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)

We describe a patient with defective tissue plasminogen activator (t-PA) release who developed internal cerebral vein thrombosis. She recovered completely and, as shown by MRI, favourable outcome was probably related to vascular recanalisation. Other members of the pedigree had a similar fibrinolytic deficiency without clinical manifestations. The use of oral contraceptives may have contributed to the patient's hypercoagulable state.
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PMID:Deep cerebral venous thrombosis and hereditary tissue plasminogen activator (t-PA) deficiency. 772 54

We studied the effects of rt-PA (recombinant tissue type-plasminogen activator) treatment on the blood-brain barrier (BBB) after thromboembolic stroke in rat. New MRI methods of diffusion and perfusion imaging to observe the hemodynamic and biophysical effects of thrombolysis were combined with methods for assessment of BBB disturbances. In untreated animals clot embolism produced a rapid drop in MRI perfusion values and the ADC (apparent diffusion coefficient), with subsequent infarction. BBB disturbances, visualised as extravasation of serum proteins on cryostat sections, were manifest in nearly all animals in the borderzone of infarcts. In animals treated with rt-PA 15 min after clot embolism thrombolysis resulted in reperfusion of affected brain regions with subsequent improvement of ADC values. Final lesion size on ADC maps was reduced by 36% relative to untreated animals. However, BBB disturbances were not improved after treatment. To the contrary, rt-PA treated animals showed further regions with serum protein extravasation in the infarcted territories and in distant non-ischemic brain regions. MR imaging with the BBB tracer GdDTPA showed more pronounced and widespread contrast enhancement in the rt-PA treated than in the untreated group. Increased blood-brain barrier disturbances have to be taken into account even when thrombolytic therapy is started very early after the onset of stroke.
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PMID:Blood-brain barrier disturbances after rt-PA treatment of thromboembolic stroke in the rat. 941 23

Surgical interventions for hypertensive intracerebral hematomas are still controversial. Many believe only hyperacute intervention is of any real utility. The majority of present interventions require a formal craniotomy with standard neurosurgical techniques. There are, however, a few reports on CT-guided stereotactic aspiration of these hematomas with favorable results. We report 10 patients treated with frameless fiduciless stereotactic means using an intraoperative MRI scanner (GE 0.5 T Signa SP). These patients were initially diagnosed as having hypertensive intracerebral hematoma and operated on within 1-34 days after hemorrhage. The actual operating time averaged less than 120 min, including intraoperative imaging. Clot volumes ranged from 2.5 to 75 cm(3) with a mean of 31 cm(3). There were 2 thalamic hematomas and 8 basal gangliar hematomas. Three patients had intraventricular hematoma extension and all 3, as well as an additional patient, required extraventricular drainage. However, no patients required permanent posthemorrhage ventriculoperitoneal shunting. Aspiration was successful in all cases to 70-90% of clot removal. Two cases utilized intrahematoma t-PA infusion with subsequent 80-90% clot removal. There were no complications or rehemorrhages. All patients showed some form of improvement that included either improved blood pressure control, speech or cognitive abilities. We conclude that using an intraoperative MRI scanner to perform frameless, fiduciless stereotactic aspiration of acute/subacute intracerebral hematoma is a safe and potentially effective means of treating intracerebral hematomas.
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PMID:Interventional MRI-guided stereotactic aspiration of acute/subacute intracerebral hematomas. 1085 64

This is the first Hungarian paper on the platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients. There are conflicting data about the role of this polymorphism in the pathogenesis of arterial thrombosis. The aim of our study was to describe the prevalence of PLA1/PLA2 in healthy persons and in stroke patients. From the same study population other polymorphism (prothrombin gene 20210 G/A) also has been determined. Blood sample was investigated by polymerase chain reaction in 173 unrelated healthy donors and 234 stroke patients. Stroke was documented by CT and MRI. We used a rutin questionnaire to study previous vascular events and conventional risk factors of patients. Prevalence of PLA1/PLA2 was 23.5% among healthy persons. That is higher than in other European countries (15%). It was 30.4% in stroke patients (OR: 1.42, 95%; CI: 0.87-2.31; p = 0.15). Heterozigous PLA was found in patients older than 50 by 33.6% (OR: 1.65, 95%; CI: 0.94-2.87; p = 0.09). Previous vascular events and conventional risk profil were not significantly different between PLA1/PLA1 and PLA1/PLA2 groups of patients. In patients under 50 having 20-85% stenosis of internal carotid artery there was a higher prevalence (p = 0.09). Comparing stroke patients to control population there was a slight increase (OR: 7.0; p = 0.06) in the frequency of two polymorphisms (PLA and factor II) together in the stroke cases. Polymorphism of GP IIb/IIIa LeuPro 33 seemed to be increased in stroke patients above 50 years. Carotid stenosis with polymorphism is a risk factor for young patients. PLA variant together with prothrombin gene polymorphism results very high risk for stroke.
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PMID:[Platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients]. 1136 63

Early intravenous thrombolysis within the first three hours has been considered in the United States as the first proven treatment in acute ischemic stroke. However, not all patients will respond to this therapy which is also associated with a risk of symptomatic, including fatal, intracranial hemorrhage. This overview addresses the issue of efficacy and safety of intravenous alteplase (tPA) in acute cerebral ischemia. The rationale for thrombolytic therapy and its limits are described. The controlled studies show that intravenous tPA is effective and safe when given under restrictive conditions within 3 hours after stroke onset, but the data for a larger therapeutic window between 3 and 6 hours remain controversial. The expected functional improvement and the risk of intracranial hemorrhage greatly depend on selective clinical and imaging criteria. For this purpose, MRI, using the diffusion- and perfusion-weighted sequences combined with MR- angiography, should be preferred to CT scan in the next future. Applicability of tPA thrombolysis in current neurological practice in Belgium is discussed. Before its generalization, this therapy should be restricted to specialized stroke centers and all treated patients should be recorded in a central data bank to guarantee continued surveillance.
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PMID:Intravenous rtPA thrombolysis in acute ischemic stroke. 1148 63

Clinical studies on rt-PA (recombinant tissue-type plasminogen activator) treatment of stroke showed a favorable outcome. However, there are reports of harmful effects of t-PA via the potentiation of excitotoxic injury. We used combined X-ray angiography and MRI imaging to study the balance between the beneficial effect of reperfusion and secondary detrimental effects of rt-PA. Therefore, rats (n=15) were assigned to three groups according to recanalization or lack thereof of the middle cerebral artery (MCA) and rt-PA or saline treatment in an embolic stroke model. Diffusion and perfusion MRI showed that animals had significantly improved perfusion values and final infarct size when recanalization was successful. However, final infarct volumes at 6 h post stroke onset were greater in the rt-PA group compared to controls at comparable perfusion values when the MCA did not recanalize after treatment (67.4+/-5.4 versus 47.7+/-17.9% of ipsilateral hemisphere, P=0.042). Our results demonstrate that the combination of angiography and MR-imaging is useful to further evaluate rt-PA treatment of thromboembolic stroke.
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PMID:Combined X-ray angiography and diffusion-perfusion MRI for studying stroke evolution after rt-PA treatment in rats. 1238 44

Systemic thrombolysis with rt-PA within 3 hours after symptom onset has developed into a standard therapy for acute stroke patients. Recombinant t-PA is now licensed in Europe for this indication. Within 3 to 6 hours, no general therapeutic standard has been established yet. Currently, the available data are in favor of intra-arterial thrombolysis for patients with proximal occlusions of the middle cerebral artery. Systemic thrombolysis is not generally recommended in this time window, but is used in some centers for selected patients. In addition to thrombolysis and new strategies to improve thrombolysis (including patient selection with MRI), several interventional and surgical recanalization techniques are discussed.
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PMID:[Recanalizing therapies in acute stroke]. 1273 98

Intravenous t-PA is effective if given to appropriate patients within 3 hours of stroke onset, and its effectiveness increases even within the first 3 hours when given as soon as possible. t-PA is reasonably safe if used in a carefully defined manner that ensures close attention to blood pressure, careful patient monitoring, no use of heparin and aspirin during first 24 hours, and appropriate patient selection. It is still unclear whether a lower dose of t-PA given with 3 hours could be as effective as but safer than the currently approved intravenous dose of 0.9 mg/kg over 1 hour. The effectiveness and safety of intravenous t-PA when given beyond 3 hours after stroke onset has yet to be conclusively demonstrated. One attractive development is the potential use of imaging, such as diffusion/perfusion MRI to determine if salvageable brain remains and if t-PA should be given in patients who are beyond the 3-hour time window. The drawback to MRI is the additional time required before the start of recanalization therapy.
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PMID:Intravenous thrombolysis for acute stroke. 1496 79

Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33 degrees C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8% +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset.
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PMID:Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke--an MRI study. 1547 93

We compared the rates of recanalization cerebral infarct and hemorrhage between intra-arterial (i.a.) reteplase and intravenous (i.v.) alteplase thrombolysis in a canine model of basilar artery thrombosis. Thrombosis was induced by injecting a clot in the basilar artery of 13 anesthetized dogs via superselective catheterization. The animals were randomized in a blinded fashion, 2 h after clot injection and verification of arterial occlusion, to receive i.v. alteplase 0.9 mg/kg over 60 min and i.a. placebo, or i.a. reteplase 0.09 units/kg over 20 min, equivalent to one-half the alteplase dose, and i.v. placebo. Recanalization was studied for 6 h after treatment with serial angiography; the images were later graded in a blinded fashion. Blinded interpretation of postmortem MRI was performed to assess the presence of brain infarcts and/or hemorrhage. At 3 h after initiation of treatment, partial or complete recanalization was observed in one of six dogs in the i.v. alteplase group and in five of seven in the i.a. reteplase group (P = 0.08). At 6 h, no significant difference in partial or complete recanalization was observed between the groups (two of six vs. five of seven; P = 0.20). Postmortem MRI revealed infarcts in four of six animals treated with i.v. alteplase and three of seven treated with i.a. reteplase (P = 0.4). Intracerebral hemorrhage was more common in the i.v. alteplase group (four of six vs. none of seven; P = 0.02). This study thus suggests that i.a. thrombolysis affords a recanalization rate similar to that of i.v. thrombolysis, but with a lower rate of intracerebral hemorrhage.
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PMID:Randomized comparison of intra-arterial and intravenous thrombolysis in a canine model of acute basilar artery thrombosis. 1558 Apr 91


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