORP-AF General Pilot Registry.

    PubMed

    Lip, Gregory Y H; Laroche, Cécile; Popescu, Mircea Iaochim; Rasmussen, Lars Hvilsted; Vitali-Serdoz, Laura; Dan, Gheorghe-Andrei; Kalarus, Zbigniew; Crijns, Harry J G M; Oliveira, Mario Martins; Tavazzi, Luigi; Maggioni, Aldo P; Boriani, Giuseppe

    2015-12-01

    Guideline-adherent therapy for stroke prevention in atrial fibrillation has been associated with better outcomes, in terms of thromboembolism (TE) and bleeding. In this report from the EuroObservational Research Programme-Atrial Fibrillation (EORP-AF) Pilot General Registry, we describe the associated baseline features of 'high risk' AF patients in relation to guideline-adherent antithrombotic treatment, i.e. whether they were adherent, over-treated, or under-treated based on the 2012 European Society of Cardiology (ESC) guidelines. Secondly, we assessed the predictors of guideline-adherent antithrombotic treatment. Thirdly, we evaluated outcomes for all-cause mortality, TE, bleeding, and the composite endpoint of 'any TE, cardiovascular death or bleeding' in relation to whether they were ESC guideline-adherent treatment. From the EORP-AF cohort, the follow-up dataset of 2634 subjects was used to assess the impact of guideline adherence or non-adherence. Of these, 1602 (60.6%) were guideline adherent, whilst 458 (17.3%) were under-treated, and 574 (21.7%) were over-treated. Non-guideline-adherent treatment can be related to region of Europe as well as associated clinical features, but not age, AF type, symptoms, or echocardiography indices. Over-treatment per se was associated with symptoms, using the EHRA score, as well as other comorbidities. Guideline-adherent antithrombotic management based on the ESC guidelines is associated with significantly better outcomes. Specifically, the endpoint of 'all cause death and any TE' is increased by >60% by undertreatment [hazard ratio (HR) 1.679 (95% confidence interval (CI) 1.202-2.347)] or over-treatment [HR 1.622 (95% CI 1.173-2.23)]. For the composite endpoint of 'cardiovascular death, any TE or bleeding', over-treatment increased risk by >70% [HR 1.722 (95% CI 1.200-2.470)]. Even in this cohort with high overall rates of oral anticoagulation use, ESC guideline-adherent antithrombotic management is associated with

  15. A Novel Role of Eruca sativa Mill. (Rocket) Extract: Antiplatelet (NF-κB Inhibition) and Antithrombotic Activities

    PubMed Central

    Fuentes, Eduardo; Alarcón, Marcelo; Fuentes, Manuel; Carrasco, Gilda; Palomo, Iván

    2014-01-01

    Background: Epidemiological studies have shown the prevention of cardiovascular diseases through the regular consumption of vegetables. Eruca sativa Mill., commonly known as rocket, is a leafy vegetable that has anti-inflammatory activity. However, its antiplatelet and antithrombotic activities have not been described. Methods: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL), was evaluated on human platelets: (i) P-selectin expression by flow cytometry; (ii) platelet aggregation induced by ADP, collagen and arachidonic acid; (iii) IL-1β, TGF-β1, CCL5 and thromboxane B2 release; and (iv) activation of NF-κB and PKA by western blot. Furthermore, (v) antithrombotic activity (200 mg/kg) and (vi) bleeding time in murine models were evaluated. Results: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL) inhibited P-selectin expression and platelet aggregation induced by ADP. The release of platelet inflammatory mediators (IL-1β, TGF-β1, CCL5 and thromboxane B2) induced by ADP was inhibited by Eruca sativa Mill. aqueous extract. Furthermore, Eruca sativa Mill. aqueous extract inhibited NF-κB activation. Finally, in murine models, Eruca sativa Mill. aqueous extract showed significant antithrombotic activity and a slight effect on bleeding time. Conclusion: Eruca sativa Mill. presents antiplatelet and antithrombotic activity. PMID:25514563

  16. Prognostic correlation of cell cycle progression score and Ki-67 as a predictor of aggressiveness, biochemical failure, and mortality in men with high-risk prostate cancer treated with external beam radiation therapy.

    PubMed

    López, Iván Henríquez; Parada, David; Gallardo, Pablo; Gascón, Marina; Besora, Arnau; Peña, Karla; Riu, Francesc; Arquez Pianetta, Miquel; Abuchaibe, Oscar; Torres Royò, Laura; Arenas, Meritxell

    2017-01-01

    Ki-67 is a proliferation marker in prostate cancer. A prognostic RNA signature was developed to characterize prostate cancer aggressiveness. The aim was to evaluate prognostic correlation of CCP and Ki-67 with biochemical failure (BF), and survival in high-risk prostate cancer patients (pts) treated with radiation therapy (RT). CCP score and Ki-67 were derived retrospectively from pre-treatment paraffin-embedded prostate cancer tissue of 33 men diagnosed from 2002 to 2006. CCP score was calculated as an average expression of 31 CCP genes. Ki-67 was determined by IHC. Single pathologist evaluated all tissues. Factors associated to failure and survival were analyzed. Median CCP score was 0.9 (-0-1 - 2.6). CCP 0: 1 pt; CCP 1: 19 pts; CCP 2: 13 pts. Median Ki-67 was 8.9. Ki-67 cutpoint was 15.08%. BF and DSM were observed in 21% and 9%. Ki-67 ≥ 15% predicted BF (p = 0.043). With a median follow-up of 8.4 years, 10-year BF, OS, DM and DSM for CCP 1 vs. CCP 2 was 76-71% (p = 0.83), 83-73% (p = 0.86), 89-85% (p = 0.84), and 94-78% (p = 0.66). On univariate, high Ki-67 was correlated with BF (p = 0.013), OS (p = 0.023), DM (p = 0.007), and DSM (p = 0.01). On Cox MVA, high Ki-67 had a BF trend (p = 0.063). High CCP score was not correlated with DSM. High Ki-67 significantly predicted outcome and provided prognostic information. CCP score may improve accuracy stratification. We did not provide prognostic correlation of CCP and DSM. It should be validated in a larger cohort of pts.

  17. Transperineal aggressive angiomyxoma.

    PubMed

    Pereira, Pedro; Melo Abreu, Elisa; Cunha, Teresa Margarida; Rolim, Inês

    2017-04-11

    A 45-year-old woman with a history of total hysterectomy with adnexal preservation for uterine leiomyomas presented to our hospital with a right gluteal palpable mass, which she first noticed 6 months before and had progressively enlarged since then.Radiological studies revealed a 14 cm lesion with translevator growth that displaced rather than invaded adjacent structures, with a peculiar whorled pattern on T2-weighted MRI, which enhanced following gadolinium administration. CT-guided biopsy was performed, and in conjunction with imaging features the diagnosis of an aggressive angiomyxoma was assumed and confirmed following surgical excision.

  18. 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

    2016-01-01

    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.

  19. Sequence determination and anticoagulant and antithrombotic activities of a novel sulfated fucan isolated from the sea cucumber Isostichopus badionotus.

    PubMed

    Chen, Shiguo; Hu, Yaqin; Ye, Xinqian; Li, Guoyun; Yu, Guangli; Xue, Changhu; Chai, Wengang

    2012-07-01

    The aim is to analyze the structure, anticoagulant and antithrombotic activities of a sulfated fucan isolated from sea cucumber Isostichopus badionotus (fucan-Ib). Fucan-Ib was hydrolyzed under mild acid conditions. The oligosaccharide fragments were fractionated by gel-filtration chromatography and the structures were determined by negative-ion electrospray tandem mass spectrometry with collision-induced dissociation and two-dimensional NMR. Anticoagulant activities were measured by activated partial thromboplastin, thrombin and prothrombin times, and by in vitro inhibition experiments with factors IIa and Xa. Antithrombotic activities were determined in vitro by measuring the length and weight of the thrombus generated. The linear polysaccharide sequence of fucan-Ib was deduced from the structures of its oligosaccharide fragments produced by acid hydrolysis. Under mild conditions, the glycosidic bonds between the non-sulfated and 2,4-O-disulfated fucose residues were selectively cleaved and highly ordered oligosaccharide fragments with a tetrasaccharide repeating unit [→3Fuc(2S,4S)α1→3Fuc(2S)α1→3Fuc(2S)α1→3Fucα1→]n were obtained. In in vitro assays fucan-Ib showed good anticoagulant and antithrombotic activities compared with heparin and the fucosylated chondroitin sulfate isolated from the same source (fCS-Ib). The two polysaccharides, fucan-Ib and fCS-Ib, differ in the mechanism of action; the former exhibited activity mainly by potentiation of antithrombin acted on thrombin and factor Xa whereas the latter mainly through heparin cofactor II. Fucan-Ib has a well defined structure with tetrasaccharide tandem repeats and good anticoagulant and antithrombotic activities. GENERAL IMPORTANCE: Fucan-Ib has a well defined structure and can be readily quality-controlled, and therefore has potential therapeutic value as an affective antithrombotic drug with low risk of bleeding. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Highly Aggressive Women in a Forensic Psychiatric Hospital.

    PubMed

    Beck, Niels C; Hammer, Joseph H; Robbins, Sharon; Tubbesing, Tara; Menditto, Anthony; Pardee, Alicia

    2017-03-01

    In this study, we compared three groups of women admitted to a public forensic inpatient facility over the course of a two-year period. Detailed and systematic examination of social and psychiatric histories revealed that the group with the most persistent levels of aggression differed from the other two groups with respect to frequency of self-harming behavior, intellectual impairment, hypothyroidism, a childhood diagnosis of attention deficit-hyperactivity disorder (ADHD), and age of onset of psychiatric and behavioral symptoms. The high-aggression group also had the highest rate of childhood physical and sexual abuse, but the difference between that group and the two lower aggression groups did not achieve statistical significance. From the standpoint of childhood adversity, 94 percent of those in the high-aggression group had been placed outside of the original home by age 11. Eighty-nine percent were intellectually impaired. At admission, physical examinations revealed that 50 percent had a history of hypothyroidism and two-thirds were obese. Before admission, most had manifested severe aggression and emotional dysregulation, as evinced by high levels of self-harm, suicide attempts, and aggressive behavior in previous institutional settings that was both frequent and intense. Patients who share these characteristics are currently placed on a ward at the hospital with a milieu and individual therapy programs that are based on a dialectical behavior therapy approach that targets key symptoms of emotional and behavioral dysregulation.

  1. The nature of human aggression.

    PubMed

    Archer, John

    2009-01-01

    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making.

  2. Psychopharmacology of aggression: an overview.

    PubMed

    Valzelli, L

    1981-01-01

    Aggression is not a single unitary behavioral entity, then it is impossible to find a single drug showing "specific' and "universal' antiaggressive efficacy and potency. Furthermore, spontaneous aggression is essential to the self-and species preservation, and plays an important role in the process of evolution. In contrast, aggressiveness induced by prolonged socioenvironmental deprivation or isolation, raises the feature of anomalous behavior. The effect of drugs on aggressive behavior must therefore be considered in the light of this distinction, that accounts for discrepancies between the results of literature on "antiaggressive' properties and potency of psychoactive drugs. In addition, and impaired inhibitory control of the brain may be responsible for violent aggression and drugs capable of restoring such control may prove useful in managing the pathology of aggressiveness.

  3. Aggression can be contagious: Longitudinal associations between proactive aggression and reactive aggression among young twins.

    PubMed

    Dickson, Daniel J; Richmond, Ashley D; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel

    2015-01-01

    The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin's reactive aggression at age 6 predicted increases in the other twin's reactive aggression from ages 6 to 7, and one twin's proactive aggression at age 6 predicted increases in the other twin's proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child's level of reactive aggression at age 6 predicted increases in the same child's proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay.

  4. Television viewing, aggression, and ethnicity.

    PubMed

    Harris, M B

    1992-02-01

    For 416 college students, questioned about their experiences with aggression and television viewing, only very weak correlations between preference for violent shows and aggression were observed. Black males watched significantly more television than other respondents. These findings suggest that the frequently reported correlation between viewing televised violence and aggression may not appear when sex, ethnicity, and education are controlled in a sample of young adults.

  5. [Aggressivity in the elderly: when and how to treat?].

    PubMed

    Monfort, J C

    1994-06-01

    Aggressivity in the elderly subject is often attributed to a personality that could be termed "difficult". This diagnosis risks over-looking required pharmacological therapy, which can ultimately lead to abrupt institution of emergency treatment, in the absence of previous diagnostic steps, of a high-dose sedative that can result in confusion and prolonged decubitus. Our experience with elderly persons who display aggressivity favors the hypothesis of a mood disorder, an anxiety-depressional state of hostility. Using an anti-depressant, sedative or not, as a therapeutic test has the interest of provoking a high response. Aggressive behaviour disappears or is better tolerated by the patient's family. Suicide can be considered as a form of aggressivity turned against oneself, and the second interest of antidepression treatment is the decreased risk of suicide.

  6. Cardiovascular drugs: implications for dental practice. Part 2--antihyperlipidemics and antithrombotics.

    PubMed

    Becker, Daniel E

    2008-01-01

    Appropriate preoperative assessment of the dental patient should always include an analysis of the patient's medications. Cardiovascular diseases are the most common group of medical disorders that dentists encounter, and the number of drugs prescribed for managing these conditions is staggering. This justifiably raises concern and probable confusion regarding side effects and possible drug interactions with medications the dentist may deem necessary for dental care. This continuing education article is the second in a series that will address essential pharmacology of medications commonly prescribed for chronic medical care. A reasonable understanding of these agents will allow the dentist to better appreciate the medical status of their patients, to appreciate the actual risks associated with antithrombotic medications, and to avoid adverse interactions with drugs the dentist might administer or prescribe.

  7. Isolation of antithrombotic phenolic compounds from the leaves of Crataegus pinnatifida.

    PubMed

    Song, Shao-Jiang; Li, Ling-Zhi; Gao, Pin-Yi; Yuan, Yan-Qiang; Wang, Ru-Ping; Liu, Ke-Chun; Peng, Ying

    2012-12-01

    Four novel phenolic compounds (1-4) were isolated from the leaves of Crataegus pinnatifida, along with three known ones (5-7). Their structures were elucidated as: methyl 4-O-β-D-glucopyranosyl-3-[(2E,6E)-8-O-β-D-glucopyranosyl-3,7-dimethyl-2,6-octadienyl] benzoate (1), biphenyl-5-ol-3-O-β-D-glucoside (2), 3,4'-dimethoxy-biphenyl-5-ol-4-O-β-D-glucoside (3), (E)-6-(benzoyloxy)-1-hydroxyhex-3-en-2-O-β-D-glucoside (4), shanyenoside A (5), eriodectyol (6), and 2″-O-rhamnosyl vitexin (7), using a combination of mass spectroscopy, 1D and 2D NMR spectroscopy, and chemical analysis. The antithrombotic activity of the isolated compounds was investigated on the transgenic zebra fish system. Among them, eriodectyol (6) potently inhibited the production of thrombus. Georg Thieme Verlag KG Stuttgart · New York.

  8. 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

  9. Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives.

    PubMed

    Kontogiorgis, Christos; Nicolotti, Orazio; Mangiatordi, Giuseppe Felice; Tognolini, Massimiliano; Karalaki, Foteini; Giorgio, Carmine; Patsilinakos, Alexandros; Carotti, Angelo; Hadjipavlou-Litina, Dimitra; Barocelli, Elisabetta

    2015-12-01

    The interest towards coumarin-based structures stems from their polypharmacological profile. Herein, we present a series of Mannich bases and 7-azomethine-linked coumarin derivatives exhibiting antiplatelet and antithrombotic activities, in addition to the already known anti-inflammatory and antioxidant activities. Among others, compounds 15 and 16 were found to be the most potent and selective inhibitors of platelet aggregation whereas compound 3 also proved to be the most potent in the clot retraction assay. Structure-activity relationship studies were conducted to elucidate the molecular determinants responsible for the herein observed activities. The chance of inhibiting cyclooxygenase-1 was also investigated for evaluating the platelet aggregation induced by arachidonic acid. Taken together, these results suggest that the investigation of other targets connected to the antiplatelet activity, such as phosphodiesterase-3 (PDE3), could be a viable strategy to shed light on the polypharmacological profile of coumarin-based compounds. Docking simulations towards PDE3 were also carried out.

  10. Cardiovascular Drugs: Implications for Dental Practice Part 2—Antihyperlipidemics and Antithrombotics

    PubMed Central

    Becker, Daniel E

    2008-01-01

    Appropriate preoperative assessment of the dental patient should always include an analysis of the patient's medications. Cardiovascular diseases are the most common group of medical disorders that dentists encounter, and the number of drugs prescribed for managing these conditions is staggering. This justifiably raises concern and probable confusion regarding side effects and possible drug interactions with medications the dentist may deem necessary for dental care. This continuing education article is the second in a series that will address essential pharmacology of medications commonly prescribed for chronic medical care. A reasonable understanding of these agents will allow the dentist to better appreciate the medical status of their patients, to appreciate the actual risks associated with antithrombotic medications, and to avoid adverse interactions with drugs the dentist might administer or prescribe. PMID:18547153

  11. Aggressive necrotizing pseudomonal sinonasal infections.

    PubMed

    Kuan, Edward C; Tajudeen, Bobby A; Welch, Kevin C; Chandra, Rakesh K; Glasgow, Ben J; Suh, Jeffrey D

    2017-09-01

    Pseudomonas aeruginosa is a gram-negative bacterium frequently implicated in recalcitrant sinonasal infections, especially in immunocompromised hosts. We report 6 cases of rapidly progressive pseudomonal acute rhinosinusitis producing tissue necrosis and, in certain cases, cranial nerve palsies. Retrospective review of 6 patients with aggressive necrotizing sinonasal infections treated at 4 tertiary academic medical centers with sinonasal cultures growing P. aeruginosa in the absence of other pathology. A total of 6 patients were identified. In all cases, there was tissue necrosis that appeared to mimic an invasive process such as mucormycosis, prompting urgent surgical intervention. Pathologic analysis revealed fibropurulent exudates in backgrounds of positive P. aeruginosa cultures without evidence of invasive fungal organisms or malignancy. Four of the 6 patients presented with cranial nerve palsies, with 3 patients having vision changes and 3 complaining of trigeminal neuropathy. Four of 6 patients improved clinically over time after surgery and antibiotic therapy; 1 remains in follow-up without complete improvement and 1 has succumbed to other causes. P. aeruginosa is a tenacious organism that is frequently associated with severe, recalcitrant sinonasal infections. We report the first case series of necrotizing sinonasal infections caused by this organism, and illustrate that, in rare cases, P. aeruginosa may mimic and behave like life-threatening conditions such as fulminant invasive fungal sinusitis or malignancy. © 2017 ARS-AAOA, LLC.

  12. Stroke Event Rates and the Optimal Antithrombotic Choice of Patients With Paroxysmal Atrial Fibrillation

    PubMed Central

    Chen, Yicong; Zhao, Yuhui; Dang, Ge; Ouyang, Fubing; Chen, Xinran; Zeng, Jinsheng

    2015-01-01

    Abstract The risks of stroke or systemic embolism and major bleeding are considered similar between paroxysmal and sustained atrial fibrillation (AF), and warfarin has demonstrated superior efficacy to aspirin, irrespective of the AF type. However, with the advent of novel oral anticoagulants (NOACs) and antiplatelet agents, the optimal antithrombotic prophylaxis for paroxysmal AF remains unclear. We searched Medline, Embase, CENTRAL, and China Biology Medicine up to October week 1, 2015. Randomized controlled trials of AF patients assigned to NOACs, warfarin, or antiplatelets, with reports of outcomes stratified by the AF type, were included. A fixed-effects model was used if no statistically significant heterogeneity was indicated; otherwise, a random-effects model was used. Six studies of 69,990 nonvalvular AF patients with ≥1 risk factor for stroke were included. Postantithrombotic treatment, paroxysmal AF patients showed lower risks of stroke (risk ratio [RR], 0.72; 95% confidence interval [CI], 0.59–0.87), stroke or systemic embolism (RR, 0.74; 95% CI, 0.63–0.86), and all-cause mortality (RR, 0.75; 95% CI, 0.67–0.83), while the major bleeding risk was comparable (RR, 0.96; 95% CI, 0.85–1.08). We were unable to detect the superiority of anticoagulation over antiplatelets for paroxysmal AF (RR, 0.72; 95% CI, 0.43–1.23), while it was more effective than antiplatelets for sustained AF (RR, 0.42; 95% CI, 0.33–0.54). NOACs showed superior efficacy over warfarin and trended to show reduced major bleeding irrespective of the AF type. The AF type is a predictor for thromboembolism, and might be helpful in stroke risk stratification model in combination with other risk factors. With the appearance of novel anticoagulant and antiplatelet agents, the best antithrombotic choice for paroxysmal AF needs further exploration. PMID:26717376

  13. The antithrombotic effect of RSNK in blood-stasis model rats.

    PubMed

    Dang, Xuan; Miao, Jing-Jing; Chen, An-Qi; Li, Peng; Chen, Lin; Liang, Jin-Ru; Xie, Ren-Ming; Zhao, Ye

    2015-09-15

    Reduction of Sheng-Nao-Kang decoction (RSNK), composed of Salvia miltiorrhiza Bge., Ligusticum chuanxiong Hort., Astragalus membranaceus (Fisch.) Bunge., Pueraria lobata (Willd.) Ohwi., Paeonia lactiflora Pall. and Panax notoginseng (Burk.) F. H. Chen., is a modified traditional Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which has been investigated its protective effect on focal cerebral ischemia-reperfusion injury in rat in our previous report. To evaluate the antithrombotic effect of RSNK in blood stasis model rats and explore the potential mechanisms. Subcutaneous injection of norepinephrine and bovine serum albumin combined with ice water bath was used to establish the acute blood stasis rat model. The anticoagulant activities were investigated by measuring activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and the content of fibrinogen (FIB). Meanwhile, the levels of thromboxane A2 (TXA2), prostaglandins I2 (PGI2), endothelial nitric oxide synthase (eNOS) and endothelin (ET) were detected. The treatment of RSNK was able to prolong APTT, TT and PT, and decrease FIB content obviously. Furthermore, it markedly suppressed TXB2 level and up-regulated 6-keto-PGF1α level of the blood-stasis model rats, accompanied with the decrease of T/K. The level of ET and TXA2 in plasma was down-regulated and the levels of eNOS in plasma and PGI2 in serum was up-regulated in RSNK-treated rats compared with model rats (P<0.05). The present study suggested that RSNK possessed remarkable antithrombotic property in blood stasis model rats induced by ice water bath and subcutaneous injection of norepinephrine and bovine serum albumin. This property could be associated with its anticoagulation activity, the regulation of active substances in vascular endothelium and maintaining the balance of TXA2 and PGI2. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Rethinking Aggression: A Typological Examination of the Functions of Aggression.

    ERIC Educational Resources Information Center

    Little, Todd D.; Brauner, Jessica; Jones, Stephanie M.; Nock, Matthew K.; Hawley, Patricia H.

    2003-01-01

    Compared five subgroups of aggressive children and adolescents on several adjustment correlates. Found that the reactive group and the group high on both instrumental and reactive reasons for aggression showed consistent maladaptive patterns across the adjustment correlates. The instrumental and typical groups (moderate on instrumental and…

  15. Intensive Insulin Therapy: Tight Blood Sugar Control

    MedlinePlus

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  16. Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

    PubMed

    Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

    2017-07-10

    The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE

  17. Reduction of Aggressive Behavior in the School.

    ERIC Educational Resources Information Center

    Petermann, Ulrike

    1988-01-01

    Discusses what may be considered aggressive behavior, what motivates aggressive students, and possible teacher responses to aggressive behavior. Describes four points on which teachers can focus to diminish the attractiveness of aggression and ensure that it is not rewarded. Identifies learning activities which provide aggressive students with the…

  18. The Effects of Pornography on Aggressive Behavior.

    ERIC Educational Resources Information Center

    Stacy, Lauri L.

    This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…

  19. The Effects of Pornography on Aggressive Behavior.

    ERIC Educational Resources Information Center

    Stacy, Lauri L.

    This document reviews existing empirical research on the effect of pornography on aggressive behavior. Two types of pornography are distinguished: aggressive pornography and non-aggressive pornography. Conclusions drawn from the research review are presented, including: (1) aggressive pornograpy consistently increases aggressive attitudes and…

  20. Mitochondrial mutations drive prostate cancer aggression.

    PubMed

    Hopkins, Julia F; Sabelnykova, Veronica Y; Weischenfeldt, Joachim; Simon, Ronald; Aguiar, Jennifer A; Alkallas, Rached; Heisler, Lawrence E; Zhang, Junyan; Watson, John D; Chua, Melvin L K; Fraser, Michael; Favero, Francesco; Lawerenz, Chris; Plass, Christoph; Sauter, Guido; McPherson, John D; van der Kwast, Theodorus; Korbel, Jan; Schlomm, Thorsten; Bristow, Robert G; Boutros, Paul C

    2017-09-22

    Nuclear mutations are well known to drive tumor incidence, aggression and response to therapy. By contrast, the frequency and roles of mutations in the maternally inherited mitochondrial genome are poorly understood. Here we sequence the mitochondrial genomes of 384 localized prostate cancer patients, and identify a median of one mitochondrial single-nucleotide variant (mtSNV) per patient. Some of these mtSNVs occur in recurrent mutational hotspots and associate with aggressive disease. Younger patients have fewer mtSNVs than those who diagnosed at an older age. We demonstrate strong links between mitochondrial and nuclear mutational profiles, with co-occurrence between specific mutations. For example, certain control region mtSNVs co-occur with gain of the MYC oncogene, and these mutations are jointly associated with patient survival. These data demonstrate frequent mitochondrial mutation in prostate cancer, and suggest interplay between nuclear and mitochondrial mutational profiles in prostate cancer.In prostate cancer, the role of mutations in the maternally-inherited mitochondrial genome are not well known. Here, the authors demonstrate frequent, age-dependent mitochondrial mutation in prostate cancer. Strong links between mitochondrial and nuclear mutational profiles are associated with clinical aggressivity.

  1. Aggression and Violence in Youth.

    ERIC Educational Resources Information Center

    William Gladden Foundation, York, PA.

    This booklet was written to provide an understanding of aggression and violence in youth. Its purpose is to help parents, professionals, and other concerned citizens prevent or reduce these potentially dangerous behaviors. The introduction notes that many experts agree that aggression and violence are on the rise in America. The first section of…

  2. Traumatic Brain Injury and Aggression.

    ERIC Educational Resources Information Center

    Miller, Laurence

    1994-01-01

    Persons who have suffered traumatic injury to the brain may subsequently display aggressive behavior. Three main syndromes of aggression following traumatic brain injury are described: (1) episodic dyscontrol; (2) frontal lobe disinhibition; and (3) exacerbation of premorbid antisociality. The neuropsychological substrates of these syndromes are…

  3. Lunar Influences on Human Aggression.

    ERIC Educational Resources Information Center

    Russell, Gordon W.; Dua, Manjula

    1983-01-01

    Used league records of all Canadian hockey games (N=426) played during a season to test a lunar-aggression hypothesis. Despite the use of multiple measures of lunar phase and interpersonal aggression, support for lunar influence was not forthcoming. Supplemental data revealed that beliefs in lunar influence are fairly common. (JAC)

  4. How To Prevent Aggressive Behavior.

    ERIC Educational Resources Information Center

    Abrams, Brian J.; Segal, Amiel

    1998-01-01

    This article reviews what teachers can do to prevent aggressive behavior in students with emotional and behavioral disorders. It considers the dynamics of aggression, the role of the therapeutic teacher, creation of the positive classroom climate, functional assessment, and teaching alternative behaviors. (DB)

  5. In search of Winnicott's aggression.

    PubMed

    Posner, B M; Glickman, R W; Taylor, E C; Canfield, J; Cyr, F

    2001-01-01

    Going beyond Winnicott's widely known ideas about creativity, in this paper the authors ask why some people are able to live creatively while others suffer recurrent feelings of anger, futility, and depression. Examining Winnicott's reframing of aggression as a life force, it attempts to answer this question by tracing the evolution of his thinking on the nature and origin of aggression. It argues that because he saw aggression as inherent and as central to emotional development, interference in its expression compromises psychic maturation. The paper explores how Winnicott arrived at the conception of a combined love-strife drive and demonstrates that for him, there is no love without aggression, no subject, no object, no reality, and no creativity. That is, for Winnicott, aggression is an achievement that leads to the capacity to live creatively and to experience authenticity. Clinical vignettes illustrate the therapeutic use of these conclusions and their value for psychoanalytic theory.

  6. The Neurobiology of Impulsive Aggression

    PubMed Central

    2016-01-01

    Abstract This selective review provides a model of the neurobiology of impulsive aggression from a cognitive neuroscience perspective. It is argued that prototypical cases of impulsive aggression, those associated with anger, involve the recruitment of the acute threat response system structures; that is, the amygdala, hypothalamus, and periaqueductal gray. It is argued that whether the recruitment of these structures results in impulsive aggression or not reflects the functional roles of ventromedial frontal cortex and dorsomedial frontal and anterior insula cortex in response selection. It is also argued that impulsive aggression may occur because of impaired decision making. The aggression may not be accompanied by anger, but it will reflect disrupted evaluation of the rewards/benefits of the action. PMID:26465707

  7. False memories for aggressive acts.

    PubMed

    Laney, Cara; Takarangi, Melanie K T

    2013-06-01

    Can people develop false memories for committing aggressive acts? How does this process compare to developing false memories for victimhood? In the current research we used a simple false feedback procedure to implant false memories for committing aggressive acts (causing a black eye or spreading malicious gossip) or for victimhood (receiving a black eye). We then compared these false memories to other subjects' true memories for equivalent events. False aggressive memories were all too easy to implant, particularly in the minds of individuals with a proclivity towards aggression. Once implanted, the false memories were indistinguishable from true memories for the same events, on several dimensions, including emotional content. Implications for aggression-related memory more generally as well as false confessions are discussed.

  8. The Neurobiology of Impulsive Aggression.

    PubMed

    Blair, Robert J R

    2016-02-01

    This selective review provides a model of the neurobiology of impulsive aggression from a cognitive neuroscience perspective. It is argued that prototypical cases of impulsive aggression, those associated with anger, involve the recruitment of the acute threat response system structures; that is, the amygdala, hypothalamus, and periaqueductal gray. It is argued that whether the recruitment of these structures results in impulsive aggression or not reflects the functional roles of ventromedial frontal cortex and dorsomedial frontal and anterior insula cortex in response selection. It is also argued that impulsive aggression may occur because of impaired decision making. The aggression may not be accompanied by anger, but it will reflect disrupted evaluation of the rewards/benefits of the action.

  9. Beliefs about aggression moderate alcohol's effects on aggression.

    PubMed

    Levinson, Cheri A; Giancola, Peter R; Parrott, Dominic J

    2011-02-01

    The goal of this investigation was to determine whether permissive beliefs about aggression moderate the relation between acute alcohol intoxication and aggression in two large experiments. Participants in Study 1 were 328 (163 men and 165 women) social drinkers and those in Study 2 were 518 (252 men and 266 women) social drinkers. Beliefs about aggression were assessed using a well-validated self-report measure. Following the consumption of either an alcohol or a placebo beverage, participants were tested on a laboratory task in which electric shocks were received from, and administered to, a fictitious opponent under the guise of a competitive reaction-time task. Aggression was operationalized as the combined mean responses for shock intensity and duration across all trials. Our central finding was that alcohol increased aggression in persons with more approving beliefs about aggression than in those who did not hold such beliefs. Our results are discussed within the context of Huesmann's (1988) cognitive script model of aggression. Suggestions for violence prevention efforts are put forth as well.

  10. Long-term follow-up of antithrombotic management patterns in patients with acute coronary syndrome in Russia: an observational study (EPICOR-RUS study).

    PubMed

    Ruda, Mikhail Ya; Averkov, Oleg V; Khomitskaya, Yunona V

    2017-07-01

    This study sought to describe the short- and long-term (up to 2 years) antithrombotic management patterns in a real-life setting for patients hospitalized for an acute coronary syndrome (ACS) event, and to document clinical outcomes. EPICOR-RUS was a multicenter (34 centers), prospective, observational, longitudinal cohort study conducted across Russia on antithrombotic management in hospitalized (within 24 hours of symptom onset) ACS patients with 2 year follow-up. NCT01373957. A total of 600 ACS patients (71.1% male, mean age 60 years) were enrolled; 599 were included for analysis. Diagnosis comprised STEMI (n = 375, 62.6%), NSTEMI (n = 147, 24.5%), and unstable angina (UA) (n = 77, 12.9%). Percutaneous coronary intervention (PCI) was conducted in 64.3% of patients with STEMI (with or without thrombolysis), 36.7% with NSTEMI, and 58.4% with UA. There was undertreatment with dual antiplatelet therapy (DAPT) for STEMI, NSTEMI, and UA: 14.7%, 25.9% and 16.9% of patients, respectively, were not receiving DAPT during hospitalization, and 10.1%, 21.8% and 16.9% at discharge. Post-discharge, of the STEMI group, only 72.4% of patients who were managed by PCI and 39.8% of conservatively treated patients received DAPT at 12 months. The respective figures in the NSTEMI group were 77.3% and 26.4%. In the STEMI cohort the cumulative incidence of all-cause mortality was 3.2% at 1 year and 5.1% at 2 years of follow-up; in the NSTEMI cohort this was 2.7% and 4.8%, respectively. There were no deaths by 12 months and one death by 24 months (1.3%) in the UA population. Despite evidence-based guidelines for the management of ACS, the real-world setting in Russia shows discrepancies in clinical practice, highlighting the need for improvements for the optimal management of high-risk patients with ACS.

  11. Aggressive Erotica and Violence against Women.

    ERIC Educational Resources Information Center

    Donnerstein, Edward

    1980-01-01

    Examines the effects of aggressive-erotic stimuli on male aggression toward females. Male subjects' deliveries of electric shocks to males or females after viewing either a neutral, erotic, or aggressive-erotic film were measured. (Author/SS)

  12. Aggressive Erotica and Violence against Women.

    ERIC Educational Resources Information Center

    Donnerstein, Edward

    1980-01-01

    Examines the effects of aggressive-erotic stimuli on male aggression toward females. Male subjects' deliveries of electric shocks to males or females after viewing either a neutral, erotic, or aggressive-erotic film were measured. (Author/SS)

  13. [The effect of media violence on aggression: is aggressive behavior mediated by aggressive cognitions and emotions?].

    PubMed

    Yukawa, S; Yoshida, F

    1999-06-01

    This study investigated whether cognitions and emotions elicited by media violence mediate aggressive behavior. Eighty undergraduates, 40 men and 40 women, participated in the experiment. First, subjects were exposed to one of four violent videos which varied in levels of violence and entertainment. Subjects' heart rate and eyeblink rate were continuously recorded while they watched the video. After watching it, subjects described their thoughts which occurred while watching it and rated their affective reactions to it. Finally, their aggressive behavior was measured. Results showed that (1) videos high in violence elicited more aggressive thoughts, more thoughts of negative affect, stronger negative affects, and stronger empty-powerless affects, whereas videos high in entertainment elicited stronger positive affects; (2) no significant differences were found among the videos in terms of physiological reactions and aggressive behavior; and (3) cognitions and emotions elicited by media violence did not mediate aggressive behavior.

  14. Antithrombotic effect of taurine in healthy Japanese people may be related to an increased endogenous thrombolytic activity.

    PubMed

    Ijiri, Yoshinobu; Ikarugi, Hideo; Tamura, Yukinori; Ura, Mayumi; Morishita, Mai; Hamada, Atsumi; Mori, Mari; Mori, Hideki; Yamori, Yukio; Ishii, Hiromitsu; Yamamoto, Junichiro

    2013-02-01

    Prevention of arterial thrombotic diseases has high priority in developed countries. Taurine (2-aminomethylsulfonic acid), which is rich in sea foods, showed antithrombotic effect in animal models of thrombosis. The present study aimed to investigate such effect in healthy human volunteers. In 101 healthy Japanese people the overall thrombotic status was accessed from non-anticoagulated blood sample by the Global Thrombosis Test (GTT). There was no significant correlation between taurine concentration in urine samples and GTT-Occlusion Times (OT; mainly reactivity of platelets). In contrast, a significant inverse correlation was demonstrated between urine taurine concentrations and GTT-Lysis Times (LT; showing spontaneous thrombolytic activity). Our findings suggest that taurine enhances endogenous thrombolytic activity which could be a mechanism of the earlier observed cardioprotective and antithrombotic effect. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. [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.

  16. Aggression Can be Contagious: Longitudinal Associations between Proactive Aggression and Reactive Aggression Among Young Twins

    PubMed Central

    Dickson, Daniel J.; Richmond, Ashley; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel

    2015-01-01

    The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin’s reactive aggression at age 6 predicted increases in the other twin’s reactive aggression from ages 6 to 7, and one twin’s proactive aggression at age 6 predicted increases in the other twin’s proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child’s level of reactive aggression at age 6 predicted increases in the same child’s proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay. PMID:25683448

  17. Features of aggressive breast cancer.

    PubMed

    Arpino, Grazia; Milano, Monica; De Placido, Sabino

    2015-10-01

    Aggressive breast cancer is a term commonly used in literature to describe breast cancer with a poor prognosis. Identifying and understanding the factors associated with aggressiveness could be helpful to the management of patients with breast cancer. Breast cancer is a heterogeneous disease, both clinically and biologically, which may be responsible for the wide range of survival durations for patients with metastatic disease. The goal of this study was to identify the factors most often described in association with aggressive metastatic breast cancer (MBC). A systematic review was performed by querying PubMed from January 1, 2012 to June 1, 2014 for "metastatic breast cancer" ("aggressive" or "poor prognosis" or "high risk"). The level of evidence to support each potential prognostic factor of aggressive MBC was also reviewed. The identified factors were grouped into 3 principle categories: clinical, biological, and patient related. Because patient-related factors may not be indicative of inherent cancer aggressiveness, this review focused only on clinical and biological factors. The factors with the highest levels of evidence to support associations with survival in metastatic breast cancer were visceral metastases, number of metastatic sites, disease-free interval, presence of CTCs, triple-negative disease, and tumour grade. Identification of these factors and understanding their contribution to the aggressiveness of MBC and disease progression may lead to more personalized treatment in this patient population. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Differential diagnosis and management of human-directed aggression in dogs.

    PubMed

    Reisner, Ilana R

    2003-03-01

    Canine aggression directed to human beings is a common presenting complaint and requires attention to safety issues and behavior modification to minimize the risks of future aggression. Dogs may bite familiar people, including family members, or unfamiliar people for a variety of reasons. Anxiety plays an important role in aggression regardless of its target or circumstances. Effective management of aggression may include education and safety counseling for owners, lifestyle changes for dogs and owners, avoidance of provocations when possible, and behavior modification to minimize the risk of future bites. Drug therapy may be indicated to facilitate behavior modification or to reduce reactivity in the dog.

  19. Investigation for anti-inflammatory and anti-thrombotic activities of methanol extract of Capparis ovata buds and fruits.

    PubMed

    Bektas, Nurcan; Arslan, Rana; Goger, Fatih; Kirimer, Nese; Ozturk, Yusuf

    2012-06-26

    Capparis ovata Desf. has wide natural distribution in Turkey and it is consumed in pickled form. Flower buds, root bark, and fruits of the plant are used traditionally due to their analgesic, anti-inflammatory, wound healing, anti-rheumatismal, tonic, and diuretic effects. The aim of this study was to investigate the possible anti-inflammatory and anti-thrombotic effects of methanol extracts prepared from flower buds (CBE) and fruits (CFE) of C. ovata. Anti-inflammatory effects of CBE and CFE were assessed using carrageenan-induced and prostaglandin E₂-induced mouse paw edema models. For the anti-thrombotic effect evaluation, carrageenan-induced tail thrombosis model was performed in mice. The extracts were administered intraperitonally (i.p.) at the doses of 100, 200, and 300 mg/kg. The anti-inflammatory effect of Capparis extracts were tested in comparison to 10 mg/kg diclofenac and anti-thrombotic activity to 10 and 100 IU heparin. CBE at the doses of 200, and 300 mg/kg and CFE at the doses of 100, 200, and 300 mg/kg showed significant anti-inflammatory activity and CFE reached therapeutic concentration early than CBE in carrageenan inflammation model. In prostaglandin E₂ inflammation model, CBE and CFE exhibited significant inhibitory effects. The C. ovata extracts did not show remarkable anti-thrombotic effect. Based on the results obtained, it can be concluded that fruits of C. ovata have more potent anti-inflammatory effect than flower buds. It has been suggested that inhibition of cyclooxygenase pathway is one of the mechanisms of the activity. C. ovata may be potentially used as therapeutic agents for inflammatory diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice.

    PubMed

    Kramkowski, K; Leszczynska, A; Przyborowski, K; Proniewski, B; Marcinczyk, N; Rykaczewska, U; Jarmoc, D; Chabielska, E; Chlopicki, S

    2017-01-01

    In humans, short-term supplementation with nitrate is hypotensive and inhibits platelet aggregation via an nitric oxide (NO)-dependent mechanism. In the present work, we analyzed whether short-term treatment with nitrate induces antithrombotic effects in rats and mice. Arterial thrombosis was evoked electrically in a rat model in which renovascular hypertension was induced by partial ligation of the left renal artery. In mice expressing green fluorescent protein, laser-induced thrombosis was analyzed intravitally by using confocal microscope. Sodium nitrate (NaNO3) or sodium nitrite (NaNO2) was administered orally at a dose of 0.17 mmol/kg, twice per day for 3 days. Short-term nitrate treatment did not modify thrombus formation in either rats or mice, while nitrite administration led to pronounced antithrombotic activity. In hypertensive rats, nitrite treatment resulted in a significant decrease in thrombus weight (0.50 ± 0.08 mg vs. VEH 0.96 ± 0.09 mg; p < 0.01). In addition, nitrite inhibited ex vivo platelet aggregation and thromboxane B2 (TxB2) generation and prolonged prothrombin time. These effects were accompanied by significant increases in blood NOHb concentration and plasma nitrite concentration. In contrast, nitrate did not affect ex vivo platelet aggregation or prothrombin time and led to only slightly elevated nitrite plasma concentration. In mice, nitrate was also ineffective, while nitrite led to decreased platelet accumulation in the area of laser-induced endothelial injury. In conclusion, although nitrite induced profound NO-dependent antithrombotic effects in vivo, conversion of nitrates to nitrite in rats and mice over short-term 3-day treatment was not sufficient to elicit NO-dependent antiplatelet or antithrombotic effects.

  1. [Case-control study on three antithrombotic agents for the prevention of venous thromboembolism after unilateral total knee arthroplasty].

    PubMed

    Miao, Shao-gang; Zhang, Xi-guang; Lu, Jing-hua; Yang, Yang; Lu, Ning

    2015-10-01

    To evaluate the efficacy and safety of three antithrombotic agents on venous thromboembolism (VTE) after unilateral total knee arthroplasty. From November 2011 to March 2014, 149 patients undergoing unilateral total knee arthroplasty for knee osteoarthritis were reviewed. Among them, there were 66 males and 83 females, ranging in age from 48 to 76 years old. All the cases were randomly divided into three groups including Aspirin group, low-molecular-weight heparin (LMWH) group, and rivaroxaban group, according to antithrombotic agents. Deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding complication (including wound ecchymosis, hematoma and other local complications, gastrointestinal, cardiovascular, urinary hemorrhage and other major bleeding events) of antithrombotic agents were observed and analyzed statistically at the 6 week, 8 week, and 12 week after operation. Among patients who received Aspirin (48 cases), 4 patients had DVT, in 1 patient had PE, and 2 patients had bleeding complication. Among 54 patients in low-molecular-weight heparin group, 3 patients had DVT, 1 patient had PE, and 3 patients had bleeding complication. While among those patients received the rivaroxaban (47 cases), 3 patients had DVT, 0 patient had PE, and 11 patients had bleeding complication. There were no statistically differences among three groups on DVT, and PE (P>0.05). The incidence of bleeding complication in rivaroxaban group was higher than the other two antithrombotic agents, and the difference among the three groups was statistically significant (P<0.05). Aspirin, low-molecular-weight heparin, and rivaroxaban could effectively reduce the incidence of VTE after total knee arthroplasty, and their efficacy was similar. Rivaroxaban has a higher incidence of bleeding complication and further clinical trials are required to be conducted to assess the safety of rivaroxaban in clinical.

  2. Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

    PubMed Central

    Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

    2017-01-01

    Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

  3. Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

    PubMed

    Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

    2017-08-04

    Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

  4. From aggressiveness to creativity.

    PubMed

    Mrevlje, Gorazd V

    2004-02-01

    Psychology has a long tradition of considering human creativity as a distinct human characteristic and a special kind of human activity. After explaining the key motives for such an attitude, the author discusses those forms of healthy aggressiveness that stand out as necessary and constitutive elements of the creative process. Taking the well-known statement of C. G. Jung's 'The person who does not build (create), will demolish and destroy' as a starting point, the author compares the basic premises for understanding the process of human creativity, at the same time drawing on Freud's psychology of the individual and Jung's principle of the collective unconscious as well as his notion of 'complexes'. In doing so, the author somewhat boldly paraphrases Jung's dictum: 'In order to be creative, rather than just constructive, one must occasionally also destroy'. With reference to Wallas, Taylor and Neumann (Wallas 1926; Taylor 1959;;Neumann 2001), the author goes on to explore those concepts which help us to investigate the phenomenon of human creativity, drawing distinctions between emergent, expressive, productive, inventive and innovative creativity. The second part of the article discusses the importance of intelligence, originality, nonconformity, subversiveness and free-mindedness for the creative process of human beings. The author concludes with a further explanation of Erich Neumann's argument that human creativity cannot be understood solely as a result of sociogenetic factors, and argues that it is only by taking into consideration Jung's perception of creativity that a global ontological understanding of these processes can be achieved.

  5. An Aggressive Retroperitoneal Fibromatosis

    PubMed Central

    Campara, Zoran; Spasic, Aleksandar; Aleksic, Predrag; Milev, Bosko

    2016-01-01

    Introduction: Aggressive fibromatosis (AF) is a heterogeneous group of mesenchymal tumors that have locally infiltrative growth and a tendency to relapse. The clinical picture is often conditioned by the obstruction of the ureter or small intestine. Diagnosis is based on clinical, radiological and histological parameters. A case report: We report a case of male patient, aged 35 years, with the retroperitoneal fibromatosis. He reported to the physician because of frequent urination with the feeling of pressure and pain. Computed tomography revealed the tumor mass on the front wall of the bladder with diameter of 70mm with signs of infiltration of the musculature of the anterior abdominal wall. Endoscopic transurethral biopsy showed proliferative lesion binders by type of fibromatosis. The tumor was surgically removed in a classical way. The patient feels well and has no recurrence thirty-six months after the operative procedure. Conclusion: The complete tumor resection is the therapeutic choice for the primary tumor as well as for a relapse. PMID:27147794

  6. Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora.

    PubMed

    Choo, Min-Kyung; Park, Eun-Kyung; Yoon, Hae-Kyung; Kim, Dong-Hyun

    2002-10-01

    To evaluate the antithrombotic activities of puerarin and daidzin from the rhizome of Pueraria lobata, in vitro and ex vivo inhibitory activities of these compounds and their metabolite, daidzein, were measured. These compounds inhibited ADP- and collagen-induced platelet aggregation. Daidzein was the most potent. However, when puerarin and daidzin were intraperitoneally administered, their antiaggregation activities were weaker than when these compounds were administered orally. When in vivo antithrombotic activities of these compounds against collagen and epinephrine were measured, these compounds showed significant protection from death due to pulmonary thrombosis in mice. To evaluate the antiallergic activity of puerarin, daidzin, and daidzein, their inhibitory effects on the release of beta-hexosaminidase from RBL 2H3 cells and on the passive cutaneous anaphylaxis (PCA) reaction in mice were examined. Daidzein exhibited potent inhibitory activity on the beta-hexosaminidase release induced by DNP-BSA and potently inhibited the PCA reaction in rats. Daidzein administered intraperitoneally showed the strongest inhibitory activity and significantly inhibited the PCA reaction at doses of 25 and 50mg/kg with inhibitory activity of 37 and 73%, respectively. The inhibitory activity of intraperitoneally administered daidzein was stronger than those of intraperitoneally and orally administered puerarin and daidzin. Therefore we believe that puerarin and daidzin in the rhizome of Pueraria lobata are prodrugs, which have antiallergic and antithrombotic activities, produced by intestinal microflora.

  7. Anti-thrombotic effect of a novel formula from Corni fructus with malic acid, succinic acid and citric acid.