Microfluidic manufacture of rt-PA -loaded echogenic liposomes.

Echogenic liposomes (ELIP), loaded with recombinant tissue-type plasminogen activator (rt-PA) and microbubbles that act as cavitation nuclei, are under development for ultrasound-mediated thrombolysis. Conventional manufacturing techniques produce a polydisperse rt-PA-loaded ELIP population with only a small percentage of particles containing microbubbles. Further, a polydisperse population of rt-PA-loaded ELIP has a broadband frequency response with complex bubble dynamics when exposed to pulsed ultrasound.

A Novel Tool for Evaluation of Mild Traumatic Brain Injury Patients in the Emergency Department: Does Robotic Assessment of Neuromotor Performance Following Injury Predict the Presence of Postconcussion Symptoms at Follow-up?

Objectives: Postconcussion symptoms (PCS) are a common complication of mild traumatic brain injury (TBI). Currently, there is no validated clinically available method to reliably predict at the time of injury who will subsequently develop PCS. The purpose of this study was to determine if PCS following mild TBI can be predicted during the initial presentation to an emergency department (ED) using a novel robotic-assisted assessment of neurologic function.

Randomized Controlled Noninferiority Trial Comparing Daptomycin to Vancomycin for the Treatment of Complicated Skin and Skin Structure Infections in an Observation Unit.

Background: Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in complicated skin and skin structure infection (cSSSI) presenting to emergency departments (EDs). Treatment is heterogeneous and can require inpatient admission to an observation unit (OU). Vancomycin is commonly used in the OU for treatment, but increasing MRSA resistance to vancomycin suggests the need for alternatives.

Quantitative assessment of post-concussion syndrome following mild traumatic brain injury using robotic technology.

Post-Concussion Syndrome (PCS) is a common sequelae of mild Traumatic Brain Injury (mTBI). Currently, there is no reliable test to determine which patients will develop PCS following an mTBI. As a result, clinicians are challenged to identify patients at high risk for subsequent PCS.

Integration of New Technology for Research in the Emergency Department: Feasibility of Deploying a Robotic Assessment Tool for Mild Traumatic Brain Injury Evaluation.

Unlabelled: The objective of this paper is to demonstrate the effective deployment of a robotic assessment tool for the evaluation of mild traumatic brain injury (mTBI) patients in a busy, resource-constrained, urban emergency department (ED).

Methods: Functional integration of new robotic technology for research in the ED presented several obstacles that required a multidisciplinary approach, including participation from electrical and computer engineers, emergency medicine clinicians, and clinical operations staff of the hospital. Our team addressed many challenges in deployment of this advanced technology including: 1) adapting the investigational device for the unique clinical environment; 2) acquisition and maintenance of appropriate testing space for point-of-care assessment; and 3) dedicated technical support and upkeep of the device.

Plasmin-loaded echogenic liposomes for ultrasound-mediated thrombolysis.

Plasmin, a direct fibrinolytic, shows a significantly superior hemostatic safety profile compared to recombinant tissue plasminogen activator (rtPA), the only FDA-approved thrombolytic for the treatment of acute ischemic stroke. The improved safety of plasmin is attributed to the rapid inhibition of free plasmin by endogenous plasmin inhibitors present in very high concentrations (1 μM). However, this rapid inhibition prevents the intravenous (IV) administration of plasmin.

In vivo testing of a non-invasive prototype device for the continuous monitoring of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a stroke subtype with the highest mortality rate. Hematoma expansion and re-bleeding post-ICH are common and exacerbate the initial cerebral insult. There is a need for continuous monitoring of the neurologic status of patients with an ICH injury.

Individual lytic efficacy of recombinant tissue plasminogen activator in an in vitro human clot model: rate of "nonresponse".

Objectives: Recombinant tissue plasminogen activator (rt-PA) is a lytic medication widely used in the emergency department to treat acute thrombotic disorders such as ischemic stroke and myocardial infarction. It is known in the clinical use of this drug that it can be less effective in approximately 25% of individuals receiving such treatment. However, there are no data on the variation of lytic efficacy of rt-PA in decreasing individuals' clot size over time.

Temperature affects thrombolytic efficacy using rt-PA and eptifibatide, an in vitro study.

The potential for hypothermia as a neuroprotectant during stroke has led to its increase in clinical use. At the same time, combination pharmaceutical therapies for ischemic stroke using recombinant tissue plasminogen activator (rt-PA), and GP IIb-IIIa inhibitors, such as Eptifibatide (Epf ), are under study. However, there is little data on how the reactions triggered by these agents are impacted by temperature.

A prototype device for non-invasive continuous monitoring of intracerebral hemorrhage.

A prototype for a non-invasive, real-time, monitoring device was developed to detect changes in the brain secondary to disease or injury such as intracerebral hemorrhage (ICH). The eventual goal is a non-invasive, real time sensor that can alert the clinician to alterations in the comatose patient's brain resulting from hemorrhage, seizure or stroke. In this work, a 400 MHz electromagnetic (EM) signal was transmitted with an antenna (T), incident on a 'brain gel' in vitro ICH model, and received by a receiving (R) antenna.

Comparison of electrical conductivities of various brain phantom gels: Developing a 'Brain Gel Model'.

The use of conducting gels to mimic brain and other tissues is of increasing interest in the development of new medical devices. Currently, there are few such models that can be utilized at physiologic temperatures. In this work, the conductivities of agar, agarose and gelatin gels were manipulated by varying NaCl concentration from 0-1 mg/ml.

Short-term high-dose effect of lovastatin on thrombolysis by rt-PA in a human whole-blood in vitro clot model.

High-dose hydroxymethylglutaryl coenzyme. A reductase inhibitor (statin) administration reduces neuronal injury and improves outcomes in experimental models of acute ischemic stroke, and has been shown to be safe in a phase 1 dose-escalation study using lovastatin at doses higher than currently approved for daily use. Statins also affect the hemostatic system by upregulating t-PA expression and decreasing plasminogen activator inhibitor (PAI-1) expression, platelet adhesion and thrombus formation in animal models.

Combination treatment with rt-PA is more effective than rt-PA alone in an in vitro human clot model.

Incidence of intra-cranial hemorrhage linked to treatment of ischemic stroke with recombinant tissue plasminogen activator (rt-PA) has led to interest in adjuvant therapies such as ultrasound (US) or plasminogen, to enhance rt-PA efficacy and improve patient safety. High-frequency US (∼MHz) such as 2-MHz transcranial Doppler (TCD) has demonstrated increased recanalization in situ. Low-frequency US (∼kHz) enhanced thrombolysis (UET) has demonstrated higher lytic capabilities but has been associated with incidence of intracerebral hemorrhage in some clinical trials.

Making the right choice: optimizing rt-PA and eptifibatide lysis, an in vitro study.

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved lytic therapy for acute ischemic stroke. However, there can be complications such as intra-cerebral hemorrhage. This has led to interest in adjuncts such as GP IIb-IIIa inhibitors.

Long-term stability of recombinant tissue plasminogen activator at -80 C.

Background: Recombinant tissue plasminogen activator (tPA) is a thrombolytic widely used clinically in the treatment of acute thrombotic disease such as ischemic stroke, myocardial infarction, and deep venous thrombosis. This has led to much interest in tPA based lytic therapies leading to laboratory based in-vitro and in-vivo investigations using this drug. However, tPA reconstituted in solution exhibits full activity for only 6-8 hours, according to the manufacturer.

Ultrasound-enhanced thrombolysis with tPA-loaded echogenic liposomes.

Background And Purpose: Currently, the only FDA-approved therapy for acute ischemic stroke is the administration of recombinant tissue plasminogen activator (tPA). Echogenic liposomes (ELIP), phospholipid vesicles filled with gas and fluid, can be manufactured to incorporate tPA. Also, transcranial ultrasound-enhanced thrombolysis can increase the recanalization rate in stroke patients.

Serum cleaved tau does not predict postconcussion syndrome after mild traumatic brain injury.

Objectives: Our objective was to determine if the biomarker for axonal injury, serum cleaved tau (C-tau), predicts postconcussion syndrome (PCS) in adults after mild traumatic brain injury (mTBI).

Methods: C-tau was measured from blood obtained in the emergency department. Outcome was assessed at 3 months post injury using the Rivermead Postconcussion Symptoms Questionnaire and Acute Medical Outcomes SF-36v2 Health Survey (SF-36).

Effect of low frequency ultrasound on combined rt-PA and eptifibatide thrombolysis in human clots.

Introduction: Fibrinolytics such as recombinant tissue plasminogen activator (rt-PA) are used to treat thrombotic disease such as acute myocardial infarction (AMI) and ischemic stroke. Interest in increasing efficacy and reducing side effects has led to the study of adjuncts such as GP IIb-IIIa inhibitors and ultrasound (US) enhanced thrombolysis. Currently, GP IIb-IIIa inhibitor and fibrinolytic treatment are often used in AMI, and are under investigation for stroke treatment.

Tissue plasminogen activator concentration dependence of 120 kHz ultrasound-enhanced thrombolysis.

It has been known for some time that the application of ultrasound can enhance the efficacy of thrombolytic medications such as recombinant tissue plasminogen activator (rt-PA). Potential clinical applications of this ultrasound-enhanced thrombolysis (UET) include the treatment of myocardial infarction, acute ischemic stroke, deep venous thrombosis and other thrombotic disorders. It may be possible to reduce the dose of rt-PA while maintaining lytic efficacy; however there is little data on the rt-PA concentration dependence of UET.

Characterization of ultrasound propagation through ex-vivo human temporal bone.

Adjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke. The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.

In vitro microscopic imaging of enhanced thrombolysis with 120-kHz ultrasound in a human clot model.

Substantial enhancement of recombinant tissue plasminogen activator (rt-PA) thrombolysis can be achieved with ultrasound, suggesting its use as an adjunctive treatment in thrombolytic therapy for stroke. A microscopic visualization method was used to measure the lysis of human whole-blood clots treated with human fresh frozen plasma (HFFP), rt-PA, and 120-kHz ultrasound for 30 min at T = 37 ° C. The clot-plasma interface was imaged using an inverted optical microscope and the thrombolytic front analyzed as a function of time.

Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model.

Introduction: Thrombolytics such as recombinant tissue plasminogen activator (rt-PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.

Objective: To improve the efficacy of this thrombolytic therapy, the synergistic effect of rt-PA and 120 kHz or 1.0 MHz ultrasound was assessed in vitro using a porcine clot model.

Arrhenius temperature dependence of in vitro tissue plasminogen activator thrombolysis.

Stroke is a devastating disease and a leading cause of death and disability. Currently, the only FDA approved therapy for acute ischemic stroke is the intravenous administration of the thrombolytic medication, recombinant tissue plasminogen activator (tPA). However, this treatment has many contraindications and can have dangerous side effects such as intra-cerebral hemorrhage.

Duty cycle dependence of ultrasound enhanced thrombolysis in a human clot model.

Combined ultrasound and tissue plasminogen activator (rt-PA) therapy, or ultrasound enhanced thrombolysis (UET), has been shown to improve recanalization in patients with acute ischemic stroke. We measured the effect of ultrasound duty cycle on the lytic efficacy of 120 kHz UET in an in vitro human clot model. The hypothesis was that an increase in duty cycle increases rt-PA lytic efficacy.