Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stroke carries a severe toll in terms of loss of life and disability for patients and their families. Until 10 years ago, physicians, and in particular neurologists, had a conservative, nonaggresive approach to this devastating disease. The advent of thrombolytic therapy not only proved that acute ischemic stroke is treatable, but also that early reperfusion can dramatically change the outcome of acute stroke patients. As a result of these trials, intravenous (IV) tissue plasminogen activator (t-PA) has been approved for treatment of acute ischemic stroke within 3 hours after symptom onset in the United States, Canada, Australia, and the European Union. The near future is extremely promising. Imaging modalities, such as diffusion- and perfusion-weighted images, as well as CT perfusion and CT angiography, to better select patients for treatment are now routinely performed in most academic medical centers. Novel IV and intra-arterial (IA) agents have been developed and tested. Emerging therapies will soon be available to increase the therapeutic windows for thrombolysis both by better screening patients using MRI or CT and by new IV and IA treatments. Several multicenter controlled trials in both imaging-guided decisions and therapeutic agents are either completed or being performed. We review data on advancement in imaging and treatment of acute ischemic stroke, in particular focusing on pharmacologic and mechanical IA thrombolysis.
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PMID:Advances in treatment of acute ischemic stroke. 1646 11

Stroke carries a severe toll in terms of loss of life and disability for patients and their families. Until 10 years ago, physicians, and in particular neurologists, had a conservative, non-aggressive approach to this devastating disease. The advent of thrombolytic therapy not only proved that acute ischemic stroke is treatable, but also that early reperfusion can dramatically change the outcome of acute stroke patients. As a result of these trials, intravenous (IV) tissue plasminogen activator (t-PA) has been approved for treatment of acute ischemic stroke within 3 hours after symptom onset in the United States, Canada, Australia, and the European Union. The near future is extremely promising. Imaging modalities, such as diffusion- and perfusion-weighted images, as well as CT perfusion and CT angiography, to better select patients for treatment are now routinely performed in most academic medical centers. Novel IV and intra-arterial (IA) agents have been developed and tested. Emerging therapies will soon be available to increase the therapeutic windows for thrombolysis both by better screening patients using MRI or CT and by new IV and IA treatments. Several multicenter controlled trials in both imaging-guided decisions and therapeutic agents are either completed or being performed. We review data on advancement in imaging and treatment of acute ischemic stroke, in particular focusing on pharmacologic and mechanical IA thrombolysis.
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PMID:Advances in treatment of acute ischemic stroke. 1646 68

There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.
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PMID:Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic Gd ions chelated to the shell layer as a potential nanoscale MRI-visible delivery system. 1804 89

After large CT-based clinical trials have failed to prove the benefits of intravenous tissue plasminogen activator (tPA) administration for ischemic stroke patients beyond 3 hours of the onset of the concept of PWI/DWI mismatch which is the volume difference between a PWI lesion and DWI lesion on MRI scans, has been proposed to facilitate the selection of patients with a salvageable area. PWI/DWI mismatch is considered to represent the tissue that is not irreversibly injured and can respond to early reperfusion therapy. When an ischemic lesion is divided into 4 regions, namely, ischemic core, reversible DWI lesion, penumbra and benign oligemia, both the reversible DWI lesion and penumbra are considered to be an optimal targets for thrombolysis. In order to clarify the clinical significance of PWI/DWI mismatch in the selection of candidates for tPA therapy, some multicenter trials were performed. The results of DIAS (desmoteplase in acute ischemic stroke)/DEDAS (dose escalation of desmoteplase for acute ischemic stroke)/DIAS-2 did not difinitly demonstrate the clinical benefits of desmoteplase administration in patients with PWI/DWI mismatch between 3 to 9 hours of onset; in fact, DIAS-2 could not prove any effect of the drug. DEFUSE (diffusion and perfusion imaging evaluation for understanding stroke evolution), in which tPA was administered to all participants between 3 to 6 hours of stroke onset, showed that the occurrence of early reperfusion led to a favorable clinical response in patients with PWI/DWI mismatch. In contrast, early reperfusion was not beneficial in patients without PWI/DWI mismatch. In EPITHET (echoplanar imaging thrombolysis evaluation trial), stroke patients who showed PWI/DWI mismatch after 3 to 6 hours of the onset were assigned to receive either alteplase or placebo administration: lesion growth was lesser in patients with alteplase than in those who received placebo, although the difference was not statistically significant because of a small number of participants. Although these results supported the importance of the PWI/DWI concept, there still remain some issues to be resolved. Regarding the definition of PWI/ DWI mismatch, a larger mismatch ratio than the one that has been typically used seems to be recommended. Most useful parameters of PWI should be determined to standardize volume evaluation using MRI scans. For the institutes where MRI scans are not available 24 hours a day, clinical DWI mismatch has been proposed as an alternative to of PWI/DWI mismatch. The application of MRI-based decision making strategy for stroke patients may facilitate the assessment and treatment of stroke patients beyond 3 hours of stroke onset, and is expected to allow the use of tPA for a substantially greater number of patients.
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PMID:[Intravenous administration of a tissue plasminogen activator beyond 3 hours of the onset of acute ischemic stroke--MRI-based decision making]. 1897 5

The management for acute stroke has been changed greatly in Japan. Because use of intravenous administration of tissue plasminogen activator (IV-t-PA) for acute brain infarction within 3 hours of onset has been approved by Japanese government from October, 2005. Now, if acute stroke patient arrivals at hospital within 3 hours of onset, we consider that such patients should be treated with t-PA therapy. The accurate diagnosis should be made by systematic evaluation using CT/MRI, neurosonology including transcranial Doppler, carotid echography, and echocardiography (TEE and TTE), SPECT, and angiography. In particular, it is important to assess the arteries from heart and brain. The grad A for treatment of acute stroke is recommended as IV-t-PA therapy, aspirin administration within 48 hours of stroke onset, and the management in stroke unit. In particular, stroke unit can improve functional outcome and to reduce the length of hospital stay. The evidence directing therapy for acute stroke is changing rapidly.
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PMID:[Diagnosis and management for acute ischemic stroke]. 1919 2

After ischaemic stroke onset, potentially viable (ie, penumbral) tissue might be salvageble for as long as 48 h. By increasing the therapeutic time window for treatment of stroke with intravenous alteplase from 3-4.5 h to 9 h, many more patients could be treated. Use of a combination of diffusion-weighted and perfusion-weighted MRI or perfusion CT might improve selection of patients with penumbral tissue. Several phase II trials of alteplase lend strong biological support to the use of this strategy for up to 6 h after stroke. However, the negative results of the phase III Desmoteplase In Acute ischaemic Stroke trial (DIAS-2) with desmoteplase given up to 9 h after stroke suggest that some refinements are needed. For trials of neuroprotection, the concept of freezing the penumbra (ie, preventing further deterioration of the vulnerable tissue) might be a more realistic expectation. Recent advances in penumbral imaging technology should enable a phase III alteplase trial to be done beyond 4.5 h by use of techniques to select patients with penumbral tissue.
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PMID:Penumbral selection of patients for trials of acute stroke therapy. 1923 36

The high fibrin specificity of Desmodus rotundus salivary plasminogen activator alpha1 (desmoteplase) renders it a promising candidate for the treatment of acute ischemic stroke. In the DIAS (Desmoteplase in Acute Ischemic Stroke) and DEDAS (Dose Escalation study of Desmoteplase in Acute ischemic Stroke) Phase II studies, doses of 90 microg/kg and 125 microg/kg desmoteplase were reported to have acceptable safety profiles, leading to potentially superior reperfusion compared with placebo, with possible clinical efficacy for up to 9 h after the onset of symptoms in patients with a significant ischemic penumbra selected from magnetic resonance perfusion-diffusion weighted mismatches imaging. However, a Phase III clinical trial (DIAS-2) was unable to detect any benefit from desmoteplase when given 3 - 9 h after stroke onset. In this study with a modest sample size, certain methodological factors may have reduced its potential to detect a desmoteplase effect, as only 30% of these patients had a visible occlusion at presentation, with only small core and mismatched lesion volumes. Indeed, it is surprising that a study testing an occluded vessel 'reopener' was conducted in a cohort of stroke patients, the majority of whom was known not to have a detected vessel occlusion. It has also been claimed that the DIAS-2 patients selection using core/penumbra mismatch calculation may not have followed an appropriate mismatch threshold. However, the corrective value of changing the mismatch threshold remains unclear, because the relative mismatch volumes were in fact higher in the 'negative' DIAS-2 than in the 'positive' DIAS and DEDAS. Two Phase II randomized trials with tPA, Diffusion-weighted imaging Evaluation For Understanding Stroke Evolution (DEFUSE) and Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) provided strong biological support for the relation between infarct growth, reperfusion and clinical outcome in the 3 - 6 h time window after onset of stroke using penumbral imaging. In this frame, why exactly desmoteplase should have specific advantages over tPA, is not clear. Taken together, these findings may also lead to the disappointing conclusion that vessel recanalization after 4.5 - 5 h from stroke onset may generally be inefficacious for tissue salvage. Nevertheless, other randomized Phase III clinical trials (DIAS-3 and DIAS-4) are currently under way with a planned sample size of 320 patients having vessel occlusion or high-grade stenosis on MRI or CT-angiography in the proximal cerebral arteries.
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PMID:Desmoteplase. 1945 11

Stroke is defined as repidly developing symptoms or signs of loss of cerebral function with no apparent cause other than vascular origin. The issues to be addressed when making diagnosis of stroke are : (1) is it a stroke? (2) What pathological type of stroke? (3) Where is the lesion? (4) What caused it? Differential diagnosis of stroke is chronic subdural haematoma, brain tumour, hypoglycaemic, metabolic encephalopathies, postictal neurological deficit and functional. CT or MRI is important investigation while dealing with a stroke patient. In treating acute stroke one has to go through the objectives eg, optimising the patient's chance of survival, minimising the risk and degree of disability and preventing recurrence. One has to think of genera care required in management of stroke. Control of blood pressure and blood sugar is important. Specific treatment includes aspirin, t-PA, low molecular weight heparin, calcium antagonists though some reservation persists over efficacy. Psychological support, cognitive impairment, motor and sensory impairment are to be addressed. Functional rehabilitation interventions, log-term management and secondary prevention are to be cared for.
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PMID:Management of stroke: a clinical approach. 1988 77

An off-resonance saturation (ORS) method was used for magnetic resonance imaging of superparamagnetic polymeric micelles (SPPM). SPPM was produced by encapsulating a cluster of magnetite nanoparticles (9.9+/-0.4 nm in diameter) in poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) copolymer micelles (micelle diameter: 60+/-9 nm). In ORS MRI, a selective radiofrequency (RF) pulse was applied at an off-resonance position (0-50 ppm) from the bulk water signal, and the SPPM particles were visualized by the contrast on a division image constructed from two images acquired with and without pre-saturation. Here, the effects of saturation offset frequencies, saturation durations, and RF powers on ORS contrasts were investigated as these parameters are critical for optimization of ORS MRI for in vivo imaging applications. The ability to turn "ON" and "OFF" ORS contrast of SPPM solutions permits for an accurate image subtraction and a contrast enhancement to visualize SPPM probes for in vivo imaging of cancer.
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PMID:Off-resonance saturation magnetic resonance imaging of superparamagnetic polymeric micelles. 1996 23

An 80-year-old white male suffered a stroke, fell to the floor, and suffered acute right hemiparesis and facial palsy. After an intravenous alteplase infusion 2.5 h later, the patient first complained of numbness in his right arm, then neck pain, followed by left leg numbness and slowly progressing paraparesis. MRI of the spine demonstrated an acute spinal dorsal epidural hematoma extending from the C6 to the T6 level; 12 h later, he underwent hematoma evacuation and laminectomy. Three months after surgery, the patient was paraplegic with moderate sensory loss below mamillary level. Acute ischemic stroke is often associated with a sudden fall, which, after thrombolysis, may result in unusual hemorrhagic complications.
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PMID:Spinal Epidural Hematoma as a Complication of Intravenous Thrombolysis in an Acute Ischemic Stroke Patient. 2068 32


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