- Differential Regulation of PAI-1 in Hantavirus Cardiopulmonary Syndrome and Hemorrhagic Fever With Renal Syndrome. [Journal Article]
- OFOpen Forum Infect Dis 2018; 5(2):ofy021
- We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with ren...
We analyzed the levels of circulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-1 in acute hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS). The levels of tPA commonly increased in both diseases, whereas PAI-1 correlated with disease severity in HCPS but not in HFRS.
- Post-IV thrombolytic headache and hemorrhagic transformation risk in acute ischemic stroke. [Journal Article]
- NCNeurol Clin Pract 2016; 6(1):22-28
- Background: Headache during or soon after administration of IV tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is a concern for hemorrhagic transfo...
Background: Headache during or soon after administration of IV tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is a concern for hemorrhagic transformation (HT). However, no data are available regarding the incidence of HT in these patients or the prognostic indication of these headaches. We examine the importance of tPA-associated headaches among AIS patients in terms of HT rates and clinical outcomes.Methods:AIS patients treated with IV tPA at a comprehensive stroke center between January 2007 and November 2012 were retrospectively reviewed for documented tPA-associated headache in the first 24 hours post-tPA. We compared the headache and nonheadache groups for differences in various clinical and radiologic outcomes.Results:Of the 193 patients, 63 (32.6%) had tPA-associated headache. Headache patients (HP) were younger than nonheadache patients (NHP) (mean ± SD, 59.5 ± 17.4 years vs 69.9 ± 15.5 years,p< 0.0001), and 53% of HP were men, compared to 49.2% of NHP (p= 0.537). Comorbid conditions did not differ between the 2 groups. There were no statistical differences between HP and NHP in admission NIH Stroke Scale (NIHSS) score (11.2 ± 5.7 vs 11.5 ± 5.5,p= 0.646), NIHSS score at 24 hours (6.5 ± 5.7 vs 7.4 ± 6.9,p= 0.466), NIHSS score at discharge (6.7 ± 10.1 vs 8.1 ± 11.6,p= 0.448), HT (12.7% vs 18.4%,p= 0.3), cervical artery dissection (4.7% vs 5.38%,p= 0.764), length of hospitalization (6.29 ± 5 days vs 6.35 ± 4.7 days,p= 0.935), and disposition.Conclusion:tPA-associated headache does not predict increased risk of HT and has no other prognostic importance in patients with AIS. Prospective studies with a larger cohort may be needed to further explore this relationship.
- Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical Thrombectomy in Large-Vessel Occlusions. [Journal Article]
- SStroke 2018; 49(1):232-235
- CONCLUSIONS: Pretreatment with systemic thrombolysis in patients with large-vessel occlusion eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the need for additional endovascular reperfusion. Tandem occlusions seem to be the least responsive to IVT pretreatment.
- Community Interventions to Increase Stroke Preparedness and Acute Stroke Treatment Rates. [Review]
- CACurr Atheroscler Rep 2017 Nov 16; 19(12):64
- Acute stroke treatments reduce the risk of post-stroke disability. These treatments, tissue plasminogen activator (tPA) and intra-arterial treatment, are highly time-dependent; thus, one of the main ...
Acute stroke treatments reduce the risk of post-stroke disability. These treatments, tissue plasminogen activator (tPA) and intra-arterial treatment, are highly time-dependent; thus, one of the main barriers to treatment is pre-hospital delay. Stroke preparedness is defined as the ability to recognize stroke symptoms and the intent to activate emergency medical services (EMS). This review describes types of acute stroke treatment and preparedness interventions, including recent mass media interventions to increase acute stroke treatment rates, and adult and youth community interventions to increase stroke preparedness.
- Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke). [Clinical Trial]
- CircCirculation 2017 Dec 12; 136(24):2311-2321
- CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes.
- Active Expression of Human Tissue Plasminogen Activator (t-PA) c-DNA from Pulmonary Metastases in the Methylotrophic Yeast Pichia Pastoris KM71H Strain [Journal Article]
- APAsian Pac J Cancer Prev 2017 08 27; 18(8):2249-2254
- CONCLUSIONS: Correspondingly, Pichia pastoris KM71H is an appropriate strain for production of active recombinant protein.
- Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry. [Multicenter Study]
- SStroke 2017; 48(10):2760-2768
- CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care.
- Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke. [Journal Article]
- ANActa Neuropathol 2017; 134(4):585-604
- Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increa...
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mechanism of PDGF-CC activation in the NVU is not known. Here, we show that the integrin Mac-1, expressed on brain microglia/macrophages (denoted microglia throughout), acts together with the endocytic receptor LRP1 in the NVU to promote tPA-mediated activation of PDGF-CC. Mac-1-deficient mice (Mac-1-/-) are protected from tPA-induced BBB permeability but not from permeability induced by intracerebroventricular injection of active PDGF-CC. Immunofluorescence analysis demonstrates that Mac-1, LRP1, and the PDGFRα all localize to the NVU of arterioles, and following middle cerebral artery occlusion (MCAO) Mac-1-/- mice show significantly less PDGFRα phosphorylation, BBB permeability, and infarct volume compared to wild-type mice. Bone-marrow transplantation studies indicate that resident CD11b+ cells, but not bone-marrow-derived leukocytes, mediate the early activation of PDGF-CC by tPA after MCAO. Finally, using a model of thrombotic stroke with late thrombolysis, we show that wild-type mice have an increased incidence of spontaneous ICH following thrombolysis with tPA 5 h after MCAO, whereas Mac-1-/- mice are resistant to the development of ICH even with late tPA treatment. Together, these results indicate that Mac-1 and LRP1 act as co-factors for the activation of PDGF-CC by tPA in the NVU, and suggest a novel mechanism for tightly regulating PDGFRα signaling in the NVU and controlling BBB permeability.
- Anxiety and depression in patients three months after myocardial infarction: Association with markers of coagulation and the relevance of age. [Journal Article]
- JPJ Psychosom Res 2017; 99:162-168
- CONCLUSIONS: We measured parameters of coagulation and fibrinolysis in patients three months after MI and found no predictive value of HADS anxiety and depression scores shortly after MI or at the time of blood sampling. The effects of age on the relationship between anxiety and haemostasis should be further investigated.
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- Neurology Concepts: Young Women and Ischemic Stroke-Evaluation and Management in the Emergency Department. [Journal Article]
- AEAcad Emerg Med 2018; 25(1):54-64
- CONCLUSIONS: Unique challenges exist in the evaluation and diagnosis of ischemic stroke in young women. There are still many opportunities for future research aimed at improving detection and treatment of this population.