This K24 application seeks support for Steven Levine, an active, mid-career, clinical neuroscientist and neurologist with independent research support, involved in patient-oriented research. With this support, Dr. Levine can achieve, with greater focus, his long-term career goal of advancing knowledge of the significance of antiphospholipid-protein antibodies (aPL-P) (the most commonly identified hematologic mechanism of ischemic stroke) through research in ischemic cerebrovascular disease. He will use this support to enhance a nationally recognized, integrated, and collaborative clinical research program, provide critical time to serve as a mentor for beginning clinical investigators, and enhance his didactic knowledge base through structured coursework. This 5-year proposal will focus on (1) the role of aPL-P titer, and isotype in predicting recurrent stroke and death in a large cohort of ischemic stroke patients, and (2) the relative prognostic importance and significance of different types of coagulation tests for the lupus anticoagulant (one type of aPL-P) and more novel aPL-P, such as antibodies to 2 glycoprotein-I and antiphosphatidylserine antibodies. Multivariate models will be built to better define the predictive ability of each aPL-P, their isotype, and their titer for recurrent thrombo-occlusive events. (3) The role of aPL-P, thrombin-antithrombin complexes, tissue plasminogen activator antigen levels, and thrombomodulin in predicting treatment response, outcome, and intracerebral hemorrhage risk in the NINDS rt-PA Stroke Trial will also be investigated. This will allow aPL-P data from a large acute stroke trial to be compared and contrasted to a large stroke prevent on trial. (4) Pilot studies will be conducted, as well in the application of telemedicine for stroke (""""""""Telestroke""""""""). The applicant will also enroll in formal coursework aimed at increasing his knowledge and skill level concerning epidemiology, biostatistics, including sophisticated data analyses techniques, and immunology. This intensive research focus will allow the applicant to provide new insights and set new directions for further study of aPL-P and hemostatic markers in acute ischemic stroke patients who receive thrombolytic therapy, and in stroke patients receiving either anticoagulant or antiplatelet therapy, as well as allow him time to initiate new studies of telemedicine for stroke. This award will also allow him to mentor trainees (beginning clinicians and clinical investigators) within a comprehensive stroke program, using the (1) largest database to date of aPL-P positive stroke patients who have been systematically evaluated, prospectively followed, (2) the NINDS rt-PA Stroke Trial database, and (3) the trainee's independent research projects. Given the rapid exponential growth of insights into cerebrovascular disease, from molecular and genetic mechanisms to large-scale epidemiological and clinical trials, there is a critical and unmet need for formally trained clinical investigators to tackle the increasing frequency and burden of stroke in America.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24NS043992-04
Application #
6934560
Study Section
Special Emphasis Panel (ZNS1-SRB-K (01))
Program Officer
Marler, John R
Project Start
2002-08-15
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
4
Fiscal Year
2005
Total Cost
$139,252
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Amory, Colum F; Levine, Steven R; Brey, Robin L et al. (2015) Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio. Cerebrovasc Dis 40:293-300
Levine, Deborah A; Walter, James M; Karve, Sudeep J et al. (2014) Smoking and mortality in stroke survivors: can we eliminate the paradox? J Stroke Cerebrovasc Dis 23:1282-90
Longstreth Jr, W T; Kronmal, Richard A; Thompson, John L P et al. (2013) Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke 44:714-9
Turan, Tanya N; Maidan, Lucian; Cotsonis, George et al. (2009) Failure of antithrombotic therapy and risk of stroke in patients with symptomatic intracranial stenosis. Stroke 40:505-9
Demchuk, Andrew M; Khan, Firosh; Hill, Michael D et al. (2008) Importance of leukoaraiosis on CT for tissue plasminogen activator decision making: evaluation of the NINDS rt-PA Stroke Study. Cerebrovasc Dis 26:120-5
Levine, Steven R; McConnochie, Kenneth M (2007) Telemedicine for acute stroke: when virtual is as good as reality. Neurology 69:819-20
Levine, Steven R (2007) The interplay of age, access to health care, and insurance status: the good, the bad, and the ugly. Arch Neurol 64:15-6
Jauch, Edward C; Lindsell, Christopher; Broderick, Joseph et al. (2006) Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke 37:2508-13
Tanne, David; Macko, Richard F; Lin, Yan et al. (2006) Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke. Stroke 37:1798-804
Belogolovkin, Victoria; Levine, Steven R; Fields, Madeline C et al. (2006) Postpartum eclampsia complicated by reversible cerebral herniation. Obstet Gynecol 107:442-5

Showing the most recent 10 out of 20 publications