Science.gov

Sample records for aggressive antithrombotic therapy

  1. [Antithrombotic therapy and pregnancy].

    PubMed

    Chauleur, Céline; Raia, Tiphaine; Gris, Jean-Christophe

    2013-09-01

    The incidence of venous thromboembolism (VTE) during pregnancy is about one event per 1000 pregnancies and placenta-mediated pregnancy complications (PC) occurred in 15%. Knowing the biological combined with clinical risk factors would help to prevent problems during the pregnancy. Several antithrombotic therapies exist, including very recent ones but LMWH and aspirin are still molecules of choice. The women should be assessed for VTE and PC risk in order to improve the outcome.

  2. Antithrombotic Therapy for Atrial Fibrillation

    PubMed Central

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

    2012-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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. PMID:27676677

  8. Hitting the target with antithrombotic therapy.

    PubMed

    Fritsma, Margaret G; Rodak, Bernadette F

    2007-05-01

    Thrombus treatment and prevention can be regulated by a number of intravenous or subcutaneous drugs, as well as oral warfarin. Many therapies require laboratory monitoring for efficacy and for detection of dangerous sequelae, such as bleeding, thrombosis, or heparin induced thrombocytopenia.

  9. 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

    Objectif : Présenter une approche, fondée sur les données actuelles, envers le diagnostic, la prise en charge et la thromboprophylaxie de la thromboembolie veineuse pendant la grossesse et la période postpartum. Résultats : La littérature publiée a été récupérée par l’intermédiaire de recherches menées dans PubMed, Medline, CINAHL et The Cochrane Library entre novembre 2011 et juillet 2013 au moyen d’un vocabulaire contrôlé (p. ex. « pregnancy », « venous thromboembolism », « deep vein thrombosis », « pulmonary embolism », « pulmonary thrombosis ») et de mots clés (p. ex. « maternal morbidity », « pregnancy complications », « thromboprophylaxis », « antithrombotic therapy ») appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles publiés en anglais ou en français. Aucune restriction n’a été imposée en matière de dates. La littérature grise (non publiée) a été identifiée par l’intermédiaire de recherches menées dans les sites Web d’organismes s’intéressant à l’évaluation des technologies dans le domaine de la santé et d’organismes connexes, dans des collections de directives cliniques, dans des registres d’essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d’étude canadien sur les soins de santé préventifs (Tableau). Recommandations 1. La tenue d’un examen objectif s’avère requise lorsque la présence d’une thrombose veineuse profonde ou d’une embolie pulmonaire est soupçonnée sur le plan clinique. (II-2A) 2. Pour diagnostiquer la présence d’une thrombose veineuse profonde, il est recommandé d’avoir recours à une échographie; lorsque l’examen initial donne des résultats n

  10. 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

  11. Experimental models for evaluating antithrombotic therapies in replantation microsurgery.

    PubMed

    Cooley, B C; Gould, J S

    1987-01-01

    A variety of anticoagulation and antiplatelet aggregation agents are in use clinically, and in applications to microvascular surgery, a clear choice for the most effective therapy has not been determined. Models of vascular trauma combined with microvascular anastomosis have been developed for comparing the efficacy of these agents in maintaining vascular patency. In a rat model of microvascular thrombosis, heparin effectively prevents occlusion in both arteries and veins, at clinical levels of administration. Aspirin helps prevent thrombosis, but not as well as heparin. These results support the beneficial effect of antithrombotic drug therapies, and suggest a more potent role of the heparin-inhibited fibrin clot over platelet aggregation in creating thrombotic occlusion of small vessels.

  12. 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.

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

    PubMed

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

    2014-11-01

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

  14. 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

  15. Antithrombotic therapy for secondary prevention of atherothrombotic events in cerebrovascular disease.

    PubMed

    Capodanno, Davide; Alberts, Mark; Angiolillo, Dominick J

    2016-10-01

    Atherothrombosis is the common underlying process for numerous progressive manifestations of cardiovascular disease, including coronary artery disease (CAD) and cerebrovascular disease (CVD). Antiplatelet therapy is the cornerstone of pharmacological management in patients with atherothrombosis. Over the past 20 years, major advances in antiplatelet pharmacotherapy have been made, particularly for the treatment of patients with CAD. The treatment of patients with concomitant CAD and CVD is complex, owing to their increased risk of both ischaemia and bleeding. When CVD arises from large artery atherosclerosis, antithrombotic therapies are essential to prevent stroke or transient ischaemic attack (TIA). However, the use of antithrombotic medications in patients with CVD can put them at high risk of intracranial haemorrhage. As such, the risk-benefit profile of various combinations of antiplatelet agents in patients with both CAD and CVD is uncertain. This Review provides a state-of-the-art account of the available evidence on antithrombotic therapies for the secondary prevention of atherothrombotic events in patients with concomitant CAD and CVD, particularly those with a history of noncardioembolic stroke or TIA.

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

    PubMed

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

    2004-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. 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.

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

    PubMed

    Deharo, Pierre; Rahbi, Hazim; Cuisset, Thomas

    2016-06-01

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

  20. The History of Antithrombotic Therapy: The Discovery of Heparin, the Vitamin K Antagonists, and the Utility of Aspirin.

    PubMed

    Handin, Robert I

    2016-10-01

    The administration of intravenous heparin to postoperative patients by Barritt and Jordan reduced the incidence of fatal and nonfatal pulmonary embolism and established heparin as the standard for parenteral anticoagulation. The coumarin family of vitamin K antagonists quickly became the standard for long-term oral anticoagulation. Aspirin became a widely used antithrombotic agent after the discovery that chronic oral administration reduced the incidence of secondary strokes and myocardial infarction. This article gives a brief history of antithrombotic therapy, including the discovery of heparin, the vitamin k antagonists, and the utility of aspirin. PMID:27637302

  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. Triple Oral Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Stenting: Searching for the Best Combination.

    PubMed

    Elewa, Hazem; Ahmed, Dina; Barnes, Geoffrey D

    2016-09-01

    Patients with atrial fibrillation (AF) who are treated with oral anticoagulants often have concurrent coronary artery disease. Triple oral antithrombotic therapy (TOAT) is often necessity to prevent stent thrombosis or myocardial infarction associated with percutaneous coronary intervention or acute coronary syndrome in patients with comorbid coronary artery disease and AF. Although the use of TOAT (aspirin, clopidogrel, and warfarin) has excellent efficacy against thrombotic complications, this comes on the expense of increased bleeding risk. This review discusses potential strategies to improve TOAT benefit-risk ratio evidence from the literature. These strategies include: (1) dropping aspirin; (2) reducing the duration of TOAT; (3) switching warfarin to a direct oral anticoagulant (DOAC); (4) the use of DOAC in combination with a single antiplatelet agent; and (5) switching clopidogrel to a novel antiplatelet agent. Although dropping aspirin and reducing TOAT duration should be considered in selected AF patients at low risk of thrombosis, the role of DOACs and novel antiplatelets in TOAT has not been thoroughly studied, and there is limited evidence to support their use currently. Ongoing studies will provide safety and efficacy data to guide clinicians who frequently face the challenge of determining the best TOAT combination for their patients. PMID:27235831

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  5. 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

  6. 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

  7. MOLECULAR MODELLING, 3D-QSAR, AND DRUG DOCKING STUDIES ON THE ROLE OF NATURAL ANTICOAGULANT COMPOUNDS IN ANTITHROMBOTIC THERAPY

    PubMed Central

    Kakarla, Prathusha; Devireddy, Amith R.; Inupakutika, Madhuri A.; Cheeti, Upender R.; Floyd, Jared T.; Mun, Mukherjee M.; Vigil, Raelyn N.; Hunter, Russell P.; Varela, Manuel F.

    2015-01-01

    Thromboembolic disorders are the leading cause of human mortality. Therefore, development of effective anticoagulant therapy is critical. Factor XIIIA (FXIIIA) protein is a crucial factor in the blood coagulation cascade, and hence it is a vital target for evolution of new antithrombotic agents. Structure-function studies of clotting factor active sites, clot formation, and thrombus structure have gained prominence in the efforts to develop novel anticoagulants. Factor XIIIA was homology modelled with the human transglutaminase-2 crystal structure as a base template for BLAST analysis. Docking and comparative binding site analysis revealed active site residue conservation and inhibitor-protein interactions. Nineteen small molecules possessing suspected anticoagulant properties were successfully docked into the FXIIIA active site following the best CoMFA and CoMSIA prediction values. Dabigatran etexilate was anticipated to be the best FXIIIA inhibitor among the nineteen anticoagulants with the highest binding affinity for the FXIIIA protein and the highest FlexX dock score of −29.8 KJ/mol. Structural properties of FXIIIA inhibitors with increased antithrombotic activity were predicted by this docking study. PMID:25750914

  8. 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

  9. The Intrinsic Pathway of Coagulation as a Target for Antithrombotic Therapy.

    PubMed

    Wheeler, Allison P; Gailani, David

    2016-10-01

    Plasma coagulation in the activated partial thromboplastin time assay is initiated by sequential activation of coagulation factors XII, XI, and IX. While this series of proteolytic reactions is not an accurate model for hemostasis in vivo, there is mounting evidence that factor XI and factor XII contribute to thrombosis, and that inhibiting them can produce an antithrombotic effect with a small effect on hemostasis. This article discusses the contributions of components of the intrinsic pathway to thrombosis in animal models and humans, and results of early clinical trials of drugs targeting factors IX, XI, and XII. PMID:27637310

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

    PubMed Central

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

    2015-01-01

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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. Novel Therapies for Aggressive B-Cell Lymphoma

    PubMed Central

    Foon, Kenneth A.; Takeshita, Kenichi; Zinzani, Pier L.

    2012-01-01

    Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper. PMID:22536253

  17. New Antithrombotic Drugs

    PubMed Central

    Eikelboom, John W.; Samama, Meyer Michel

    2012-01-01

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

  18. Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis

    PubMed Central

    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.

    2012-01-01

    Background 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. Methods 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. Results 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. Conclusions 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.) PMID

  19. 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.

  20. Radiation therapy in the treatment of aggressive fibromatoses (desmoid tumors).

    PubMed

    Kiel, K D; Suit, H D

    1984-11-15

    Twenty-five patients with aggressive fibromatoses (desmoid tumors) have been treated or followed in the Department of Radiation Medicine at the Massachusetts General Hospital between 1972 and 1982. Seventeen patients were treated by radiation, 4 for primary and 13 for recurrent disease. Seven patients were treated in conjunction with surgery. Partial or complete regression was achieved in 76%, and 59% are without evidence of disease (NED) at 9 to 94 months follow-up. Eight of ten patients treated primarily with radiation have achieved complete response without an attempt at resection (five) or have achieved stabilization (three) of their disease after some regression. Consistent complete control was seen with doses above 60 Gy. Periods to 27 months were required to observe complete responses. Only three failures within the radiation field were observed, two after low doses (22 and 24 Gy, respectively). Eight patients were seen after resection but with uncertain or histologically minimum positive margins, and were followed regularly and not treated. One patient has failed to date and is NED after resection. Radiation therapy is recommended in those situations where wide-field resection without significant morbidity is not possible for gross local disease. If minimally positive margins exist after resection in a patient who may be followed carefully, frequent follow-up and prompt treatment at recurrence may be an effective alternative to immediate radiation therapy.

  1. Newer antithrombotic drugs

    PubMed Central

    Sikka, Pranav; Bindra, V. K.

    2010-01-01

    Thromboembolic disorders are one of the disorders for which we are still on the look out for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows our inefficiency in searching efficacious and safe antithrombotic drugs. We have reached the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, we can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, we are using Clopidogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide). Warfarin is an old antithrombotic drug which is still being used; but due to various side effects and drug interactions, we are bound to use newer drugs. Newer antiplatelet drugs include Prasugrel, Ticagrelor and Cangrelor, whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban is also a newer entry in this category as factor Xa inhibitor. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are ongoing. PMID:21572750

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

    PubMed

    Wahl, Michael J; Schmitt, Margaret M

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2016-08-01

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

  5. 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

  6. Aggressive family communication, weight gain, and improved eating attitudes during systemic family therapy for anorexia nervosa.

    PubMed

    Shugar, G; Krueger, S

    1995-01-01

    During systemic family therapy with 15 hospitalized anorexics, family communication was evaluated, using a Family Aggression Scale developed by one of the authors. Initially members communicated aggression covertly. This finding may partially explain the common clinical observation that the families of anorexics present a strong facade of togetherness and avoid overt conflict. During therapy members shifted from covert communication of aggression to covert communication of aggression. This shift correlated with improvement in subjects' eating attitudes reflected by their EAT-26 scores. All subjects gained weight. Greater weight gain occurred in subjects whose families had low levels of covert or indirect aggression. A regression analysis showed that 86% of the variance in weight gain was predicted by two leading indicators in the middle phase of treatment. Two other factors accounted for 64% of the variance in EAT scores. The findings of this study suggest that family aggression as measured by the Family Aggression Scale is a significant index of pathology in anorexics' families and is also a clinically meaningful measure of improved conflict resolution during systemic family therapy.

  7. Antithrombotic Therapy in Cardiac Embolism

    PubMed Central

    Cervera, Álvaro; Chamorro, Ángel

    2010-01-01

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

  8. Advances in antithrombotic agents.

    PubMed

    Chakrabarti, Ranjan; Das, Saibal Kumar

    2007-07-01

    Thrombosis is the condition where an imbalance in the homeostatic mechanism results in unwanted intravascular thrombus formation. Imbalances in this highly regulated process of coagulation and anticoagulation can lead to a variety of pathophysiological conditions leading to stroke, pulmonary heart attack and other serious conditions. In the western world, thromboembolic diseases are the leading cause of morbidity and mortality. Remarkable progress has occurred over the last decade in the development of antithrombotic drugs, which can be classified into 3 major categories - Anticoagulants, Antiplatelets and thrombolytics. Increased understanding of the pathobiology of thrombotic and vascular disorders has helped researchers to target novel pathways involving the coagulation, thrombolytic, fibrinolytic and integrin systems. Traditionally aspirin and unfractionated heparin was used for myocardial infarction. Newer antiplatelet agents such as, clopidogrel, GP IIb/IIIa inhibitors, low molecular weight heparin, direct thrombin inhibitors and several improved thrombolytic agents have been introduced for clinical use. This review will discuss different important drugs, which have been launched in recent years and also some new targets pursued by different companies. PMID:17630943

  9. CHADS2 and CHA2DS2-VASc scores as bleeding risk indices for patients with atrial fibrillation: the Bleeding with Antithrombotic Therapy Study.

    PubMed

    Toyoda, Kazunori; Yasaka, Masahiro; Uchiyama, Shinichiro; Iwade, Kazunori; Koretsune, Yukihiro; Nagata, Ken; Sakamoto, Tomohiro; Nagao, Takehiko; Yamamoto, Masahiro; Gotoh, Jun; Takahashi, Jun C; Minematsu, Kazuo

    2014-05-01

    The CHADS2 and CHA2DS2-VASc scores, that is, ischemic stroke risk indices for patients having atrial fibrillation (AF), may also be useful as bleeding risk indices. Japanese patients with AF, who routinely took oral antithrombotic agents were enrolled from a prospective, multicenter study. The CHADS2 and CHA2DS2-VASc scores were assessed based on information at entry. Scores of 0, 1 and ⩾2 were defined as the low, intermediate and high ischemic risk categories, respectively, for each index. Of 1221 patients, 873 took warfarin, 114 took antiplatelet agents and 234 took both. The annual incidence of ischemic stroke was 0.76% in the low-risk category, 1.46% in the intermediate-risk category and 2.90% in the high-risk category by CHADS2 scores, and 1.44, 0.42 and 2.50%, respectively, by CHA2DS2-VASc scores. The annual incidence of major bleeding in each category was 1.52, 2.19 and 2.25% by CHADS2, and 1.44, 1.69 and 2.24% by CHA2DS2-VASc. After multivariate adjustment, the CHADS2 was associated with ischemia (odds ratio 1.76, 95% confidence interval 1.03-3.38 per 1-category increase) and the CHA2DS2-VASc tended to be associated with ischemia (2.18, 0.89-8.43). On the other hand, associations of the indices with bleeding were weak. In conclusion, bleeding risk increased gradually as the CHADS2 and CHA2DS2-VASc scores increased in Japanese antithrombotic users, although the statistical impact was rather weak compared with their predictive power for ischemic stroke.

  10. 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

  11. Use of Antithrombotic Medications among Elderly Ischemic Stroke Patients

    PubMed Central

    Lichtman, Judith H.; Naert, Lisa; Allen, Norrina B.; Watanabe, Emi; Jones, Sara B.; Barry, Lisa C.; Bravata, Dawn M.; Goldstein, Larry B.

    2011-01-01

    Background The use of antithrombotic medications after ischemic stroke is recommended for deep vein thrombosis (DVT) prophylaxis and secondary stroke prevention. We assessed the rate of receipt of these therapies among eligible ischemic stroke patients aged ≥65 years and determined the effects of age and other patient characteristics on treatment. Methods and Results The analysis included Medicare fee-for-service beneficiaries discharged with ischemic stroke (ICD-9 433, 434, 436) randomly selected for inclusion in the Medicare Health Care Quality Improvement Program’s National Stroke Project 1998–1999, 2000–2001. Patients discharged from non-acute facilities, transferred, or terminally ill were excluded. Receipt of in-hospital pharmacological DVT prophylaxis, antiplatelet medication, anticoagulants for atrial fibrillation, and antithrombotic medications at discharge were assessed in eligible patients, stratified by age (65–74, 75–84, 85+ yrs). Descriptive models identified characteristics associated with treatment. Among 31,554 patients, 14.9% of those eligible received pharmacologic DVT prophylaxis, 83.9% antiplatelet drugs, 82.8% anticoagulants for atrial fibrillation, and 74.2% were discharged on an antithrombotic medication. Rates of treatment decreased with age, and were lowest for patients aged 85 years or older. Admission from a skilled nursing facility and functional dependence were associated with lower treatment rates. Conclusions There was substantial underuse of antithrombotic therapies among elderly ischemic stroke patients, particularly among the very elderly, those admitted from skilled nursing facilities, and patients with functional dependence. The reasons for low use of antithrombotic therapies, including the apparent underuse of DVT prophylaxis in otherwise eligible patients, require further investigation. PMID:21098780

  12. Etiology of hypercoagulable state in women with recurrent fetal loss without other causes of miscarriage from Southern Italy: new clinical target for antithrombotic therapy

    PubMed Central

    D’Uva, Maristella; Di Micco, Pierpaolo; Strina, Ida; Ranieri, Antonio; Alviggi, Carlo; Mollo, Antonio; Fabozzi, Francesca; Cacciapuoti, Lucia; di Frega, Maria Teresa Scotto; Iannuzzo, Mariateresa; De Placido, Giuseppe

    2008-01-01

    Background: Recurrent fetal loss (RPL) is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL. Patients and methods: Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M. Results: Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data. Conclusion: After a thorough evaluation of other causes of miscarriage women affected by RPL should be tested for thrombophilia. Our data demonstrated 78% of women with one or combined thrombophilic conditions. Differences with previous studies should be related to difference in the inclusion and exclusion criteria and ethnic background. Because these patients often also show a hypercoagulable state, it an antithrombotic treatment before and during pregnancy may improve their clinical outcome (ie, secondary prevention of miscarriage and primary thromboprophylaxis). PMID:19707467

  13. Adjunct Antimicrobial Therapy and Periodontal Surgery to Treat Generalized Aggressive Periodontitis: A Case Report.

    PubMed

    Irokawa, Daisuke; Makino-Oi, Asako; Fujita, Takahisa; Yamamoto, Shigeki; Tomita, Sachiyo; Saito, Atsushi

    2016-01-01

    Here we report a case of generalized aggressive periodontitis treated with periodontal therapy including adjunct antimicrobial therapy and periodontal surgery. The patient was a 22-year-old woman who presented with the chief complaint of gingival recession. Baseline examination revealed generalized plaque deposition and gingival inflammation. Thirty-nine percent of the sites had a probing depth (PD) of 4-6 mm and 2% a PD of ≥7 mm; 63% exhibited bleeding on probing (BOP). Radiographic examination revealed vertical bone loss in the molars and horizontal bone loss in other teeth. Microbiological examination of subgingival plaque revealed the presence of Aggregatibacter actinomycetemcomitans and Tannerella forsythia. Oral health-related quality of life was assessed as a measure of patient-reported outcome. Based on a clinical diagnosis of generalized aggressive periodontitis, initial periodontal therapy and adjunct antimicrobial therapy were implemented. After reducing inflammation and subgingival bacteria, open flap debridement was performed for teeth with a PD of ≥4 mm. Reevaluation showed no sites with a PD of ≥5 mm, a minimal level of BOP, and a marked reduction in the level of the targeted periodontal pathogens. The patient's oral health-related quality of life was slightly worsened during supportive periodontal therapy (SPT). Implementation of adjunct antimicrobial therapy targeting periodontal pathogens and subsequent periodontal surgery resulted in improvement in periodontal and microbiological parameters. This improvement has been adequately maintained over a 2-year period. However, additional care is necessary to further improve the patient's oral health-related quality of life during SPT. PMID:27320300

  14. Radiation therapy for aggressive fibromatosis (desmoid tumors): Results of a national Patterns of Care Study

    SciTech Connect

    Micke, Oliver . E-mail: omicke@benign-news.de; Seegenschmiedt, M. Heinrich

    2005-03-01

    Purpose: After a general Patterns of Care Study (PCS) the German Cooperative Group on Radiotherapy for Benign Diseases (GCG-BD) initiated a multicenter cohort study to analyze the radiation therapy practice for aggressive fibromatosis. Methods and materials: In 2002 a PCS was conducted in all German radiotherapy (RT) institutions by mailing a standardized structured questionnaire, to assess patients accrual, number, pretreatment, treatment indications, RT, and target volume concepts for irradiation in aggressive fibromatosis. In addition, the treatment outcome of individual patients was evaluated. The PCS was structured and analyzed according to the model for quality assessment by Donabedian in three major components: structure, process, and outcome evaluation. Results: A total of 101 institutions returned the questionnaire: 52.7% reported satisfactory clinical data and experience for inclusion in this analysis. A total accrual rate of 278 patients per year was reported with median number of 2 cases (1-7 cases) per institution. Satisfactory data for a long-term clinical evaluation was reported for 345 patients from 19 different institutions. The applied total doses ranged between 36 and 65 Gy (median, 60 Gy). The local control rate was 81.4% in primary RT for unresectable tumors and 79.6% in postoperative RT. No acute or late radiation toxicities > Grade 2 (RTOG) were observed. No clear dose-response relationship could be established, but there was a tendency toward a lower local control rate in patients with a higher number of operative procedures before RT and patients treated for recurrent aggressive fibromatosis. Conclusions: This study comprises the largest database of cases reported for RT in aggressive fibromatosis. Radiotherapy provides a high local control rate in the postoperative setting and in unresectable tumors. This PCS may serve as a starting point for a national or international prospective multicenter study or registry, or both.

  15. An overview of antithrombotics in ischemic stroke.

    PubMed

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

    2016-06-19

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

  16. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina

    PubMed Central

    Bruno, Oscar D.; Juárez-Allen, Lea; Christiansen, Silvia B.; Manavela, Marcos; Danilowicz, Karina; Vigovich, Carlos; Gómez, Reynaldo M.

    2015-01-01

    We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson's syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing's disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration. PMID:26106414

  17. 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

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

    PubMed

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

    2004-04-01

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

  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

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

    2016-07-01

    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. 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.

  2. 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

  3. 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

  4. Results of a consensus meeting on the use of argatroban in patients with heparin-induced thrombocytopenia requiring antithrombotic therapy - a European Perspective.

    PubMed

    Alatri, Adriano; Armstrong, Anna-Elina; Greinacher, Andreas; Koster, Andreas; Kozek-Langenecker, Sibylle A; Lancé, Marcus D; Link, Andreas; Nielsen, Jørn D; Sandset, Per M; Spanjersberg, Alexander J; Spannagl, Michael

    2012-04-01

    Argatroban has been introduced as an alternative parenteral anticoagulant for HIT-patients in several European countries in 2005. In 2009 a panel of experts discussed their clinical experience with argatroban balancing risks and benefits of argatroban treatment in managing the highly procoagulant status of HIT-patients. This article summarizes the main conclusions of this round table discussion. An ongoing issue is the appropriate dosing of argatroban in special patient groups. Therefore, dosing recommendations for different HIT-patient groups (ICU patients; non-ICU patients, paediatric patients, and for patients undergoing renal replacement therapies) are summarized in this consensus statement. Because of the strong correlation between argatroban dosing requirements and scores used to characterize the severity of illness (APACHE; SAPS, SOFA) suitable dosing nomograms are given. This consensus statement contributes to clinically relevant information on the appropriate use and monitoring of argatroban based on the current literature, and provides additional information from clinical experience. As the two other approved drugs for HIT, danaparoid and lepirudin are either currently not available due to manufacturing problems (danaparoid) or will be withdrawn from the market in 2012 (lepirudin), this report should guide physicians who have limited experience with argatroban how to use this drug safely in patients with HIT. PMID:22178575

  5. Efficacy of Cognitive-Behavioral Therapy in the Treatment of Children with ADHD, with and without Aggressiveness.

    ERIC Educational Resources Information Center

    Miranda, Ana; Presentacion, Maria Jesus

    2000-01-01

    Examines the efficacy of a cognitive-behavioral self-control therapy on children with ADHD Explores whether the combination of training in self-control with training in anger management has better outcomes on two subgroups of hyperactive children, aggressive (n=16) and nonaggressive (n=16). Overall improvements were found, however improvements of…

  6. Patient's Guide to Perioperative Antithrombotic Therapy

    MedlinePlus

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

  7. Patient's Guide to Antithrombotic Therapy in Stroke

    MedlinePlus

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

  8. 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.

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

    PubMed

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

    1998-01-01

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

  10. Optimal Oral Antithrombotic Regimes for Patients with Acute Coronary Syndrome: A Network Meta-Analysis

    PubMed Central

    Ye, Yicong; Xie, Hongzhi; Zeng, Yong; Zhao, Xiliang; Tian, Zhuang; Zhang, Shuyang

    2014-01-01

    Objective We performed a network meta-analysis to investigate the optimal antithrombotic regime by indirectly comparing new antithrombotic regimes (new P2Y12 inhibitors plus aspirin or novel oral anticoagulants on top of traditional dual antiplatelet therapy [DAPT]) in patients with acute coronary syndrome (ACS). Methods A systematic search of MEDLINE, EMBASE, and the Cochrane databases was performed to identify all phase 3 randomized controlled trials (RCTs) involving novel oral anticoagulants or oral P2Y12 inhibitors in patients with ACS. Major adverse cardiac events (MACE) were regarded as the efficacy endpoint, and thrombolysis in myocardial infarction (TIMI) major bleeding events were used as the safety endpoint. The net clinical benefit was calculated as the sum of MACE and TIMI major bleeding events. Results Five phase 3 RCTs with 64,476 ACS patients were included. Although there were no significant differences among new antithrombotic regimes, rivaroxaban 5 mg twice daily plus traditional DAPT might be the most effective in reducing the incidence of MACE, accompanying the highest risk of TIMI major bleeding. Ticagrelor plus aspirin presented slight advantage on the net clinical benefit over other new antithrombotic regimes, with the highest probability of being the best regimes for net clinical benefit (35.0%), followed by prasugrel plus aspirin (28.0%), and rivaroxaban 2.5 mg twice daily plus traditional DAPT (19.5%). Conclusion Novel antithrombotic regime with ticagrelor plus aspirin brings a larger clinical benefit in comparison with other regimes, suggesting that it may be the optimal antithrombotic regime for patients with ACS. PMID:24614630

  11. Protein disulfide isomerase inhibitors constitute a new class of antithrombotic agents

    PubMed Central

    Jasuja, Reema; Passam, Freda H.; Kennedy, Daniel R.; Kim, Sarah H.; van Hessem, Lotte; Lin, Lin; Bowley, Sheryl R.; Joshi, Sucharit S.; Dilks, James R.; Furie, Bruce; Furie, Barbara C.; Flaumenhaft, Robert

    2012-01-01

    Thrombosis, or blood clot formation, and its sequelae remain a leading cause of morbidity and mortality, and recurrent thrombosis is common despite current optimal therapy. Protein disulfide isomerase (PDI) is an oxidoreductase that has recently been shown to participate in thrombus formation. While currently available antithrombotic agents inhibit either platelet aggregation or fibrin generation, inhibition of secreted PDI blocks the earliest stages of thrombus formation, suppressing both pathways. Here, we explored extracellular PDI as an alternative target of antithrombotic therapy. A high-throughput screen identified quercetin-3-rutinoside as an inhibitor of PDI reductase activity in vitro. Inhibition of PDI was selective, as quercetin-3-rutinoside failed to inhibit the reductase activity of several other thiol isomerases found in the vasculature. Cellular assays showed that quercetin-3-rutinoside inhibited aggregation of human and mouse platelets and endothelial cell–mediated fibrin generation in human endothelial cells. Using intravital microscopy in mice, we demonstrated that quercetin-3-rutinoside blocks thrombus formation in vivo by inhibiting PDI. Infusion of recombinant PDI reversed the antithrombotic effect of quercetin-3-rutinoside. Thus, PDI is a viable target for small molecule inhibition of thrombus formation, and its inhibition may prove to be a useful adjunct in refractory thrombotic diseases that are not controlled with conventional antithrombotic agents. PMID:22565308

  12. 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

  13. 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

  14. 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…

  15. 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.

  16. 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

  17. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    2015-01-01

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

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

    PubMed Central

    2014-01-01

    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. PMID:24438319

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

    PubMed

    Buccheri, Sergio; Capodanno, Davide

    2016-06-01

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

  3. Perspective on the Use of Sulfated Polysaccharides from Marine Organisms as a Source of New Antithrombotic Drugs

    PubMed Central

    Mourão, Paulo A. S.

    2015-01-01

    Thromboembolic diseases are increasing worldwide and always require anticoagulant therapy. We still need safer and more secure antithrombotic drugs than those presently available. Sulfated polysaccharides from marine organisms may constitute a new source for the development of such drugs. Investigation of these compounds usually attempts to reproduce the therapeutic effects of heparin. However, we may need to follow different routes, focusing particularly in the following aspects: (1) defining precisely the specific structures required for interaction of these sulfated polysaccharides with proteins of the coagulation system; (2) looking for alternative mechanisms of action, distinct from those of heparin; (3) identifying side effects (mostly pro-coagulant action and hypotension rather than bleeding) and preparing derivatives that retain the desired antithrombotic action but are devoid of side effects; (4) considering that sulfated polysaccharides with low anticoagulant action on in vitro assays may display potent effects on animal models of experimental thrombosis; and finally (5) investigating the antithrombotic effect of these sulfated polysaccharides after oral administration or preparing derivatives that may achieve this effect. If these aspects are successfully addressed, sulfated polysaccharides from marine organisms may conquer the frontier of antithrombotic therapy and open new avenues for treatment or prevention of thromboembolic diseases. PMID:25955754

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

    PubMed

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

    2016-07-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. [Aggressive fibromatoses].

    PubMed

    Döhler, J R; Hamelmann, H; Lasson, U

    1984-03-01

    Benign by nature, aggressive fibromatoses (desmoid fibromas) may represent as difficult therapeutic problems as malignant tumours. When subtotally resected they tend to recur. But spontaneous regression is possible. Expense and limits of their surgical treatment are discussed with reference to seven patients. In five cases primary affliction of bone was evident. There are three reports given in detail: In the first, malignant transformation may be due to radiation therapy and hemipelvectomy could not prevent recurrence. In the second, spontaneous regression of untreated pelvic affection may have occurred. In the third, several resections and amputation of the leg failed to cure congenital infantile fibromatosis.

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

    PubMed

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

    2015-01-01

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

  8. 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

  9. [Comparative analysis of arterial bioprostheses with various antithrombotic modification].

    PubMed

    Barbarash, L S; Burkov, N N; Kudriavtseva, Iu A; Anufriev, A I; Zhuravleva, I Iu

    2012-01-01

    The present study was aimed at comparing the results of remote patency ol arterial bioprosthcses «KemAngioprosthesis» in infrainguinal position with various antithromhotic modifi cation. We analyzed the outcomes in a total of 133 patients who were subdivided into two groups: Group I (n=91) underwent implantation of hioprostheses with antithrombotic modifi calion by non-fractionated heparin. and Group II (n=42) received prostheses treated with low-molecular-weight heparin «Clexane». Patients of the both groups underwent comprehensive analysis of the haemostatic system, blood plasma lipid spectrum, as well as duplex scanning of the prosthesis. 39 (42.9%) Group I patients and 6 (13.6%) Group II patients were found to have developed thromboses. Besides, 14 (I5.4%) Group I patients were diagnosed as hawing restenosis of the anastomosis site, with this complication observed in 3 (7.3%) Group II patients. The results of the analysis demonstrated better remote patency of bioprostheses with antithromhotic modifi cation by low-molecular-weight heparin «Clexane». Dynamic follow up of the patients made it possible to carry out timely correction of medicamentous therapy, as well as at early stages to reveal restenosis of anastomoses followed by endovascular correction. PMID:22929666

  10. Implementation of a Hemostatic and Antithrombotic Stewardship program.

    PubMed

    Reardon, David P; Atay, Julie K; Ashley, Stanley W; Churchill, William W; Berliner, Nancy; Connors, Jean M

    2015-10-01

    Hemostatic and antithrombotic (HAT) agents are high risk, high cost products. They require close monitoring and dose titration to adequately treat or prevent thrombosis while avoiding bleeding events. Incorporating the principles of inpatient anticoagulation management service into a stewardship program not only improves outcomes and decreases cost, but also improves transitions of care, exposes gaps in therapy management, and leads to the development of institution specific protocols and guidelines. We implemented a HAT Stewardship to provide real time clinical surveillance and management of these agents in an effort to optimize appropriate use, decrease serious adverse events, and minimize costs. The stewardship is staffed daily by an interdisciplinary team comprised of a pharmacist, hematology attending, and medical director. The stewardship focuses on (1) management of heparin-induced thrombocytopenia (HIT), (2) management of patients with Hemophilia A/B with inhibitors and acquired Factor VIII deficiency due to inhibitors, (3) oversight of anticoagulation in patients on extracorporeal membrane oxygenation and (4) assistance with anticoagulation management for patients with mechanical cardiac assist devices. Through implementation of this service, we have been able to demonstrate improved patient care and a positive economic impact exceeding the cost of this program by almost sixfold. Other centers should consider instituting a HAT Stewardship to maximize patient outcomes and minimize adverse events.

  11. Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs.

    PubMed

    Islam, Md Asiful; Alam, Fahmida; Khalil, Md Ibrahim; Sasongko, Teguh Haryo; Gan, Siew Hua

    2016-01-01

    Globally, thrombosis-associated disorders are one of the main contributors to fatalities. Besides genetic influences, there are some acquired and environmental risk factors dominating thrombotic diseases. Although standard regimens have been used for a long time, many side effects still occur which can be life threatening. Therefore, natural products are good alternatives. Although the quest for antithrombotic natural products came to light only since the end of last century, in the last two decades, a considerable number of natural products showing antithrombotic activities (antiplatelet, anticoagulant and fibrinolytic) with no or minimal side effects have been reported. In this review, several natural products used as antithrombotic agents including medicinal plants, vegetables, fruits, spices and edible mushrooms which have been discovered in the last 15 years and their target sites (thrombogenic components, factors and thrombotic pathways) are described. In addition, the side effects, limitations and interactions of standard regimens with natural products are also discussed. The active compounds could serve as potential sources for future research on antithrombotic drug development. As a future direction, more advanced researches (in quest of the target cofactor or component involved in antithrombotic pathways) are warranted for the development of potential natural antithrombotic medications (alone or combined with standard regimens) to ensure maximum safety and efficacy. PMID:26951101

  12. 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

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

    PubMed

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

    2016-01-01

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

  14. Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment

    PubMed Central

    Taira, Al V.; Butler, Wayne M.; Galbreath, Robert W.; Fiano, Ryan; Wallner, Kent E.; Adamovich, Edward

    2013-01-01

    Purpose To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods Two thousand two hundred and thirty four patients were treated with prostate brachytherapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D90 was 119% and V100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non-prostate death as a competing risk. Results For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions With the dose escalation achieved by high quality brachytherapy dosimetry, even high-risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the presence of micrometastatic disease prior to treatment is rare, even in high risk patients. PMID:24474970

  15. 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

  16. Translation and Clinical Development of Antithrombotic Aptamers.

    PubMed

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

    2016-06-01

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

  17. 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. PMID:23026665

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

    PubMed

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

    2016-05-01

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

  19. Aggressive Therapy for Patients with Non-small Cell Lung Carcinoma and Synchronous Brain-only Oligometastatic Disease is Associated with Long-term Survival

    PubMed Central

    Gray, Phillip J.; Mak, Raymond H.; Yeap, Beow Y.; Cryer, Sarah K.; Pinnell, Nancy E.; Christianson, Laura W.; Sher, David J.; Arvold, Nils D.; Baldini, Elizabeth H.; Chen, Aileen B.; Kozono, David E.; Swanson, Scott J.; Jackman, David M.; Alexander, Brian M.

    2015-01-01

    Objectives Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation. Materials and Methods We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain. Results Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046). Conclusion Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively. PMID:24974152

  20. 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

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

    MedlinePlus

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

  2. 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.

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

    PubMed

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

    2016-09-01

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

  4. 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…

  5. A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs.

    PubMed

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

    2016-08-01

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

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

    PubMed

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

    2015-08-01

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

  7. Factor Xa inhibitors: new anti-thrombotic agents and their characteristics.

    PubMed

    Ieko, Masahiro; Tarumi, Takashi; Nakabayashi, Toru; Yoshida, Mika; Naito, Sumiyoshi; Koike, Takao

    2006-01-01

    Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin. Various types of low molecular weight (LMW) heparin, which function as semi-selective and indirect FXa inhibitors, are replacing unfractionated heparin (UFH) as agents for the prevention and treatment of venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those, heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of heparin-induced thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW heparin, though it was also associated with an increased rate of major bleeding. Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. For thrombosis therapy, the most desirable type of antithrombotic agent is an orally active drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized therapy strategies. PMID:16146728

  8. Locally advanced adenocarcinoma of the rectum presenting with necrotising fasciitis of the perineum: successful management with early aggressive surgery and multimodal therapy.

    PubMed

    Ferreira, Luís; Alexandrino, Henrique; Soares Leite, Júlio; Castro Sousa, Francisco

    2015-12-16

    Colorectal cancer is a common malignant neoplasm and its treatment usually involves surgery associated, in some cases, depending on the staging, with chemoradiotherapy. Necrotising fasciitis of the perineum is a highly lethal infection of the perineum, perirectal tissues and genitals, requiring emergency surgical debridement, broad-spectrum antibiotics and control of sepsis. We present the case of a 59-year-old man with necrotising fasciitis of the perineum as the first clinical manifestation of locally advanced adenocarcinoma of the rectum, in which successful management consisted of early and aggressive surgical debridement, followed by multimodal therapy with curative intent. 2 years and 6 months after surgery the patient is well, with no evidence of local or systemic relapse.

  9. Antithrombotic Medication for Cardioembolic Stroke Prevention

    PubMed Central

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

    2011-01-01

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

  10. 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.

  11. 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…

  12. 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.

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

    PubMed

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

    2016-03-01

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

  14. Antithrombotic Effects of Amaranthus hypochondriacus Proteins in Rats.

    PubMed

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

    2016-03-01

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

  15. 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.

  16. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis.

    PubMed

    van Rhee, Frits; Bolejack, Vanessa; Hollmig, Klaus; Pineda-Roman, Mauricio; Anaissie, Elias; Epstein, Joshua; Shaughnessy, John D; Zangari, Maurizio; Tricot, Guido; Mohiuddin, Abid; Alsayed, Yazan; Woods, Gail; Crowley, John; Barlogie, Bart

    2007-08-01

    Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain-only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain-only secretion (P < .001), creatinine level 176.8 microM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline-reflecting more aggressive disease-and steeper reductions after therapy identified patients with inferior survival.

  17. New approaches in tail-bleeding assay in mice: improving an important method for designing new anti-thrombotic agents.

    PubMed

    Saito, Max Seidy; Lourenço, André Luiz; Kang, Hye Chung; Rodrigues, Carlos Rangel; Cabral, Lucio Mendes; Castro, Helena Carla; Satlher, Plínio Cunha

    2016-06-01

    This report describes a modified, simple, low-cost and more sensitive method to determine bleeding patterns and haemoglobin concentration in a tail-bleeding assay using BALB/c mice and tail tip amputation. The cut tail was immersed in Drabkin's reagent to promote erythrocyte lysis and haemoglobin release, which was monitored over 30 min. The operator was blinded to individual conditions of the mice, which were treated with either saline (NaCl 0.15m), DMSO (0.5%) or clinical anti-thrombotic drugs. Our experimental protocols showed good reproducibility and repeatability of results when using Drabkin's reagent than water. Thus, the use of Drabkin's reagent offered a simple and low-cost method to observe and quantify the bleeding and rebleeding episodes. We also observed the bleeding pattern and total haemoglobin loss using untreated animals or those under anti-coagulant therapy in order to validate the new Drabkin method and thus confirm that it is a useful protocol to quantify haemoglobin concentrations in tail-bleeding assay. This modified method provided a more accurate results for bleeding patterns in mice and for identifying new anti-thrombotic drugs.

  18. Antithrombotic treatment in elderly patients with atrial fibrillation.

    PubMed

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

    2015-04-01

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

  19. 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.

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

    PubMed

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

    2016-11-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2016-11-01

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

  3. Antithrombotic or Anti-Platelet Agents in Patients Undergoing Permanent Pacemaker Implantation

    PubMed Central

    Lee, Chang Kun; Yoo, Sang Yong; Hong, Man Yong

    2012-01-01

    Background and Objectives The growing implantations of electrophysiological devices in the context of increasing rates of chronic antithrombotic therapy in cardiovascular disease patients underscore the importance of an effective periprocedural prophylactic strategy for prevention of bleeding complications. We assessed the risk of significant bleeding complications in patients receiving anti-platelet agents or anticoagulants at the time of permanent pacemaker (PPM) implantation. Subjects and Methods We reviewed bleeding complications in patients undergoing PPM implantation. The use of aspirin or clopidogrel was defined as having taking drugs within 5 days of the procedure and warfarin was changed to heparin before the procedure. A significant bleeding complication was defined as a bleeding incident requiring pocket exploration or blood transfusion. Results Permanent pacemaker implantations were performed in 164 men and 96 women. The mean patient age was 73±11 years old. Among the 260 patients, 14 patients took warfarin (in all of them, warfarin was changed to heparin at least 3 days before procedure), 54 patients took aspirin, 4 patients took clopidogrel, and 25 patients took both. Significant bleeding complications occurred in 8 patients (3.1%), all of them were patients with heparin bridging (p<0.0001). Heparin bridging markedly increased the length of required hospital stay when compare with other groups and the 4 patients (1.5%) that underwent the pocket revision for treatment of hematoma. Conclusion This study suggests that hematoma formation after PPM implantation was rare, even among those who had taken the anti-platelet agents. The significant bleeding complications frequently occurred in patients with heparin bridging therapy. Therefore, heparin bridging therapy was deemed as high risk for significant bleeding complication in PPM implantation. PMID:22977449

  4. Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.

    PubMed

    Pacheco, R G; Vicente, C P; Zancan, P; Mourão, P A

    2000-09-01

    The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent. PMID:10997797

  5. Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from an echinoderm.

    PubMed

    Pacheco, R G; Vicente, C P; Zancan, P; Mourão, P A

    2000-09-01

    The antithrombotic activity of a fucosylated chondroitin sulfate extracted from the body wall of a sea cucumber was assessed using a stasis thrombosis model in rats. Intravenous administration of the polysaccharide reduced thrombosis in a dose-dependent manner. We also compared the antithrombotic action of the sea cucumber chondroitin sulfate with that of standard mammalian glycosaminoglycans, mainly heparin and dermatan sulfate. Intravascular injection of fucosylated chondroitin sulfate at the dose totally preventing thrombus formation produced a much more intense modification of the plasma anticoagulant activity than antithrombotic doses of unfractionated heparin, low-molecular-weight heparin and mammalian dermatan sulfate. Thus, it is possible that the mechanism of antithrombotic action of these polysaccharides are different. For fucosylated chondroitin sulfate, it depends mostly on modifications of the plasma anticoagulant activity, but it may involve additional effects in the case of mammalian glycosaminoglycans, perhaps modifications induced in the cells of the vessel wall. The anticoagulant and possibly the antithrombotic actions of fucosylated chondroitin sulfate are mostly dependent on heparin cofactor II activity, and both are markedly reduced with the decrease of the chain size of the polymer. Overall, the sulfated polysaccharide from the invertebrate revealed an unequivocal effect in preventing experimental venous thrombosis, is a useful tool to investigate the antithrombotic action in mammals and may offer an alternative for future development of a new therapeutic agent.

  6. 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.…

  7. 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

  8. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids.

    PubMed

    Robinson, Jennifer G; Stone, Neil J

    2006-08-21

    Omega-3 fatty acids from both marine and plant sources have been shown to reduce the risk of coronary artery disease death. Although their beneficial cardiovascular effects are thought to be due to their antiarrhythmic properties, omega-3 fatty acids also have been shown to have a wide range of antiatherosclerotic and antithrombotic effects in animal and human studies. Review of the findings of randomized, controlled trials published through August 2005 shows that omega-3 fatty acids of marine origin consistently lower elevated plasma triglyceride levels in a dose-dependent fashion, with greater efficacy at higher triglyceride levels. Smaller effects on lowering blood pressure, improving endothelial function, and increasing plasma levels of high-density lipoprotein cholesterol were also found. No consistent effects on other lipid, hemostatic, inflammatory, glucose tolerance, or plaque stabilization parameters were found. Epidemiologic studies show more consistent reductions in the incidence of nonfatal myocardial infarction and ischemic stroke than do the clinical trials of increased omega-3 fatty acid intake, which suggests important confounding factors in observational studies. Ongoing clinical trials may clarify the non-antiarrhythmic benefits of omega-3 fatty acid supplementation. PMID:16919516

  9. Fucosylated chondroitin sulfate as a new oral antithrombotic agent.

    PubMed

    Fonseca, Roberto J C; Mourão, Paulo A S

    2006-12-01

    Fucosylated chondroitin sulfate is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of sulfated fucose branches. We have shown that intravascular injection of fucosylated chondroitin sulfate inhibits thrombus formation in a venous and an arterial shunt model in rats. Since this compound resists digestion by enzymes that cleave mammalian glycosaminoglycans, we investigated the possibility that fucosylated chondroitin sulfate might be absorbed after oral administration. In fact, after oral administration of fucosylated chondroitin sulfate to rats, we observed a dose-dependent increase in the plasma anticoagulant activity, as assessed by assays for activated partial thromboplastin time (aPTT) and thrombin time (TT) (about 3- and 5-fold, respectively) and by anti-IIa activity. Furthermore, animals receiving daily oral doses of this glycosaminoglycan showed a decrease in thrombus weight on experimental models of venous and arterial shunt thrombosis. This antithrombotic action clearly has a strong relationship with anticoagulant activity. Similar doses of heparin administered orally had no effect on the plasma anticoagulant activity or on the thrombus weight. Finally, we observed that fucosylated chondroitin sulfate given orally to rats did not modify the bleeding time. Overall, our results indicate that fucosylated chondroitin sulfate is absorbed after oral administration and could become a promising oral anticoagulant.

  10. [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

  11. 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.

  12. Aggressive behavior problems.

    PubMed

    Beaver, B V

    1986-12-01

    Accurate diagnosis of the cause of aggression in horses is essential to determining the appropriate course of action. The affective forms of aggression include fear-induced, pain-induced, intermale, dominance, protective, maternal, learned, and redirected aggressions. Non-affective aggression includes play and sex-related forms. Irritable aggression and hypertestosteronism in mares are medical problems, whereas genetic factors, brain dysfunction, and self-mutilation are also concerns. PMID:3492250

  13. 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.

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

    PubMed Central

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

    2014-01-01

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

  15. Antithrombotic properties of SSR182289A, a new, orally active thrombin inhibitor.

    PubMed

    Lorrain, J; Millet, L; Lechaire, I; Lochot, S; Ferrari, P; Visconte, C; Sainte-Marie, M; Lunven, C; Berry, C N; Schaeffer, P; Herbert, J-M; O'Connor, S E

    2003-02-01

    N-[3-[[[(1S)-4-(5-Amino-2-pyridinyl)-1-[[4-difluoromethylene)-1-piperidinyl]carbonyl]butyl]amino]sulfonyl][1,1'-biphenyl]-2-yl]acetamide hydrochloride (SSR182289A) is a novel, potent, and selective thrombin inhibitor. We have examined the antithrombotic properties of SSR182289A administered by i.v. and p.o. routes in several different animal thrombosis models in comparison with reference antithrombotic agents. Oral administration of SSR182289A produced dose-related antithrombotic effects in the following models; rat venous thrombosis (ED(50) 0.9 mg/kg p.o.), rat silk thread arterio-venous (AV) shunt (ED(50) 3.8 mg/kg p.o.), rat thromboplastin-induced AV shunt (ED(50) 3.1 mg/kg p.o.), rat carotid artery thrombosis (ED(200) 5.9 mg/kg p.o.), and rabbit venous thrombosis (ED(50) 7.5 mg/kg p.o.). Administered as an i.v. bolus, SSR182289A showed antithrombotic activity in the above models with ED(50)/ED(200) values in the range of 0.2 to 1.9 mg/kg i.v. SSR182289A increased rat tail transection bleeding time at doses > or =10 mg/kg p.o. In the rat thromboplastin-induced AV shunt model, SSR182289A 10 mg/kg p.o. produced marked antithrombotic effects at 30, 60, 120, and 240 min after administration. Hence, SSR182289A demonstrates potent oral antithrombotic properties in animal venous, AV-shunt, and arterial thrombosis models.

  16. New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous antithrombotics.

    PubMed

    Mignon, Laurent; Goichot, Christophe; Ratel, Philippe; Cagnin, Gérald; Baudry, Michel; Praly, Jean-Pierre; Boubia, Benaïssa; Barberousse, Véronique

    2003-06-16

    In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides. PMID:12791280

  17. Relational aggression in marriage.

    PubMed

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

    2010-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. Punishment of elicited aggression.

    PubMed

    Azrin, N H

    1970-07-01

    Aversive shocks are known to produce aggression when the shocks are not dependent on behavior and to suppress behavior when the shocks are arranged as a dependent punisher. These two processes were studied by presenting non-dependent shock to monkeys at regular intervals, thereby producing biting attacks on a pneumatic tube. Immediate shock punishment was stimultaneously delivered for each biting attack. The attacks were found to decrease as a function of increasing punishment intensity. These results show that aggression is eliminated by direct punishment of the aggression even when the stimulus that is used as a punisher otherwise causes the aggression. PMID:4988590

  2. 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

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

    PubMed

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

    2016-01-01

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

  4. 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

    2015-06-01

    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.

  5. A Strategic Approach to Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    2001-01-01

    Discusses two issues raised by Underwood et al.: the distinction between indirect and relational forms of aggression, and implications of indirect aggression for definitions of aggression; and the normative view of aggression that indicates that aggressive individuals may be socially skilled. Suggests that both issues lead to the conclusion that…

  6. 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.

  7. Third Person Instigated Aggression.

    ERIC Educational Resources Information Center

    Gaebelein, Jacquelyn

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

  8. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

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

  9. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-02-01

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

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

    PubMed

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

    2014-01-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene-haemin-glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π-π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene-haemin-glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices. PMID:24518643

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

    PubMed Central

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

    2014-01-01

    The integration of multiple synergistic catalytic systems can enable the creation of biocompatible enzymatic mimics for cascading reactions under physiologically relevant conditions. Here we report the design of a graphene–haemin–glucose oxidase conjugate as a tandem catalyst, in which graphene functions as a unique support to integrate molecular catalyst haemin and enzymatic catalyst glucose oxidase for biomimetic generation of antithrombotic species. Monomeric haemin can be conjugated with graphene through π–π interactions to function as an effective catalyst for the oxidation of endogenous L-arginine by hydrogen peroxide. Furthermore, glucose oxidase can be covalently linked onto graphene for local generation of hydrogen peroxide through the oxidation of blood glucose. Thus, the integrated graphene–haemin–glucose oxidase catalysts can readily enable the continuous generation of nitroxyl, an antithrombotic species, from physiologically abundant glucose and L-arginine. Finally, we demonstrate that the conjugates can be embedded within polyurethane to create a long-lasting antithrombotic coating for blood-contacting biomedical devices. PMID:24518643

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

    PubMed

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

    2016-01-01

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

  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. PMID:26974373

  15. 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.

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. 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

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

    PubMed

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

    2015-09-01

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

  20. Treatment of heparin-induced thrombocytopenia before and after the implementation of a hemostatic and antithrombotic stewardship program.

    PubMed

    Ritchie, Brianne M; Sylvester, Katelyn W; Reardon, David P; Churchill, William W; Berliner, Nancy; Connors, Jean M

    2016-11-01

    In October 2013, we implemented a hemostatic and antithrombotic (HAT) stewardship program with the primary focus of ensuring appropriate use of intravenous direct thrombin inhibitors (DTI) in patients with heparin-induced thrombocytopenia (HIT). We sought to compare the duration and cost of DTI therapy for the management of HIT before and after implementation of the HAT stewardship program. Following institutional review board approval, we conducted a single center, retrospective chart review of all patients with a suspected diagnosis of HIT as assessed by an anti-heparin-PF4 enzyme-linked immunosorbent assay 6 months pre-HAT and post-HAT implementation. Patients were excluded if they were initiated on a DTI at an outside hospital, had a prior episode of HIT, or received mechanical circulatory support. Clinical characteristics, including demographics, comorbidities, medications, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. A total of 592 patients were included; 333 patients were evaluated pre-HAT, while 259 patients were evaluated post-HAT. The mean duration of DTI treatment was significantly decreased in the post-HAT cohort (6.64 vs 5.17 days, p = 0.01), primarily driven by decreased duration of use for patients with suspected HIT (4.07 vs 2.86 days, p = 0.01). The HAT Stewardship program demonstrated a total decrease in annual costs associated with the diagnosis and management of HIT of $248,500. Our results indicate that the implementation of the HAT stewardship program had a significant impact on reducing the duration and costs of DTI therapy and the costs of laboratory evaluations in the management of HIT at our institution.

  1. 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.

  2. [Treatment of aggressive non-Hodgkin's lymphomas].

    PubMed

    Moreno Nogueira, J A; Ruiz Borrego, M; Pérez Valderrama, B; Valero Azbiru, M

    2009-02-01

    Aggressive non-Hodgkin's lymphomas (NHL) in localized stages I and II, without bulky areas and a fair International Prognostic Factor (IPI) (30% of all cases) have high possibilities of cure (80%) when treated with combined chemotherapy, CHOP or CHOP-like (3-4 courses) followed by locoregional radiation therapy. Localized aggressive non-Hodgkin's lymphomas with signs of poor prognosis or advanced stages (III and IV) must be treated with rituximab-containing immunochemotherapy. As second line in responding patients (DHAP, ESHAP, MINE, VIM, DICE, etc., and rituximab) high doses chemotherapy with hematopoietic growth factor support should be considered, although not in refractory patients.

  3. 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…

  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. Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases.

    PubMed

    Silverberg, D S; Wexler, D; Blum, M; Sheps, D; Schwartz, D; Yachnin, T; Baruch, R; Tchebiner, J; Zubkov, A; Shaked, M; Steinbruch, S; Keren, G; Iaina, A

    2001-01-01

    The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.

  6. Fatal persistent methicillin-resistant Staphylococcus aureus bacteremia and vascular graft infections complicated with the formation of multiple abscesses despite aggressive medical therapy

    PubMed Central

    Shiba, Mikio; Maeda, Hideaki; Shiono, Motomi

    2015-01-01

    A 40-year-old man underwent ascending aorta replacement for an acute type A aortic dissection. After the operations, methicillin-resistant Staphylococcus aureus was identified in sputum and blood cultures. Although anti-methicillin-resistant Staphylococcus aureus drugs were administered, most of the intermittent blood cultures remained positive. The focus of methicillin-resistant Staphylococcus aureus infection was not evident in the early stages, and no specific symptoms such as abscess or endocarditis were observed. However, abscesses in the brain, mediastinum and spleen were found 3 years after the operation. The minimum inhibitory concentration of vancomycin gradually increased from 1 to 4 µg/mL during the course of treatment. This case provides evidence for a potential role of combination therapy. PMID:27489691

  7. 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…

  8. 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.

  9. Antithrombotic activity of NSP-513, a novel selective phosphodiesterase 3 inhibitor, on femoral arterial thrombosis induced by physical stenosis and electrical current: comparison of antithrombotic and hemodynamic effects.

    PubMed

    Hirose, H; Mashiko, S; Kimura, T; Ishida, F; Mochizuki, N; Nishibe, T; Nishikibe, M

    2000-04-01

    NSP-513, a novel potent and selective phosphodiesterase 3 (PDE 3) inhibitor, and cilostazol, a previously developed PDE 3 inhibitor, were compared with respect to antiplatelet, antithrombotic, and hemodynamic effects. In the in vitro antiplatelet aggregation studies, NSP-513 and cilostazol inhibited collagen-induced canine platelet aggregation with median inhibitory concentration (IC50) values of 0.093 and 3.1 miccroM, respectively, and inhibited adenosine diphosphate (ADP)-induced canine platelet aggregation with IC50 values of 0.15 and 12 microM, respectively. For ADP-induced platelet aggregation, the presence of prostaglandin E1 (PGE1; 3 and 10 nM) further decreased the IC50 values for NSP-513 to 0.11 and 0.032 microM, respectively. In ex vivo antiplatelet aggregation studies, orally administered NSP-513 (0.03-1 mg/kg) and cilostazol (50 mg/kg) inhibited collagen-induced canine platelet aggregation. In an in vivo canine femoral arterial thrombosis model, intraduodenally administered NSP-513 (0.01-0.03 mg/ kg) dose-dependently prevented thrombus formation without any changes in blood pressure, heart rate, or bleeding time. In conscious dogs, NSP-513 at oral doses of > or =0.3 mg/kg produced hemodynamic changes such as decreased blood pressure and increased heart rate and LVdP/dt(max). Thus the minimal hemodynamically effective dose of NSP-513 was 0.3 mg/kg, and the hemodynamic effects of this dose were comparable to those of 50 mg/kg of cilostazol. In conclusion, these data suggest that NSP-513 has in vivo selectivity for antiplatelet and antithrombotic activities over hemodynamic activity, and that the selectivity of NSP-513 is higher than that of cilostazol in dogs.

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

    PubMed

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

    2013-08-19

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

  11. 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.

  12. 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

  13. 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.

  14. Aggression in Drosophila.

    PubMed

    Kravitz, Edward A; Fernandez, Maria de la Paz

    2015-10-01

    Aggression is used by essentially all species of animals to gain access to desired resources, including territory, food, and potential mates: Fruit flies are no exception. In Drosophila, both males and females compete in same sex fights for resources, but only males establish hierarchical relationships. Many investigators now study aggression using the fruit fly model, mainly because (a) aggression in fruit flies is a quantifiable well-defined and easily evoked behavior; (b) powerful genetic methods allow investigators to manipulate genes of interest at any place or time during embryonic, larval, pupal or adult life, and while flies are behaving; (c) the growth of the relatively new field of optogenetics makes physiological studies possible at single neuron levels despite the small sizes of neurons and other types of cells in fly brains; and (d) the rearing of fly stocks with their short generation times and limited growth space requirements can easily be performed at relatively low cost in most laboratories. This review begins with an examination of the behavior, both from a historical perspective and then from the birth of the "modern" era of studies of aggression in fruit flies including its quantitative analysis. The review continues with examinations of the roles of genes, neurotransmitters and neurohormones, peptides, nutritional and metabolic status, and surface cuticular hydrocarbons in the initiation and maintenance of aggression. It concludes with suggestions for future studies with this important model system.

  15. 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

  16. 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. PMID:25777266

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

    PubMed

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

    2015-02-01

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

  18. 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.

  19. Interaction of an annexin V homodimer (Diannexin) with phosphatidylserine on cell surfaces and consequent antithrombotic activity.

    PubMed

    Kuypers, Frans A; Larkin, Sandra K; Emeis, Jef J; Allison, Anthony C

    2007-03-01

    Annexin V (AV), a protein with anticoagulant activity, exerts antithrombotic activity by binding to phosphatidylserine (PS), inhibiting activation of serine proteases important in blood coagulation. The potential use of this protein as an anticoagulant is limited as it rapidly passes from the blood into the kidneys due to its relatively small size (36 kDa). We used recombinant DNA technology to produce a homodimer of human AV (DAV, 73 kDa), which exceeds the renal filtration threshold, and has a 6.5-hour half-life in the rat circulation. Human red blood cells with externalized PS were used to show that DAV had a higher affinity for PS-exposing cells than AV. DAV labeling sensitively identifies PS-exposing cells, was found to be a potent inhibitor of the activity of the prothombinase complexes and inhibits the ability of secretory phospholipaseA(2) to hydrolyze phospholipids of PS-exposing cells, reducing the formation of mediators of blood coagulation and reperfusion injury. DAV exerts dose-dependent antithrombotic activity in rat veins. This combination of activities suggests that DAV is a valuable probe to measure PS exposure and may be efficacious as a novel drug in a wide range of clinical situations.

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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

  10. 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

  11. Reverse Discrimination and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Johnson, Stephen D.

    1980-01-01

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

  12. "Ladettes," Social Representations, and Aggression.

    ERIC Educational Resources Information Center

    Muncer, Steven; Campbell, Anne; Jervis, Victoria; Lewis, Rachel

    2001-01-01

    Examined the relationship among "laddishness" (traditionally working-class, youthful, male social behavior by young women), social representations, and self-reported aggression among English college students. Measures of aggression correlated with holding more instrumental representations of aggression. Females indicated no relationship between…

  13. Antithrombotic activity of F 16618, a new PAR1 antagonist evaluated in extracorporeal arterio-venous shunt in the rat.

    PubMed

    Létienne, Robert; Leparq-Panissié, Anne; Calmettes, Yannick; Nadal-Wollbold, Florence; Perez, Michel; Le Grand, Bruno

    2010-06-01

    The purpose of the present work was the evaluation of the antithrombotic activity of a new PAR1 antagonist, F 16618 in arterio-venous shunt in the rat. Arterial thrombosis was induced by insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. F 16618 was administered either by intravenous route (0.63-2.5mg/kg) or by oral route (20-80mg/kg). Oral activity of F 16618 was compared to that of aspirin (20-80mg/kg) and clopidogrel (0.63-10mg/kg). Finally, F 16618 was associated to aspirin and/or clopidogrel to test for possible antithrombotic activity and its effects on bleeding time. SFLLR-induced human platelet aggregation was evaluated in the presence of F 16618, demonstrating the anti-aggregant activity of this compound. F 16618 (1.25mg/kg) significantly delayed the time leading to occlusion by 52+/-17%, without affecting bleeding time and in absence of hemodynamic effects. F 16618 given orally dose-dependently increased the time to occlusion. The maximal effect was observed at 40mg/kg (984+/-95s versus 644+/-17s in vehicle group). Aspirin and clopidogrel also dose-dependently lengthened time to occlusion, but this effect was associated with an increase of bleeding time. F 16618 (20mg/kg) orally associated with either aspirin (40mg/kg) or with clopidogrel (1.25mg/kg) potentiated the antithrombotic effects of both compounds without further increasing of bleeding time. In conclusion, F 16618 exerted a potent antithrombotic activity by intravenous and oral routes, without affecting bleeding time. Furthermore, the antithrombotic activity was potentiated when combined with aspirin or clopidogrel.

  14. 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. PMID:24430131

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

    PubMed

    Huesmann, L R; Guerra, N G

    1997-02-01

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

  16. 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

  17. Aggressive drowsy cache cells

    NASA Astrophysics Data System (ADS)

    Shawkey, H. A.; El-Dib, D. A.; Abid, Z.

    2010-01-01

    An aggressive drowsy cache block management, where the cache block is forced into drowsy mode all the time except during write and read operations, is proposed. The word line (WL) is used to enable the normal supply voltage (V DD_high) to the cache line only when it is accessed for read or write whereas the drowsy supply voltage (V DD_low) is enabled to the cache cell otherwise. The proposed block management neither needs extra cycles nor extra control signals to wake the drowsy cache cell, thereby reducing the performance penalty associated with traditional drowsy caches. In fact, the proposed aggressive drowsy mode can reduce the total power consumption of the traditional drowsy mode by 13% or even more, depending on the cache access rate, access frequency and the CMOS technology used.

  18. 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

  19. 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.

  20. Venous thrombosis after abdominal surgery. A comparison between subcutaneous heparin and antithrombotic stockings, or both

    SciTech Connect

    Rasmussen, A.; Hansen, P.T.; Lindholt, J.; Poulsen, T.D.; Toftdahl, D.B.; Gram, J.; Toftgaard, C.; Jespersen, J.

    1988-01-01

    In an open controlled study, 248 consecutive patients (age more than 40 yrs) admitted for major abdominal surgery were randomized to one of three prophylactic antithrombotic treatments. Eighty-five patients received subcutaneous heparin, 74 patients had graduated compression stockings to the knee (TED stockings), and 89 patients had both subcutaneous heparin and stockings. Treatment began on the evening before operation and continued to complete mobilization, or for not less than five days postoperatively. On the fourth or fifth postoperative day, the patients underwent a /sup 99m/Tc-plasmin test of the lower limbs as a test for deep vein thrombosis. There were 29.7% positive tests in the stocking group, 29.4% in the group with heparin prophylaxis, and 25.8% in the combined group. Differences between treatments were not statistically significant.

  1. [Aggressive fibromatoses in orthopedics].

    PubMed

    Adler, C P; Stock, D

    1986-01-01

    Aggressive fibromatoses which may develop either in soft tissue or in the bone present considerable problems for the pathologist trying to establish a diagnosis as well as for the radiologist and surgeon. In radiographs, a destruction of the soft and osseous tissue is seen which suggests a malignant tumor. Histologically a monomorphic connective tissue prevails in the biopsy showing no essential signs of malignancy. Under pathoanatomical aspects often a benign proliferation of the connective tissue is assumed. Surgically the tumor may either be removed in a too radical and mutilating way, or the excision may remain incomplete. Two cases of desmoplastic bone fibroma (aggressive fibromatosis in the ulna and in the sacrum) are described in which the complete tumor removal led to healing, whereas the incomplete excision of the tumor resulted in recurrences. Aggressive fibromatosis represents a semimalignant tumor which has a locally destructive and invasive growth tendency but does not metastasize. The various fibromatoses are defined with regard to their biological growth tendency and the therapeutic consequences are discussed.

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

    PubMed

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

    2001-03-01

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

  3. Interspecies comparison of the antiplatelet, antithrombotic, and hemorrhagic effects of SR 121566A, a novel nonpeptide GP IIb/IIIa antagonist.

    PubMed

    Bernat, A; Hoffmann, P; Savi, P; Lalé, A; Herbert, J M

    1999-06-01

    We report the results from an interspecies comparison of the antiplatelet, antithrombotic, and hemorrhagic actions of SR 121566A, a novel nonpeptide antiplatelet agent with high affinity and specificity for the GP IIb/IIIa complex. SR 121566A exhibited in vitro antiplatelet activity against adenosine diphosphate (ADP)-induced aggregation with a rank order of potency [humans = baboons = dogs] > marmosets > guinea pigs > rabbits. These in vitro findings were predictive for the ex vivo antiplatelet potency after i.v. administration of SR 121566A to dogs, guinea pigs, and rabbits [median effective dose (ED50) values, 0.02, 0.05, and 0.15 mg/kg]. The antiplatelet actions of SR 121566A translated into an acute antithrombotic effect in an arteriovenous shunt model after i.v. administration in dogs, guinea pigs, rabbits, and marmosets (ED50, 0.08, 0.10, 0.50, and 0.007 mg/kg). Hemorrhagic effects of SR 121566A were observed in guinea pigs and rabbits at doses that represented 2-3 times the antithrombotic ED50, whereas in marmosets, no bleeding was observed at the antithrombotic ED90. These results demonstrate that SR 121566A exhibits favorable actions in terms of antithrombotic potency and hemostatic safety in different animal species, suggesting that, in humans, SR 121566A will be a good candidate as an antithrombotic compound.

  4. Girls, aggression, and emotion regulation.

    PubMed

    Conway, Anne M

    2005-04-01

    Many studies have demonstrated that boys are more aggressive than girls (see J. D. Coie & K. Dodge, 1997, for a review) and that emotion regulation difficulties are associated with problematic behaviors (N. Eisenberg & R. A. Fabes, 1999; M. Gilliom, D. S. Shaw, J. E. Beck, M. A. Schonberg, & J. L. Lukon, 2002). However, recent findings indicate that gender differences in aggressive behaviors disappear when assessments are broadened to include relational aggression--behaviors designed to harm the relationship goals of others by spreading rumors, gossiping, and eliciting peer rejection of others. Moreover, although difficulties regulating emotions have been reported for physically aggressive children, little research has examined these processes in relationally aggressive children. This article argues that investigation into the associations between emotion regulation and relational aggression is a critical direction for future research on the etiology and prevention of mental health problems in girls. PMID:15839769

  5. [The aggressive child (author's transl)].

    PubMed

    Harbauer, H

    1978-08-01

    In children a "normal" aggressiveness should be distinguished from "hostile" and "inhibited" aggression; the latter usually become apparent as heteroaggressive or autoaggressive behaviour. Autoaggression is more common with younger children. Different hypotheses about the origin of aggressiveness are discussed. In the younger child nail biting, trichotillomania, rocking, an intensified phase of contrariness and enkopresis may have components of aggressiveness. In older children and adolescents dissocial forms of development, drug taking, attempted suicid, and anorexia nervosa may be parts of aggressive behaviour. Minimal brain dysfunction, autism, and postencephalitic syndromes predominate amongst organic alterations of the brain as causes for aggressive behaviour. Particularly the Lesch-Nyhan-syndrome, but equally the Cornelia de Lange-syndrome show autoaggressive tendencies.

  6. Why does aspirin decrease the risk of venous thromboembolism? On old and novel antithrombotic effects of acetyl salicylic acid.

    PubMed

    Undas, A; Brummel-Ziedins, K; Mann, K G

    2014-11-01

    It is well established that aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, is effective in secondary prevention of arterial thromboembolic events. The pooled results of the recent randomized, multicenter WARFASA and ASPIRE aspirin trials showed a 32% reduction in the rate of recurrence of venous thromboembolism (VTE) in patients receiving aspirin following VTE. These clinical data support evidence that platelets contribute to the initiation and progression of venous thrombosis and aspirin inhibits thrombin formation and thrombin-mediated coagulant reactions. In addition to the known acetylation of serine 529 residue in platelet cyclooxygenase-1, the postulated mechanisms of aspirin-induced antithrombotic actions also involve the acetylation of other proteins in blood coagulation, including fibrinogen, resulting in more efficient fibrinolysis. This review summarizes current knowledge on the aspirin-induced antithrombotic effects that potentially explain clinical studies showing reduced rates of VTE events in aspirin-treated subjects.

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

    PubMed

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

    2002-01-01

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

  8. A sulfated polysaccharide, fucans, isolated from brown algae Sargassum vulgare with anticoagulant, antithrombotic, antioxidant and anti-inflammatory effects.

    PubMed

    Dore, Celina Maria P Guerra; das C Faustino Alves, Monique Gabriela; Will, Luiza Sheyla E Pofírio; Costa, Thiago G; Sabry, Diego A; de Souza Rêgo, Leonardo Augusto R; Accardo, Camila M; Rocha, Hugo Alexandre O; Filgueira, Luciana Guimarães A; Leite, Edda Lisboa

    2013-01-01

    Fucan (SV1) sulfated polysaccharides from the brown algae Sargassum vulgare were extracted, fractionated in acetone and examined with respect to chemical composition, anticoagulant, anti-inflammatory, antithrombotic effects and cellular proliferation. These polysaccharides contain low levels of protein, high level of carbohydrate and sulfate. Monosaccharides analysis revealed that SV1 was composed of fucose, galactose, xylose, glucuronic acid and mannose. SV1 polysaccharide prolonged activated partial thromboplastin time (aPTT) and exhibited high antithrombotic action in vivo, with a concentration ten times higher than heparin activity. PSV1, a purified form in gel filtration showed very low biological activities. SV1 stimulated the enzymatic activity of FXa. Its action on DPPH radical scavenging activity was 22%. This polymer has no cytotoxic action (hemolytic) on ABO and Rh blood types in different erythrocyte groups. It displays strong anti-inflammatory action at all concentrations tested in the carrageenan-induced paw edema model, demonstrated by reduced edema and cellular infiltration. PMID:23044157

  9. Aggressive fibromatosis of anterior maxilla

    PubMed Central

    Shetty, Devi C; Urs, Aadithya B; Ahuja, Puneet; Sikka, Seema

    2011-01-01

    Aggressive fibromatosis is a comparitively rare tumor with unpredictable growth and varying local recurrence rates. It does not develop distant metastases but locally it shows an aggressive and infiltrative behavior. Clinically, aggressive fibromatosis manifests as a painless, firm, often rapidly enlarging mass, fixed to underlying bone or soft tissue. It is never encapsulated. Histologically, it is rich in collagen and fibroblastic cells that are devoid of hyperchromatic or atypical nuclei, but with more variable cellularity in different tumor sections. PMID:21731285

  10. Anti-thrombotic effect of a novel formula from Corni fructus with malic acid, succinic acid and citric acid.

    PubMed

    Zhang, Qi-Chun; Zhao, Yue; Bian, Hui-Min

    2014-05-01

    Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2 , 6-K-PGF1α , cAMP, cGMP and NO in rat plasma were determined. In vitro assay of αIIbβ3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF1α , cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit αIIbβ3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis.

  11. 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…

  12. Plasma butyrylcholinesterase regulates ghrelin to control aggression.

    PubMed

    Chen, Vicky Ping; Gao, Yang; Geng, Liyi; Parks, Robin J; Pang, Yuan-Ping; Brimijoin, Stephen

    2015-02-17

    Ongoing mouse studies of a proposed therapy for cocaine abuse based on viral gene transfer of butyrylcholinesterase (BChE) mutated for accelerated cocaine hydrolysis have yielded surprising effects on aggression. Further investigation has linked these effects to a reduction in circulating ghrelin, driven by BChE at levels ∼ 100-fold above normal. Tests with human BChE showed ready ghrelin hydrolysis at physiologic concentrations, and multiple low-mass molecular dynamics simulations revealed that ghrelin's first five residues fit sterically and electrostatically into BChE's active site. Consistent with in vitro results, male BALB/c mice with high plasma BChE after gene transfer exhibited sharply reduced plasma ghrelin. Unexpectedly, such animals fought less, both spontaneously and in a resident/intruder provocation model. One mutant BChE was found to be deficient in ghrelin hydrolysis. BALB/c mice transduced with this variant retained normal plasma ghrelin levels and did not differ from untreated controls in the aggression model. In contrast, C57BL/6 mice with BChE gene deletion exhibited increased ghrelin and fought more readily than wild-type animals. Collectively, these findings indicate that BChE-catalyzed ghrelin hydrolysis influences mouse aggression and social stress, with potential implications for humans.

  13. THE IMPACT OF AGGRESSION IN THE CLASSROOM.

    ERIC Educational Resources Information Center

    MCNEIL, ELTON B.; AND OTHERS

    IN THIS INVESTIGATION, AGGRESSION WAS MEASURED FROM FOUR PERSPECTIVES--(1) THE PERCEPTION THAT THE SUBJECT HAD OF HIS AGGRESSION, (2) HIS SATISFACTION, AS HE VIEWED IT, WITH HIS OWN AGGRESSION, (3) THE PERCEPTION THAT THE TEACHER HAD OF THE SUBJECT'S AGGRESSIVENESS, AND (4) THE PERCEPTION OF THE SUBJECT'S AGGRESSIVENESS HELD BY HIS CLASSMATES. IN…

  14. 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…

  15. Psychological Research on Human Aggressiveness

    ERIC Educational Resources Information Center

    Hamburg, D. A.; Brodie, H. K. H.

    1973-01-01

    Discusses research relating to the effects of hormones, neurophysiology, and the environment on animal and human aggression. Indicates that the interactions of biological, psychological and social processes in the development of human aggressiveness should constitute one of the principal frontiers for science in the next two decades. (JR)

  16. 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…

  17. Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities.

    PubMed

    Fuentes, Eduardo; Rodríguez-Pérez, Wilson; Guzmán, Luis; Alarcón, Marcelo; Navarrete, Simón; Forero-Doria, Oscar; Palomo, Iván

    2013-01-01

    Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography-mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation.

  18. Cloning of habutobin cDNA and antithrombotic activity of recombinant protein

    SciTech Connect

    Sunagawa, Masanori Nakamura, Mariko; Kosugi, Tadayoshi

    2007-11-03

    The habutobin cDNA was cloned from total RNA extracted from venom glands of Trimeresurus flavoviridis (the habu snake). The conceptual translation of 1539 bp of habutobin cDNA consists of 236 amino acids and its molecular weight is 25.7 kDa. Histidine (His)-tagged recombinant habutobin fusion protein, pET-r-habutobin and AcNPV-r-habutobin, was purified by bacterial system and baculoviral system, respectively. After refolding pET-r-habutobin, there were two protein bands at about 32 kDa and 65 kDa, indicating that habutobin might be produced as a monomer protein and processed to form two concatenated protein. Purified AcNPV-r-habutobin dose-dependently increased fibrin forming activity and inhibited collagen-induced aggregation of rabbit washed platelets. Thus, AcNPV-r-habutobin produced by baculoviral system is very useful for study on structure-function relationship, which is necessary for developing an antithrombotic drug from habutobin.

  19. Towards a new method of assessing the antithrombotic properties of pharmaceutical compounds.

    PubMed

    Hartley, R W

    1992-01-01

    This paper describes the initial development of a novel technique which, following further work, may prove suitable for the in vivo screening of pharmaceutical compounds for evidence of antithrombotic activity. Its inception is shown to be a consequence of an amalgamation of those ultrasonic methods associated with the clinical detection of occlusions and laser Doppler velocimetry. Both topics are discussed and then brought together through a concept whereby the efficacy of compounds might be evaluated in animal models by measuring the velocity of blood in the fluid jet formed distal to an induced thrombus. In accord with the evolved measurement rationale there then follows a description of a laser Doppler microscope, an analyser for extracting the required velocity information from the Doppler shift spectrum and a series of experiments using a thrombus analogue in a narrow-bore glass flow tube. Finally, the results from one in vivo experiment are presented. Speculation about how the method might be developed further is contained within the discussion. PMID:1533255

  20. The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity

    PubMed Central

    Ampofo, Emmanuel; Später, Thomas; Müller, Isabelle; Eichler, Hermann; Menger, Michael D.; Laschke, Matthias W.

    2015-01-01

    Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine in vivo the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound. PMID:26569265

  1. Antithrombotic effect of chikusetsusaponin IVa isolated from Ilex paraguariensis (Maté).

    PubMed

    Dahmer, Tabitha; Berger, Markus; Barlette, Adriana Gregory; Reck, José; Segalin, Jéferson; Verza, Simone; Ortega, George González; Gnoatto, Simone Cristina Baggio; Guimarães, Jorge Almeida; Verli, Hugo; Gosmann, Grace

    2012-12-01

    The triterpene chikusetsusaponin IVa was isolated from the fruit of Ilex paraguariensis. Using biochemical and pharmacological methods, we demonstrated that chikusetsusaponin IVa (1) prolongs the recalcification time, prothrombin time, activated partial thromboplastin time, and thrombin time of normal human plasma in a dose-dependent manner, (2) inhibits the amidolytic activity of thrombin and factor Xa upon synthetic substrates S2238 and S2222, (3) inhibits thrombin-induced fibrinogen clotting (50% inhibition concentration, 199.4 ± 9.1 μM), and (4) inhibits thrombin- and collagen-induced platelet aggregation. The results also indicate that chikusetsusaponin IVa preferentially inhibits thrombin in a competitive manner (K(i)=219.6 μM). Furthermore, when administered intravenously to rats, chikusetsusaponin IVa inhibited thrombus formation in a stasis model of venous thrombosis, although it did not induce a significant bleeding effect. Chikusetsusaponin IVa also prolonged the ex vivo activated partial thromboplastin time. Altogether, these data suggest that chikusetsusaponin IVa exerts antithrombotic effects, including minor hemorrhagic events. This appears to be important for the development of new therapeutic agents.

  2. Next-generation antithrombotics in ischemic stroke: preclinical perspective on ‘bleeding-free antithrombosis'

    PubMed Central

    Kraft, Peter; De Meyer, Simon F; Kleinschnitz, Christoph

    2012-01-01

    The present antithrombotic drugs used to treat or prevent ischemic stroke have significant limitations: either they show only moderate efficacy (platelet inhibitors), or they significantly increase the risk for hemorrhages (thrombolytics, anticoagulants). Although most strokes are caused by thrombotic or embolic vessel occlusions, the pathophysiological role of platelets and coagulation is largely unclear. The introduction of novel transgenic mouse models and specific coagulation inhibitors facilitated a detailed analysis of molecular pathways mediating thrombus formation in models of acute ischemic stroke. Prevention of early platelet adhesion to the damaged vessel wall by blocking platelet surface receptors glycoprotein Ib alpha (GPIbα) or glycoprotein VI (GPVI) protects from stroke without provoking bleeding complications. In addition, downstream signaling of GPIbα and GPVI has a key role in platelet calcium homeostasis and activation. Finally, the intrinsic coagulation cascade, activated by coagulation factor XII (FXII), has only recently been identified as another important mediator of thrombosis in cerebrovascular disease, thereby disproving established concepts. This review summarizes the latest insights into the pathophysiology of thrombus formation in the ischemic brain. Potential clinical merits of novel platelet inhibitors and anticoagulants as powerful and safe tools to combat ischemic stroke are discussed. PMID:22805877

  3. Flurbinitroxybutylester: a novel anti-inflammatory drug has enhanced antithrombotic activity.

    PubMed

    Cirino, G; Cicala, C; Mancuso, F; Baydoun, A R; Wallace, J L

    1995-07-01

    We have recently shown that the introduction of a nitroxybutylester moiety into flurbiprofen, to form Flurbi-NO, results in a compound with markedly reduced undesired effects in the gastrointestinal tract. This effect has been shown to be linked to nitric oxide release from the Flurbi-NO. Here we have investigated whether this is associated with a reduction in platelet aggregability in vivo, as assessed in a mouse model of thromboembolism and a rat model of platelet aggregation, and found in both models that Flurbi-NO is more potent than flurbiprofen at inhibiting collagen-induced platelet aggregation. Further in vitro studies using human washed platelets and cells in culture suggest that this is due to the release of NO from Flurbi-NO following the action of (possibly plasma) esterases. Together with our earlier data, these results strongly suggest that Flurbi-NO and other members of this class of drugs, have particular potential as anti-thrombotic agents devoid of gastrointestinal side effects.

  4. Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities

    PubMed Central

    Fuentes, Eduardo; Rodríguez-Pérez, Wilson; Guzmán, Luis; Alarcón, Marcelo; Navarrete, Simón; Forero-Doria, Oscar; Palomo, Iván

    2013-01-01

    Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography—mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation. PMID:24454503

  5. Heparin alters viral serpin, serp-1, anti-thrombolytic activity to anti-thrombotic activity.

    PubMed

    Li, Xing; Schneider, Heather; Peters, Andrew; Macaulay, Colin; King, Elaine; Sun, Yunming; Liu, Liying; Dai, Erbin; Davids, Jennifer A; McFadden, Grant; Lucas, Alexandra

    2008-01-01

    Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways. PMID:18949070

  6. Instrumental and Social Outcome Expectations of High-Aggressive and Low-Aggressive Boys.

    ERIC Educational Resources Information Center

    Cillessen, Antonius H. N.; Hubbard, Julie A.

    This study examined high-aggressive and low-aggressive boys' ratings of the effectiveness of aggressive and assertive strategies for solving social problems involving hypothetical peers and actual peers. Subjects were 66 third-grade boys (11 groups of 6 boys each for a total of 22 high-aggressive, 22 low-aggressive, and 22 average aggressive boys)…

  7. Role of genetic factors in the pathogenesis of aggressive periodontitis.

    PubMed

    Vieira, Alexandre R; Albandar, Jasim M

    2014-06-01

    This article critically reviews the evidence for a role of genetic factors in the pathogenesis of aggressive periodontitis and discusses the study approaches commonly used to identify genetic risk factors of this disease. Available data suggest that aggressive periodontitis is caused by mutations in multiple genes, combined with environmental effects. Syndromic periodontal diseases include certain monogenic disorders that express phenotypes showing aggressive forms of periodontitis, and the genetic triggering factors of most of these syndromes have been identified. Other periodontal disease phenotypes seem to occur through different genetic predisposition patterns. Case-control and genome-wide studies have been used to investigate the association with gene polymorphisms. Association studies and the familial aggregation of aggressive periodontitis suggest a significant genetic component in the increased predisposition to this disease. There is evidence to support the contribution of a few major genes or of multiple small-effects genes. In addition, there is evidence of gene-gene and gene-environment interaction effects. Early studies suggested an X-linked mode of transmission of aggressive periodontitis, and subsequent studies support an autosomal mode. Genetic studies have the potential to improve the screening programs of subjects at risk for developing aggressive periodontitis and may enhance treatment outcome through gene therapy.

  8. 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)

  9. Involvement in internet aggression during early adolescence.

    PubMed

    Werner, Nicole E; Bumpus, Matthew F; Rock, Daquarii

    2010-06-01

    The current study examined concurrent and longitudinal predictors of early adolescents' involvement in Internet aggression. Cross-sectional results (N = 330; 57% female) showed that the likelihood of reporting Internet aggression was higher among youth who spent more time using Internet-based technologies to communicate with friends and who were themselves targets of Internet aggression. Offline relational aggression and beliefs supportive of relational and physical aggression also predicted concurrent involvement in Internet aggression. We used longitudinal data (N = 150; 51% female) to distinguish between youth who were aggressive in traditional contexts only (i.e., school) from those who were aggressive both online and offline. These results indicated that youth who were aggressive both online and offline were older at the initial assessment, were targets of Internet aggression, and held beliefs more supportive of relational aggression than youth who were aggressive offline only. Implications and directions for future research are discussed.

  10. 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

  11. Predicting workplace aggression and violence.

    PubMed

    Barling, Julian; Dupré, Kathryne E; Kelloway, E Kevin

    2009-01-01

    Consistent with the relative recency of research on workplace aggression and the considerable media attention given to high-profile incidents, numerous myths about the nature of workplace aggression have emerged. In this review, we examine these myths from an evidence-based perspective, bringing greater clarity to our understanding of the predictors of workplace aggression. We conclude by pointing to the need for more research focusing on construct validity and prevention issues as well as for methodologies that minimize the likelihood of mono-method bias and that strengthen the ability to make causal inferences.

  12. Gender differences in reactive and proactive aggression.

    PubMed

    Connor, Daniel F; Steingard, Ronald J; Anderson, Jennifer J; Melloni, Richard H

    2003-01-01

    The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth. PMID:12723901

  13. Massage Therapy Research

    ERIC Educational Resources Information Center

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria

    2007-01-01

    Massage therapy has been notably effective in preventing prematurity, enhancing growth of infants, increasing attentiveness, decreasing depression and aggression, alleviating motor problems, reducing pain, and enhancing immune function. This review covers massage therapy research from the last decade, as an update to the American Psychologist 1998…

  14. Therapy of Lies

    ERIC Educational Resources Information Center

    Price, Sean

    2012-01-01

    Conversion therapy comes in many forms, ranging from informal chats with counselors to aggressive physical coercion, but all are based on the belief that a gay male or a lesbian can be changed "back" to heterosexual behavior. It is not just alarmed parents who turn to this therapy. Many LGBT individuals seek out such treatment in an effort to…

  15. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    patient who underwent en bloc resection who continued to have back pain. CONCLUSIONS Gross-total resection or subtotal resection in combination with vertebroplasty or adjuvant radiation therapy to treat residual tumor seems sufficient in the treatment of aggressive vertebral hemangiomas. En bloc resection appears to provide a similar oncological benefit, but it carries higher morbidity to the patient. PMID:27476849

  16. Surgical treatment of aggressive vertebral hemangiomas.

    PubMed

    Vasudeva, Viren S; Chi, John H; Groff, Michael W

    2016-08-01

    patient who underwent en bloc resection who continued to have back pain. CONCLUSIONS Gross-total resection or subtotal resection in combination with vertebroplasty or adjuvant radiation therapy to treat residual tumor seems sufficient in the treatment of aggressive vertebral hemangiomas. En bloc resection appears to provide a similar oncological benefit, but it carries higher morbidity to the patient.

  17. Quantifying Aggressive Behavior in Zebrafish.

    PubMed

    Teles, Magda C; Oliveira, Rui F

    2016-01-01

    Aggression is a complex behavior that influences social relationships and can be seen as adaptive or maladaptive depending on the context and intensity of expression. A model organism suitable for genetic dissection of the underlying neural mechanisms of aggressive behavior is still needed. Zebrafish has already proven to be a powerful vertebrate model organism for the study of normal and pathological brain function. Despite the fact that zebrafish is a gregarious species that forms shoals, when allowed to interact in pairs, both males and females express aggressive behavior and establish dominance hierarchies. Here, we describe two protocols that can be used to quantify aggressive behavior in zebrafish, using two different paradigms: (1) staged fights between real opponents and (2) mirror-elicited fights. We also discuss the methodology for the behavior analysis, the expected results for both paradigms, and the advantages and disadvantages of each paradigm in face of the specific goals of the study. PMID:27464816

  18. Investigation into the mechanism(s) of antithrombotic effects of carbon monoxide releasing molecule-3 (CORM-3).

    PubMed

    Soni, Hitesh; Jain, Mukul; Mehta, Anita A

    2011-06-01

    Carbon monoxide (CO) like nitric oxide (NO) has been recognized as activator of soluble guanylate cyclase (sGC) in many physiological functions. Studies, which demonstrate the mechanisms by which CO inhibits platelet aggregation in in vivo models, are few. Here we investigated the possible involvement of sGC, NO, plasminogen activator inhibitor (PAI-1) and p38 MAP Kinase in antithrombotic effects of CO released by a novel, water-soluble, CO releasing molecule-3 (CORM-3) using rat. The effects of CORM-3 on in vitro and ex vivo platelet aggregation induced by thrombin as well as in in vivo thrombosis models were studied. When added to rat washed platelets in in vitro study, CORM-3 (100 and 200 μM) inhibited thrombin-induced platelet aggregation. Similarly, antiplatelet effect was also observed when 3mg/kg i.v. infusion of CORM-3 administered for 10 minutes in ex vivo study using rat. Interestingly, in presence of inhibitor of sGC (ODQ, 10mg/kg,i.p.) and inhibitor of nitric oxide synthase (L-NAME, 30 mg/kg,i.p.), inhibition of thrombin-induced aggregation by CORM-3 was significantly blocked. Notably, in presence of inhibitor of K(ATP) channel (glibenclamide, 10mg/kg,i.p.) and p38 MAP Kinase (SCIO-469, 1mg/kg, i.p.), inhibition of aggregation by CORM-3 was not blocked. In in vivo studies using animal models of thrombosis, we found that CORM-3-mediated antithrombotic effect was dependent on activation of sGC, NO and suppression of PAI-1 in arterial thrombosis and Arterio-Venous (A-V) shunt models. Therefore, we concluded that antithrombotic activity of CORM-3 may be mediated by activation of sGC, NO and inhibition of PAI-1.

  19. Antiplatelet and antithrombotic activities of essential oil from wild Ocotea quixos (Lam.) Kosterm. (Lauraceae) calices from Amazonian Ecuador.

    PubMed

    Ballabeni, Vigilio; Tognolini, Massimiliano; Bertoni, Simona; Bruni, Renato; Guerrini, Alessandra; Rueda, Gabriela Moreno; Barocelli, Elisabetta

    2007-01-01

    Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors.

  20. Music, Substance Use, and Aggression

    PubMed Central

    Chen, Meng-Jinn; Miller, Brenda A.; Grube, Joel W.; Waiters, Elizabeth D.

    2016-01-01

    Objective This study investigated whether young people’s substance use and aggressive behaviors are related to their listening to music containing messages of substance use and violence. Method Data were collected using self-administered questionnaires and from a sample of community college students aged 15-25 (N = 1056; 43% male). A structural equation modeling method was used to simultaneously assess the associations between listening to various genres of music, alcohol use, illicit drug use, and aggressive behaviors, taking into account respondents’ age, gender, race/ethnicity, and level of sensation seeking. Results Listening to rap music was significantly and positively associated with alcohol use, problematic alcohol use, illicit drug use, and aggressive behaviors when all other variables were controlled. Additionally, alcohol and illicit drug use were positively associated with listening to musical genres of techno and reggae. Control variables such as sensation seeking, age, gender and race/ethnicity were significantly related to substance use and aggressive behaviors. Conclusion The findings suggest that young people’s substance use and aggressive behaviors may be related to their frequent exposure to music containing references to substance use and violence. Conversely, music listening preference may reflect some personal predispositions or lifestyle preferences. Alternatively, substance use, aggression and music preference are independent constructs, but share common “third factors.” PMID:16608146

  1. Antithrombotic effect of argatroban on the pial vessels of the rat: a study with He-Ne laser-induced thrombus formation.

    PubMed

    Sasaki, Y; Morii, S; Yamashita, T; Yamamoto, J

    1993-01-01

    The antithrombotic effect of the synthetic thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (argatroban) was investigated in cerebral vessels of the rat. An occlusive thrombus was formed in pial vessels using a He-Ne laser in a closed cranial window technique. Argatroban retarded the formation of thrombi in a dose-dependent manner. The antithrombotic effect of a single intravenous dose of argatroban at 0.5 mg/kg was diminished after 30 min in arterioles and after 50 min in venules, respectively. The antithrombotic activity was maintained, however, by continuous intravenous infusion (2 mg/kg/h). PMID:8365687

  2. Bleeding Risk and Antithrombotic Strategy in Patients with Sinus Rhythm Heart Failure with Reduced Ejection Fraction Treated with Warfarin or Aspirin

    PubMed Central

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y. H.; Buchsbaum, Richard; Sacco, Ralph L.; Levin, Bruce; Di Tullio, Marco R.; Qian, Min; Mann, Douglas L.; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J.P.; Graham, Susan; Labovitz, Arthur J.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L.P.; Homma, Shunichi

    2015-01-01

    We sought to assess the performance of existing bleeding risk scores, such as HAS-BLED or OBRI, in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell’s c-statistic and net-reclassification improvement (NRI) index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly higher c-statistic (0.72 vs 0.61; p=0.03) compared to HAS-BLED, though the NRI for comparing OBRI to HAS-BLED was not significant (0.32, 95% CI - 0.18-0.37). Performance of the OBRI and HAS-BLED risk scores were similar for the aspirin arm. For participants with OBRI score of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (HR 0.51, 95% CI 0.26-0.98, p=0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66-2.30, p=0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27-1.15, p=0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99-8.22, p<0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in HFrEF patients in SR, and could be tested for potentially identifying patients with a favorable risk / benefit profile for antithrombotic therapy with warfarin. PMID:26189039

  3. Normative beliefs about aggression and cyber aggression among young adults: a longitudinal investigation.

    PubMed

    Wright, Michelle F; Li, Yan

    2013-01-01

    This longitudinal study examined normative beliefs about aggression (e.g., face-to-face, cyber) in relation to the engagement in cyber aggression 6 months later among 126 (69 women) young adults. Participants completed electronically administered measures assessing their normative beliefs, face-to-face and cyber aggression at Time 1, and cyber aggression 6 months later (Time 2). We found that men reported more cyber relational and verbal aggression when compared to women. After controlling for each other, Time 1 face-to-face relational aggression was positively related to Time 2 cyber relational aggression, whereas Time 1 face-to-face verbal aggression was positively related to Time 2 cyber verbal aggression. Normative beliefs regarding cyber aggression was positively related to both forms of cyber aggression 6 months later, after controlling for normative beliefs about face-to-face aggression. Furthermore, a significant two-way interaction between Time 1 cyber relational aggression and normative beliefs about cyber relational aggression was found. Follow-up analysis showed that Time 1 cyber relational aggression was more strongly related to Time 2 cyber relational aggression when young adults held higher normative beliefs about cyber relational aggression. A similar two-way interaction was found for cyber verbal aggression such that the association between Time 1 and Time 2 cyber verbal aggression was stronger at higher levels of normative beliefs about cyber verbal aggression. Results are discussed in terms of the social cognitive and behavioral mechanisms associated with the engagement of cyber aggression.

  4. Normative beliefs about aggression and cyber aggression among young adults: a longitudinal investigation.

    PubMed

    Wright, Michelle F; Li, Yan

    2013-01-01

    This longitudinal study examined normative beliefs about aggression (e.g., face-to-face, cyber) in relation to the engagement in cyber aggression 6 months later among 126 (69 women) young adults. Participants completed electronically administered measures assessing their normative beliefs, face-to-face and cyber aggression at Time 1, and cyber aggression 6 months later (Time 2). We found that men reported more cyber relational and verbal aggression when compared to women. After controlling for each other, Time 1 face-to-face relational aggression was positively related to Time 2 cyber relational aggression, whereas Time 1 face-to-face verbal aggression was positively related to Time 2 cyber verbal aggression. Normative beliefs regarding cyber aggression was positively related to both forms of cyber aggression 6 months later, after controlling for normative beliefs about face-to-face aggression. Furthermore, a significant two-way interaction between Time 1 cyber relational aggression and normative beliefs about cyber relational aggression was found. Follow-up analysis showed that Time 1 cyber relational aggression was more strongly related to Time 2 cyber relational aggression when young adults held higher normative beliefs about cyber relational aggression. A similar two-way interaction was found for cyber verbal aggression such that the association between Time 1 and Time 2 cyber verbal aggression was stronger at higher levels of normative beliefs about cyber verbal aggression. Results are discussed in terms of the social cognitive and behavioral mechanisms associated with the engagement of cyber aggression. PMID:23440595

  5. The CBM signalosome: Potential therapeutic target for aggressive lymphoma?

    PubMed Central

    Yang, Chenghua; David, Liron; Qiao, Qi; Damko, Ermelinda; Wu, Hao

    2014-01-01

    The CBM signalosome plays a pivotal role in mediating antigen-receptor induced NF-κB signaling to regulate lymphocyte functions. The CBM complex forms filamentous structure and recruits downstream signaling components to activate NF-κB. MALT1, the protease component in the CBM complex, cleaves key proteins in the feedback loop of the NF-κB signaling pathway and enhances NF-κB activation. The aberrant activity of the CBM complex has been linked to aggressive lymphoma. Recent years have witnessed dramatic progresses in understanding the assembly mechanism of the CBM complex, and advances in the development of targeted therapy for aggressive lymphoma. Here, we will highlight these progresses and give an outlook on the potential translation of this knowledge from bench to bedside for aggressive lymphoma patients. PMID:24411492

  6. Current Perioperative Management of Anticoagulant and Antiplatelet Use in Neuroendovascular Therapy: Analysis of JR-NET1 and 2

    PubMed Central

    ENOMOTO, Yukiko; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; EGASHIRA, Yusuke

    2014-01-01

    To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patient's data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p < 0.001), hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5% vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p < 0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001, postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients. PMID:24305029

  7. Do Teachers Misbehave? Aggression in School Teams

    ERIC Educational Resources Information Center

    Ben Sasson, Dvora; Somech, Anit

    2015-01-01

    Purpose: Despite growing research on school aggression, significant gaps remain in the authors' knowledge of team aggression, since most studies have mainly explored aggression on the part of students. The purpose of this paper is to focus on understanding the phenomenon of workplace aggression in school teams. Specifically, the purpose of the…

  8. Adolescents' Social Reasoning about Relational Aggression

    ERIC Educational Resources Information Center

    Goldstein, Sara E.; Tisak, Marie S.

    2010-01-01

    We examined early adolescents' reasoning about relational aggression, and the links that their reasoning has to their own relationally aggressive behavior. Thinking about relational aggression was compared to thinking about physical aggression, conventional violations, and personal behavior. In individual interviews, adolescents (N = 103) rated…

  9. Kindergarten Children's Genetic Vulnerabilities Interact with Friends' Aggression to Promote Children's Own Aggression

    ERIC Educational Resources Information Center

    van Lier, Pol; Boivin, Michel; Dionne, Ginette; Vitaro, Frank; Brendgen, Mara; Koot, Hans; Tremblay, Richard E.; Perusse, Daniel

    2007-01-01

    Objective: To examine whether kindergarten children's genetic liability to physically aggress moderates the contribution of friends' aggression to their aggressive behaviors. Method: Teacher and peer reports of aggression were available for 359 6-year-old twin pairs (145 MZ, 212 DZ) as well as teacher and peer reports of aggression of the two best…

  10. Successful treatment of mechanical mitral valve thrombosis without thrombolytic therapy or surgery.

    PubMed

    Al Habib, Hamad F; Tarola, Christopher; Diamantorous, Pantelis; Chu, Michael W A

    2013-11-01

    Prosthetic valve thrombosis is an uncommon, life-threatening complication that often mandates urgent repeat surgery or thrombolytic therapy. We present an alternative approach in a patient with rheumatic heart disease who presented with subacute thrombosis of a recently implanted On-X mechanical mitral valve (On-X Life Technologies Inc, Austin, TX), diagnosed on echocardiography and valve fluoroscopy. The patient refused surgery, hence we elected to treat the patient with high-dose antithrombotic therapy alone. Echocardiographic monitoring demonstrated complete reabsorption of the thrombus within 6 months without any embolic complications. Endogenous fibrinolysis with appropriate antithrombotic therapy might be a suitable option for select, high-risk patients with mechanical mitral valve thrombosis.

  11. Anticoagulant therapy during pregnancy for maternal and fetal acquired and inherited thrombophilia.

    PubMed

    Giannubilo, S R; Tranquilli, A L

    2012-01-01

    Thromboembolism is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Antithrombotic treatment and prophylaxis both before and during pregnancy are based on unfractionated heparin (UH), low-molecularweight heparin (LMWH), Warfarin and Aspirin. The prevalence and severity of thromboembolism during pregnancy and puerperium warrant special consideration of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for those at increased risk of thrombotic events. This paper assesses the safety and efficacy of antithrombotic therapy during pregnancy and the peripartum period. Its cardiovascular and obstetric indications, the evidence of association between thrombophilias and adverse pregnancy outcome, regimens and maternal and fetal side-effects are also discussed. PMID:22876895

  12. [Treatment of inter-specific aggression in cats with the selective serotonin reuptake inhibitor fluvoxamine. A case report].

    PubMed

    Sprauer, S

    2012-01-01

    The article describes the redirected, inter-specific aggression of a Maine Coon cat, which was principally directed towards the owners. The cat reacted towards different, nonspecific sounds with abrupt aggressive behaviour and injured the victims at this juncture with moderate scratching and biting. Exclusively using behaviour therapy did not achieve the desired result, thus the therapy was supported with pharmaceuticals. The cat orally received the selective serotonin re-uptake inhibitor fluvoxamine at an initial dosage of 0.5mg/kg BW once daily. After 4 weeks the application rate was increased to 1.0 mg/kg BW once daily. The medication did not cause any side effects. Together with the behaviour-modulating therapy, carried out parallel to the medication therapy, the aggressive behaviour problem of the cat was resolved. After administration for a period of 63 weeks the fluvoxamine therapy was discontinued by gradually reducing the dose without recurrence of the aggressive behaviour. PMID:23242225

  13. Aggressive Cunninghamella pneumonia in an adolescent.

    PubMed

    Malkan, Alpin D; Wahid, Fazal N; Rao, Bhaskar N; Sandoval, John A

    2014-10-01

    Children with hematologic malignancies may be challenged with life-threatening, invasive fungal infections by organisms that would otherwise have a low potential for virulence in healthy hosts. Presented is a case of a 15-year-old adolescent with B-cell acute lymphoblastic leukemia who was receiving steroids and chemotherapy. He developed cough associated with left chest pain with suspicion for fungal pneumonia. He began systemic antifungal therapy, underwent computed tomography of the chest demonstrating a large cavitary lesion (reversed halo sign) in the left lung. Over a 48-hour period the patient clinically deteriorated with worsening pneumonia and required left thoracotomy with nonanatomic pulmonary resection. This case illustrates the aggressive nature of Cunninghamella pneumonia in patients with hematologic malignancies, and the multidisciplinary approach required to have the greatest possible outcome. PMID:25089609

  14. A two-factor model of aggression.

    PubMed

    Kingsbury, S J; Lambert, M T; Hendrickse, W

    1997-01-01

    This article synthesizes theoretical material from psychology research into a practical model for conceptualizing violence in psychiatric settings. Relevant research and theory are reviewed, focusing on two important behavioral models of aggressive behavior, hostile aggression and instrumental aggression. The concepts of reinforcement, anticipated rewards, specific and nonspecific stimulus-driven aggression, intermediary emotional states in aroused persons, and the aggression stimulus threshold are developed into a bimodal model applicable to the clinical management of violence. The model provides a broad framework for categorizing, understanding, and addressing aggressive behavior in clinical settings.

  15. Nonsurgical treatment of aggressive fibromatosis in the head and neck

    SciTech Connect

    West, C.B. Jr.; Shagets, F.W.; Mansfield, M.J. )

    1989-09-01

    Aggressive fibromatosis is a poorly defined, locally aggressive, yet histologically benign fibroblastic proliferative lesion that may occur in the head and neck. The lesion is highly cellular and locally infiltrative and has a propensity to invade and erode bone, compromising vital structures within the head and neck. However, it is not a true malignancy because it does not have malignant cytologic characteristics nor does it metastasize. We present two cases of aggressive fibromatosis occurring in young adult men. The first case involved a rapidly enlarging mass of the anterior maxilla that involved the upper lip, nasal alae, nasal septum, inferior turbinates, and hard palate. The patient underwent incisional biopsy to confirm the diagnosis. Because of difficulty in determining the actual margins of this extensive lesion and the significant morbidity that would have resulted from surgical resection, we elected to treat this patient with chemotherapy and radiation therapy. The second case was an extensive lesion involving the right temporal bone, pterygomaxillary space, and infratemporal, temporal, and middle cranial fossae. Incisional biopsy confirmed the diagnosis. Because of the lack of functional and cosmetic deficits and the unavoidable morbidity of a surgical resection, this patient was treated with radiation therapy. Although wide field resection is the most satisfactory form of treatment, in situations in which this modality would result in unacceptable morbidity or if surgical margins are positive, then radiation therapy and chemotherapy should be considered. Support for these therapeutic modalities is found in larger series of cases outside the head and neck.

  16. Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

    NASA Astrophysics Data System (ADS)

    Halasa, Salaheldin; Dickinson, Eva

    2014-02-01

    From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

  17. Warfarin therapy for an octogenarian who has atrial fibrillation.

    PubMed

    Gage, B F; Fihn, S D; White, R H

    2001-03-20

    In North America, atrial fibrillation is associated with at least 75 000 ischemic strokes each year. Most of these strokes occur in patients older than 75 years of age. The high incidence of stroke in very elderly persons reflects the increasing prevalence of atrial fibrillation that occurs with advanced age, the high incidence of stroke in elderly patients, and the failure of physicians to prescribe antithrombotic therapy in most of these patients. This failure is related to the increased risk for major hemorrhage with advanced age, obfuscating the decision to institute stroke prophylaxis with antithrombotic therapy. This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy. After concluding that the benefits of warfarin outweigh its risks in this patient, we describe how to initiate warfarin therapy cautiously and how to monitor and dose the drug. We then review five recent randomized, controlled trials that document the increased risk for stroke when an international normalized ratio (INR) of less than 2.0 is targeted among patients with atrial fibrillation. Next, we make the case that cardioversion is not needed for this asymptomatic patient with chronic atrial fibrillation. Instead, we choose to leave the patient in atrial fibrillation and to control his ventricular rate with atenolol. Later, when the INR increases to 4.9, we advocate withholding one dose of warfarin and repeating the INR test. Finally, when the patient develops dental pain, we review the analgesic agents that are safe to take with warfarin and explain why warfarin therapy does not have to be interrupted during a subsequent dental extraction. PMID:11255522

  18. The Passive Aggressive Conflict Cycle

    ERIC Educational Resources Information Center

    Whitson, Signe

    2013-01-01

    Understanding the Passive Aggressive Conflict Cycle (PACC) helps observers to be able to look beyond behavior and better understand what is occurring beneath the surface. This article presents a real-life example of a seemingly minor conflict between a teacher and child that elicited an apparent major overreaction by the adult. Also provided is a…

  19. Epilepsy, aggression, and criminal responsibility.

    PubMed

    Borum, R; Appelbaum, K L

    1996-07-01

    Although epilepsy-related violence can occur, accounts of criminal behavior caused by epilepsy remain rare and unconvincing. The authors describe a case of apparent postictal aggression, resulting in felony assault charges, by a patient who had nocturnal complex partial seizures, followed by what appeared to be sleepwalking and periods of postictal wandering and confusion.

  20. Television Portrayal and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Comstock, George

    This is a review of research relating to the attributes of portrayals which play a role in affecting aggressive behavior. The effects of portrayal can occur at any of three successive stages: acquisition, disinhibition/stimulation/arousal, performance. The older the individual, the more likely the influence is to be in all three stages of…

  1. Enrichment and aggression in primates.

    PubMed

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  2. Biochemistry and Aggression: Psychohematological Model.

    ERIC Educational Resources Information Center

    Foster, Hilliard G., Jr.; Spitz, Reuben T.

    1994-01-01

    Examines biochemical measures in a population of forensic psychiatric inpatients. Regression equations utilizing chemical and biological variables were developed and evaluated to determine their value in predicting the severity and frequency of aggression. Findings strongly suggest the presence of specific biochemical alteration among those…

  3. Risperidone and Explosive Aggressive Autism.

    ERIC Educational Resources Information Center

    Horrigan, Joseph P.; Barnhill, L. Jarrett

    1997-01-01

    In this study, 11 males with autism and mental retardation were administered risperidone. Substantial clinical improvement was noted almost immediately; patients with aggression, self-injury, explosivity, and poor sleep hygiene were most improved. The modal dose for optimal response was 0.5 mg bid. Weight gain was a significant side effect.…

  4. Antithrombotic effect of repeated doses of the ethanolic extract of local olive (Olea europaea L.) leaves in rabbits.

    PubMed

    Dub, Abdallah M; Dugani, Aisha M

    2013-05-22

    The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, which has known cardiovascular health benefits, including those on blood pressure, cholesterol level, and thrombogenesis. All previous animal and clinical studies investigating the beneficial antithrombotic effects of olives have focused on olive oil and a few on olive leaves (OLEs). In this study, the ethanolic extract of OLE was evaluated for its antithrombotic activity in the rabbit model of thrombosis induced by ligature of the vena cava and intravenous administration of tissue thromboplastin. Pre-treatment with 100 or 200 mg/kg per day of the ethanolic extract for 8 weeks significantly prolonged the prothrombin time (PT) in comparison to the control group (12.10 ± 0.35 sec and 14.38 ± 0.29 sec vs. 10.8 ± 0.32 sec, p < 0.05 and 0.001, respectively). In comparison to the control group, the same doses had no statistically significant effect on thrombus weight (16.85 ± 0.67 mg, 16.32 ± 0.35 mg, and 17.81 ± 0.75 mg; p = 0.18 and 0.06) or on activated partial thromboplastin time (APTT) (19.17 ± 0.33 sec, 19.12 ± 0.73 sec, and 18.97 ± 0.41 sec; p = 0.36 and 0.43, respectively). One important finding in this study concerns thrombus morphology. In the extract treatment groups, the thrombus was filament-like and did not adhere to blood vessel walls, whereas in the control group the thrombus was thick and almost completely occluded the vein. Therefore, these results suggest that OLE ethanolic extract can modify the extrinsic coagulation pathway as evidenced by the prolongation of PT and changes in thrombus morphology, enough to justify further research to evaluate its possible antithrombotic effects.

  5. Personal standards for judging aggression by a relationship partner: How much aggression is too much?

    PubMed

    Arriaga, Ximena B; Capezza, Nicole M; Daly, Christine A

    2016-01-01

    What determines whether people tolerate partner aggression? This research examined how norms, relationship experiences, and commitment predict personal standards for judging aggressive acts by a partner. Studies 1a and 1b (n = 689) revealed that experiencing aggression in a current relationship and greater commitment predicted greater tolerance for common partner aggression. Study 2 longitudinally tracked individuals who had never experienced partner aggression (n = 52). Once aggression occurred, individuals adopted more tolerant standards, but only if they were highly committed. Study 3 involved experimentally manipulating the relevance of partner aggression among individuals who reported current partner aggression (n = 73); they were more tolerant of aggressive acts imagined to occur by their partner (vs. the same acts by a stranger), but only if they were highly committed. Personal standards for judging partner aggression are dynamic. They shift toward greater tolerance when committed people experience aggression in a current relationship.

  6. Implicit cognitive aggression among young male prisoners: Association with dispositional and current aggression.

    PubMed

    Ireland, Jane L; Adams, Christine

    2015-01-01

    The current study explores associations between implicit and explicit aggression in young adult male prisoners, seeking to apply the Reflection-Impulsive Model and indicate parity with elements of the General Aggression Model and social cognition. Implicit cognitive aggressive processing is not an area that has been examined among prisoners. Two hundred and sixty two prisoners completed an implicit cognitive aggression measure (Puzzle Test) and explicit aggression measures, covering current behaviour (DIPC-R) and aggression disposition (AQ). It was predicted that dispositional aggression would be predicted by implicit cognitive aggression, and that implicit cognitive aggression would predict current engagement in aggressive behaviour. It was also predicted that more impulsive implicit cognitive processing would associate with aggressive behaviour whereas cognitively effortful implicit cognitive processing would not. Implicit aggressive cognitive processing was associated with increased dispositional aggression but not current reports of aggressive behaviour. Impulsive implicit cognitive processing of an aggressive nature predicted increased dispositional aggression whereas more cognitively effortful implicit cognitive aggression did not. The article concludes by outlining the importance of accounting for implicit cognitive processing among prisoners and the need to separate such processing into facets (i.e. impulsive vs. cognitively effortful). Implications for future research and practice in this novel area of study are indicated.

  7. Husbands' and Wives' Marital Adjustment, Verbal Aggression, and Physical Aggression as Longitudinal Predictors of Physical Aggression in Early Marriage

    ERIC Educational Resources Information Center

    Schumacher, Julie A.; Leonard, Kenneth E.

    2005-01-01

    Marital adjustment, verbal aggression, and physical aggression have long been associated in the marital literature, but the nature of their associations remains unclear. In this study, the authors examined these 3 constructs as risk factors for physical aggression during the first 2 years of marriage in 634 couples recruited as they applied for…

  8. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  9. The effects of treatment with aspirin and an antithrombotic agent SH1117 upon platelet thrombus formation in living blood vessels.

    PubMed Central

    Honour, A. J.; Carter, R. D.; Mann, J. I.

    1977-01-01

    The work reported here describes an in vivo study, over several days in each animal, of the formation and behaviour of platelet thrombi in injured living blood vessels in response to topically applied adenosine diphosphate in rabbits which have been treated with oral doses of SH1117 alone or together with acetyl-salicylic (ASA) before and after i.v. injection of alloxan. These two substances SH1117 and ASA when given together display a synergism which is similar to that described for dipyridamole and ASA, but the antithrombotic action of SH1117 and ASA seems to be more profound. It may be of significance that oral SH1117 given alone appears to confer a degree of insensitivity of the injured vessel in its response to ADP, as such an effect is not displayed by dipyridamole. PMID:588441

  10. Relational Aggression among Middle School Girls

    ERIC Educational Resources Information Center

    Dallape, Aprille

    2008-01-01

    The purpose of this study was to examine the correlates that define relational aggression among middle school girls, the relationships among these factors, and the association between the correlates of relational aggression and the type of relational aggression (e.g., verbal, withdrawal) exhibited among middle school girls. The findings of this…

  11. Aggression induced by intermittent positive reinforcement.

    PubMed

    Looney, T A; Cohen, P S

    1982-01-01

    Mammalian and non-mammalian species engage in aggressive behavior toward animate and inanimate targets when exposed to intermittent access to a positive reinforcer. This behavior, called extinction- or schedule-induced aggression, typically includes a biting or striking topography that inflicts damage on a target. This paper critically reviews research and theoretical issues concerning such aggression and suggests directions for future investigation.

  12. Coronary and mortality risk of novel oral antithrombotic agents: a meta-analysis of large randomised trials

    PubMed Central

    Mak, Koon-Hou

    2012-01-01

    Objective Oral direct thrombin and anti-Xa inhibitors have been shown to be efficacious in the prevention and treatment of venous thromboembolism, and prevention of embolic events in atrial fibrillation. Recent studies showed that dabigatran may be associated with increased rates of myocardial infarction (MI). Coronary risk for the other agents was unclear. The aim of the study is to determine the coronary risk among four novel antithrombotic agents. Design Mixed treatment comparison meta-analysis. Data sources and study selection Randomised controlled trials (RCTs) on ximelagatran, dabigatran, rivaroxaban and apixaban were obtained from PubMed search (February 2012) and major scientific meeting in 2011. The random-effects model was used to evaluate the effect of these agents on MI or acute coronary syndrome (MI/ACS), major bleeding complication and all-cause mortality. Results From 28 RCTs (n=138 948), the risk for MI/ACS was higher for dabigatran (OR 1.30; 95% CI 1.04 to 1.63; p=0.021) but lower for rivaroxaban (OR 0.78; 95% CI 0.69 to 0.89; p<0.001). Ximelagatran showed a higher risk for MI/ACS, which was not statistically significant, while apixaban demonstrated a non-significant lower likelihood. Among the RCTs for MI/ACS among the four agents, only those pertaining to ximelagatran showed heterogeneity. Major bleeding complication rates varied considerably among different agents. Importantly, these agents were associated with a lower all-cause mortality, without heterogeneity among the studies. Conclusions The risk for coronary events was significantly higher for dabigatran but not significantly higher for ximelagatran. Conversely, this risk was lower among anti-Xa inhibitors. All-cause mortality was lower among those receiving novel antithrombotic agents. This information may be useful in selecting agents for specific subsets of patients requiring anticoagulation. PMID:23043126

  13. Periprocedural Prophylactic Antithrombotic Strategies in Interventional Radiology: Current Practice in the Netherlands and Comparison with the United Kingdom

    SciTech Connect

    Wiersema, Arno M.; Vos, Jan-Albert; Bruijninckx, Cornelis M. A.; Delden, Otto M. van; Reijnen, Michel M. P. J.; Vahl, Anco; Zeebregts, Clark J.; Moll, Frans L.

    2013-12-15

    Purpose: The use of prophylactic antithrombotic drugs to prevent arterial thrombosis during the periprocedural period during (percutaneous) peripheral arterial interventions (PAIs) is still a matter of dispute, and clear evidence-based guidelines are lacking. To create those guidelines, a study group was formed in the Netherlands in cooperation with the Dutch Society of Vascular Surgery and the Society of Interventional Radiology. The study group is called 'Consensus on Arterial PeriProcedural Anticoagulation (CAPPA).' Materials and Methods: The CAPPA study group devised and distributed a comprehensive questionnaire amongst Dutch interventional radiologists (IRs). Results: One hundred forty-two IRs responded (68 %) to the questionnaire. Almost no IR stopped acetyl salicylic acid before interventions, and 40 % stopped clopidogrel before PAI but not before carotid artery stenting (CAS). A flushing solution on the sideport of the sheath was used routinely by 30 % of IRs in PAI and by 50 % of IRs during CAS. A minority of IRs used a heparinised flushing solution (28 %). Unfractionated heparin was used by 95 % of IRs as bolus; 5000 IU was the most used dosage. Timing of administration varied widely. A majority of IRs (75 %) repeated heparin administration after 1 h. Conclusion: A substantial variety exists amongst IRs in the Netherlands regarding the use of prophylactic periprocedural antithrombotic drugs to prevent arterial thrombosis during PAI. When compared with varying results regarding the use of heparin in the United Kingdom, the variety in the Netherlands showed a different pattern. The proven variety in these countries, and also between these countries, emphasises the need for authoritative studies to develop evidence-based practical guidelines.

  14. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft

    PubMed Central

    Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.

    2015-01-01

    Background Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis. Methods A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries. Results No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft

  15. Normative Beliefs and Relational Aggression: An Investigation of the Cognitive Bases of Adolescent Aggressive Behavior

    ERIC Educational Resources Information Center

    Werner, Nicole E.; Nixon, Charisse L.

    2005-01-01

    The relations between normative beliefs about different forms of aggression and corresponding aggressive behaviors were investigated in 2 studies of adolescents. In Study 1, we revised an instrument designed to assess normative beliefs about aggression to include beliefs about the acceptability of relational aggression, and we examined the…

  16. Social Aggression on Television and Its Relationship to Children's Aggression in the Classroom

    ERIC Educational Resources Information Center

    Martins, Nicole; Wilson, Barbara J.

    2012-01-01

    A survey was conducted with over 500 children in grades K-5 to examine whether exposure to socially aggressive content was related to children's use of social aggression. The results of the survey revealed a significant relationship between exposure to televised social aggression and increased social aggression at school, but only for girls and…

  17. Multimodal treatment of aggressive forms of breast cancer

    PubMed Central

    Mihai, D; Voiculescu, S; Cristian, D; Constantinescu, F; Popa, E; Burcos, T

    2014-01-01

    Abstract Aggressive breast cancer is an invasive form with G3, G4 differentiation degree, the absence of receptors for estrogen and progesterone and the absence or presence of HER2 (+ or 3+) gene. The final diagnosis is established by cumulating the clinical, paraclinical, histopathological and immunohistochemical diagnosis. Material and method: 84 out of 268 aggressive breast cancer cases were presented in the study, which were operated in October 2011-September 2013. The inclusion and exclusion criteria are exposed in the study lot and the treatment schemes. Results: For the study lot (lot A made up of 36 cases, lot B made up of 41 cases, lot C made up of 7 cases) the distribution was presented on age groups, histopathological and immunohistochemical classification, etiologic factors, type of surgery, postoperative staging and complications. Conclusions: The treatment of aggressive breast cancer depends on the level of the aggressiveness of the disease, the biologic status and the age that imposes the order of chemotherapy, radiotherapy, surgical treatment and target therapy. PMID:25408768

  18. Read anything mean lately? associations between reading aggression in books and aggressive behavior in adolescents.

    PubMed

    Stockdale, Laura A; Coyne, Sarah M; Nelson, David A; Padilla-Walker, Laura M

    2013-01-01

    Although there have been hundreds of studies on media violence, few have focused on literature, with none examining novels. Accordingly, the aim of the current study was to examine whether reading physical and relational aggression in books was associated with aggressive behavior in adolescents. Participants consisted of 223 adolescents who completed a variety of measures detailing their media use and aggressive behavior. A non-recursive structural equation model revealed that reading aggression in books was positively associated with aggressive behavior, even after controlling for exposure to aggression in other forms of media. Associations were only found for congruent forms of aggression. Implications regarding books as a form of media are discussed.

  19. Molecular Profiling of Aggressive Lymphomas

    PubMed Central

    Rossi, Maura; Laginestra, Maria Antonella; Gazzola, Anna; Sapienza, Maria Rosaria; Pileri, Stefano A.; Piccaluga, Pier Paolo

    2012-01-01

    In the last years, several studies of molecular profiling of aggressive lymphomas were performed. In particular, it was shown that DLBCL can be distinguished in two different entities according to GEP. Specifically, ABC and GCB subtypes were characterized by having different pathogenetic and clinical features. In addition, it was demonstrated that DLBCLs are distinct from BL. Indeed, the latter is a unique molecular entity. However, relevant pathological differences emerged among the clinical subtypes. More recently, microRNA profiling provided further information concerning BL-DLBCL distinction as well as for their subclassification. In this paper, the authors based on their own experience and the most updated literature review, the main concept on molecular profiling of aggressive lymphomas. PMID:22190944

  20. Mapping Brain Development and Aggression

    PubMed Central

    Paus, Tomás

    2005-01-01

    Introduction This article provides an overview of the basic principles guiding research on brain-behaviour relationships in general, and as applied to studies of aggression during human development in particular. Method Key literature on magnetic resonance imaging of the structure and function of a developing brain was reviewed. Results The article begins with a brief introduction to the methodology of techniques used to map the developing brain, with a special emphasis on magnetic resonance imaging (MRI). It then reviews briefly the current knowledge of structural maturation, assessed by MRI, of the human brain during childhood and adolescence. The last part describes some of the results of neuroimaging studies aimed at identifying neural circuits involved in various aspects of aggression and social cognition. Conclusion The article concludes by discussing the potential and limitations of the neuroimaging approach in this field. PMID:19030495

  1. Homeostatic disturbances and human aggression.

    PubMed

    Naisberg, Y

    1997-04-01

    A new model on the nature of human aggression is presented. It rests on the assumption that a pre-established organismic homeostatic modification, based on a decrease in neuronal membrane electric threshold, causes neural facilitation. In turn, this influences the cut-off phenomenon, in particular, neuronal network and therefore either inherited schemata representation, or acquired engram linkage programs run inadequately. These programs adjust the response to working loads of the eight normal serial stages in the body's operational regime activity. The effect of facilitation on these programs is: (1) loss of discrimination when approaching involuntary multi-stimuli; (2) the corruption of acquired engram linkage portions used in neural networks; (3) significant reduction of the voluntary degrees of freedom of response, thus narrowing the body's operational regime activity. This results in damage to certain cognitive links from some acquired engram linkages, enhancing impulse-like program mismatches and causing a unilateral 'fight' response of an aggressive nature.

  2. Leptin increases prostate cancer aggressiveness.

    PubMed

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  3. Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.

    PubMed

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y H; Buchsbaum, Richard; Sacco, Ralph L; Levin, Bruce; Di Tullio, Marco R; Qian, Min; Mann, Douglas L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Mohr, J P; Graham, Susan; Labovitz, Arthur J; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

    2015-09-15

    We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. PMID:26189039

  4. Neurobiology of aggression and violence.

    PubMed

    Siever, Larry J

    2008-04-01

    Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of "top-down" control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of "top-down" control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance "top-down" control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic.

  5. Lateralization of aggression in fish.

    PubMed

    Bisazza, Angelo; de Santi, Andrea

    2003-05-15

    Recent research has suggested that lateralization of aggressive behaviors could follow an homogeneous pattern among all vertebrates. A left eye/right hemisphere dominance in eliciting aggressive responses has been demonstrated for all groups of tetrapods but teleost fish for which data is lacking. Here we studied differential eye use during aggressive interactions in three species of teleosts: Gambusia holbrooki, Xenotoca eiseni and Betta splendens. In the first experiment we checked for lateralization in the use of the eyes while the subject was attacking its own mirror image. In order to confirm the results, other tests were performed on two species and eye preference was scored during attacks or displays directed toward a live rival. All three species showed a marked preference for using the right eye when attacking a mirror image or a live rival. Thus, the direction of asymmetry in fish appears the opposite to that shown by all the other groups of vertebrates. Hypotheses on the origin of the difference are discussed.

  6. Rural neighborhoods and child aggression.

    PubMed

    Bowen, Natasha K; Wretman, Christopher J

    2014-12-01

    Structural equation modeling with latent variables was used to evaluate the direct and mediated effects of a neighborhood risk factor (negative teen behaviors) on the parent-report aggressive behavior of 213 students in grades 3 through 5 attending a school in a low-income, rural community. Contagion and social control hypotheses were examined as well as hypotheses about whether the neighborhood served as a microsystem or exosystem for rural pre-adolescents. Analyses took into account the clustering of students and ordinal nature of the data. Findings suggest that rural neighborhoods may operate as both a microsystem and exosystem for children, with direct contagion effects on their aggressive behaviors as well as indirect social control effects through parenting practices. Direct effects on aggression were also found for parenting practices and child reports of friends' negative behaviors. Pre-adolescence may be a transitional stage, when influences of the neighborhood on child behavior begin to compete with influences of caregivers. Findings can inform the timing and targets of violence prevention in rural communities.

  7. Lateralization of aggression in fish.

    PubMed

    Bisazza, Angelo; de Santi, Andrea

    2003-05-15

    Recent research has suggested that lateralization of aggressive behaviors could follow an homogeneous pattern among all vertebrates. A left eye/right hemisphere dominance in eliciting aggressive responses has been demonstrated for all groups of tetrapods but teleost fish for which data is lacking. Here we studied differential eye use during aggressive interactions in three species of teleosts: Gambusia holbrooki, Xenotoca eiseni and Betta splendens. In the first experiment we checked for lateralization in the use of the eyes while the subject was attacking its own mirror image. In order to confirm the results, other tests were performed on two species and eye preference was scored during attacks or displays directed toward a live rival. All three species showed a marked preference for using the right eye when attacking a mirror image or a live rival. Thus, the direction of asymmetry in fish appears the opposite to that shown by all the other groups of vertebrates. Hypotheses on the origin of the difference are discussed. PMID:12742249

  8. Management of agitation and aggression associated with Alzheimer disease.

    PubMed

    Ballard, Clive G; Gauthier, Serge; Cummings, Jeffrey L; Brodaty, Henry; Grossberg, George T; Robert, Philippe; Lyketsos, Constantine G

    2009-05-01

    Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

  9. Minimally Invasive Surgical Therapies for Atrial Fibrillation

    PubMed Central

    Nakamura, Yoshitsugu; Kiaii, Bob; Chu, Michael W. A.

    2012-01-01

    Atrial fibrillation is the most common sustained arrhythmia and is associated with significant risks of thromboembolism, stroke, congestive heart failure, and death. There have been major advances in the management of atrial fibrillation including pharmacologic therapies, antithrombotic therapies, and ablation techniques. Surgery for atrial fibrillation, including both concomitant and stand-alone interventions, is an effective therapy to restore sinus rhythm. Minimally invasive surgical ablation is an emerging field that aims for the superior results of the traditional Cox-Maze procedure through a less invasive operation with lower morbidity, quicker recovery, and improved patient satisfaction. These novel techniques utilize endoscopic or minithoracotomy approaches with various energy sources to achieve electrical isolation of the pulmonary veins in addition to other ablation lines. We review advancements in minimally invasive techniques for atrial fibrillation surgery, including management of the left atrial appendage. PMID:22666609

  10. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs. PMID:34189

  11. [Pharmacological treatment of syndromes of aggressivity].

    PubMed

    Itil, T M

    1978-01-01

    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs.

  12. Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma

    PubMed Central

    Gisselbrecht, Christian; Schmitz, Norbert; Mounier, Nicolas; Singh Gill, Devinder; Linch, David C.; Trneny, Marek; Bosly, Andre; Milpied, Noel J.; Radford, John; Ketterer, Nicolas; Shpilberg, Ofer; Dührsen, Ulrich; Hagberg, Hans; Ma, David D.; Viardot, Andreas; Lowenthal, Ray; Brière, Josette; Salles, Gilles; Moskowitz, Craig H.; Glass, Bertram

    2012-01-01

    Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT. PMID:23091101

  13. "Primary" aggressive chondroblastoma of the humerus: a case report

    PubMed Central

    Harish, K; Janaki, MG; Alva, N Kishore

    2004-01-01

    Background Chondroblastomas are rare epiphyseal bone tumors. Very few cases with extra-cortical aggressive soft tissue invasion or metastasis are reported. Case presentation We report a 28 year-old adult male who presented with a large swelling over the left shoulder region. Pre-operative imaging revealed a large tumor arising from upper end of humerus with extensive soft tissue involvement necessitating a fore-quarter amputation. Patient received adjuvant radiation. Conclusions This patient is one of the largest chondroblastomas to be reported. Although chondroblastomas are typically benign, rarely they can be locally aggressive or metastatic. Early diagnosis and institution of proper primary therapy would prevent mutilating surgeries and recurrences. PMID:15113430

  14. Moderating role of trait aggressiveness in the effects of violent media on aggression.

    PubMed

    Bushman, B J

    1995-11-01

    Three studies were conducted to test the hypothesis that high trait aggressive individuals are more affected by violent media than are low trait aggressive individuals. In Study 1, participants read film descriptions and then chose a film to watch. High trait aggressive individuals were more likely to choose a violent film to watch than were low trait aggressive individuals. In Study 2, participants reported their mood before and after the showing of a violet or nonviolent videotape. High trait aggressive individuals felt more angry after viewing the violent videotape than did low trait aggressive individuals. In Study 3, participants first viewed either a violent or a nonviolent videotape and then competed with an "opponent" on a reaction time task in which the loser received a blast of unpleasant noise. Videotape violence was more likely to increase aggression in high trait aggressive individuals than in low trait aggressive individuals.

  15. High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

    PubMed

    Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

    2014-11-01

    Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

  16. How Collaborative Is Structural Family Therapy?

    ERIC Educational Resources Information Center

    Hammond, Ryan T.; Nichols, Michael P.

    2008-01-01

    In response to the charge by "collaborative" therapies, such as solution focused and narrative, that structural family therapy is an aggressive, confrontational, and impositional approach, this investigation examines the role of therapist empathy in creating a collaborative partnership in structural family therapy. Twenty-four videotaped therapy…

  17. Preparation of the antithrombotic and antimicrobial coating through layer-by-layer self-assembly of nattokinase-nanosilver complex and polyethylenimine.

    PubMed

    Wei, Xuetuan; Luo, Mingfang; Liu, Huizhou

    2014-04-01

    The bifunctional coating with antithrombotic and antimicrobial activity was developed using nattokinase (NK) and nanosilver (AgNPs). Firstly, the adsorption interactions between NK and AgNPs were confirmed, and the composite particles of NK-AgNPs were prepared by adsorption of NK with AgNPs. At 5FU/mL of NK concentration, the saturation adsorption capacity reached 24.35 FU/mg AgNPs with a high activity recovery of 97%, and adsorption by AgNPs also enhanced the heat stability and anticoagulant effect of NK. Based on the electrostatic force driven layer-by-layer self-assembly, the NK-AgNPs were further assembled with polyethylenimine (PEI) to form coating. UV-vis analysis showed that the self-assembly process was regular, and atom force microscopy analysis indicated that NK-AgNPs were uniformly embedded into the coating. The NK-AgNPs-PEI composite coating showed potent antithrombotic activity and antibacterial activity. This study developed a novel strategy to construct the bifunctional coating with antithrombotic and antimicrobial properties, and the coating material showed promising potential to be applied in the medical device.

  18. Preparation of the antithrombotic and antimicrobial coating through layer-by-layer self-assembly of nattokinase-nanosilver complex and polyethylenimine.

    PubMed

    Wei, Xuetuan; Luo, Mingfang; Liu, Huizhou

    2014-04-01

    The bifunctional coating with antithrombotic and antimicrobial activity was developed using nattokinase (NK) and nanosilver (AgNPs). Firstly, the adsorption interactions between NK and AgNPs were confirmed, and the composite particles of NK-AgNPs were prepared by adsorption of NK with AgNPs. At 5FU/mL of NK concentration, the saturation adsorption capacity reached 24.35 FU/mg AgNPs with a high activity recovery of 97%, and adsorption by AgNPs also enhanced the heat stability and anticoagulant effect of NK. Based on the electrostatic force driven layer-by-layer self-assembly, the NK-AgNPs were further assembled with polyethylenimine (PEI) to form coating. UV-vis analysis showed that the self-assembly process was regular, and atom force microscopy analysis indicated that NK-AgNPs were uniformly embedded into the coating. The NK-AgNPs-PEI composite coating showed potent antithrombotic activity and antibacterial activity. This study developed a novel strategy to construct the bifunctional coating with antithrombotic and antimicrobial properties, and the coating material showed promising potential to be applied in the medical device. PMID:24534431

  19. Impact of different antithrombotics on the microcirculation and viability of perforator-based ischaemic skin flaps in a small animal model

    PubMed Central

    Fichter, Andreas M.; Ritschl, Lucas M.; Robitzky, Luisa K.; Wagenpfeil, Stefan; Mitchell, David A.; Wolff, Klaus-Dietrich; Mücke, Thomas

    2016-01-01

    The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical ischaemia model was used to evaluate the effects of different perioperatively administered pharmaceutical agents on tissue ischaemia and to assess the potential additional haemorheological or vasodilative effects of antithrombotics on flap microcirculation. Combined laser Doppler flowmetry and remission spectroscopy revealed an increase in certain microcirculation parameters in most groups in comparison with saline controls, and these changes correlated with flap survival. Clopidogrel and hirudin significantly improved the amount of viable flap tissue in comparison with controls, while unfractioned heparin had a negative effect on flap survival. Low molecular weight heparin, aspirin, pentoxifylline, and hydroxyethyl starch had no impact on the amount of viable flap tissue. A higher complication rate was observed in all experimental groups, but only clopidogrel had a negative impact on the flap viability. Our results add to the body of evidence supporting the conclusion that perioperative antithrombotic treatment improves flap survival. Clopidogrel and hirudin are effective pharmacological agents that significantly increased the viability of perforator-based skin flaps in rats, but at a higher risk of postoperative bleeding. PMID:27767060

  20. Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study

    PubMed Central

    Nagata, Naoyoshi; Niikura, Ryota; Yamada, Atsuo; Sakurai, Toshiyuki; Shimbo, Takuro; Kobayashi, Yuka; Okamoto, Makoto; Mitsuno, Yuzo; Ogura, Keiji; Hirata, Yoshihiro; Fujimoto, Kazuma; Akiyama, Junichi; Uemura, Naomi; Koike, Kazuhiko

    2016-01-01

    Background Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs. Methods In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use. Results In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545). Conclusions One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs

  1. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  2. Studying aggression in Drosophila (fruit flies).

    PubMed

    Mundiyanapurath, Sibu; Certel, Sarah; Kravitz, Edward A

    2007-01-01

    Aggression is an innate behavior that evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, hormonal and environmental factors. In many organisms, aggression is critical to survival but controlling and suppressing aggression in distinct contexts also has become increasingly important. In recent years, invertebrates have become increasingly useful as model systems for investigating the genetic and systems biological basis of complex social behavior. This is in part due to the diverse repertoire of behaviors exhibited by these organisms. In the accompanying video, we outline a method for analyzing aggression in Drosophila whose design encompasses important eco-ethological constraints. Details include steps for: making a fighting chamber; isolating and painting flies; adding flies to the fight chamber; and video taping fights. This approach is currently being used to identify candidate genes important in aggression and in elaborating the neuronal circuitry that underlies the output of aggression and other social behaviors.

  3. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness.

  4. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. PMID:26216041

  5. An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis

    PubMed Central

    Palejwala, Sheri K.; Zangeneh, Tirdad T.; Goldstein, Stephen A.; Lemole, G. Michael

    2016-01-01

    Background: Rhinocerebral mucormycosis occurs in immunocompromised hosts with uncontrolled diabetes, solid organ transplants, and hematologic malignancies. Primary disease is in the paranasal sinuses but often progresses intracranially, via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal with a mortality rate of 85%, even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes. Methods: We performed a retrospective chart review of patients with rhinocerebral mucormycosis from 2011 to 2014. These patients were analyzed for symptoms, surgical and medical management, and outcome. We found four patients who were diagnosed with rhinocerebral mucormycosis. All patients underwent rapid aggressive surgical debridement and were started on antifungal therapy on the day of diagnosis. Overall, we observed a mortality rate of 50%. Results: An early aggressive multidisciplinary approach with surgical debridement, antifungal therapy, and correction of underlying disease have been shown to improve survivability in rhinocerebral mucormycosis. Conclusion: A multidisciplinary approach to rhinocerebral mucormycosis with otolaryngology, neurosurgery, and ophthalmology, infectious disease and medical intensivists can help reduce mortality in an otherwise largely fatal disease. Even despite these measures, outcomes remain poor, and a high index of suspicion must be maintained in at-risk populations, in order to rapidly execute a multifaceted approach. PMID:27280057

  6. Novel Therapeutics for Aggressive Non-Hodgkin's Lymphoma

    PubMed Central

    Mahadevan, Daruka; Fisher, Richard I.

    2011-01-01

    Application of advances in genomic and proteomic technologies has provided molecular insights into distinct types of aggressive B- and T-cell non-Hodgkin's lymphomas (NHLs). This has led to the validation of novel biomarkers of classification, risk-stratification, and druggable targets. The promise of novel treatments from genomic research has been slow to materialize because of the lack of a therapeutic signature for the distinct NHL subtypes. Patients with lymphoma with aggressive disease urgently require the development of novel therapies on the basis of investigation of dysregulated intracellular oncogenic processes that arise during lymphomagenesis. Although monoclonal antibodies have made significant contributions to the armamentarium of B-cell NHL therapy (eg, anti-CD20), parallel development of small-molecule inhibitors (SMIs) to intracellular targets has lagged behind. Despite these deficiencies, several promising anti-NHL therapies are in development that target immune kinases of the B-cell receptor signaling pathway, mammalian target of rapamycin complex, proteasome, DNA/histone epigenetic complex, antiapoptosis, neoangiogenesis, and immune modulation. This review focuses on novel SMI therapeutic strategies that target overlapping core oncogenic pathways in the context of the 10 hallmarks of cancer. Furthermore, we have developed the concept of a therapeutic signature using the 10 hallmarks of cancer, which may be incorporated into novel phase I/II drug development programs. PMID:21483007

  7. Video media-induced aggressiveness in children.

    PubMed

    Cardwell, Michael Steven

    2013-09-01

    Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented.

  8. [Aggressive clients in Dutch veterinary practice].

    PubMed

    Barbonis, T S A E; Endenburg, N

    2007-05-15

    Aggressive clients seem to be becoming more common. This article describes a study in which questionnaires on client behaviour were sent to veterinary assistants and veterinarians in randomly selected practices in the Netherlands. Results showed that 26.4% of the veterinarians and 29.3% of the assistants had experienced aggressive clients in the last year. Age, experience, and sex of the veterinarian or assistant did not influence the frequency with which aggressive clients were encountered. The same was true for the type of veterinary practice (companion animals, farm animals, horses, etc). The risk of encountering aggressive clients was higher among practices in large towns and in practices with a small turnover Of the veterinarians who had encountered aggressive clients at least once in their career, 31% has taken some kind of action after the aggressive encounter Nearly a quarter (24.9%) of veterinary practices have adopted a Risk Inventarization and Evaluation (RI&E) approach to preventing client aggression and 26.6% of practices have adopted another approach. While veterinarians tend not to consider aggression a big problem, they are often open to the suggestion that more attention should be paid to aggression in veterinary practice. PMID:17578228

  9. Intimate partner aggression and women's work outcomes.

    PubMed

    LeBlanc, Manon Mireille; Barling, Julian; Turner, Nick

    2014-10-01

    Using conservation of resources theory, we examined the relationship between intimate partner aggression enacted against heterosexual women and 3 types of work-related outcomes for these women: withdrawal while at work (i.e., cognitive distraction, work neglect), withdrawal from work (i.e., partial absenteeism, intentions to quit), and performance. In Study 1, we compared withdrawal both at and from work across 3 clinically categorized groups of women (n = 50), showing that experiencing physical aggression is related to higher work neglect. We replicated and extended these findings in Study 2 using a community sample of employed women (n = 249) by considering the incremental variance explained by both physical aggression and psychological aggression on these same outcomes. Results showed that physical aggression predicted higher levels of withdrawal both at and from work, with psychological aggression predicting additional variance in partial absenteeism over and above the effects of physical aggression. Study 3 extended the model to include academic performance as an outcome in a sample of female college students (n = 122) in dating relationships. Controlling for the women's conscientiousness, psychological aggression predicted lower academic performance after accounting for the effects of physical aggression. We discuss theoretical and practical implications of these results, as well as directions for future research. PMID:25068818

  10. Aggression and coexistence in female caribou

    USGS Publications Warehouse

    Weckerly, Floyd W.; Ricca, Mark A.

    2014-01-01

    Female caribou (Rangifer tarandus) are highly gregarious, yet there has been little study of the behavioral mechanisms that foster coexistence. Quantifying patterns of aggression between male and female, particularly in the only cervid taxa where both sexes grow antlers, should provide insight into these mechanisms. We asked if patterns of aggression by male and female caribou followed the pattern typically noted in other polygynous cervids, in which males display higher frequencies and intensity of aggression. From June to August in 2011 and 2012, we measured the frequency and intensity of aggression across a range of group sizes through focal animal sampling of 170 caribou (64 males and 106 females) on Adak Island in the Aleutian Archipelago, Alaska. Males in same-sex and mixed-sex groups and females in mixed-sex groups had higher frequencies of aggression than females in same-sex groups. Group size did not influence frequency of aggression. Males displayed more intense aggression than females. Frequent aggression in mixed-sex groups probably reflects lower tolerance of males for animals in close proximity. Female caribou were less aggressive and more gregarious than males, as in other polygynous cervid species.

  11. Video media-induced aggressiveness in children.

    PubMed

    Cardwell, Michael Steven

    2013-09-01

    Transmission of aggressive behaviors to children through modeling by adults has long been a commonly held psychological concept; however, with the advent of technological innovations during the last 30 years, video media-television, movies, video games, and the Internet-has become the primary model for transmitting aggressiveness to children. This review explores the acquisition of aggressive behaviors by children through modeling behaviors in violent video media. The impact of aggressive behaviors on the child, the family, and society is addressed. Suggestive action plans to curb this societal ill are presented. PMID:24002556

  12. Neural control of aggression in Drosophila.

    PubMed

    Hoopfer, Eric D

    2016-06-01

    Like most animal species, fruit flies fight to obtain and defend resources essential to survival and reproduction. Aggressive behavior in Drosophila is genetically specified and also strongly influenced by the fly's social context, past experiences and internal states, making it an excellent framework for investigating the neural mechanisms that regulate complex social behaviors. Here, I summarize our current knowledge of the neural control of aggression in Drosophila and discuss recent advances in understanding the sensory pathways that influence the decision to fight or court, the neuromodulatory control of aggression, the neural basis by which internal states can influence both fighting and courtship, and how social experience modifies aggressive behavior. PMID:27179788

  13. Gibbon Aggression During Introductions: An International Survey.

    PubMed

    Harl, Heather; Stevens, Lisa; Margulis, Susan W; Petersen, Jay

    2016-01-01

    Little is known regarding the prevalence of aggression seen during introductions of captive gibbons (Hylobatidae). In this study, an online survey was developed to quantify and collect contextual details regarding the frequency and types of aggression seen during introductions of captive gibbons (Hylobatidae). Nineteen percent of institutions (17 institutions) reported observing aggression, and 6 of these institutions recorded multiple instances of aggression, though a vast majority of these cases resulted in mild injuries or none at all. The female was the primary aggressor in 23% of cases, the male was the primary aggressor in 58% of cases, and both were the primary aggressor in 1 case. Although these aggressive interactions were often not associated with a known cause, 27% of cases were associated with food displacement. In most cases, management changes, including trying new pairings, greatly reduced situational aggression, suggesting that individual personalities may play a factor in aggression. These data begin to explain the extent of aggression observed in captive gibbons; future studies will address possible correlations with aggression and introduction techniques. PMID:26963568

  14. [Motives and interpersonal functions of aggression].

    PubMed

    Ohbuchi, K

    1987-06-01

    In this review, the author theoretically and empirically examined motives and interpersonal functions of aggression. A factor-analysis of Averill's questionnaire items on anger revealed that motives involved in aggressive responses were clustered into two groups: the hostile and the instrumental. It was also clarified that an individual is likely to engage in aggression particularly when some hostile motives are evoked. Concerning the interpersonal functions, the author proposed that aggression might serve four principal goals. (1) Aggression can be generated as an avoidance response to an aversive stimulus, such as frustration, annoyance, or pain, and so on. It depends on the severity of the stimulus. It was however emphasized that aggression is also mediated by social cognition, such as an attribution of intent to a harm-doer. (2) Aggression can be used as a means of coercing the other person into doing something. An individual is likely to use such a power strategy if he/she is lacking in self-confidence or a perspective for influencing the target person by more peaceful strategies. (3) Aggression can be interpreted as a punishment when it is directed toward a transgressor. In this case, aggression is motivated by restoration of a social justice, and thus its intensity is determined by the perceived moral responsibility of the transgressor. Further, it was indicated that aggression is intensified if it is justified as a sanctional conduct against the immoral. (4) Aggression can be also evoked when an individual's social identity is threatened. It was suggested that impression management motives are involved in aggression by an unexpected finding that the presence of audience or the identifiability rather facilitated retaliative aggression. The aggression-inhibition effect of apology was also explained in terms of impression management. In conclusion, it was presented that aggression is a behavioral strategy as an attempt to resolve interpersonal conflicts

  15. Gibbon Aggression During Introductions: An International Survey.

    PubMed

    Harl, Heather; Stevens, Lisa; Margulis, Susan W; Petersen, Jay

    2016-01-01

    Little is known regarding the prevalence of aggression seen during introductions of captive gibbons (Hylobatidae). In this study, an online survey was developed to quantify and collect contextual details regarding the frequency and types of aggression seen during introductions of captive gibbons (Hylobatidae). Nineteen percent of institutions (17 institutions) reported observing aggression, and 6 of these institutions recorded multiple instances of aggression, though a vast majority of these cases resulted in mild injuries or none at all. The female was the primary aggressor in 23% of cases, the male was the primary aggressor in 58% of cases, and both were the primary aggressor in 1 case. Although these aggressive interactions were often not associated with a known cause, 27% of cases were associated with food displacement. In most cases, management changes, including trying new pairings, greatly reduced situational aggression, suggesting that individual personalities may play a factor in aggression. These data begin to explain the extent of aggression observed in captive gibbons; future studies will address possible correlations with aggression and introduction techniques.

  16. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review

    PubMed Central

    Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy. PMID:27489751

  17. Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant Temozolomide Chemotherapy: A Review.

    PubMed

    Moisi, Marc; Cruz, Aurora S; Benkers, Tara; Rostad, Steven; Broyles, Frances Broyles; Yuen, Kevin; Mayberg, Marc

    2016-01-01

    Most prolactin-secreting pituitary adenomas demonstrate slow growth and are effectively managed with medical/surgical therapy. Rarely, these tumors can behave aggressively with rapid growth and invasion of local tissues, and are refractory to medical, surgical, or radio-surgical therapies. We report a case of a prolactin-secreting adenoma in a young woman, which became progressively aggressive and refractory to usual treatment modalities, but responded to treatment with the chemotherapeutic agent temozolomide. In addition, we review the literature for treatment of refractory adenomas with temozolomide. The clinical and pathologic characteristics of aggressive prolactin-secreting adenomas are reviewed, as well as their response to dopamine agonists, surgery, radiotherapy, and chemotherapy.

  18. [Insular carcinoma of the thyroid. An uncommon but aggressive neoplasm].

    PubMed

    Naranjo-Gómez, José Manuel; Folqué-Gómez, Emilio; Moreno-Mata, Nicolás; Moldes-Rodríguez, Milagros; Martínez-Martínez, Patricia; González-Aragoneses, Federico; Orusco-Palomino, Eduardo

    2005-04-01

    Insular carcinoma of the thyroid is an infrequent entity, named in 1984 by Carcangiu when he described its characteristic histology. Clinically and morphologically it is considered to be in an intermediate position between well-differentiated carcinoma of the thyroid (papillary or follicular) and undifferentiated or anaplastic carcinoma of the thyroid. However, most authors believe it to be an independent entity. The prognosis of this tumor is worse than that of classic carcinoma of the thyroid, and most authors advise aggressive therapy, which in some cases can achieved prolonged survival. We describe 2 patients who experienced recurrence after treatment for the primary tumor. The recurrences were treated but the clinical courses differed.

  19. Nuclear Morphometry Identifies a Distinct Aggressive Cellular Phenotype in Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Glazer, Evan S.; Bartels, Peter H.; Prasad, Anil R.; Yozwiak, Michael L.; Bartels, Hubert G.; Einspahr, Janine G.; Alberts, David S.; Krouse, Robert S.

    2011-01-01

    By identifying aggressive cutaneous squamous cell carcinoma (cSCC) in patients who are at high risk for recurrences or second primaries after resection, intensive surveillance and therapy may decrease morbidity and mortality. We investigated the role of nuclear morphometry (karyometry) in differentiating between aggressive and nonaggressive cSCC. We retrospectively analyzed cSCC lesions from 40 male patients. 22 patients had evidence of aggressive cSCC (local/regional recurrence or a second primary cSCC), and 18 patients were identified with similar ages and sites of disease as control patients with nonaggressive cSCC (no evidence of recurrence, metastasis, or second primary). We performed karyometric analysis to identify nuclear features that discriminate between aggressive and nonaggressive cSCC nuclei. We used statistically significant differences (Kruskal-Wallis test P < 0.0001) to compose a quantitative aggressive classification score (proportion of aggressive nuclei from 0% to 100%). For comparisons, we used Fisher’s exact test or Student t test. The mean age was 79 ± 7 years for aggressive cSCC and 80 ± 9 years for nonaggressive cSCC (P = 0.66). We analyzed a mean of 96 nuclei in each group. The mean classification score for aggressive cSCC was significantly higher (69% ± 6%) than for nonaggressive cSCC (28% ± 5%, P = 0.00002). Overall, the classification score accurately categorized 80% of our patients (P = 0.0004). In most patients, karyometry differentiated between aggressive and nonaggressive cSCC. We found that classification scores, which provide information on individual lesions, could be used for risk stratification. PMID:21636541

  20. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    PubMed

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis.

  1. Anticoagulant and antithrombotic evaluation of native fucosylated chondroitin sulfates and their derivatives as selective inhibitors of intrinsic factor Xase.

    PubMed

    Wu, Mingyi; Wen, Dandan; Gao, Na; Xiao, Chuang; Yang, Lian; Xu, Li; Lian, Wu; Peng, Wenlie; Jiang, Jianmin; Zhao, Jinhua

    2015-03-01

    Fucosylated chondroitin sulfate (FCS), a structurally unusual glycosaminoglycan, has distinct anticoagulant properties, and is an especially strong inhibitor of the intrinsic factor Xase (anti-Xase). To obtain a highly selective inhibitor of human Xase, we purified six native FCSs with various sulfation patterns, prepared a series of FCS derivatives, and then elucidated the relationship between the structures and the anticoagulant activities of FCSs. FCSs 1-3 containing higher Fuc2S4S exhibit stronger AT-dependent anti-IIa activities, whereas 4-6 containing more Fuc3S4S produce potent HCII-dependent anti-IIa activities. Saccharides containing a minimum of 6-8 trisaccharide units, free carboxyl groups, and full fucosylation of GlcA may be required for potent anti-Xase activity, and approximately six trisaccharide units and partial fucosylation of GlcA may contribute to potent HCII-dependent activity. Decreasing of the molecular weights markedly reduces their AT-dependent anti-IIa activities, and even eliminates human platelet and factor XII activation. Furthermore, in vitro and in vivo studies suggested that fractions of 6-12 kDa may be very promising compounds as putative selective intrinsic Xase inhibitors with antithrombotic action, but without the consequences of major bleeding and factor XII activation.

  2. Balancing the Expression and Production of a Heterodimeric Protein: Recombinant Agkisacutacin as a Novel Antithrombotic Drug Candidate

    PubMed Central

    Guo, Yugang; Wu, Jing; Jia, Hao; Chen, Wei; Shao, Changsheng; Zhao, Lei; Ma, Jiajia; Li, Rui; Zhong, Yongjun; Fang, Fang; Wang, Dong; Sun, Jie; Qian, Fang; Dai, Xiangrong; Zhang, Guohui; Tian, Zhigang; Xiaoyi Li, Benjamin; Xiao, Weihua

    2015-01-01

    Agkisacucetin extracted from the venom of Agkistrodon acutus has been demonstrated to be a promising antithrombotic drug candidate in clinical studies due to its function as a novel platelet membrane glycoprotein (GP) Ib inhibitor. Agkisacucetin is a heterodimeric protein composed of α- and β-subunits with seven disulphide bonds. Both subunits form inactive homodimeric products, which cause difficulties for recombinant production. In this study, Agkisacucetin α- and β-subunits were inserted sequentially into the chromosome of Pichia pastoris at the mutant histidinol dehydrogenase gene and ribosomal DNA repeat sites, respectively. By optimizing the gene copies and productivity of each subunit by drug screening, we successfully obtained a recombinant strain with balanced expression of the two subunits. Using this strain, a yield greater than 100 mg/L recombinant Agkisacucetin in fed-batch fermentation was reached. The recombinant Agkisacucetin possessed extremely similar binding affinity to recombinant GPIb and human platelets in in vitro assays, and its ristocetin-induced platelet aggregation activity ex vivo was identical to that of the extracted native Agkisacucetin, demonstrating that the yeast-derived Agkisacucetin could be an effective alternative to native Agkisacucetin. Moreover, this study provides an effective strategy for balancing the expression and production of heterodimeric proteins in P. pastoris. PMID:26144864

  3. Balancing the Expression and Production of a Heterodimeric Protein: Recombinant Agkisacutacin as a Novel Antithrombotic Drug Candidate.

    PubMed

    Guo, Yugang; Wu, Jing; Jia, Hao; Chen, Wei; Shao, Changsheng; Zhao, Lei; Ma, Jiajia; Li, Rui; Zhong, Yongjun; Fang, Fang; Wang, Dong; Sun, Jie; Qian, Fang; Dai, Xiangrong; Zhang, Guohui; Tian, Zhigang; Xiaoyi Li, Benjamin; Xiao, Weihua

    2015-01-01

    Agkisacucetin extracted from the venom of Agkistrodon acutus has been demonstrated to be a promising antithrombotic drug candidate in clinical studies due to its function as a novel platelet membrane glycoprotein (GP) Ib inhibitor. Agkisacucetin is a heterodimeric protein composed of α- and β-subunits with seven disulphide bonds. Both subunits form inactive homodimeric products, which cause difficulties for recombinant production. In this study, Agkisacucetin α- and β-subunits were inserted sequentially into the chromosome of Pichia pastoris at the mutant histidinol dehydrogenase gene and ribosomal DNA repeat sites, respectively. By optimizing the gene copies and productivity of each subunit by drug screening, we successfully obtained a recombinant strain with balanced expression of the two subunits. Using this strain, a yield greater than 100 mg/L recombinant Agkisacucetin in fed-batch fermentation was reached. The recombinant Agkisacucetin possessed extremely similar binding affinity to recombinant GPIb and human platelets in in vitro assays, and its ristocetin-induced platelet aggregation activity ex vivo was identical to that of the extracted native Agkisacucetin, demonstrating that the yeast-derived Agkisacucetin could be an effective alternative to native Agkisacucetin. Moreover, this study provides an effective strategy for balancing the expression and production of heterodimeric proteins in P. pastoris. PMID:26144864

  4. Threatened Retaliation as an Inhibitor of Human Aggression: Mediating Effects of the Instrumental Value of Aggression.

    ERIC Educational Resources Information Center

    Baron, Robert A.

    Whereas threatened punishment proves effective under conditions where the instrumental value of aggressive behavior is quite low, the following techniques of control may work better in situations where the value of aggression is relatively high: (1) the use of restrained, non-aggressive models; (2) empathic arousal among aggressors; or (3)…

  5. Predicting Aggressive Behavior in Children with the Help of Measures of Implicit and Explicit Aggression

    ERIC Educational Resources Information Center

    Grumm, Mandy; Hein, Sascha; Fingerle, Michael

    2011-01-01

    Aggressive behavior between children in schools is a topic that receives much interest as violence and aggressive behavior cause many maladaptive social outcomes in the school setting. In the current study the Implicit Association Test (IAT) was adapted as a measure of children's implicit aggression, by assessing the association of the self…

  6. Stability of Aggression during Early Adolescence as Moderated by Reciprocated Friendship Status and Friend's Aggression

    ERIC Educational Resources Information Center

    Adams, Ryan E.; Bukowski, William M.; Bagwell, Catherine

    2005-01-01

    The effect of friendship reciprocation and friend aggression on the stability of aggression across a 6-month period following the transition to secondary school was studied in a sample of 298 Grade 6 children from a predominately white, middle-class, Midwestern American community. The stability of aggression was generally high but it varied as a…

  7. Daily associations among anger experience and intimate partner aggression within aggressive and nonaggressive community couples.

    PubMed

    Crane, Cory A; Testa, Maria

    2014-10-01

    Anger is an empirically established precipitant to aggressive responding toward intimate partners. The current investigation examined the effects of anger, as experienced by both partners, as well as gender and previous aggression, on in vivo intimate-partner aggression (IPA) using a prospective daily diary methodology. Participants (N = 118 couples) individually provided 56 consecutive, daily reports of affective experience and partner aggression. Multilevel models were estimated using the actor-partner interdependence model (APIM) framework to analyze the daily associations between anger and partner-aggression perpetration among participating men and women, as moderated by aggression history. Results revealed that both actor and partner anger were generally associated with subsequently reported daily conflict. Further, increases in daily partner anger were associated with corresponding increases in partner aggression among both women who reported high levels of anger and men, regardless of their own anger experience. Increases in actor anger were associated with increases in daily partner aggression only among previously aggressive women. Previously aggressive men and women consistently reported greater perpetration than their nonaggressive counterparts on days of high levels of actors' anger experiences. Results emphasize the importance of both actor and partner factors in partner aggression and suggest that female anger may be a stronger predictor of both female-to-male and male-to-female partner aggression than male anger, when measured at the daily level.

  8. Physiological Arousal, Exposure to a Relatively Lengthy Aggressive Film, and Aggressive Behavior.

    ERIC Educational Resources Information Center

    Thomas, Margaret Hanratty

    1982-01-01

    Studied male students who viewed an aggressive television program or a neutral one. Half of the students were then angered by a confederate. Results indicated angered men who had seen the aggressive film were most aggressive and exhibited the lowest average pulse rates both before and after shock delivery. (Author/JAC)

  9. Relational and Overt Aggression in Urban India: Associations with Peer Relations and Best Friends' Aggression

    ERIC Educational Resources Information Center

    Bowker, Julie C.; Ostrov, Jamie M.; Raja, Radhi

    2012-01-01

    This study explored the associations between relational and overt aggression and social status, and tested whether the peer correlates of aggression vary as a function of best friends' aggression during early adolescence in urban India. One hundred and ninety-four young adolescents from primarily middle-to-upper-class families in Surat, India…

  10. The Relationship of Aggression and Bullying to Social Preference: Differences in Gender and Types of Aggression

    ERIC Educational Resources Information Center

    Lee, Eunju

    2009-01-01

    With 338 fifth-grade students as subjects, this study found the variations in the relation between school bullying and social preference as a function of gender and types of aggressive behavior utilized. Aggressive boys were likely to be rejected by peers, whereas aggressive girls were both rejected and accepted by peers. Children nominated…

  11. Competitive Aggression without Interaction: Effects of Competitive versus Cooperative Instructions on Aggressive Behavior in Video Games.

    ERIC Educational Resources Information Center

    Anderson, Craig A.; Morrow, Melissa

    1995-01-01

    Extended and tested Deutsch's theory of competition effects. Predicted that people view competitive situations as inherently more aggressive than cooperative ones. Predicted that leading people to think of an aggressive situation in competitive terms would increase aggressive behavior. Increase of kill ratio occurred in absence of changes in…

  12. Neurotransmitters regulating feline aggressive behavior.

    PubMed

    Siegel, A; Schubert, K

    1995-01-01

    The experiments described in this review reveal that the expression and modulation of aggressive responses in the cat are organized by two distinct sets of pathways. One set of pathways is associated with the elicitation of a specific form of attack behavior. It includes the medial hypothalamus and its projections to the PAG for the expression of defensive rage behavior and the lateral hypothalamus and its descending projections for the expression of predatory attack behavior. The primary focus of the present review is upon the analysis of defensive rage behavior. It was demonstrated that the pathway from the medial hypothalamus to the PAG, which appears to be essential for elicitation of defensive rage, is powerfully excitatory and utilizes excitatory amino acids that act upon NMDA receptors within the PAG. The other pathways examined in this review arise from different nuclei of the amygdala and are modulatory in nature. Here, two facilitatory systems have been identified. The first involves a projection system from the basal complex of amygdala that projects directly to the PAG. Its excitatory effects are manifest through excitatory amino acids that act upon NMDA receptors within the PAG. The second facilitatory pathway arises from the medial nucleus of the amygdala. However, its projection system is directed to the medial hypothalamus rather than the PAG. Its neurotransmitter appears to be substance P that acts upon NK1 receptors within the medial hypothalamus (see Figure 10). It has yet to be determined whether substance P acts upon any of the other neurokinin receptor subtypes. It should also be pointed out that the substance P pathway from the medial amygdala to the medial hypothalamus functions to suppress predatory attack behavior elicited from the lateral hypothalamus. In this network, it is likely that the modulatory effects of the medial amygdala require the presence of a second, inhibitory pathway from the medial hypothalamus that innervates the

  13. Aggressive Angiomyxoma in Pregnancy: A Rare Condition, a Common Misdiagnosis.

    PubMed

    Sampaio, J; Sarmento-Gonçalves, I; Ramada, D; Amaro, T; Tiago-Silva, P

    2016-01-01

    Introduction. Aggressive angiomyxoma is a rare mesenchymal neoplasm. Although benign in the majority of the cases, these neoplasms usually present a locally infiltrative nature and high rates of recurrence. Due to its rarity, misdiagnosis is a common problem. Case Presentation. We present one case of aggressive angiomyxoma in a 25-year-old pregnant woman. The patient presented with a large vaginal mass that was interpreted as a vaginal cyst. We performed surgical resection of the neoplasm and the correct diagnosis was only achieved after histological examination. With this case, we highlight the importance of considering this diagnosis in patients with genital and perineal masses of unknown origin and the impact of a correct preoperative diagnosis in patient's management and follow-up. Conclusion. Although aggressive angiomyxoma is rare, it should be considered in differential diagnosis of pelviperineal masses in young women. Its positivity to estrogen and progesterone receptors can justify enlargement and recurrence during pregnancy, although few cases are reported. Early recognition demands high index of suspicion for both gynaecologists and pathologists. Wide surgical excision with tumor free margins is the basis of curative treatment. Adjuvant therapy may be necessary for residual or recurrent tumors. Long-term follow-up is recommended. PMID:27274877

  14. Genetics of aggressive behavior: An overview.

    PubMed

    Veroude, Kim; Zhang-James, Yanli; Fernàndez-Castillo, Noèlia; Bakker, Mireille J; Cormand, Bru; Faraone, Stephen V

    2016-01-01

    The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative. PMID:26345359

  15. A Positive Approach to the Treatment of Aggressive Brain Injured Clients.

    ERIC Educational Resources Information Center

    Burke, William H.; And Others

    1988-01-01

    A broad spectrum behavior therapy approach was used to treat physical aggression in 5 brain-injured males (ages 18-28). The approach employed high density reinforcement, reinforcer sampling, environmental control, selection of appropriate responses, inconvenience review, self-control training, and self-monitoring. All five subjects showed…

  16. Desensitization to Media Violence: Links With Habitual Media Violence Exposure, Aggressive Cognitions, and Aggressive Behavior

    PubMed Central

    Krahé, Barbara; Möller, Ingrid; Huesmann, L. Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja

    2015-01-01

    This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content. PMID:21186935

  17. Desensitization to media violence: links with habitual media violence exposure, aggressive cognitions, and aggressive behavior.

    PubMed

    Krahé, Barbara; Möller, Ingrid; Huesmann, L Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja

    2011-04-01

    This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content. PMID:21186935

  18. Desensitization to media violence: links with habitual media violence exposure, aggressive cognitions, and aggressive behavior.

    PubMed

    Krahé, Barbara; Möller, Ingrid; Huesmann, L Rowell; Kirwil, Lucyna; Felber, Juliane; Berger, Anja

    2011-04-01

    This study examined the links between desensitization to violent media stimuli and habitual media violence exposure as a predictor and aggressive cognitions and behavior as outcome variables. Two weeks after completing measures of habitual media violence exposure, trait aggression, trait arousability, and normative beliefs about aggression, undergraduates (N = 303) saw a violent film clip and a sad or a funny comparison clip. Skin conductance level (SCL) was measured continuously, and ratings of anxious and pleasant arousal were obtained after each clip. Following the clips, participants completed a lexical decision task to measure accessibility of aggressive cognitions and a competitive reaction time task to measure aggressive behavior. Habitual media violence exposure correlated negatively with SCL during violent clips and positively with pleasant arousal, response times for aggressive words, and trait aggression, but it was unrelated to anxious arousal and aggressive responding during the reaction time task. In path analyses controlling for trait aggression, normative beliefs, and trait arousability, habitual media violence exposure predicted faster accessibility of aggressive cognitions, partly mediated by higher pleasant arousal. Unprovoked aggression during the reaction time task was predicted by lower anxious arousal. Neither habitual media violence usage nor anxious or pleasant arousal predicted provoked aggression during the laboratory task, and SCL was unrelated to aggressive cognitions and behavior. No relations were found between habitual media violence viewing and arousal in response to the sad and funny film clips, and arousal in response to the sad and funny clips did not predict aggressive cognitions or aggressive behavior on the laboratory task. This suggests that the observed desensitization effects are specific to violent content.

  19. Parental Behavior, TV Habits, IQ Predict Aggression.

    ERIC Educational Resources Information Center

    Greenberg, J.

    1983-01-01

    Highlights a longitudinal study on key factors in the metamorphosis of childhood aggression into adult crime in more than 400 males/females. Results (which began with study of 875 third graders in 1960) indicate that aggressive youngsters at age eight have much higher rates of criminal/violent behavior at age 30. (JN)

  20. Moral Judgments of Aggressive and Nonaggressive Children.

    ERIC Educational Resources Information Center

    Keltikangas-Jarvinen, Liisa

    1989-01-01

    Reports on a study of moral judgments in aggressive and nonaggressive children. Assessed moral judgment by presenting the children with stories of moral conflict in everyday life using peer rating. Results showed significant differences according to gender and no constant level of moral reasoning was measured in either aggressive or nonaggressive…

  1. Forgivingness, anger, and hostility in aggressive driving.

    PubMed

    Kovácsová, Natália; Rošková, Eva; Lajunen, Timo

    2014-01-01

    This study was aimed at investigating the relationship between trait forgivingness, general anger, hostility, driving anger, and self-reported aggressive driving committed by the driver him/herself ("self" scale) and perceiving him/herself as an object of other drivers' aggressive acts ("other" scale). The Slovak version of questionnaires was administrated to a sample of 612 Slovak and Czech drivers. First, the factor structure of the Driver Anger Indicators Scale (DAIS) was investigated. Factor analyses of the self and other parts of the DAIS resulted in two factors, which were named as aggressive warnings and hostile aggression and revenge. Next, the results showed that from all dependent variables (scales of the DAIS), self-reported aggressive warnings (self) on the road were predicted best by chosen person-related factors. The path model for aggressive warnings (self) suggested that trait forgivingness and general anger were fully mediated by driving anger whereas hostility proved to be a unique predictor of aggressive behavior in traffic. Driving anger was found to be the best predictor of perceptions that other drivers behave aggressively. PMID:24211562

  2. Understanding Aggressive Behavior Across the Life Span

    PubMed Central

    Liu, Jianghong; Lewis, Gary; Evans, Lois

    2012-01-01

    Aggressive behavior is the observable manifestation of aggression and is often associated with developmental transitions and a range of medical and psychiatric diagnoses across the lifespan. As healthcare professionals involved in the medical and psychosocial care of patients from birth through death, nurses frequently encounter—and may serve as—both victims and perpetrators of aggressive behavior in the workplace. While the nursing literature has continually reported research on prevention and treatment approaches, less emphasis has been given to understanding the etiology, including contextual precipitants of aggressive behavior. This paper provides a brief review of the biological, social, and environmental risk factors that purportedly give rise to aggressive behavior. Further, many researchers have focused specifically on aggressive behavior in adolescence and adulthood. Less attention has been given to understanding the etiology of such behavior in young children and older adults. This paper emphasizes the unique risk factors for aggressive behavior across the developmental spectrum, including childhood, adolescence, adulthood, and late life. Appreciation of the risk factors of aggressive behavior, and, in particular, how they relate to age-specific manifestations, can aid nurses in better design and implementation of prevention and treatment programs. PMID:22471771

  3. Sibling Aggression: Sex Differences and Parents' Reactions

    ERIC Educational Resources Information Center

    Martin, Jacqueline L.; Ross, Hildy S.

    2005-01-01

    Thirty-nine families were observed extensively at home when children were 2 1/2 and 4 1/2 years of age and again 2 years later. The Social Relations Model is used to investigate children's sex differences in aggression and parents' prohibiting aggression during sibling conflict. In the first observation period, boys engaged in more severe and mild…

  4. Involvement in Internet Aggression during Early Adolescence

    ERIC Educational Resources Information Center

    Werner, Nicole E.; Bumpus, Matthew F.; Rock, Daquarii

    2010-01-01

    The current study examined concurrent and longitudinal predictors of early adolescents' involvement in Internet aggression. Cross-sectional results (N = 330; 57% female) showed that the likelihood of reporting Internet aggression was higher among youth who spent more time using Internet-based technologies to communicate with friends and who were…

  5. Aggressive and foraging behavioral interactions among ruffe

    USGS Publications Warehouse

    Savino, Jacqueline F.; Kostich, Melissa J.

    2000-01-01

    The ruffe, Gymnocephalus cernuus, is a nonindigenous percid in the Great Lakes. Ruffe are aggressive benthivores and forage over soft substrates. Laboratory studies in pools (100 cm in diameter, 15 cm water depth) were conducted to determine whether fish density (low = 2, medium = 4, high = 6 ruffe per pool) changed foraging and aggressive behaviors with a limited food supply of chironomid larvae. All fish densities demonstrated a hierarchy based on aggressive interactions, but ruffe were most aggressive at low and high fish densities. Time spent in foraging was lowest at the low fish density. The best forager at the low fish density was the most aggressive individual, but the second most aggressive fish at the medium and high fish density was the best forager and also the one chased most frequently. A medium fish density offered the best energetic benefits to ruffe by providing the lowest ratio of time spent in aggression to that spent foraging. Based on our results, ruffe should grow best at an intermediate density. With high ruffe densities, we would also expect disparity in size as the more aggressive fish are able to garner a disproportionate amount of the resources. Alternatively, as the Great Lakes are a fairly open system, ruffe could migrate out of one area to colonize another as populations exceed optimal densities.

  6. Relational Aggression and Victimization in College Students

    ERIC Educational Resources Information Center

    Dahlen, Eric R.; Czar, Katherine A.; Prather, Emily; Dyess, Christy

    2013-01-01

    For this study we explored relational aggression and victimization in a college sample (N = 307), examining potential gender and race differences, correlates, and the link between relational aggression and common emotional and behavioral problems, independent of relational victimization. Gender and race differences were observed on relational…

  7. Human Aggression: Current Theories and Research.

    ERIC Educational Resources Information Center

    Geen, Russell G.

    The literature on human aggression is large and diverse. Some of it is theory-driven, but much of it dwells on solving social problems rather than on building general models and research paradigms. This paper examines some of the research programs and theoretical emphases in aggression research and presents theory convergences to see how these…

  8. Game location and aggression in rugby league.

    PubMed

    Jones, Marc V; Bray, Steven R; Olivier, Stephen

    2005-04-01

    The present study examined the relationship between aggression and game location in rugby league. We videotaped a random sample of 21 professional rugby league games played in the 2000 Super League season. Trained observers recorded the frequency of aggressive behaviours. Consistent with previous research, which used territoriality theories as a basis for prediction, we hypothesized that the home team would behave more aggressively than the away team. The results showed no significant difference in the frequency of aggressive behaviours exhibited by the home and away teams. However, the away teams engaged in substantially more aggressive behaviours in games they lost compared with games they won. No significant differences in the pattern of aggressive behaviours for home and away teams emerged as a function of game time (i.e. first or second half) or game situation (i.e. when teams were winning, losing or drawing). The findings suggest that while home and away teams do not display different levels of aggression, the cost of behaving aggressively (in terms of game outcome) may be greater for the away team.

  9. Normative Beliefs Regarding Aggression in Emerging Adulthood

    ERIC Educational Resources Information Center

    Nelson, David A.; Springer, Melanie M.; Nelson, Larry J.; Bean, Nathaniel H.

    2008-01-01

    Few studies have examined the nature of aggression in emerging adulthood (ages 18-25), a unique developmental period wherein relationships become increasingly important and intimate. Consistent with a greater emphasis on relationships, relationally manipulative forms of aggression may be particularly salient during this time period. Based on…

  10. The Barrier within: Relational Aggression among Women

    ERIC Educational Resources Information Center

    Brock, Barbara L.

    2010-01-01

    Relational aggression among women presents an overlooked barrier to women's quest for advancement in the workplace. Although research on women's leadership extols their ability to collaborate and form lasting, supportive relationships, one cannot assume that all women are supportive of other women. Research reveals that relational aggression,…

  11. Forgivingness, anger, and hostility in aggressive driving.

    PubMed

    Kovácsová, Natália; Rošková, Eva; Lajunen, Timo

    2014-01-01

    This study was aimed at investigating the relationship between trait forgivingness, general anger, hostility, driving anger, and self-reported aggressive driving committed by the driver him/herself ("self" scale) and perceiving him/herself as an object of other drivers' aggressive acts ("other" scale). The Slovak version of questionnaires was administrated to a sample of 612 Slovak and Czech drivers. First, the factor structure of the Driver Anger Indicators Scale (DAIS) was investigated. Factor analyses of the self and other parts of the DAIS resulted in two factors, which were named as aggressive warnings and hostile aggression and revenge. Next, the results showed that from all dependent variables (scales of the DAIS), self-reported aggressive warnings (self) on the road were predicted best by chosen person-related factors. The path model for aggressive warnings (self) suggested that trait forgivingness and general anger were fully mediated by driving anger whereas hostility proved to be a unique predictor of aggressive behavior in traffic. Driving anger was found to be the best predictor of perceptions that other drivers behave aggressively.

  12. Problems in Aggression: Three Case Studies.

    ERIC Educational Resources Information Center

    Holt, Wilma J.

    This paper reviews three studies which illustrate the use of two different techniques of behavior modification to control aggression in preschool children in classroom situations. The first technique demonstrated the use of "time-out" as a mild punishment procedure. The teacher changed events following aggression by briefly removing the child from…

  13. [Aggressive and prosocial behavior in childhood psychopathology].

    PubMed

    Vida, Péter; Halász, József; Gádoros, Júlia

    2013-01-01

    Aggressive/attacking and helpful/emphatic/prosocial behaviors are extremely important in human relationships. Both high levels of aggression and deficits of prosociality play important role in the development and conservation of mental disorders. We review the measurement options and clinical importance of aggressive and prosocial behavior. The typical developmental pathways and the genetic and environmental background of these behaviors are presented. The clinical tools used in the measurement of aggression and prosociality are summarized in the present paper, with specific attention on questionnaires applied in Hungarian practice. The connections between diagnostic categories (conduct disorder, oppositional-defiant disorder, attention deficit and hyperactive disorder, autism spectrum disorders) and the two behaviors are evaluated. In the end, we present those additional research projects that explore the cognitive-emotional background of aggressive or prosocial behavior with clinical relevance either in the diagnosis or in the treatment of child psychiatric diseases. PMID:24142292

  14. When do normative beliefs about aggression predict aggressive behavior? An application of I3 theory.

    PubMed

    Li, Jian-Bin; Nie, Yan-Gang; Boardley, Ian D; Dou, Kai; Situ, Qiao-Min

    2015-01-01

    I(3) theory assumes that aggressive behavior is dependent on three orthogonal processes (i.e., Instigator, Impellance, and Inhibition). Previous studies showed that Impellance (trait aggressiveness, retaliation tendencies) better predicted aggression when Instigator was strong and Inhibition was weak. In the current study, we predicted that another Impellance (i.e., normative beliefs about aggression) might predict aggression when Instigator was absent and Inhibition was high (i.e., the perfect calm proposition). In two experiments, participants first completed the normative beliefs about aggression questionnaire. Two weeks later, participants' self-control resources were manipulated either using the Stroop task (study 1, N = 148) or through an "e-crossing" task (study 2, N = 180). Afterwards, with or without being provoked, participants played a game with an ostensible partner where they had a chance to aggress against them. Study 1 found that normative beliefs about aggression negatively and significantly predicted aggressive behavior only when provocation was absent and self-control resources were not depleted. In Study 2, normative beliefs about aggression negatively predicted aggressive behavior at marginal significance level only in the "no-provocation and no-depletion" condition. In conclusion, the current study provides partial support for the perfect calm proposition and I(3) theory.

  15. The relationships among perceived peer acceptance of sexual aggression, punishment certainty, and sexually aggressive behavior.

    PubMed

    Strang, Emily; Peterson, Zoë D

    2013-12-01

    Researching the correlates of men's sexually aggressive behavior (i.e., verbal coercion and rape) is critical to both understanding and preventing sexual aggression. This study examined 120 men who completed an anonymous online questionnaire. The study aimed to determine the relative importance of two potential correlates of men's self-reported use of sexual aggression: (a) perceptions that male peers use and support sexual aggression and (b) perceptions of punishment likelihood associated with sexual aggression. Results revealed that perceptions of male friends' acceptance of sexual aggression were strongly associated with individual men's reports of using verbal coercion and rape. Perceptions of punishment likelihood were negatively correlated with verbal coercion but not with rape through intoxication and force. Implications for sexual aggression prevention are discussed.

  16. The relationships among perceived peer acceptance of sexual aggression, punishment certainty, and sexually aggressive behavior.

    PubMed

    Strang, Emily; Peterson, Zoë D

    2013-12-01

    Researching the correlates of men's sexually aggressive behavior (i.e., verbal coercion and rape) is critical to both understanding and preventing sexual aggression. This study examined 120 men who completed an anonymous online questionnaire. The study aimed to determine the relative importance of two potential correlates of men's self-reported use of sexual aggression: (a) perceptions that male peers use and support sexual aggression and (b) perceptions of punishment likelihood associated with sexual aggression. Results revealed that perceptions of male friends' acceptance of sexual aggression were strongly associated with individual men's reports of using verbal coercion and rape. Perceptions of punishment likelihood were negatively correlated with verbal coercion but not with rape through intoxication and force. Implications for sexual aggression prevention are discussed. PMID:24014542

  17. Aggression on inpatient units: Clinical characteristics and consequences.

    PubMed

    Renwick, Laoise; Stewart, Duncan; Richardson, Michelle; Lavelle, Mary; James, Karen; Hardy, Claire; Price, Owen; Bowers, Len

    2016-08-01

    Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression-containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation.

  18. Aggression on inpatient units: Clinical characteristics and consequences.

    PubMed

    Renwick, Laoise; Stewart, Duncan; Richardson, Michelle; Lavelle, Mary; James, Karen; Hardy, Claire; Price, Owen; Bowers, Len

    2016-08-01

    Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression-containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation. PMID:26892149

  19. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS. PMID:26757550

  20. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

  1. Stability of preclinical models of aggressive renal cell carcinomas.

    PubMed

    Varna, Mariana; Bousquet, Guilhem; Ferreira, Irmine; Goulard, Marie; El-Bouchtaoui, Morad; Artus, Pierre Mongiat; Verine, Jérome; de Kerviler, Eric; Hernandez, Lucie; Leboeuf, Christophe; Escudier, Bernard; Legrès, Luc; Setterblad, Niclas; Soliman, Hany; Feugeas, Jean-Paul; Janin, Anne; Bertheau, Philippe

    2014-01-01

    Renal-cell carcinomas (RCC) are often resistant to conventional cytotoxic agents. Xenograft models are used for in vivo preclinical studies and drug development. The validity of these studies is highly dependent on the phenotypic and genotypic stability of the models. Here we assessed the stability of six aggressive human RCC xenografted in nude/NMRI mice. We compared the initial samples (P0), first (P1) and fifth (P5) passages for the following criteria: histopathology, immunohistochemistry for CK7, CD10, vimentin and p53, DNA allelic profiles using 10 microsatellites and CGH-array. Next we evaluated the response to sunitinib in primary RCC and corresponding xenografted RCC. We observed a good overall stability between primary RCC and corresponding xenografted RCC at P1 and P5 regarding histopathology and immunohistochemistry except for cytokeratin 7 (one case) and p53 (one case) expression. Out of 44 groups with fully available microsatellite data (at P0, P1 and P5), 66% (29 groups) showed no difference from P0 to P5 while 34% (15 groups) showed new or lost alleles. Using CGH-array, overall genomic alterations at P5 were not different from those of initial RCC. The xenografted RCC had identical response to sunitinib therapy compared to the initial human RCC from which they derive. These xenograft models of aggressive human RCC are clinically relevant, showing a good histological and molecular stability and are suitable for studies of basic biology and response to therapy. PMID:25031714

  2. Antithrombotic treatment of splanchnic vein thrombosis: results of an international registry.

    PubMed

    Ageno, Walter; Riva, Nicoletta; Schulman, Sam; Bang, Soo Mee; Sartori, Maria Teresa; Grandone, Elvira; Beyer-Westendorf, Jan; Barillari, Giovanni; Di Minno, Matteo Nicola Dario; Dentali, Francesco

    2014-02-01

    Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease.

  3. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  4. [Therapy-resistant aggressive cystic lesion of the mandible].

    PubMed

    Ziegler, C M; Bergstrand, S; Lund, J-A; Viset, T

    2011-10-01

    Several extensive surgical interventions of a cystic lesion in the left mandible were followed by recurrences. The lesion extended from the primary mandibular region into the area of pterygopalatine fossa finally infiltrating the orbital region and the skull base. Histological results could never demonstrate a malignancy with certainty. Due to the patient's poor general condition, the refusal for further surgical inventions and due to the malignoma-like growth pattern radiation treatment was performed. However, this had no effect on tumor progression. PMID:21845481

  5. T2 Gallbladder Cancer-Aggressive Therapy Is Warranted.

    PubMed

    Sheikh, Mohd Raashid; Osman, Houssam; Cheek, Susannah; Hunter, Shenee; Jeyarajah, Dhiresh Rohan

    2016-06-01

    Treatment of gall bladder cancer (GBC) has traditionally been viewed with pessimism and lymph node positivity has been associated with worse prognosis. The aim of this study is to analyze the role of radical cholecystectomy in T2 tumors. All patients who underwent surgery for GBC between September 2005 and June 2014 were identified retrospectively. Data collected included clinical presentation, operative findings, and histopathological data. Twenty-five patients had incidental GBC diagnosis after cholecystectomy. Ten patients were T2 on initial cholecystectomy pathology and all underwent radical resection. Two patients were N1 on initial cholecystectomy pathology. Four were upstaged to N1 and two patients were upstaged to T3 after further surgery. Overall, 60 per cent patients with T2 disease had node positivity and 60 per cent were upstaged by further surgery. Eleven patients were diagnosed on imaging. Four of these patients were unresectable and six were either stage T3 or higher or node positive. Sixty per cent of T2 GBC was node positive and 60 per cent were upstaged with radical cholecystectomy. This finding supports the call for radical resection in patients with incidental diagnosis of T2 tumor on cholecystectomy. This study also emphasizes the role of radical surgery in accurate T staging. PMID:27305883

  6. Safety training: the elimination of avoidance-motivated aggression in dogs.

    PubMed

    Tortora, D F

    1983-06-01

    This study sought to identify the behavioral characteristics and appropriate treatment of a form of instrumental aggression in companion dogs, herein recognized as avoidance-motivated aggression. In Experiment 1, retrospective data on 92 cases of dangerously aggressive dogs demonstrated the avoidance nature of the aggressive response and its intractability to established counterconditioning treatments. In Experiment 2, safety training, a modified avoidance-learning procedure, resulted in complete and permanent elimination of aggression in all of the 36 dogs tested. In addition, it produced extremely extinction-resistant prosocial avoidance responses, significant increases in the dogs' emotional stability, an avoidance-learning and safety acquisition response set, and improvements in measures of the dog's "carriage." Experiment 3 showed how effective safety training is when compared with other behavior modification techniques that, in theory, should have an impact on avoidance-motivated aggression. Experiment 4 demonstrated the critical importance of using the conditioned safety cue as a positive reinforcement. The relationship of avoidance-motivated aggression to other forms of aggression is discussed. The success of safety training compared with the failure of electrical aversion therapy is analyzed. The theoretical concepts of behavioral balance and an avoidance-learning set are presented. Suggestions to improve the effectiveness of counterconditioning for human avoidance-motivated pathologies are offered. All in all, the data seem to suggest that safety training may create in dogs a sense of control over environmental stressors. By teaching the dogs a behaviorally balanced battery of prosocial "coping" responses, they may be developing the canine counterpart of "self-efficacy" or "courage." It is suggested that this cognitive modification may provide the antithesis of "learned helplessness" and may be of prime importance to the success and stability of the

  7. Anti-thrombotic and vascular effects of AR246686, a novel 5-HT2A receptor antagonist.

    PubMed

    Adams, John W; Ramirez, Juan; Ortuno, Danny; Shi, Yunqing; Thomsen, William; Richman, Jeremy G; Morgan, Michael; Dosa, Peter; Teegarden, Bradley R; Al-Shamma, Hussien; Behan, Dominic P; Connolly, Daniel T

    2008-05-31

    We have evaluated the anti-platelet and vascular pharmacology of AR246686, a novel 5-hydroxytryptamine2A (5-HT2A) receptor antagonist. AR246686 displayed high affinity binding to membranes of HEK cells stably expressing recombinant human and rat 5-HT2A receptors (Ki=0.2 nM and 0.4 nM, respectively). Functional antagonism (IC50=1.9 nM) with AR246686 was determined by inhibition of ligand-independent inositol phosphate accumulation in the 5-HT2A stable cell line. We observed 8.7-fold and 1360-fold higher affinity of AR246686 for the 5-HT2A receptor vs. 5-HT2C and 5-HT2B receptors, respectively. AR246686 inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC50=21 nM). Similar potency was observed for inhibition of 5-HT stimulated DNA synthesis in rat aortic smooth muscle cells (IC(50)=10 nM) and 5-HT-mediated contraction in rat aortic rings. Effects of AR246686 on arterial thrombosis and bleeding time were studied in a rat model of femoral artery occlusion. Oral dosing of AR246686 to rats resulted in prolongation of time to occlusion at 1 mg/kg, whereas increased bleeding time was observed at a dose of 20 mg/kg. In contrast, both bleeding time and time to occlusion were increased at the same dose (10 mg/kg) of clopidogrel. These results demonstrate that AR246686 is a high affinity 5-HT2A receptor antagonist with potent activity on platelets and vascular smooth muscle. Further, oral administration results in anti-thrombotic effects at doses that are free of significant effects on traumatic bleeding time.

  8. Anti-inflammatory, Antithrombotic and Cardiac Remodeling Preventive Effects of Eugenol in Isoproterenol-Induced Myocardial Infarction in Wistar Rat.

    PubMed

    Mnafgui, Kais; Hajji, Raouf; Derbali, Fatma; Gammoudi, Anis; Khabbabi, Gaddour; Ellefi, Hedi; Allouche, Noureddine; Kadri, Adel; Gharsallah, Neji

    2016-10-01

    This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups. Isoproterenol-induced myocardial infarcted rats showed notable changes in the ECG pattern, increase in heart weight index, deterioration in the hemodynamic function and rise in plasma level of troponin-T, CK-MB and LDH and ALT by 316, 74, 172 and 45 %, respectively, with histological myocardium necrosis and cells inflammatory infiltration. In addition, significant increases in plasma levels of inflammatory biomarkers such as fibrinogen, α1, α2, β1, β2 and γ globulins with decrease level of albumin were observed in infarcted rats as compared to normal ones. Else, the angiotensin-converting enzyme (ACE) activity in plasma, kidney and heart of the isoproterenol-induced rats was significantly increased by 34, 47 and 93 %, respectively, as compared to normal group. However, the administration of eugenol induced a clear improvement in cardiac biomarkers injury, reduced inflammatory mediators proteins, increased heart activities of superoxide dismutase and glutathione peroxidase with reduce in thiobarbituric acid-reactive substances content and inhibition of ventricular remodeling process through inhibition of ACE activity. Overall, eugenol evidences high preventive effects from cardiac remodeling process.

  9. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    PubMed

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-01

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions. PMID:24553755

  10. Assessment of aggression in inpatient settings.

    PubMed

    McDermott, Barbara E; Holoyda, Brian J

    2014-10-01

    The threat of violence is a major concern for all individuals working or receiving treatment in an inpatient psychiatric setting. One major focus in forensic psychology and psychiatry over the past several decades has been the development of risk assessments to aid in the identification of those individuals most at risk of exhibiting violent behavior. So-called second- and third-generation risk assessments were developed to improve the accuracy of decision making. While these instruments were developed for use in the community, many have proven to be effective in identifying patients more likely to exhibit institutional aggression. Because the purpose of risk assessment is the reduction of violence, dynamic factors were included in third-generation risk instruments to provide opportunities for intervention and methods for measuring change. Research with these instruments indicates that both static factors (second-generation) and dynamic factors (third-generation) are important in identifying those patients most likely to engage in institutional aggression, especially when the aggression is categorized by type (impulsive/reactive, organized/predatory/instrumental, psychotic). Recent research has indicated that developing a typology of aggressive incidents may provide insight both into precipitants to assaults as well as appropriate interventions to reduce such aggression. The extant literature suggests that both static and dynamic risk factors are important, but may be differentially related to the type of aggression exhibited and the characteristics of the individuals exhibiting the aggression. PMID:25296966

  11. Predicting aggression in children with ADHD

    PubMed Central

    2014-01-01

    Objective The present study uses structural equation modeling of latent traits to examine the extent to which family factors, cognitive factors and perceptions of rejection in mother-child relations differentially correlate with aggression at home and at school. Methods Data were collected from 476 school-age (7–15 years old) children with a diagnosis of ADHD who had previously shown different types of aggressive behavior, as well as from their parents and teachers. Structural equation modeling was used to examine the differential relationships between maternal rejection, family, cognitive factors and aggression in home and school settings. Results Family factors influenced aggression reported at home (.68) and at school (.44); maternal rejection seems to be related to aggression at home (.21). Cognitive factors influenced aggression reported at school (.-05) and at home (-.12). Conclusions Both genetic and environmental factors contribute to the development of aggressive behavior in ADHD. Identifying key risk factors will advance the development of appropriate clinical interventions and prevention strategies and will provide information to guide the targeting of resources to those children at highest risk. PMID:24860616

  12. The neurobiology of aggression and violence.

    PubMed

    Rosell, Daniel R; Siever, Larry J

    2015-06-01

    Aggression and violence represent a significant public health concern and a clinical challenge for the mental healthcare provider. A great deal has been revealed regarding the neurobiology of violence and aggression, and an integration of this body of knowledge will ultimately serve to advance clinical diagnostics and therapeutic interventions. We will review here the latest findings regarding the neurobiology of aggression and violence. First, we will introduce the construct of aggression, with a focus on issues related to its heterogeneity, as well as the importance of refining the aggression phenotype in order to reduce pathophysiologic variability. Next we will examine the neuroanatomy of aggression and violence, focusing on regional volumes, functional studies, and interregional connectivity. Significant emphasis will be on the amygdala, as well as amygdala-frontal circuitry. Then we will turn our attention to the neurochemistry and molecular genetics of aggression and violence, examining the extensive findings on the serotonergic system, as well as the growing literature on the dopaminergic and vasopressinergic systems. We will also address the contribution of steroid hormones, namely, cortisol and testosterone. Finally, we will summarize these findings with a focus on reconciling inconsistencies and potential clinical implications; and, then we will suggest areas of focus for future directions in the field.

  13. Verbal versus Physical Aggression in Intermittent Explosive Disorder

    PubMed Central

    Look, Amy E.; McCloskey, Michael S.; Coccaro, Emil F.

    2015-01-01

    Intermittent Explosive Disorder (IED) is the only adult psychiatric diagnosis for which pathological aggression is primary. DSM-IV criteria focused on physical aggression, but DSM-5 allows for an IED diagnosis in the presence of frequent verbal aggression with or without concurrent physical aggression. It remains unclear how individuals with verbal aggression differ from those with physical aggression with respect to cognitive-affective deficits and psychosocial functioning. The current study compared individuals who met IED criteria with either frequent verbal aggression without physical aggression (IED-V), physical aggression without frequent verbal aggression (IED-P), or both frequent verbal aggression and physical aggression (IED-B) as well as a non-aggressive personality-disordered (PD) comparison group using behavioral and self-report measures of aggression, anger, impulsivity, and affective lability, and psychosocial impairment. Results indicate all IED groups showed increased anger/aggression, psychosocial impairment, and affective lability relative to the PD group. The IED-B group showed greater trait anger, anger dyscontrol, and aggression compared to the IED-V and IED-P groups. Overall, the IED-V and IED-P groups reported comparable deficits and impairment. These results support the inclusion of verbal aggression within the IED criteria and suggest a more severe profile for individuals who engage in both frequent verbal arguments and repeated physical aggression. PMID:25534757

  14. Aggressive behaviors in the psychiatric emergency service

    PubMed Central

    Chaput, Yves; Beaulieu, Lucie; Paradis, Michel; Labonté, Edith

    2011-01-01

    Introduction: Studies of aggressive behaviors in a nonforensic mental health setting have focused primarily on the inpatient ward and, on event prediction, using behavior-based clinical rating scales. Few studies have specifically targeted aggressive behaviors in the psychiatric emergency service or determined whether assessing the demographic and clinical characteristics of such patients might prove useful for their more rapid identification. Methods: We used a prospectively acquired database of over 20,900 visits to four services in the province of Quebec, Canada, over a two-year period from September 2002 onwards. A maximum of 72 variables could be acquired per visit. Visits with aggression (any verbally or physically intimidating behavior), both present and past, were tagged. Binary logistic regressions and cross-tabulations were used to determine whether the profile of a variable differed in visits with aggression from those without aggression. Results: About 7% of visits were marked by current aggression (verbal 49%, physical 12%, verbal and physical 39%). Including visits with a “past only” history of aggression increased this number to 20%. Variables associated with aggression were gender (male), marital status (single/separated), education (high school or less), employment (none), judicial history (any type), substance abuse (prior or active), medication compliance (poor), type of arrival to psychiatric emergency services (involuntary, police, judiciary, landlord), reason for referral (behavioral dyscontrol), diagnosis (less frequent in anxiety disorders), and outcome (more frequently placed under observation or admitted). Conclusion: Our results suggest that many state-independent variables are associated with aggressive behaviors in the psychiatric emergency service. Although their sum may not add up to a specific patient profile, they can nevertheless be useful in service planning, being easily integrated alongside state-dependent rating scales in a

  15. Testosterone and Aggressive Behavior in Man

    PubMed Central

    Batrinos, Menelaos L.

    2012-01-01

    Atavistic residues of aggressive behavior prevailing in animal life, determined by testosterone, remain attenuated in man and suppressed through familial and social inhibitions. However, it still manifests itself in various intensities and forms from; thoughts, anger, verbal aggressiveness, competition, dominance behavior, to physical violence. Testosterone plays a significant role in the arousal of these behavioral manifestations in the brain centers involved in aggression and on the development of the muscular system that enables their realization. There is evidence that testosterone levels are higher in individuals with aggressive behavior, such as prisoners who have committed violent crimes. Several field studies have also shown that testosterone levels increase during the aggressive phases of sports games. In more sensitive laboratory paradigms, it has been observed that participant’s testosterone rises in the winners of; competitions, dominance trials or in confrontations with factitious opponents. Aggressive behavior arises in the brain through interplay between subcortical structures in the amygdala and the hypothalamus in which emotions are born and the prefrontal cognitive centers where emotions are perceived and controlled. The action of testosterone on the brain begins in the embryonic stage. Earlier in development at the DNA level, the number of CAG repeats in the androgen receptor gene seems to play a role in the expression of aggressive behavior. Neuroimaging techniques in adult males have shown that testosterone activates the amygdala enhancing its emotional activity and its resistance to prefrontal restraining control. This effect is opposed by the action of cortisol which facilitates prefrontal area cognitive control on impulsive tendencies aroused in the subcortical structures. The degree of impulsivity is regulated by serotonin inhibiting receptors, and with the intervention of this neurotransmitter the major agents of the neuroendocrine

  16. A COGNITIVE PERSPECTIVE ON AGGRESSIVE MIMICRY

    PubMed Central

    JACKSON, ROBERT R.; CROSS, FIONA R.

    2013-01-01

    We use the term ‘aggressive mimic’ for predators that communicate with their prey by making signals to indirectly manipulate prey behaviour. For understanding why the aggressive mimic’s signals work, it is important to appreciate that these signals interface with the prey’s perceptual system, and that the aggressive mimic can be envisaged as playing mind games with its prey. Examples of aggressive mimicry vary from instances in which specifying a model is straight forward to instances where a concise characterisation of the model is difficult. However, the less straightforward examples of aggressive mimicry may be the more interesting examples in the context of animal cognition. In particular, there are spiders that prey on other spiders by entering their prey’s web and making signals. Web invasion brings about especially intimate contact with their prey’s perceptual system because the prey spider’s web is an important component of the prey spider’s sensory apparatus. For the web-invading spider, often there is also a large element of risk when practising aggressive mimicry because the intended prey is also a potential predator. This element of risk, combined with exceptionally intimate interfacing with prey perceptual systems, may have favoured the web-invading aggressive mimic’s strategy becoming strikingly cognitive in character. Yet a high level of flexibility may be widespread among aggressive mimics in general and, on the whole, we propose that research on aggressive mimicry holds exceptional potential for advancing our understanding of animal cognition. PMID:23976823

  17. Agreeableness and Alcohol-Related Aggression: The Mediating Effect of Trait Aggressivity

    PubMed Central

    Miller, Cameron A.; Parrott, Dominic J.; Giancola, Peter R.

    2009-01-01

    This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality. PMID:19968409

  18. Understanding the personality disorder and aggression relationship: an investigation using contemporary aggression theory.

    PubMed

    Gilbert, Flora; Daffern, Michael; Talevski, Diana; Ogloff, James R P

    2015-02-01

    Research has consistently demonstrated a link between certain personality disorders (PDs) and increased rates of aggression and violence. At present, understanding of the mechanisms that underlie this relationship is limited. This study was designed to examine the contention (Gilbert & Daffern, 2011) that the application of a contemporary psychological aggression theory, the General Aggression Model (GAM; Anderson & Bushman, 2002), may assist in elucidating the PD-aggression relationship. Eighty-seven offenders undergoing presentence evaluation were assessed for Axis II PDs and psychopathy, aggression, and three constructs delineated by the GAM: scripts, normative beliefs, and anger. Regression analyses were undertaken to examine the relative contributions of these variables to aggression. The results upheld a relationship between several PDs and aggression, and suggested that for these PDs, the consideration of scripts, beliefs supportive of aggression, and anger facilitated an improved understanding of aggressiveness. Overall, the findings indicate that the GAM offers valuable insight into the psychological features that characterize individuals with PD who are prone to aggression.

  19. Escalation of aggression: experimental studies.

    PubMed

    Goldstein, J H; Davis, R W; Herman, D

    1975-01-01

    A finding commonly obtained in research using the Buss "aggression machine" is a main effect for trail blocks, indicating an escalation in shock intensity over trails. Theoretical explanations for this effect were tested in a modified verbal operant-conditioning situation. In Experiment 1, subjects could administer any of 10 levels of positive reinforcement to a "learner" for correct verbal responses or any of 10 levels of negative reinforcement to a learner for incorrect responses. Half of the subjects were required to begin with weak, half with strong, reinforcements. Results indicated that, regardless of condition, subjects gave more intense reinforcements as the learning trails progressed. Those who administered negative reinforcements devalued the learner relative to those who administered positive reinforcements. In Experiment 2, a role-playing procedure was used in which subjects administered either positive or negative reinforcements to a learner whose performance either did or did not improve over trials. Again, in all experimental groups, subjects administered increasingly intense reinforcements over trials. The results are interpreted as supporting a disinhibition theory of anti- and prosocial behavior.

  20. In vivo antithrombotic properties of a heparin from the oocyte test cells of the sea squirt Styela plicata(Chordata-Tunicata).

    PubMed

    Cardilo-Reis, L; Cavalcante, M C M; Silveira, C B M; Pavão, M S G

    2006-11-01

    In the ascidian Styela plicata, the oocytes are surrounded by two types of accessory cells named follicle cells and test cells. A heparin-like substance with an anticoagulant activity equivalent to 10% of mammalian heparin and about 5% as potent as the mammalian counterpart for the inhibition of thrombin by antithrombin was isolated from the oocyte test cells. In the present study, we compared the antithrombotic and hemorrhagic effects of sea squirt oocyte test cell heparin with those of porcine heparin in rat models of venous thrombosis and blood loss. Intravenous administration of the oocyte test cell heparin to Wistar rats (both sexes, weighing approximately 300 g, N = 4 in each group) at a dose of 5.0 mg/kg body weight, which produced a 1.8-fold increase in plasma activated partial thromboplastin time, inhibited thrombosis by 45 +/- 13.5% (mean +/- SD) without any bleeding effect. The same dose of porcine heparin inhibited thrombosis by 100 +/- 1.4%, but produced a blood loss three times greater than that of the saline-treated control. However, 10-fold reduction of the dose of porcine heparin to 0.5 mg/kg body weight, which produced a 5-fold increase in plasma-activated partial thromboplastin time, inhibited thrombosis by 70 +/- 13% without any bleeding effect. The antithrombotic properties of a new heparin isolated from test cells of the sea squirt S. plicata, reported here for the first time, indicate that, although sea squirt oocyte test cell heparin was a poor anticoagulant compared to porcine heparin, it had a significant antithrombotic effect without causing bleeding.

  1. The antithrombotic activity of EP224283, a neutralizable dual factor Xa inhibitor/glycoprotein IIbIIIa antagonist, exceeds that of the coadministered parent compounds.

    PubMed

    Hechler, Béatrice; Freund, Monique; Alame, Ghina; Leguay, Cécile; Gaertner, Sébastien; Cazenave, Jean-Pierre; Petitou, Maurice; Gachet, Christian

    2011-08-01

    EP224283 combines in a single molecule idraparinux and tirofiban, which allows obtaining a predictable and sustained antiplatelet effect through the transfer of the pharmacokinetics properties of idraparinux to the anti-αIIbβ3 antagonist. The activity can be instantaneously neutralized by injection of avidin, a specific antidote. We have tested the effects of this new profile anticoagulant in various thrombosis models. The antithrombotic effect of EP224283 was compared with those of the parent compounds used alone or in association at doses achieving low to moderate inhibition of platelet aggregation ex vivo. In a model of systemic thromboembolism independent of thrombin generation, tirofiban and EP224283 had similar effects at equimolar doses. On the other hand, EP224283 was more potent than tirofiban or idraparinux under thrombin-dependent conditions. In a ferric chloride-induced thrombosis model, EP224283 was more potent than either parent compound or their combination. Similar results were obtained after atherosclerotic plaque rupture in ApoE(-/-) mice. Thus, the dual action of EP224283 exceeds that of the parent compounds used in combination. A possible explanation is that EP224283 could concentrate antithrombin inside the thrombus by binding to αIIbβ3 through the tirofiban moiety, as shown by immunolabeling of the occluded vessel. No prolongation of the bleeding time was observed at doses achieving strong antithrombotic effects, suggesting that low to moderate αIIbβ3 inhibition combined with factor Xa inhibition minimizes the bleeding risk. The favorable antithrombotic profile of EP224283 together with its possible neutralization by avidin makes it an interesting drug candidate for the treatment and prevention of acute ischemic events.

  2. [Aggressive behavior: theoretical and biological aspects].

    PubMed

    Giotakos, O

    2013-01-01

    The susceptibility to aggression may manifest differently depending on the psychological context in which it occurs. In the context of psychopathy, characterized by a lack of empathy, this may manifest in aggression with criminal acts, which is characteristic of antisocial personality disorder. When the susceptibility is associated with psychotic impairment, aggression may be manifested in highly deviant behavior, like murder or serial killing. While the great majority of persons with schizophrenia do not commit violent acts, clinicians suggest that some schizophrenics may pose a risk in the community, particularly those patients with co-occurring substance abuse diagnoses, those who are noncompliant with prescribed psychiatric treatment, and those with a history of frequent relapses resulting in hospitalization or arrest. Episodic violence and aggression often accompany dementia. When coupled with emotional dysregulation, impulsive aggression often occurs in an interpersonal context, as in borderline personality disorder. However, the most common comorbidity is the substance abuse disorder, which contributes to both the cognitive distortions and disinhibition associated with the substance use. According to the biological data, aggression seems to emerge when the drive of limbic-mediated affective prefrontal response to provocative producing stimuli is insufficiently constrained by inhibition. Thus, excessive reactivity in the amygdale, coupled with inadequate prefrontal regulation, increase the possibility of aggressive behavior. The PET/SPECT studies focusing on schizophrenia have shown reduced activity in fronto-temoral circuitry. The fMRI studies concord with the hypothesis that among violent persons with schizophrenia, those with sociopathetic features and/or substance abuse constitute a highly different subgroup, in which cognitive, neurological and behavioral patterns are more closely associated with the personality traits than schizophrenia. It is known

  3. Trajectories of change in physical aggression and marital satisfaction.

    PubMed

    Lawrence, Erika; Bradbury, Thomas N

    2007-06-01

    Physical aggression and marital satisfaction were assessed in 172 newlywed couples annually over the first 4 years of marriage to examine (a) stability of aggression over time and (b) the degree to which fluctuations in aggression precede versus follow fluctuations in marital satisfaction. The stability of aggression varied as a function of initial levels of severity; spouses who were most aggressive early in marriage had greater fluctuations in aggression. Rates of change in aggression predicted changes in satisfaction more than dissatisfaction predicted aggression. Husbands' physical aggression predicted marital discord, whereas wives' aggression predicted marital dissolution. By indicating that aggression (a) is a precursor to adverse marital outcomes and (b) varies across spouses in initial levels and in patterns of temporal change, the present findings highlight the need to understand the contextual factors that govern within-person and within-couple fluctuations in intimate violence.

  4. Role of antibiotics in generalized aggressive periodontitis: A review of clinical trials in humans

    PubMed Central

    Ahuja, Annapurna; Baiju, C. S.; Ahuja, Vipin

    2012-01-01

    Background: It is well-recognized fact that periodontal diseases are caused by multifactorial etiologies, in which microorganisms play an important role. An essential component of therapy is to eliminate or manage these pathogens. This has been traditionally accomplished through mechanical means by scaling and root planning which is ineffective in some of the aggressive periodontal diseases. These aggressive diseases involve particular groups of microorganisms which are not eliminated by mechanical means; and they require anti-infective therapy, which includes local and systemic antimicrobials. This approach of therapy is of interest to periodontist due to the aforementioned shortcomings of conventional methods. Materials and Methods: A manual and electronic search was made for human studies up to March 2011 that presented clinical and microbiological data for the efficacy of a systemic antibiotics in generalized aggressive periodontitis along with scaling and root planning. A systematic approach was followed by two independent reviewers and included eligibility criteria for study inclusion, quality assessment, and determination of outcome measures, data extraction, data synthesis, and drawing of conclusion. Results: Only three randomized controlled human trials qualified, and they concluded that both scaling and root planing (SRP) mono-therapy and SRP with antibiotics proves beneficial in improving clinical and microbiological parameters in aggressive periodontitis. Better results were seen in SRP with antibiotic groups as compared with SRP alone. Conclusion: Because of the insufficient quantity and heterogenecity of studies, no adequate evidence could be gathered to use the beneficial effects of these antibiotics along with SRP in aggressive periodontitis compared with SRP alone. PMID:23162322

  5. The aggression paradox: understanding links among aggression, sensation seeking, and the consideration of future consequences.

    PubMed

    Joireman, Jeff; Anderson, Jonathan; Strathman, Alan

    2003-06-01

    Four studies involving 573 female and 272 male college students demonstrated that multiple forms and measures of aggression were associated with high levels of sensation seeking, impulsivity, and a focus on the immediate consequences of behavior. Multiple regression analyses and structural equation models supported a theoretical model based on the general aggression model (C.A. Anderson & B.J. Bushman. 2002), positing that hostile cognition and negative affect mediate the relationships between the aforementioned individual differences and aggression. Sensation seeking also predicted a desire to engage in physical and verbal aggression. The final study demonstrated that relative to those scoring low, individuals scoring high on the consideration of future consequences are only less aggressive when aggression is likely to carry future costs. PMID:12793590

  6. Aggressive dogs: assessment and treatment considerations.

    PubMed

    Crowell-Davis, Sharon L

    2008-05-01

    The question of what to do with an aggressive dog involves clinical, legal, and ethical considerations. This first column on the subject addresses the clinical aspects from the standpoint of the general veterinarian. PMID:18581290

  7. Human Aggression Linked to Chemical Balance

    ERIC Educational Resources Information Center

    Science News, 1978

    1978-01-01

    Recent studies done by federal researchers indicate that human aggression may be affected by a critical balance of two or three key brain chemical neurotransmitters. Results of this study with human beings are included in this article. (MA)

  8. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  9. Behavioral and Pharmacogenetics of Aggressive Behavior

    PubMed Central

    Takahashi, Aki; Quadros, Isabel M.; de Almeida, Rosa M. M.; Miczek, Klaus A.

    2013-01-01

    Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or

  10. Androgen receptors, sex behavior, and aggression.

    PubMed

    Cunningham, Rebecca L; Lumia, Augustus R; McGinnis, Marilyn Y

    2012-01-01

    Androgens are intricately involved in reproductive and aggressive behaviors, but the role of the androgen receptor in mediating these behaviors is less defined. Further, activity of the hypothalamic-pituitary-gonadal axis and hypothalamic-pituitary-adrenal axis can influence each other at the level of the androgen receptor. Knowledge of the mechanisms for androgens' effects on behaviors through the androgen receptor will guide future studies in elucidating male reproductive and aggressive behavior repertoires.

  11. Psychoanalytic views of aggression: some theoretical problems.

    PubMed

    Pedder, J

    1992-06-01

    Various problems in relation to psychoanalytic theories of aggression are considered in a review which is by no means exhaustive but includes areas which have puzzled and interested the author. First to be considered is why the concept of aggression as a major drive was a relative late-comer in psychoanalysis; next the contentious concept of a 'death instinct' and some of the factors in Freud's lifetime which may have contributed to both. Then it is suggested that we seem to have theories of aggression which might be called primary or secondary in two different senses. First is the question whether aggression is innate or secondary to frustration. In another sense, primary and secondary theories of aggression seem to survive paralleling Freud's original primary and secondary theories of anxiety. In this sense the primary theory survives as an explanation of psychosomatic disorder. Lastly, the link between suicide and murder is considered and the turning of aggression against the self in depression and self-destructive attacks. PMID:1633126

  12. Female competition and aggression: interdisciplinary perspectives

    PubMed Central

    Stockley, Paula; Campbell, Anne

    2013-01-01

    This paper introduces a Theme Issue combining interdisciplinary perspectives in the study of female competition and aggression. Despite a history of being largely overlooked, evidence is now accumulating for the widespread evolutionary significance of female competition. Here, we provide a synthesis of contributions to this Theme Issue on humans and other vertebrates, and highlight directions for future research. Females compete for resources needed to survive and reproduce, and for preferred mates. Although female aggression takes diverse forms, under most circumstances relatively low-risk competitive strategies are favoured, most probably due to constraints of offspring production and care. In social species, dominance relationships and threats of punishment can resolve social conflict without resort to direct aggression, and coalitions or alliances may reduce risk of retaliation. Consistent with these trends, indirect aggression is a low cost but effective form of competition among young women. Costs are also minimized by flexibility in expression of competitive traits, with aggressive behaviour and competitive signalling tailored to social and ecological conditions. Future research on female competition and the proximate mediators of female aggression will be greatly enhanced by opportunities for interdisciplinary exchange, as evidenced by contributions to this Theme Issue. PMID:24167303

  13. Neural mechanisms of predatory aggression in rats-implications for abnormal intraspecific aggression.

    PubMed

    Tulogdi, Aron; Biro, Laszlo; Barsvari, Beata; Stankovic, Mona; Haller, Jozsef; Toth, Mate

    2015-04-15

    Our recent studies showed that brain areas that are activated in a model of escalated aggression overlap with those that promote predatory aggression in cats. This finding raised the interesting possibility that the brain mechanisms that control certain types of abnormal aggression include those involved in predation. However, the mechanisms of predatory aggression are poorly known in rats, a species that is in many respects different from cats. To get more insights into such mechanisms, here we studied the brain activation patterns associated with spontaneous muricide in rats. Subjects not exposed to mice, and those which did not show muricide were used as controls. We found that muricide increased the activation of the central and basolateral amygdala, and lateral hypothalamus as compared to both controls; in addition, a ventral shift in periaqueductal gray activation was observed. Interestingly, these are the brain regions from where predatory aggression can be elicited, or enhanced by electrical stimulation in cats. The analysis of more than 10 other brain regions showed that brain areas that inhibited (or were neutral to) cat predatory aggression were not affected by muricide. Brain activation patterns partly overlapped with those seen earlier in the cockroach hunting model of rat predatory aggression, and were highly similar with those observed in the glucocorticoid dysfunction model of escalated aggression. These findings show that the brain mechanisms underlying predation are evolutionarily conservative, and indirectly support our earlier assumption regarding the involvement of predation-related brain mechanisms in certain forms of escalated social aggression in rats.

  14. Hormone-dependent aggression in female rats: testosterone implants attenuate the decline in aggression following ovariectomy.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1990-04-01

    Female rats were individually housed with a sterile male for a 4- to 5-week period. Each female was then tested for aggression toward an unfamiliar female intruder at weekly intervals. Those females that displayed a high level of aggression on each of three weekly tests were ovariectomized and given subcutaneous implants of testosterone-filled tubes, ovariectomized and given subcutaneous implants of empty tubes, or sham-ovariectomized and implanted with empty tubes. These implants should produce a serum testosterone concentration of about 0.6 ng/ml, compared to 0.17 ng/ml in intact females. Beginning 1 week postoperatively, the aggression of each female was tested weekly for 4 weeks. Ovariectomized females with testosterone implants displayed a level of aggression significantly higher than that of ovariectomized females with empty implants on 3 of 4 weekly tests. The level of aggression by females with testosterone implants was not significantly different from that of sham-ovariectomized females on the first postoperative test. Additional observations showed that testosterone implants did not produce an increase in aggression in females whose preoperative level of aggression was low. Further, Silastic implants containing estrogen (1 to 2 mm long) sufficient to maintain a serum estrogen level of 20 to 30 pg/ml also attenuated the decline of aggression following ovariectomy. These results suggest that testosterone and estrogen may both contribute to the biological substrate of hormone-dependent aggression in female rats.

  15. Perpetration and Victimization of Intimate Partner Aggression Among Rural Mothers

    PubMed Central

    Schwab Reese, Laura M.; Harland, Karisa; Smithart, Kelsey

    2015-01-01

    Abstract Intimate partner aggression is a leading cause of injury among women of child-bearing age. Research suggests that pregnancy and the postpartum period are times of increased vulnerability to aggression. Since rural women are at an increased risk of intimate partner aggression, research is needed to examine the role of pregnancy and the presence of children on intimate partner aggression among this vulnerable population. The purpose of this study is to examine the association between young children and intimate partner aggression victimization and perpetration among a rural sample. This analysis utilized data from biologic females of child-bearing age from the Keokuk County Rural Health Study, a cohort study of over 1,000 rural families conducted from 1994 to 2011. Crude and adjusted logistic regression was used to determine the relationship between having a young child and experiencing four forms of intimate partner aggression: verbal aggression perpetration, verbal aggression victimization, physical aggression perpetration, and physical aggression victimization. Having young children was significantly associated with increased odds of perpetrating verbal aggression but not victimization of verbal aggression or perpetration and victimization of physical aggression. This significant relationship persisted after adjustment for education, employment, or location of residence but not age or marital status. The increased odds of perpetrating verbal aggression among mothers in a rural area highlight the need for interventions designed for rural parents. One method of reducing intimate partner aggression may be to incorporate intimate partner aggression prevention activities into existing child abuse intervention activities.

  16. Relational Aggression and Academic Performance in Elementary School

    ERIC Educational Resources Information Center

    Risser, Scott D.

    2013-01-01

    To investigate the relationship between relational aggression and school performance, this study examined the relative and combined associations among relational aggression, overt aggression, and victimization and children's academic performance. Additionally this study examined the relative associations among relational and overt aggression and…

  17. The dopaminergic system and aggression in laying hens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The dopaminergic system regulates aggression in humans and other mammals. To investigate if birds with genetic propensity for high and low aggressiveness may exhibit distinctly different aggressive mediation via dopamine (DA) D1 and D2 receptor pathways, two high aggressive (DXL and LGPS) and one lo...

  18. Relational Aggression in Middle Childhood: Predictors and Adolescent Outcomes

    ERIC Educational Resources Information Center

    Spieker, Susan J.; Campbell, Susan B.; Vandergrift, Nathan; Pierce, Kim M.; Cauffman, Elizabeth; Susman, Elizabeth J.; Roisman, Glenn I.

    2012-01-01

    This study examined gender differences in the level and developmental course of relational aggression in middle childhood, as well as early predictors and outcomes of relational aggression, after controlling for concurrent physical aggression. Relational (RAgg) and Physical aggression (PAgg) scores for 558 boys and 545 girls at the ages of eight…

  19. [Current management of antithrombotic treatment in patients with non valvular atrial fibrillation and prior history of stroke or transient ischemic attack].

    PubMed

    Masjuán, Jaime; Álvarez-Sabín, José; Blanco, Miguel; de Felipe, Alicia; Gil-Núñez, Antonio; Gállego-Culleré, Jaime; Vivancos, José

    2014-07-01

    Atrial fibrillation is the most frequent arrhythmia seen in clinical practice and is one of the most important risk factors for suffering a stroke. Strokes associated to atrial fibrillation are more severe, present higher mortality and disability rates, and there is a greater risk of recurrence. Consequently, both primary and secondary prevention of stroke associated to atrial fibrillation by means of suitable antithrombotic treatment is clearly essential in order to lower this risk. Chronic oral anticoagulants are the cornerstone of antithrombotic treatment in patients with non-valvular atrial fibrillation, especially in those who have already had a stroke. Vitamin K antagonists have traditionally been used for this purpose. Yet, these drugs have several important disadvantages (narrow therapeutic window, unpredictable response, numerous interactions with drugs and foods, as well as starting and finishing their action slowly), which limit their use in clinical practice. The new oral anticoagulants not only overcome these disadvantages but also have proved to be at least as effective as warfarin in the prevention of strokes and systemic embolism in patients with non-valvular atrial fibrillation. Additionally, they have been shown to have a better safety profile, especially with an important drop in the risk of intracranial haemorrhage, regardless of the antecedents of stroke or transient ischaemic attack, which makes them first-choice drugs in the treatment of these patients.

  20. A Comprehensive Literature Review of Mode Deactivation Therapy

    ERIC Educational Resources Information Center

    Houston, Marsha Ann; Apsche, Jack A.; Bass, Christopher K.

    2007-01-01

    In this article literature published on Mode Deactivation Therapy (MDT) was reviewed in depth. Several studies were identified that used a common outcome measure of reduction of physical and sexual aggression, other risk related behaviors. Comparisons of MDT and, other standardized approaches typically used in treating aggression in juveniles,…

  1. Psychosis, aggression, and self-destructive behavior in hospitalized adolescents.

    PubMed

    Delga, I; Heinssen, R K; Fritsch, R C; Goodrich, W; Yates, B T

    1989-04-01

    The authors studied the history of aggressive and self-destructive behaviors in psychotic and nonpsychotic hospitalized adolescents (N = 137). A multidimensional measure of self- and other-directed aggression was retrospectively applied to each patient's social and developmental history. Nonsignificant gender and diagnostic differences were obtained on ratings of violence and suicide. Broader definitions of internal and external aggression yielded nonsignificant diagnostic differences, but gender differences were observed on both internal and external aggression measures. Females displayed greater internal aggression, and males reported higher external aggression scores. These results, compared to those of other investigators, suggest the importance of social and cultural variables in understanding adolescent psychosis and aggression.

  2. [Progress of anticoagulation therapy in atrial fibrillation].

    PubMed

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-01

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.

  3. Levels of Aggression among Turkish Adolescents and Factors Leading to Aggression.

    PubMed

    Avci, Dilek; Kilic, Mahmut; Tari Selcuk, Kevser; Uzuncakmak, Tugba

    2016-07-01

    Aggression, an increasing problem among adolescents, is a potential threat to public health as it can lead to violence. Determining the factors causing aggression plays an important role in taking measures to reduce violence. This study aimed at determining the level of aggression among adolescents and at identifying the factors associated with high levels of aggression. This cross-sectional study was conducted with 2,409 Turkish adolescents. Data were collected with the Socio-demographic Questionnaire, Aggression Scale, Perceived Social Support Scale, and Communication Skills Attitude Scale. Data were analyzed using descriptive statistics, the chi-square test, t-test, and logistic regression. The participants' mean aggression score was 91.83 ± 24.05, and 24.0% of the adolescents' aggression levels rated high. According to the logistic regression model, aggression was 1.26 times higher among males, 1.92 times higher among those who perceived their mental health as poor, 1.58 times higher among those with suicidal ideation, 1.29 times higher among those who did not get prepared for university entrance exams, and 1.62 times higher among those who perceived their school performance as poor. Perceived family social support was a protective factor against high aggression. Approximately one out of every four adolescents in the two Turkish high schools where the study was conducted was determined to display high levels of aggression. Therefore, in order to reduce aggression among adolescents, programs such as coping management and coping with anger should be applied by nurses. Programs should include not only students but also families. PMID:27111434

  4. Levels of Aggression among Turkish Adolescents and Factors Leading to Aggression.

    PubMed

    Avci, Dilek; Kilic, Mahmut; Tari Selcuk, Kevser; Uzuncakmak, Tugba

    2016-07-01

    Aggression, an increasing problem among adolescents, is a potential threat to public health as it can lead to violence. Determining the factors causing aggression plays an important role in taking measures to reduce violence. This study aimed at determining the level of aggression among adolescents and at identifying the factors associated with high levels of aggression. This cross-sectional study was conducted with 2,409 Turkish adolescents. Data were collected with the Socio-demographic Questionnaire, Aggression Scale, Perceived Social Support Scale, and Communication Skills Attitude Scale. Data were analyzed using descriptive statistics, the chi-square test, t-test, and logistic regression. The participants' mean aggression score was 91.83 ± 24.05, and 24.0% of the adolescents' aggression levels rated high. According to the logistic regression model, aggression was 1.26 times higher among males, 1.92 times higher among those who perceived their mental health as poor, 1.58 times higher among those with suicidal ideation, 1.29 times higher among those who did not get prepared for university entrance exams, and 1.62 times higher among those who perceived their school performance as poor. Perceived family social support was a protective factor against high aggression. Approximately one out of every four adolescents in the two Turkish high schools where the study was conducted was determined to display high levels of aggression. Therefore, in order to reduce aggression among adolescents, programs such as coping management and coping with anger should be applied by nurses. Programs should include not only students but also families.

  5. Normative influences on aggression in urban elementary school classrooms.

    PubMed

    Henry, D; Guerra, N; Huesmann, R; Tolan, P; VanAcker, R; Eron, L

    2000-02-01

    We report a study aimed at understanding the effects of classroom normative influences on individual aggressive behavior, using samples of 614 and 427 urban elementary school children. Participants were assessed with measures of aggressive behavior and normative beliefs about aggression. We tested hypotheses related to the effects of personal normative beliefs, descriptive classroom norms (the central tendency of classmates' aggressive behavior), injunctive classroom normative beliefs (classmates' beliefs about the acceptability of aggression), and norm salience (student and teacher sanctions against aggression) on longitudinal changes in aggressive behavior and beliefs. injunctive norms affected individual normative beliefs and aggression, but descriptive norms had no effect on either. In classrooms where students and teachers made norms against aggression salient, aggressive behavior diminished over time. Implications for classroom behavior management and further research are discussed.

  6. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  7. FAM5C Contributes to Aggressive Periodontitis

    PubMed Central

    Carvalho, Flavia M.; Tinoco, Eduardo M. B.; Deeley, Kathleen; Duarte, Poliana M.; Faveri, Marcelo; Marques, Marcelo R.; Mendonça, Adriana C.; Wang, Xiaojing; Cuenco, Karen; Menezes, Renato; Garlet, Gustavo P.; Vieira, Alexandre R.

    2010-01-01

    Aggressive periodontitis is characterized by a rapid and severe periodontal destruction in young systemically healthy subjects. A greater prevalence is reported in Africans and African descendent groups than in Caucasians and Hispanics. We first fine mapped the interval 1q24.2 to 1q31.3 suggested as containing an aggressive periodontitis locus. Three hundred and eighty-nine subjects from 55 pedigrees were studied. Saliva samples were collected from all subjects, and DNA was extracted. Twenty-one single nucleotide polymorphisms were selected and analyzed by standard polymerase chain reaction using TaqMan chemistry. Non-parametric linkage and transmission distortion analyses were performed. Although linkage results were negative, statistically significant association between two markers, rs1935881 and rs1342913, in the FAM5C gene and aggressive periodontitis (p = 0.03) was found. Haplotype analysis showed an association between aggressive periodontitis and the haplotype A-G (rs1935881-rs1342913; p = 0.009). Sequence analysis of FAM5C coding regions did not disclose any mutations, but two variants in conserved intronic regions of FAM5C, rs57694932 and rs10494634, were found. However, these two variants are not associated with aggressive periodontitis. Secondly, we investigated the pattern of FAM5C expression in aggressive periodontitis lesions and its possible correlations with inflammatory/immunological factors and pathogens commonly associated with periodontal diseases. FAM5C mRNA expression was significantly higher in diseased versus healthy sites, and was found to be correlated to the IL-1β, IL-17A, IL-4 and RANKL mRNA levels. No correlations were found between FAM5C levels and the presence and load of red complex periodontopathogens or Aggregatibacter actinomycetemcomitans. This study provides evidence that FAM5C contributes to aggressive periodontitis. PMID:20383335

  8. 6-hydroxydopamine and aggression in cats.

    PubMed

    Beleslin, D B; Samardzić, R; Stefanović-Denić, K

    1981-01-01

    The effect of 6-hydroxydopamine (6-OHDA) injected into the cerebral ventricles on behaviour of singly- and group-housed cats was investigated. 6-OHDA in doses of 0.5, 1 and 2 mg was administered every morning for 5 to 8 days. In small doses 6-OHDA in singly- and group-housed cats evoked motor phenomena such as tremor, ataxia, rigidity, weakness and sometimes clonic-tonic convulsions. Occasionally restlessness, irritability and rage were observed. Large doses of 6-OHDA in group-housed cats, after a short latent period (2-3 days) produced aggression which intensified on subsequent injections, and thereafter, on repeated administrations, no longer occurred. The aggression consisted of restlessness, irritability, anger, rage, apprehension, threat, attack, fighting, flight and crying. Of autonomic phenomena mydriasis, dyspnea and sometimes piloerection were observed. The aggression was initiated by the most restless cat, or by disturbing the animals, such as by moving the cage. When 6-OHDA no longer produced aggressive behaviour, motor changes such as tremor, ataxia, rigidity, walking on broad base, weakness with adynamia and clonic-tonic convulsions developed. These latter symptoms were produced by large doses of 6-OHDA in singly-housed cats. In these animals spontaneous signs of aggressive behaviour usually were not observed, although if handled they showed rage, snarling and hissing. When singly-housed cats were kept in the same cage with group-housed animals, the singly-housed cats usually became aggressive. It appears that hyperactivity induced aggression in 6-OHDA-treated cats. PMID:7195585

  9. Cruel Intentions on Television and in Real Life: Can Viewing Indirect Aggression Increase Viewers' Subsequent Indirect Aggression?

    ERIC Educational Resources Information Center

    Coyne, Sarah M.; Archer, John; Eslea, Mike

    2004-01-01

    Numerous studies have shown that viewing violence in the media can influence an individual's subsequent aggression, but none have examined the effect of viewing indirect aggression. This study examines the immediate effect of viewing indirect and direct aggression on subsequent indirect aggression among 199 children ages 11 to 14 years. They were…

  10. Popular and Nonpopular Subtypes of Physically Aggressive Preadolescents: Continuity of Aggression and Peer Mechanisms during the Transition to Middle School

    ERIC Educational Resources Information Center

    Shi, Bing; Xie, Hongling

    2012-01-01

    Using peer nominations of physical aggression and perceived popularity in the spring semester of fifth grade, we identified 54 popular aggressive and 42 nonpopular aggressive preadolescents in a diverse sample of 318 participants recruited from an urban school district. Physical aggression in the spring semester of sixth grade was included to…

  11. Effects of Viewing Relational Aggression on Television on Aggressive Behavior in Adolescents: A Three-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Coyne, Sarah M.

    2016-01-01

    Most researchers on media and aggression have examined the behavioral effects of viewing physical aggression in the media. Conversely, in the current study, I examined longitudinal associations between viewing "relational aggression" on TV and subsequent aggressive behavior. Participants included 467 adolescents who completed a number of…

  12. Aggressive and Nonaggressive Children's Moral Judgments and Moral Emotion Attributions in Situations Involving Retaliation and Unprovoked Aggression

    ERIC Educational Resources Information Center

    Gasser, Luciano; Malti, Tina; Gutzwiller-Helfenfinger, Eveline

    2012-01-01

    The authors investigated 7- and 9-year-old children's moral understanding of retaliation as compared to unprovoked aggression with regard to their aggressive behavior status. Based on peer ratings, 48 children were selected as overtly aggressive and 91 as nonaggressive. Their moral understanding of retaliation and unprovoked aggression was…

  13. Brief report: the adolescent Child-to-Parent Aggression Questionnaire: an examination of aggressions against parents in Spanish adolescents.

    PubMed

    Calvete, E; Gamez-Guadix, M; Orue, I; Gonzalez-Diez, Z; Lopez de Arroyabe, E; Sampedro, R; Pereira, R; Zubizarreta, A; Borrajo, E

    2013-12-01

    The objective of this study was to develop a questionnaire to assess child-to-parent aggression in adolescents and to document the extent of the problem. The questionnaire developed in this study, the Child-to-Parent Aggression Questionnaire (CPAQ), includes forms of physical and psychological aggression directed at both the mother and the father. It also includes open questions about the reasons for the aggressive acts. The CPAQ was completed by a sample of 2719 adolescents (age range: 13-18 years old, 51.4% girls). Confirmatory factor analysis supported a four-factor correlated structure (physical aggression against mother, physical aggression against father, psychological aggression against mother, and psychological aggression against father). Psychological and physical aggression against the mother was more frequent than against the father. However, there were no differences with regard to severe forms of aggression. Girls scored significantly higher on all indicators of psychological aggression, including severe psychological aggression. Nevertheless, except for the prevalence of physical aggression against mothers, which was higher in females, there were no significant differences in physical aggression against parents. Finally, the reasons provided by the adolescents for the aggression included both instrumental (e.g., to obtain permission to get home late and to access their computers) and reactive reasons (e.g., anger and self-defense). These findings highlight the complexity of child-to-parent aggression in adolescence.

  14. Aggression in humans: what is its biological foundation?

    PubMed

    Albert, D J; Walsh, M L; Jonik, R H

    1993-01-01

    Although human aggression is frequently inferred to parallel aggression based on testosterone in nonprimate mammals, there is little concrete support for this position. High- and low-aggression individuals do not consistently differ in serum testosterone. Aggression does not change at puberty when testosterone levels increase. Aggression does not increase in hypogonadal males (or females) when exogenous testosterone is administered to support sexual activity. Similarly, there are no reports that aggression increases in hirsute females even though testosterone levels may rise to 200% above normal. Conversely, castration or antiandrogen administration to human males is not associated with a consistent decrease in aggression. Finally, changes in human aggression associated with neuropathology are not consistent with current knowledge of the neural basis of testosterone-dependent aggression. In contrast, human aggression does have a substantial number of features in common with defensive aggression seen in nonprimate mammals. It is present at all age levels, is displayed by both males and females, is directed at both males and females, and is not dependent on seasonal changes in hormone levels or experiential events such as sexual activity. As would be expected from current knowledge of the neural system controlling defensive aggression, aggression in humans increases with tumors in the medial hypothalamus and septal region, and with seizure activity in the amygdala. It decreases with lesions in the amygdala. The inference that human aggression has its roots in the defensive aggression of nonprimate mammals is in general agreement with evidence on the consistency of human aggressiveness over age, with similarities in male and female aggressiveness in laboratory studies, and with observations that some neurological disturbances contribute to criminal violence. This evidence suggests that human aggression has its biological roots in the defensive aggression of nonprimate

  15. The Aggression-Inhibiting and Aggression-Facilitating Influence of Heightened Sexual Arousal.

    ERIC Educational Resources Information Center

    Baron, Robert A.; Bell, Paul A.

    Eighty-six undergraduate males participated in an experiment designed to investigate the impact of various types of erotic stimuli upon aggression. On the basis of previous research, it was hypothesized that exposure to mild erotic stimuli would tend to inhibit subsequent aggression, while exposure to more arousing stimuli of this type would…

  16. Witnessed aggression: influence of an observer's sex and values on aggressive responding.

    PubMed

    Borden, R J

    1975-03-01

    Two experiments investigated the effects of the presence of an observer on aggressive responding. In one experiment, male subjects observed by a male aggressed more than those observed by a female. When the male observer was removed from the situation, subjects' level of aggressiveness more closely matched the level manifested by the opponent. The removal of the female observer had little effect on the subjects' behavior. In the second experiment, the male or female observer of the subject's behavior was disguised as a member of an organization with explicit values (aggressive or pacifistic) regarding the use of aggression. In this case, significant differences in aggression were associated with the observer's values but not the observer's sex. Following the departure of the observer, the shock settings of subjects in the two aggressive-value observer groups showed a signifcant decrease. The average shock setting of subjects in the two pacifistic-value observer groups remained at about the same level. In sum, the results indicated that the subjects' aggressive behavior was apparently a function of their expectations of approval for such behavior, based on the inferred or explicit values of the observer. The results were further discussed in terms of social learning theory.

  17. The Relationship between Unstable Self-Esteem and Aggression: Differences in Reactive and Proactive Aggression

    ERIC Educational Resources Information Center

    Lee, Eunju J.

    2014-01-01

    This study examines whether the instability of self-esteem (i.e., a high intraindividual variability in self-esteem) is differentially associated with different types of aggressive behavior by using a sample of 235 preadolescent children. Self-esteem was measured four times for four consecutive days, and proactive and reactive aggressive behaviors…

  18. The impact of classroom aggression on the development of aggressive behavior problems in children.

    PubMed

    Thomas, Duane E; Bierman, Karen L

    2006-01-01

    Prior research suggests that exposure to elementary classrooms characterized by high levels of student aggression may contribute to the development of child aggressive behavior problems. To explore this process in more detail, this study followed a longitudinal sample of 4,907 children and examined demographic factors associated with exposure to high-aggression classrooms, including school context factors (school size, student poverty levels, and rural vs. urban location) and child ethnicity (African American, European American). The developmental impact of different temporal patterns of exposure (e.g., primacy, recency, chronicity) to high-aggression classrooms was evaluated on child aggression. Analyses revealed that African American children attending large, urban schools that served socioeconomically disadvantaged students were more likely than other students to be exposed to high-aggressive classroom contexts. Hierarchical regressions demonstrated cumulative effects for temporal exposure, whereby children with multiple years of exposure showed higher levels of aggressive behavior after 3 years than children with primacy, less recent, and less chronic exposure, controlling for initial levels of aggression. Implications are discussed for developmental research and preventive interventions.

  19. Intra- Versus Intersex Aggression: Testing Theories of Sex Differences Using Aggression Networks.

    PubMed

    Wölfer, Ralf; Hewstone, Miles

    2015-08-01

    Two theories offer competing explanations of sex differences in aggressive behavior: sexual-selection theory and social-role theory. While each theory has specific strengths and limitations depending on the victim's sex, research hardly differentiates between intrasex and intersex aggression. In the present study, 11,307 students (mean age = 14.96 years; 50% girls, 50% boys) from 597 school classes provided social-network data (aggression and friendship networks) as well as physical (body mass index) and psychosocial (gender and masculinity norms) information. Aggression networks were used to disentangle intra- and intersex aggression, whereas their class-aggregated sex differences were analyzed using contextual predictors derived from sexual-selection and social-role theories. As expected, results revealed that sexual-selection theory predicted male-biased sex differences in intrasex aggression, whereas social-role theory predicted male-biased sex differences in intersex aggression. Findings suggest the value of explaining sex differences separately for intra- and intersex aggression with a dual-theory framework covering both evolutionary and normative components.

  20. Beliefs about Aggression and Submissiveness: A Comparison of Aggressive and Nonaggressive Individuals with Mild Intellectual Disability

    ERIC Educational Resources Information Center

    Kirk, Jamie; Jahoda, Andrew; Pert, Carol

    2008-01-01

    Recent research has examined the relevance of the social information processing model of aggression to individuals with intellectual disability (ID). This study investigated the "response access" and "response decision" steps of this model. Photo stories were used to compare aggressive and nonaggressive individuals' beliefs about the outcomes of…

  1. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

    PubMed Central

    Pozza, Carlotta; Graziadio, Chiara; Giannetta, Elisa; Lenzi, Andrea; Isidori, Andrea M.

    2012-01-01

    Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors. PMID:22934113

  2. MS Stem Cell Therapy Succeeds but Poses Risks

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159285.html MS Stem Cell Therapy Succeeds But Poses Risks Toxic ... transplant could represent a major advance against aggressive multiple sclerosis, experts say. This new treatment destroys the immune ...

  3. Maternal Depression and Childhood Aggression: Literature Review

    PubMed Central

    Hendricks, Katherine; Liu, Jianghong

    2012-01-01

    Introduction Childbearing depression (CBD) and childhood aggression are serious and international problems that encumber public health. Although maternal depression has received much attention in the literature in the last three decades, clinically it remains under-diagnosed and under-treated, especially during pregnancy. As a result, many mothers and families are left to suffer its long-lasting physical and psychosocial effects. This article's aim is to review the current literature on whether CBD increases the likelihood of childhood aggression in children ages six years and younger. Methods Using keywords, an electronic search was performed using Cumulative Index of Nursing and Allied Health, PsycINFO, and PubMed databases. Search limits included the following: 2000-2010, English, peer-review, human, All Child: 0-18. From more than 2,000 search results, 13 articles were reviewed based on relevance to paper's inquiry and sample size greater than 50. Results In all, the articles agreed that depression in women increases the likelihood of early childhood aggression by causing negative parenting behaviors. However, this finding is tempered by a number of weaknesses in the quality of articles reviewed and by the complexity of the topic. Conclusion More research is needed to determine the etiology and interplay of mediating factors between CBD and childhood aggression. This could inform the study and implementation of effective and early prevention, screening, and treatment measures and programs for maternal depression and childhood aggression. PMID:22739482

  4. Predicting hospital aggression in secure psychiatric care

    PubMed Central

    Priday, Lee J.; Ireland, Carol A.; Chu, Simon; Kilcoyne, Jennifer; Mulligan, Caroline

    2016-01-01

    Background Risk assessment instruments have become a preferred means for predicting future aggression, claiming to predict long-term aggression risk. Aims To investigate the predictive value over 12 months and 4 years of two commonly applied instruments (Historical, Clinical and Risk Management - 20 (HCR-20) and Violence Risk Appraisal Guide (VRAG)). Method Participants were adult male psychiatric patients detained in a high secure hospital. All had a diagnosis of personality disorder. The focus was on aggression in hospital. Results The actuarial risk assessment (VRAG) was generally performing better than the structured risk assessment (HCR-20), although neither approach performed particularly well overall. Any value in their predictive potential appeared focused on the longer time period under study (4 years) and was specific to certain types of aggression. Conclusions The value of these instruments for assessing aggression in hospital among patients with personality disorder in a high secure psychiatric setting is considered. Declaration of interest J.L.I., C.A.M. and J.K. are employed by the trust where the data were collected. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703760

  5. Digit ratio (2D:4D), aggression, and testosterone in men exposed to an aggressive video stimulus.

    PubMed

    Kilduff, Liam P; Hopp, Renato N; Cook, Christian J; Crewther, Blair T; Manning, John T

    2013-01-01

    The relative lengths of the 2(nd) and 4(th) digits (2D:4D) is a negative biomarker for prenatal testosterone, and low 2D:4D may be associated with aggression. However, the evidence for a 2D:4D-aggression association is mixed. Here we test the hypothesis that 2D:4D is robustly linked to aggression in "challenge" situations in which testosterone is increased. Participants were exposed to an aggressive video and a control video. Aggression was measured after each video and salivary free testosterone levels before and after each video. Compared to the control video, the aggressive video was associated with raised aggression responses and a marginally significant increase in testosterone. Left 2D:4D was negatively correlated with aggression after the aggressive video and the strength of the correlation was higher in those participants who showed the greatest increases in testosterone. Left 2D:4D was also negatively correlated to the difference between aggression scores in the aggressive and control conditions. The control video did not influence testosterone concentrations and there were no associations between 2D:4D and aggression. We conclude that 2D:4D moderates the impact of an aggressive stimulus on aggression, such that an increase in testosterone resulting from a "challenge" is associated with a negative correlation between 2D:4D and aggression.

  6. The socializing effect of classroom aggression on the development of aggression and social rejection: A two-wave multilevel analysis.

    PubMed

    Rohlf, Helena; Krahé, Barbara; Busching, Robert

    2016-10-01

    The current study examined the moderating effect of classroom aggression on the development of individual aggression and on the path from individual aggression to social rejection over time. The study included 1,284 elementary school children and consisted of two data waves 10months apart. At both time points, teachers assessed the children's physical and relational aggression and their social rejection status. Multi-level analyses revealed that the classroom level of relational aggression moderated the link between individual relational aggression at T1 and T2 (b=-0.18, 95% CI [-0.32, -0.05], p<.01) and the link between T1 relational aggression and T2 social rejection (b=-0.12, 95% CI [-0.23, -0.003], p<.01). Being in a classroom where relational aggression was prevalent increased relational aggression among children with a low level of relational aggression at T1. Furthermore, a high individual level of relational aggression predicted greater social rejection in classrooms with a low level of relational aggression. Children were mainly influenced by their same-gender peers. Boys as a group had a greater influence than girls on their peers of either gender in the domain of relational aggression, whereas girls as a group had a greater influence in the domain of physical aggression. The contributions of analyzing cross-level interaction to understanding the developmental patterns of aggression and social rejection in middle childhood are discussed.

  7. The socializing effect of classroom aggression on the development of aggression and social rejection: A two-wave multilevel analysis.

    PubMed

    Rohlf, Helena; Krahé, Barbara; Busching, Robert

    2016-10-01

    The current study examined the moderating effect of classroom aggression on the development of individual aggression and on the path from individual aggression to social rejection over time. The study included 1,284 elementary school children and consisted of two data waves 10months apart. At both time points, teachers assessed the children's physical and relational aggression and their social rejection status. Multi-level analyses revealed that the classroom level of relational aggression moderated the link between individual relational aggression at T1 and T2 (b=-0.18, 95% CI [-0.32, -0.05], p<.01) and the link between T1 relational aggression and T2 social rejection (b=-0.12, 95% CI [-0.23, -0.003], p<.01). Being in a classroom where relational aggression was prevalent increased relational aggression among children with a low level of relational aggression at T1. Furthermore, a high individual level of relational aggression predicted greater social rejection in classrooms with a low level of relational aggression. Children were mainly influenced by their same-gender peers. Boys as a group had a greater influence than girls on their peers of either gender in the domain of relational aggression, whereas girls as a group had a greater influence in the domain of physical aggression. The contributions of analyzing cross-level interaction to understanding the developmental patterns of aggression and social rejection in middle childhood are discussed. PMID:27586070

  8. Targeted antithrombotic protein micelles.

    PubMed

    Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E; Liu, David R; Peter, Karlheinz; Chaikof, Elliot L

    2015-01-26

    Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one-pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the ligand-induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

  9. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  10. [Self aggressive-behaviours in prison].

    PubMed

    Ammar, Malek M; Borras, L; Eytan, A

    2008-01-01

    Suicide among prisoners is a relatively well documented public health issue. On the other hand, data about self-aggressive behaviours in prisons are scarce, despite the fact that this problem seems to be highly prevalent. We conducted a retrospective study over a fifteen months period in a remand prison situated in the French speaking area of Switzerland. During this time period, 161 self-aggressive behaviours were recorded, corresponding to 80 inmates. The most frequent acts were self-cuttings and self-mutilations, followed by strangulations. All these patients were male and their mean age was 25. Some of these behaviours (ingesting cutting objects and sewing of the lips) were specific to some ethno-cultural groups. Copycat behaviours play a significant role in closed communities such as prisons. These results underline the necessity of taking into account self-aggressive behaviours in penitentiary institutions. PMID:19024369

  11. Sun-induced frowning fosters aggressive feelings.

    PubMed

    Marzoli, Daniele; Custodero, Mariagrazia; Pagliara, Alessandra; Tommasi, Luca

    2013-01-01

    We tested whether aggressiveness can be triggered by the involuntary frowning that occurs when people face the sun, due to the fact that sun-induced frowning involves the same pattern of facial muscle activation as in the expression of anger (interestingly, Charles Darwin remarked on the sunshade-like nature of frowning). In line with data showing that experimentally and unobtrusively induced facial and body displays facilitate congruent feelings, we found that participants walking against the sun without sunglasses scored higher in a self-report measure of anger and aggression compared to those walking with the sun behind and/or wearing sunglasses. We also suggest that frowning at the sun affects mood very quickly, because we did not find any effect of walking time on self-reported aggressiveness. Our results provide the first evidence of the ecological validity of the facial feedback hypothesis.

  12. Proactive and reactive aggression in referred children and adolescents.

    PubMed

    Connor, Daniel F; Steingard, Ronald J; Cunningham, Julie A; Anderson, Jennifer J; Melloni, Richard H

    2004-04-01

    Investigating different types of aggression is important to facilitate a better understanding of excessive maladaptive aggression in referred youth. Using regression analysis, the authors investigated demographic, historical, diagnostic, and treatment correlates of proactive aggression and reactive aggression in a heterogeneous population (N = 323) of psychiatrically referred youths. Ratings of proactive and reactive aggression significantly correlated with more established measures of aggression. Results suggest the importance of hyperactive/impulsive behavior, disruptive behavior disorders, and self-reported hostility in youths with both reactive and proactive aggression. Substance use disorders, a family history of substance abuse, and family violence were specifically associated with proactive aggression. Younger age and a history of abuse were correlated with reactive aggression. Implications for clinical interventions and future research are discussed. PMID:15113242

  13. Intergenerational Transmission of Relationship Aggression: A Prospective Longitudinal Study

    PubMed Central

    Cui, Ming; Durtschi, Jared A.; Donnellan, M. Brent; Lorenz, Frederick O.; Conger, Rand D.

    2012-01-01

    The present study examined whether physical and verbal aggression in the family of origin were associated with similar patterns of aggression in young adult couples. Hypotheses were tested using a sample of 213 focal individuals who were followed from adolescence to adulthood. Results suggested that aggression in the family when focal participants were adolescents predicted aggression with romantic partners when participants were adults. The association between interparental aggression and later aggression in adult romantic unions was partially mediated through parents’ aggression to focal participants when they were adolescents. Both physical and verbal aggression revealed the same pattern of findings. All together, these findings are consistent with a developmental-interactional perspective (Capaldi & Gorman-Smith, 2003) concerning the developmental origins of aggression in intimate relationships. PMID:21171767

  14. Validation of a laboratory play measure of child aggression.

    PubMed

    Johnston, A; DeLuca, D; Murtaugh, K; Deiner, E

    1977-03-01

    The validity of laboratory play measures of aggression has been called into question. Critics have charged that laboratory findings on childhood aggression cannot be generalized to everyday aggression. In the present study, the validity of striking a Bobo clown as a measure of aggression was assessed by correlating the rate of this behavior with peer ratings, teaching ratings, and self-ratings of aggressiveness in a preschool. Laboratory aggression correlated significantly with both peer ratings, r = .76, p less than .01, and teacher ratings, r = .57, p less than .05, but not with self-ratings, r = .36. Laboratory aggression correlated more highly with aggression ratings for males (N = 9) than for females (N = 9), but not significantly so. The findings support the use of laboratory play as a valid measure of aggression in children.

  15. A One Year Study of Adolescent Males with Aggression and Problems of Conduct and Personality: A Comparison of MDT and DBT

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Houston, Marsha-Ann

    2006-01-01

    This study examines the effectiveness of Mode Deactivation Therapy, (MDT) and Dialectical Behavior Therapy, (DBT) in a Residential Treatment Center for adolescent males. All clients were admitted to the same Residential Treatment Center. Clients presented with physical aggression, suicidal ideation, with mixed personality disorders/traits. One…

  16. Boys’ and Girls’ Relational and Physical Aggression in Nine Countries

    PubMed Central

    Lansford, Jennifer E.; Skinner, Ann T.; Sorbring, Emma; Di Giunta, Laura; Deater-Deckard, Kirby; Dodge, Kenneth A.; Malone, Patrick S.; Oburu, Paul; Pastorelli, Concetta; Tapanya, Sombat; Tirado, Liliana Maria Uribe; Zelli, Arnaldo; Al-Hassan, Suha M.; Alampay, Liane Peña; Bacchini, Dario; Bombi, Anna Silvia; Bornstein, Marc H.; Chang, Lei

    2012-01-01

    Distinguishing between relational and physical aggression has become a key feature of many developmental studies in North America and Western Europe, but very little information is available on relational aggression in more diverse cultural contexts. This study examined the factor structure of, gender differences in, and associations between relational and physical aggression in China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States. Children ages 7 to 10 years (N = 1410) reported on their relationally and physically aggressive behavior. Relational and physical aggression shared a common factor structure across countries. Unsurprisingly, boys reported being more physically aggressive than girls across all nine countries; surprisingly, there were no significant gender differences in relational aggression. In all nine countries, relational and physical aggression were significantly correlated (average r = .49). The countries differed significantly in the mean levels of both relational and physical aggression that children reported using and with respect to whether children reported using more physical than relational aggression or more relational than physical aggression. Despite mean level differences in relational and physical aggression across countries, the findings provided support for cross-country similarities in associations between relational and physical aggression, as well as links between gender and aggression. PMID:23935227

  17. [Fluid therapy in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2013-12-01

    Severe acute pancreatitis (AP) is associated with an increased need for fluids due to fluid sequestration and, in the most severe cases, with decreased peripheral vascular tone. For several decades, clinical practice guidelines have recommended aggressive fluid therapy to improve the prognosis of AP. This recommendation is based on theoretical models, animal studies, and retrospective studies in humans. Recent studies suggest that aggressive fluid administration in all patients with AP could have a neutral or harmful effect. Fluid therapy based on Ringer's lactate could improve the course of the disease, although further studies are needed to confirm this possibility. Most patients with AP do not require invasive monitoring of hemodynamic parameters to guide fluid therapy administration. Moreover, the ability of these parameters to improve prognosis has not been demonstrated.

  18. [Managing aggression and violence associated with psychosis].

    PubMed

    Hallikainen, Tero; Repo-Tiihonen, Eila

    2015-01-01

    Risk for violence in psychosis is associated with the subject's history of early-onset antisocial behavior, substance abuse, suicidal ideation, lack of insight, and non-adherence to antipsychotic medication. These risk factors can be managed by effective treatment for psychosis, with the exception of predatory antisocial aggression. Generally, this group of patients is at considerable risk for untreated conditions. There is, however, no pharmacological treatment indicated solely for aggression. Physical violence can often be avoided by alertness and risk monitoring, and by attentive customer service skills. Safety at work is our shared responsibility. PMID:26427235

  19. [Effect of sodium valproate on aggressive behavior of male mice with various aggression experience].

    PubMed

    Smagin, D A; Bondar', N P; Kudriavtseva, N N

    2010-01-01

    Sector of Social Behavior Neurogenetics, Institute of Cytology and Genetics, Siberian Branch, Effects of sodium valproate on the aggressive behavior of male mice with 2- and 20-day positive fighting experience have been studied. It is established that valproate administered in a singe dose of 100 mg/kg has no effect on the behavior of male mice with a 2-day experience of aggression. The treatment of mice with 300 mg/kg of valproate significantly decreased the level of aggressive motivation and the percentage of animals demonstrating attacks and threats. In male mice with a 20-day experience of aggression, valproate decreased the time of hostile behavior in a dose-dependent manner. Valproate in a single dose of 300 mg/kg significantly decreased the level of aggressive motivation, but also produced a toxic effect, whereby 73% of aggressive males demonstrated long-term immobility and 45% exhibited movement abnormalities (falls) upon the treatment. It is suggested that changes in the brain neurochemical activity, which are caused by a prolonged experience of aggression, modify the effects of sodium valproate.

  20. Disentangling impulsiveness, aggressiveness and impulsive aggression: an empirical approach using self-report measures.

    PubMed

    García-Forero, Carlos; Gallardo-Pujol, David; Maydeu-Olivares, Alberto; Andrés-Pueyo, Antonio

    2009-06-30

    There is confusion in the literature concerning the concept of impulsive aggression. Based on previous research, we hypothesize that impulsivity and aggression may be related, though not as closely as to consider them the same construct. So, our aim was to provide empirical evidence of the relationship between the impulsivity and aggressiveness constructs when considered as traits. Two widely used questionnaires [Barratt's Impulsiveness Scale (BIS) and Aggression Questionnaire-Refined (AQ-R)] were administered to 768 healthy respondents. Product-moment and canonical correlations were then calculated. In addition, a principal components analysis was conducted to explore whether impulsive aggression can be defined phenotypically as the expression of a single trait. The common variance between impulsivity and aggressiveness was never higher than 42%. The principal components analysis reveals that one component is not enough to represent all the variables. In conclusion, our results show that impulsivity and aggressiveness are two separate, although related constructs. This is particularly important in view of the misconceptions in the literature.

  1. Isolated cleft lip with generalized aggressive periodontitis: A rare entity

    PubMed Central

    Metgud, Renuka; Kumar, Ajay; Bhat, Kishore

    2015-01-01

    Oro-facial clefts are one of the most common birth defects and may be associated with other genetic anomalies. Aggressive periodontitis is a rare condition that progresses rapidly, but affects only a small percentage of the population. Most of the cases of aggressive periodontitis are familial. Even though, literature has documented the association of various genetic disorders with aggressive periodontitis, the aggressive periodontitis in patients with isolated cleft lip (CL) have never been addressed. Here, we report a rare case of isolated CL with generalized aggressive periodontitis. The concomitant presentation of isolated CL with aggressive periodontitis in an individual has clinical significance for multi-disciplinary care. PMID:25810600

  2. Child abuse and aggression among seriously emotionally disturbed children.

    PubMed

    Ford, Julian D; Fraleigh, Lisa A; Connor, Daniel F

    2010-01-01

    Abused children may be at risk for problems with aggression. In a sample of 397 seriously emotionally disturbed children, reactive aggression was associated with documented history of physical abuse but not sexual abuse. Girls were equally likely to be classified as reactively aggressive regardless of physical abuse history, but boys with physical abuse histories were 50% more likely to be classified as reactively aggressive than boys with no physical abuse history. Proactive aggression was unrelated to physical or sexual abuse history. The association of physical abuse and reactive aggression warrants further scientific study and attention in clinical assessment and treatment with seriously emotionally disturbed children.

  3. Aggressive and nonaggressive children's moral judgments and moral emotion attributions in situations involving retaliation and unprovoked aggression.

    PubMed

    Gasser, Luciano; Malti, Tina; Gutzwiller-Helfenfinger, Eveline

    2012-01-01

    The authors investigated 7- and 9-year-old children's moral understanding of retaliation as compared to unprovoked aggression with regard to their aggressive behavior status. Based on peer ratings, 48 children were selected as overtly aggressive and 91 as nonaggressive. Their moral understanding of retaliation and unprovoked aggression was assessed by an interview including questions about their moral judgments and emotion attributions. Aggressive children judged retaliations as less serious than did nonaggressive children. They also referred less often to the harmful consequences of retaliation and were more likely to excuse the retaliation because of the provocation. In unprovoked aggressive situations younger aggressive children, compared with the younger nonaggressive children, attributed more happiness to transgressors, more anger to victims, and less sadness to transgressors and victims. The results are discussed in terms of previous research on aggressive children's moral understanding of retaliation and unprovoked aggression.

  4. Design, synthesis and evaluation of isoxazolo[5,4-d]pyrimidin-4(5H)-one derivatives as antithrombotic agents.

    PubMed

    Yang, Jiabin; Su, Guoqiang; Ren, Yu; Chen, Yang

    2015-02-01

    A series of isoxazolo[5,4-d]pyrimidin-4(5H)-one derivatives have been designed and synthesized as novel antithrombotic agents. The 4-acetoxyl substituted derivative (6g) displays very strong FXa inhibitory activity (IC50=0.013μM), excellent anticoagulant effect in human plasma (2×PT=2.12μM) and high selectivity to thrombin and trypsin. Docking investigation of 6g with FXa protein revealed that the pyrimidone ring of 6g formed a π-π interaction with the phenyl ring of Tyr99, and the carbonyl group in the P1 moiety formed multiple hydrogen bonds to Ser214 and Trp215. These results showed that isoxazolo[5,4-d]pyrimidin-4(5H)-one is an attractive scaffold for designing novel factor Xa inhibitors and 4-carbonyl substituted phenyl ring could be used as novel S1 binding element. PMID:25559742

  5. THE RELATIONSHIP BETWEEN ENCODING ABILITY AND AGGRESSIVE BEHAVIOR.

    PubMed

    Tsamis, Vasiliki J; Rebok, George W; Montague, David R

    2009-03-26

    While past research efforts have reported a relationship between encoding ability and aggressive behavior in children, the relationship between encoding ability and adult aggressiveness has not been examined. Encoding, an element of attention, refers to the ability to recall and reorder information stored in memory. Using selected cognitive tests and a self-report measure of aggressive behavior in a sample of community college students (n=55), this study investigated the relationship between encoding ability and aggressive behavior, (i.e., physical aggression, verbal aggression, anger, hostility, indirect aggression, and total aggression). Aggressive behavior was assessed by the Aggression Questionnaire of the Buss-Durkee Hostility Inventory, a widely-used measure of aggressive behavior. Encoding was measured using the WAIS-III Digit Span and Arithmetic subtests. Initial analyses showed no significant correlations between the cognitive measures and the five scales of aggressive behavior. However, there was a significant age-related association between scores on the cognitive measures and the indices of aggressive behavior. Two groups were created, those who reported attention problems and those who did not report attention problems. When the two groups were compared, participants who had a history of attention problems were verbally more aggressive than participants with a negative history of attention problems, and they were generally more aggressive. A composite score, called an "encoding score," was related to scores on the aggressive behavior scales. Moreover, the age-related relationship between these two variables suggests that the relationship is maturational and may disappear as an individual ages. Concerning the latter, participants in the current study were enrolled in junior college. Therefore, persons who had attention problems and were aggressive may not have pursued higher education. PMID:19953190

  6. Aggression and Violence in the Workplace.

    ERIC Educational Resources Information Center

    Grant, Frank

    2003-01-01

    Adults who work in positions of authority with young people must be prepared for the possibility of conflict, which could lead to aggressive behavior. Incorrect handling of a crisis will produce a conflict cycle, the four stages of which are described. Legal issues surrounding physical intervention (in the United Kingdom) are summarized, and…

  7. Controlling Aggressive Students. Fastback Series, No. 387.

    ERIC Educational Resources Information Center

    Blendinger, Jack; And Others

    Coping with aggressive student behavior is crucial to providing a safe and orderly classroom and school environment. Approaches for improving student behavior, ranging from enhancing a student's interpersonal skills to restraint techniques (such as the prudent use of physical force) are covered in this booklet. The material blends information in…

  8. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    ERIC Educational Resources Information Center

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  9. Emotion Regulation and Childhood Aggression: Longitudinal Associations

    ERIC Educational Resources Information Center

    Roll, Judith; Koglin, Ute; Petermann, Franz

    2012-01-01

    Accumulating evidence suggests that emotion dysregulation is associated with psychopathology. This paper provides a review of recent longitudinal studies that investigate the relationship between emotion regulation and aggressive behavior in childhood age. While there is substantial evidence for assuming a close relation of emotion regulation and…

  10. Observing Aggression of Teachers in School Teams

    ERIC Educational Resources Information Center

    Ben Sasson, Dvora; Somech, Anit

    2015-01-01

    To fill the gap in theoretical and empirical knowledge on workplace aggression by teachers working in teams, this study explored its components, its targets, and its contextual determinants. Data were collected through three observations at different schools and at different times on 29 math, homeroom, language, and science studies teams.…

  11. Aggression Exposure and Mental Health among Nurses.

    ERIC Educational Resources Information Center

    Lam, Lawrence T.

    2002-01-01

    Investigates the extent of aggression exposure and the effects of exposure on the psychological health of nursing staff in hospitals. Results suggested that nearly 40% of staff experienced psychological distress, while nearly 10% experienced moderate to severe depression. Results of the logistic analyses indicated that frequent exposure to…

  12. Parental Deprivation and the Development of Aggression.

    ERIC Educational Resources Information Center

    Mitchell, G.

    The research on parental deprivation done at the Wisconsin primate laboratories and related laboratories is summarized. Social isolation and certain other social conditions were observed in their effects on aggressive behavior. Isolate-reared rhesus monkeys show more abnormality in postures and movements than do socially reared monkeys from…

  13. Aggression and Dominance Relations in Young Children.

    ERIC Educational Resources Information Center

    Missakian, Elizabeth; Hamer, Karen

    This study is an attempt to apply ethological tools of observation and analysis to the social behavior of 25 communally-reared children, ages 6 months to 4 years. The focus of this analysis is aggression and dominance relations. Findings indicate that: (1) agonistic behavior reveals stable and linear dominance hierarchies for children from 6…

  14. Pathways to Relationship Aggression between Adult Partners

    ERIC Educational Resources Information Center

    Busby, Dean M.; Holman, Thomas B.; Walker, Eric

    2008-01-01

    In this study, the pathways to adult aggression beginning in the family of origin (FOO) and continuing through adult relationships were investigated. With a sample of 30,600 individuals, a comprehensive model was evaluated that included the unique influences of violent victimization in the family, witnessing parental violence, perpetrating…

  15. Aggression Replacement Training and Childhood Trauma

    ERIC Educational Resources Information Center

    Amendola, A. Mark; Oliver, Robert W.

    2013-01-01

    Aggression Replacement Training (ART) was developed by the late Arnold Goldstein of Syracuse University to teach positive alternatives to children and youth with emotional and behavioral problems (Glick & Gibbs, 2011; Goldstein, Glick, & Gibbs, 1998). ART provides cognitive, affective, and behavioral interventions to build competence in…

  16. Digital Aggression: Cyberworld Meets School Bullies

    ERIC Educational Resources Information Center

    Wong-Lo, Mickie; Bullock, Lyndal M.

    2011-01-01

    Cyberbullying is a category of bullying that occurs in the digital realm and affects students at astonishing rates. Unlike traditional bullying, in which displays of aggression may be evident to bystanders, the ramification of cyberbullying occurs through unconventional strategies (e.g., text messaging, online Web logs, video sharing). As a…

  17. PROGRAMED EXCHANGES AND THE CONTROL OF AGGRESSION.

    ERIC Educational Resources Information Center

    ELLIS, DESMOND P.; HAMBLIN, ROBERT L.

    SYSTEMS OF EXCHANGE - USING THE EXTINCTION, DISTRACTION, AND SUBSTITUTION EFFECTS SYSTEMS - WERE IMPLEMENTED TO DECREASE AGGRESSION AND PROMOTE COOPERATION AND SCHOLARLY BEHAVIOR, THREE SYSTEMS WERE TESTED USING EXCHANGE THEORY AS A GUIDE. THE SUBJECTS WERE FIVE 4- AND 5-YEAR-OLD BOYS DIAGNOSED AS HYPERAGGRESSIVE. EXPERIMENTAL CONDITIONS INCLUDED…

  18. Television Viewing and Aggression: Some Alternative Perspectives.

    PubMed

    Feshbach, Seymour; Tangney, June

    2008-09-01

    The focus of this article is on the examination of variables that moderate the influence of exposure to TV violence. The research on the relationship between TV violence and aggressive behavior of the audience has largely focused on addressing the social policy issue of whether witnessing TV violence fosters aggressive behavior in viewers, particularly children. There has been a dearth of research addressing the conditions that enhance the aggression stimulating effects of media violence, those that mitigate these effects, and those that may even result in reduced aggression after one witnesses media violence. To illustrate the importance of potential moderating factors, we present longitudinal correlational data relating the degree of viewing TV violence to various social behaviors and cognitive attributes of White and African-American male and female elementary-school-age children. Although TV violence viewing was associated with lower cognitive attributes and negative social behaviors in White males and females and African-American females, a very different pattern of relationships was found for African-American males. PMID:26158956

  19. Genes and gene networks implicated in aggression related behaviour.

    PubMed

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour.

  20. Limbic system seizures and aggressive behavior (superkindling effects).

    PubMed

    Andy, O J; Velamati, S

    1978-01-01

    This study was done to further analyze the neural mechanisms underlying aggressive behavior associated with psychomotor or temporal lobe seizures. The studies revealed that superkindling the aggressive system by sequential stimulations at seizure-inducing thresholds, of two or more sites in the limbic, hypothalamic, and basal ganglia structures facilitated the production of aggressive seizures. Aggressive behavior in the freely moving cat was evaluated in relation to the occurrence of hissing and growling during stimulation, after-discharge and postictal period. The behavior was correlated with the frequency of the elicited seizures and the seizure durations. Aggression did develop as a component behavioral manifestation of the limbic (psychomotor) seizure. Development of aggressive seizures was facilitated by "priming" the aggressive system. Optimum levels of aggressive behavior occurred with seizures of medium duration. Catecholamine blockers tended to attentuate the occurrence of aggression, whereas the agonist tended to facilitate it. Once the aggressive system was rendered hyperexcitable, exteroceptive stimuli also evoked aggressive attack behavior. It was concluded that repeatedly recurring limbic system seizures through superkindling mechanisms can eventually render the limbic-basal ganglia-preoptico-hypothalamic aggressive system hyper-responsive to both recurring seizures and to exteroceptive stimuli with resulting aggressive behavior with or without an accompanying seizure. PMID:571080

  1. Proactive and reactive sibling aggression and adjustment in adolescence.

    PubMed

    Tucker, Corinna Jenkins; Van Gundy, Karen T; Wiesen-Martin, Desireé; Hiley Sharp, Erin; Rebellon, Cesar J; Stracuzzi, Nena F

    2015-03-01

    Existing research on aggression tends to narrowly focus on peers; less is known about sibling aggression, most likely due to its historical acceptance. Aggression is characterized by its forms (i.e., physical vs. social or relational aggression) and its functions (i.e., the motivations behind the aggressive act and categorized as proactive vs. reactive aggression). We use data from a two-wave study of middle (n = 197; M age = 12.63 years at Wave 1) and older (n = 159; M age = 16.50 years at Wave 1) adolescents to assess the extent to which proactive and reactive functions of sibling aggression make unique or conditional contributions to adolescent adjustment (i.e., depression, delinquency, and substance use). We find that proactive sibling aggression increases risk for problem substance use and delinquent behavior, reactive sibling aggression increases risk for depressed mood and delinquent behavior, and such results are observed even with statistical adjustments for sociodemographic and family variables, stressful life events, and prior adjustment. Few conditional effects of proactive or reactive sibling aggression by sex or grade are observed; yet, for all three outcomes, the harmful effects of reactive sibling aggression are strongest among adolescents who report low levels of proactive sibling aggression. The results speak to the importance of understanding the proactive and reactive functions of sibling aggressive behaviors for adolescent adjustment.

  2. Intervention for aggressive victims of school bullying in Hong Kong: a longitudinal mixed-methods study.

    PubMed

    Fung, Annis Lai-Chu

    2012-08-01

    The distinction between aggressive and passive victims of school bullying is well documented. Aggressive victims exhibit restlessness and hot-temperedness, are easily provoked, and take revenge when irritated, whereas passive victims are quiet and timid when attacked or insulted and withdraw rather than retaliate. To date, there has been no evidence-based evaluative study examining interventions designed specifically to reduce aggressive victimization, and neither has there been an inclusive assessment screening of high-risk aggressive victims prior to intervention. This study addressed these research gaps by employing multi-stage assessment procedures and a mixed-mode methodology in a one-year longitudinal design. Data were collected from student self-reports, parent and teacher rating scales, and individual structured interviews with students, parents and teachers. A total of 269 potential high-risk aggressive victims were identified from among 5,089 schoolchildren, 68 of whom were screened out and randomly assigned to 10 treatment groups, with 39 completing a one-year follow-up study. Multivariate analysis of variance identified significant improvements in physical and verbal victimization (F(2,47, 93.99) = 10.73, p < 0.01), verbal victimization (F(2.74, 104.14) = 12.80, p < 0.01) and social exclusion scores at the three follow-up assessments compared to the pre-treatment scores, and the qualitative results were consistent, showing participants' cognition, emotion, and behavior to have been positively reconstructed by the group intervention. The consistent quantitative and qualitative results confirm that the cognitive-behavioral group therapy program reported herein is effective in reducing aggressive victims' anxious and depressed emotions and reactive cognition.

  3. Experimental thrombosis on a collagen coated arterioarterial shunt in rats: a pharmacological model to study antithrombotic agents inhibiting thrombin formation and platelet deposition.

    PubMed

    Freund, M; Mantz, F; Nicolini, P; Gachet, C; Mulvihill, J; Meyer, L; Beretz, A; Cazenave, J P

    1993-05-01

    A rat thrombosis model was developed to assess the efficacity of antithrombotic drugs. It had the following characteristics: controlled hemodynamic and rheological conditions corresponding to arterial flow, a collagen coated surface as a relevant thrombogenic stimulus, a method of measurement allowing dynamic monitoring of thrombus formation and the possibility to assess the thrombus structure. A shunt composed of polyethylene and silicone catheters, including in the middle of the shunt a collagen coated glass capillary, was inserted between the two primitive carotids of the rat. The duration of patency of the shunt was recorded using a thermic probe fixed on its central part. In this model, the patency of the shunt was 539 +/- 55 s. Platelet and fibrinogen-fibrin accumulation in successive one centimeter segments along the shunt were measured using 111In labeled platelets and 125I labeled fibrinogen. Platelet accumulation occurred on the collagen coated surface and at the junctions between the different components of the shunt, where flow was disturbed. The effects of four antithrombotic agents were measured: aspirin, clopidogrel, heparin and r-hirudin. Clopidogrel, heparin and hirudin significantly prolonged patency duration of the shunt, whereas aspirin was inactive. Aspirin did not reduce platelet or fibrinogen-fibrin accumulation on the collagen coated surface. Platelet accumulation on the collagen surface was significantly lower in the clopidogrel group (50 mg/kg) than in the group treated with heparin (500 U/kg), demonstrating the direct antiplatelet effect of clopidogrel. Hirudin at doses giving similar values of APTT as heparin (500 U/kg) prolonged the occlusion time to over 2 h while the heparin occlusion time was only 20 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8322274

  4. Localized Aggressive Periodontitis Treatment Response in Primary and Permanent Dentitions

    PubMed Central

    MERCHANT, SHERIN. N.; VOVK, ANDREA.; KALASH, DANNY.; HOVENCAMP, NICOLE; AUKHIL, IKRAMUDDIN.; HARRISON, PETER; ZAPERT, EDWARD; BIDWELL, JOHN; VARNADO, PHYLLIS; SHADDOX, LUCIANA. M.

    2014-01-01

    Background The comparative treatment response of children and young adults with localized aggressive periodontitis (LAP) affecting primary and permanent dentition is unknown. The objective of this study was to evaluate the influence of non-surgical periodontal therapy with adjunctive systemic antibiotics on the clinical outcome of children/young adults with primary versus permanent dentition affected by LAP. Methods A cohort of 97 African-American participants between the ages of 5–21 (30M; 66F; 22 primary and 75 permanent dentition affected), diagnosed with LAP were included. Patients presented with no significant medical history. All patients underwent periodontal therapy, which consisted of full mouth mechanical debridement at baseline, 3, 6, and 12 month appointments. Additionally, all patients were prescribed a one-week regimen of systemic antibiotics at the initial appointment. Clinical parameters were analyzed, including probing depth (PD), clinical attachment levels (CAL), bleeding on probing (BOP) and percentage of visible plaque. Results Overall, periodontal therapy was found to be effective in improving the clinical outcomes of both primary and permanent dentitions. Although baseline CAL were similar between the groups, the reductions in mean CAL at 3, 6 and 12 months as well as reduction in % Plaque at 3 months were significantly greater in primary dentition as compared to permanent dentition. Conclusions Non-surgical therapy with systemic antibiotics is effective for LAP in both primary and permanent dentitions. A greater reduction in CAL in LAP of primary dentition may suggest that younger children may carry a greater propensity for positive treatment outcomes and healing potential as compared to children/young adults with permanent dentition. PMID:25186780

  5. Spontaneous subdural hematoma and antiplatelet therapy: Does efficacy of Ticagrelor come with added risk?

    PubMed

    Suryanarayana Sharma, Pattanagere Manjunatha; Tekkatte Jagannatha, Aniruddha; Javali, Mahendra; Hegde, Anupama Venkatasubba; Mahale, Rohan; Madhusudhan; Srinivasa, Rangasetty

    2015-12-01

    Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH) is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective. PMID:26995425

  6. Current antiplatelet agents: place in therapy and role of genetic testing.

    PubMed

    Yang, Eugene

    2015-04-01

    Antiplatelet therapies play a central role in reducing the risk of cardiovascular events such as myocardial infarction and stroke. While aspirin, a cyclo-oxygenase-1 inhibitor has been the cornerstone of antithrombotic treatment for several decades, P2Y12 receptor inhibitors cangrelor, clopidogrel, prasugrel, and ticagrelor and protease-activated receptor-1 antagonist vorapaxar, have emerged as additional therapies to reduce the risk of recurrent cardiovascular events in high-risk patients. Recent clinical trials evaluating the role of these agents and major society guideline updates for use of antiplatelet therapies for secondary prevention of cardiovascular events will be examined. The latest studies regarding the appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention will be presented. The current state of genetic and platelet function testing will be reviewed.

  7. Family Mode Deactivation Therapy in a Residential Setting: Treating Adolescents with Conduct Disorder and Multi-Axial Diagnosis

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.; Zeiter, J. Scott; Houston, Marsha Ann

    2008-01-01

    Mode Deactivation Therapy (MDT) has been shown to be an effective treatment for a variety of adolescent disorders including emotional dysregulation, behavioral dysregulation, physical aggression, sexual aggression, and many harmful symptoms of anxiety and traumatic stress. MDT Family Therapy has been effective in reducing family disharmony in case…

  8. Aggressive Behaviors and Verbal Communication Skills in Autism Spectrum Disorders.

    PubMed

    De Giacomo, Andrea; Craig, Francesco; Terenzio, Vanessa; Coppola, Annamaria; Campa, Maria Gloria; Passeri, Gianfranco

    2016-01-01

    Aggressive behavior is a common problem among children with autism spectrum disorder (ASD) and could negatively affect family functioning and school and social competence. The aim of the present study was to investigate the relationship between aggressive behavior, such as self-aggression and other-aggression, with verbal communication ability and IQ level in children with ASD. The sample examined in this study included 88 children with a diagnosis of ASD. For the purposes of our study, much attention was focused on individual items of the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised that were useful to evaluate the aggressive behavior. We have not found any association between aggressive behavior (other-aggression and self-aggression) and the absence of language or low IQ in children with ASD. Thus, the degree of severity of autism is probably the most important risk factor for this behavior. PMID:27336016

  9. Extensive Surgery Best for an Aggressive Brain Cancer

    MedlinePlus

    ... fullstory_159415.html Extensive Surgery Best for an Aggressive Brain Cancer: Study Although larger procedure carries more ... News) -- When it comes to battling a particularly aggressive form of brain tumor, more extensive surgeries may ...

  10. Appetitive Aggression in Women: Comparing Male and Female War Combatants

    PubMed Central

    Meyer-Parlapanis, Danie; Weierstall, Roland; Nandi, Corina; Bambonyé, Manassé; Elbert, Thomas; Crombach, Anselm

    2016-01-01

    Appetitive aggression refers to positive feelings being associated with the perpetration of violent behavior and has been shown to provide resilience against the development of PTSD in combatants returning from the battlefield. Until this point, appetitive aggression has been primarily researched in males. This study investigates appetitive aggression in females. Female and male combatants and civilians from Burundi were assessed for levels of appetitive aggression. In contrast to non-combatants, no sex difference in appetitive aggression could be detected for combatants. Furthermore, each of the female and male combatant groups displayed substantially higher levels of appetitive aggression than each of the male and female civilian control groups. This study demonstrates that in violent contexts, such as armed conflict, in which individuals perpetrate numerous aggressive acts against others, the likelihood for an experience of appetitive aggression increases- regardless of whether the individuals are male or female. PMID:26779084

  11. Maternal Defense: Breast Feeding Increases Aggression by Reducing Stress

    PubMed Central

    Hahn-Holbrook, Jennifer; Holt-Lunstad, Julianne; Holbrook, Colin; Coyne, Sarah M.; Lawson, E. Thomas

    2012-01-01

    Mothers in numerous species exhibit heightened aggression in defense of their young. This shift typically coincides with the duration of lactation in nonhuman mammals, which suggests that human mothers may display similarly accentuated aggressiveness while breast feeding. Here we report the first behavioral evidence for heightened aggression in lactating humans. Breast-feeding mothers inflicted louder and longer punitive sound bursts on unduly aggressive confederates than did formula-feeding mothers or women who had never been pregnant. Maternal aggression in other mammals is thought to be facilitated by the buffering effect of lactation on stress responses. Consistent with the animal literature, our results showed that while lactating women were aggressing, they exhibited lower systolic blood pressure than did formula-feeding or never-pregnant women while they were aggressing. Mediation analyses indicated that reduced arousal during lactation may disinhibit female aggression. Together, our results highlight the contributions of breast feeding to both protecting infants and buffering maternal stress. PMID:21873570

  12. It's in Our Nature: Verbal Aggressiveness as Temperamental Expression.

    ERIC Educational Resources Information Center

    Beatty, Michael J.; McCroskey, James C.

    1997-01-01

    Delineates a metatheoretic rationale for a biologically based theory of verbal aggressiveness. Integrates neurobiological principles into the concept of verbal aggressiveness. Presents a working model, and addresses the implications of this theoretical position. (SR)

  13. Relations between key executive functions and aggression in childhood.

    PubMed

    Granvald, Viktor; Marciszko, Carin

    2016-01-01

    The present study examined relationships between three key executive functions (working memory, inhibition, and mental set-shifting) and multiple types of aggression in a general population sample of 9-year-old children. One hundred and forty-eight children completed a battery of executive function tasks and were rated on aggression by their primary teachers. All executive function (EF) composites were related to a composite measure of aggression. Working memory (WM) was most consistently related to the different types of aggression (overt, relational, reactive, and proactive), whereas inhibition and mental set-shifting only were related to relational and reactive aggression, respectively. Specificity in relations (studied as independent contributions) was generally low with the exception of the relation between WM and relational aggression. Taken together, our results highlight the roles of WM and relational aggression in EF-aggression relations in middle childhood.

  14. Adolescents' experience with workplace aggression: school health implications.

    PubMed

    Smith, Carolyn R; Fisher, Bonnie S; Gillespie, Gordon L; Beery, Theresa A; Gates, Donna M

    2013-12-01

    Aggression exposure is a critical health issue facing adolescents in the United States. Exposure occurs in various settings including home, school, and the community. An emerging context for aggression exposure is in the workplace. Thirty adolescent employees age 16-18 participated in a qualitative study exploring proposed responses to future workplace aggression. Semistructured interviews were used to gather participants' proposed responses to a series of hypothetical aggressive incidents in the workplace. Conventional content analysis identified patterns and themes among the participants' responses. Results indicated adolescent employees' proposed responses to workplace aggression are similar to other forms of aggression such as peer-bullying and teen dating violence. Education and training are needed within the school setting to promote appropriate responses to various forms of aggression encountered by adolescents. Implications for school health professionals' involvement in addressing responses to such aggression and further research opportunities are explored.

  15. Appetitive Aggression in Women: Comparing Male and Female War Combatants.

    PubMed

    Meyer-Parlapanis, Danie; Weierstall, Roland; Nandi, Corina; Bambonyé, Manassé; Elbert, Thomas; Crombach, Anselm

    2015-01-01

    Appetitive aggression refers to positive feelings being associated with the perpetration of violent behavior and has been shown to provide resilience against the development of PTSD in combatants returning from the battlefield. Until this point, appetitive aggression has been primarily researched in males. This study investigates appetitive aggression in females. Female and male combatants and civilians from Burundi were assessed for levels of appetitive aggression. In contrast to non-combatants, no sex difference in appetitive aggression could be detected for combatants. Furthermore, each of the female and male combatant groups displayed substantially higher levels of appetitive aggression than each of the male and female civilian control groups. This study demonstrates that in violent contexts, such as armed conflict, in which individuals perpetrate numerous aggressive acts against others, the likelihood for an experience of appetitive aggression increases- regardless of whether the individuals are male or female. PMID:26779084

  16. Aggressive Behaviors and Verbal Communication Skills in Autism Spectrum Disorders

    PubMed Central

    De Giacomo, Andrea; Craig, Francesco; Terenzio, Vanessa; Coppola, Annamaria; Campa, Maria Gloria; Passeri, Gianfranco

    2016-01-01

    Aggressive behavior is a common problem among children with autism spectrum disorder (ASD) and could negatively affect family functioning and school and social competence. The aim of the present study was to investigate the relationship between aggressive behavior, such as self-aggression and other-aggression, with verbal communication ability and IQ level in children with ASD. The sample examined in this study included 88 children with a diagnosis of ASD. For the purposes of our study, much attention was focused on individual items of the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview–Revised that were useful to evaluate the aggressive behavior. We have not found any association between aggressive behavior (other-aggression and self-aggression) and the absence of language or low IQ in children with ASD. Thus, the degree of severity of autism is probably the most important risk factor for this behavior. PMID:27336016

  17. Should Relational Aggression Be Included in DSM-V?

    ERIC Educational Resources Information Center

    Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.

    2008-01-01

    The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.

  18. Trait Verbal Aggressiveness and Argumentativeness: Relations with Parenting Style.

    ERIC Educational Resources Information Center

    Bayer, Cherie L.; Cegala, Donald J.

    1992-01-01

    Finds that persons scoring positively on argumentativeness and negatively on aggressiveness reported behaviors consistent with the authoritative parenting style and that negative argumentativeness and positive aggressiveness is associated with the authoritarian prototype. (SR)

  19. Validation of a Laboratory Play Measure of Child Aggression

    ERIC Educational Resources Information Center

    Johnston, Ann; And Others

    1977-01-01

    This study assessed the validity of striking a Bobo clown as a measure of aggression by correlating the rate of this behavior with peer ratings, teacher ratings, and self-ratings of aggressiveness in a preschool. (Author/JMB)

  20. Sleep deprivation lowers reactive aggression and testosterone in men.

    PubMed

    Cote, Kimberly A; McCormick, Cheryl M; Geniole, Shawn N; Renn, Ryan P; MacAulay, Stacey D

    2013-02-01

    The role of sleep deprivation in aggressive behavior has not been systematically investigated, despite a great deal of evidence to suggest a relationship. We investigated the impact of 33 h of sleep loss on endocrine function and reactive aggression using the Point Subtraction Aggression Paradigm (PSAP) task. PSAP performance was assessed in 24 young men and 25 women who were randomly assigned to a sleep deprivation or control condition. Sleep deprivation lowered reactive aggression and testosterone (but not cortisol) in men, and disrupted the positive relationship between a pre-post PSAP increase in testosterone and aggression that was evident in rested control men. While women increased aggression following provocation as expected, no influence of sleep deprivation was found. This is the first experimental study to demonstrate that sleep deprivation lowers reactive aggression in men. Testosterone, but not cortisol, played a role in the relationship between sleep and reactive aggression in men.

  1. The Effects on Arousal of Frustration and Aggressive Films

    ERIC Educational Resources Information Center

    Doob, Anthony N.; Kirshenbaum, Hershi M.

    1973-01-01

    Research supported by grant from the Canada Council. Studies effects of film violence on aggressive behavior. Suggests that for high levels of arousal, an aggressive movie could stop frustration-produced stimuli and hostility. (DS)

  2. The sex-->aggression link: a perception-behavior dissociation.

    PubMed

    Mussweiler, T; Förster, J

    2000-10-01

    Four studies suggest that priming may yield directionally different effects on social perception and behavior if perceptual and behavioral experiences with the stimulus diverge. This seems true for sex and aggression: Men are more likely to behave aggressively than women, whereas women are more likely to perceive aggressive behavior than men. Using a sequential priming paradigm, Study 1 demonstrates that a basic semantic link between sex and aggression exists for both genders. This link, however, has opposing behavioral and perceptual consequences for men and women. Studies 2 and 3 demonstrate that sex priming facilitates aggressive behavior only for men. Study 4 shows that only women perceive the ambiguously aggressive behavior of a male target person as more aggressive after sex priming. Thus, the perceptual and behavioral responses to sex priming are consistent with the experiences men and women typically have with sex and aggression.

  3. Aggression by ovariectomized female rats with testosterone implants: competitive experience activates aggression toward unfamiliar females.

    PubMed

    Albert, D J; Jonik, R H; Walsh, M L

    1990-04-01

    Female hooded rats (250 to 325 g) were ovariectomized and bilaterally implanted with testosterone-filled or empty Silastic tubes. The testosterone-filled space in each tube was 10 mm long and this should produce a serum testosterone concentration 4 to 5 times that of an intact female, but well below that of a male. Three weeks following surgery, half of the animals with testosterone implants were housed with an animal with an empty implant and left for 6 weeks. The remaining animals were placed on a 23-hr food deprivation schedule, housed in testosterone implant/empty implant pairs, and then subjected to a series of food competition tests. Following the competition tests, all animals were individually tested in their living cage for aggression toward an unfamiliar female. In food competition, females with testosterone implants were more successful and more aggressive than their cagemates with empty implants. When tested for aggression toward an unfamiliar intruder, females with testosterone implants given competitive experience were more aggressive toward an intruder than were their cagemates with empty implants or females with testosterone implants not given the competitive experience. Females with testosterone implants but without competitive experience were not more aggressive toward an unfamiliar female than were their cagemates with empty implants. These results suggest that, in ovariectomized females with testosterone implants, hormone-dependent aggression fostered by a competitive situation is displayed toward unfamiliar females.

  4. "The Power to Squash People": Understanding Girls' Relational Aggression

    ERIC Educational Resources Information Center

    Currie, Dawn H.; Kelly, Deirdre M.; Pomerantz, Shauna

    2007-01-01

    While researchers and concerned adults alike draw attention to relational aggression among girls, how this aggression is associated with girls' agency remains a matter of debate. This paper explores relational aggression among girls designated by their peers as "popular" in order to understand how social power constructs girls' agency as…

  5. Do You Have to be Angry to be Aggressive?

    ERIC Educational Resources Information Center

    Wienir, Paul L.

    Seven hypotheses regarding the role of anger for aggressive behavior were testes in an experimental exchange situation using male children as subjects. In previous studies, anger had not actually been employed as the intervening variable in a provocation/aggressive cue-aggression model. The results indicate a strong relationship between…

  6. An integrated review of indirect, relational, and social aggression.

    PubMed

    Archer, John; Coyne, Sarah M

    2005-01-01

    Over the last decade, researchers have found that girls may be just as aggressive as boys when manipulative forms of aggression, such as gossiping and spreading rumors, are included. These forms of aggression are known by 3 different names: indirect aggression, relational aggression, and social aggression. This review examines their commonalities and differences, and concludes that they are essentially the same form of aggression. We show that analogous forms are not found in other species. We offer a functional account: indirect aggression is an alternative strategy to direct aggression, enacted when the costs of direct aggression are high, and whose aim is to socially exclude, or harm the social status of, a victim. In this light, we consider sex differences and developmental trends and the impact of this aggression on victims. We conclude that indirect, relational, and social aggression are much more similar than they are different, and we suggest ways in which future research can be facilitated by integrating the three areas under an adaptive framework.

  7. The Implications of Relational Aggression toward Females Pursuing Educational Administration

    ERIC Educational Resources Information Center

    Dryier, Kimberly J.

    2009-01-01

    The purpose of this study was to examine the existence and implications of relational aggression toward female educational administrators. This qualitative study examined the impacts of relational aggression toward ten female superintendents, their observations of relational aggression in the workplace, strategies to overcome relational…

  8. Effects of Attack and Uncontrollable Noise on Aggression

    ERIC Educational Resources Information Center

    Geen, Russell G.

    1978-01-01

    The past decade has been marked by mounting public concern over noise as a source of environmental pollution. Simultaneously, research has shown that noise is also a potent cause of physiological stress. This research relates noise to aggression concluding that noise facilitates aggression in subjects who have been instigated to aggress to the…

  9. Predicting Mild and Severe Husband-to-Wife Physical Aggression.

    ERIC Educational Resources Information Center

    Pan, Helen S.; And Others

    1994-01-01

    Estimated odds of mild and severe husband-to-wife physical aggression in 11,870 white men. Being younger, having lower income, and having alcohol problem significantly increased odds of either mild or severe physical aggression. Drug problem uniquely increased risk of severe physical aggression. Marital discord and depression further increased…

  10. The Development of Sex Differences in Aggression: A Revised Model.

    ERIC Educational Resources Information Center

    Hyde, Janet S.; Schuck, John R.

    In response to Maccoby and Jacklin's (1974) conclusion that sex differences in aggression must be biological in origin, we suggest alternative social-learning mechanisms to explain the differences. These mechanisms include: (1) punishment for aggression increases aggression in boys, particularly because boys do not identify with the punisher; (2)…

  11. Exploring Parental Aggression toward Teachers in a Public School Setting

    ERIC Educational Resources Information Center

    May, David C.; Johnson, Jerry; Chen, Yanfen; Hutchinson, Lisa; Ricketts, Melissa

    2010-01-01

    Almost all of the extant research examining aggressive activity uses data from student populations. In this study, we extend that literature by examining teacher perceptions of parental aggression in public schools in Kentucky. Using data from a sample of 5,971 public school teachers, we determine that parental aggression directed at public school…

  12. Relational Aggression in School Settings: Definition, Development, Strategies, and Implications

    ERIC Educational Resources Information Center

    Dailey, Alicia L.; Frey, Andy J.; Walker, Hill M.

    2015-01-01

    Relational aggression (RA) is a nonphysical form of aggression whereby the perpetrator's goal is to inflict or threaten damage to relationships, including harm to the target child's social standing or reputation. This form of aggression may result in long-term psychological harm to victims. This article defines RA, summarizes its development, and…

  13. Aggression Replacement Training: Putting Theory and Research to Work

    ERIC Educational Resources Information Center

    Hollin, Clive R.

    2003-01-01

    There are many problems posed by aggressive youth, the harm to victims and the loss of young people into the criminal justice system and penal confinement. Aggression Replacement Training (ART) was developed by Arnold Goldstein and his colleagues as a means of working with aggressive young people to help them learn new, prosocial ways of behaving.…

  14. Attentional Processes in Children's Overt and Relational Aggression

    ERIC Educational Resources Information Center

    Arsenault, Darin J.; Foster, Sharon L.

    2012-01-01

    This study examined attention and memory processes assumed by the social information-processing model to be biased in aggressive children. We also explored whether similar biases were associated with overt and relational aggression. A total of 96 fourth through sixth graders saw videos of overtly and relationally aggressive child actors and…

  15. The dopaminergic system and aggression in laying hens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aggression and pecking behavior in laying hens is a serious concern to the production and well-being of the hens. Current breeding programs attempt to reduce aggression in hens without altering production have had limited success. Improved understanding of the neural mediation of aggression, will be...

  16. Shared Targets for Aggression by Early Adolescent Friends

    ERIC Educational Resources Information Center

    Card, Noel A.; Hodges, Ernest V. E.

    2006-01-01

    Similarity in early adolescent friends' general aggressiveness is well known, but questions remain regarding the degree to which friends aggress against the same victims. The authors examined this by administering the newly created Dyadic Aggression and Victimization Inventory to 417 sixth- through eighth-grade boys and girls (53%). Friends …

  17. Girls Just Being Girls? Mediating Relational Aggression and Victimization

    ERIC Educational Resources Information Center

    Radliff, Kisha M.; Joseph, Laurice M.

    2011-01-01

    Although physical aggression has received much attention in the literature, relational aggression has only been explored in the past decade or so. This is problematic given that relational aggression is increasingly prevalent among middle school girls and has become a cause for alarm, as this phenomenon leads to several negative psychological,…

  18. Risk Factors for Violence and Relational Aggression in Adolescence

    ERIC Educational Resources Information Center

    Herrenkohl, Todd I.; McMorris, Barbara J.; Catalano, Richard F.; Abbott, Robert D.; Hemphill, Sheryl A.; Toumbourou, John W.

    2007-01-01

    Analyses examined risk factors for seventh- and ninth-grade youth categorized as nonoffenders, physically violent, relationally aggressive, and both violent and relationally aggressive. Bivariate and multivariate results showed that relationally aggressive youth were elevated on most risks above levels for nonoffenders but lower than those for…

  19. Parental Influences on the Prevalence and Development of Child Aggressiveness

    ERIC Educational Resources Information Center

    Wahl, Klaus; Metzner, Cornelia

    2012-01-01

    The development of aggressiveness between 5 and 17 years and some parental influences on this development were analyzed using data from Germany. International studies have shown a "camel humps" curve, i.e., a peak of aggression of children (primarily boys) between 2 and 4 years and a second peak of antisocial or aggressive behavior of boys between…

  20. Mothers' Responses to Preschoolers' Relational and Physical Aggression

    ERIC Educational Resources Information Center

    Werner, Nicole E.; Senich, Samantha; Przepyszny, Kathryn A.

    2006-01-01

    This study focused on mothers' affective and behavioral responses to hypothetical displays of preschoolers' relational and physical aggression. We hypothesized that lower levels of negative affect and a lower likelihood of intervening in conflicts would occur for relational aggression than for physical aggression. We also expected significant…