Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In five patients with idiopathic osteonecrosis (ON) of the hip, four having hypofibrinolysis mediated by high plasminogen activator inhibitor (PAI-Fx), and one with high Lp(a), our specific aim was to determine whether therapy (Rx) with the anabolic-androgenic steroid, Stanozolol (6 mg/day), would normalize PAI-Fx and Lp(a) and thus potentially ameliorate ON. Prior to Rx, none of the four patients with high PAI-Fx could normally elevate tissue plasminogen activator (tPA-Fx) after 10 min venous occlusion at 100 mm Hg. After 12-18 weeks on Rx, PAI-Fx and stimulated tPA-Fx normalized in all four patients. Prior to Rx, mean (SD) stimulated tPA-Fx was low, 0.4 +/- 0.3 IU/ml (lower limit of normal 2.28 IU/ml). On Rx, stimulated tPA-Fx normalized, rising to 2.83 +/- 1.9 IU/ml, P = .004. Prior to Rx, mean (SD) basal PAI-Fx was high, 99 +/- 68 (upper limit of normal 26.9 U/ml), and fell on Rx to 22.5 +/- 22, P = .004. In two of the five patients normalization of hypofibrinolysis or high Lp(a) was accompanied by major symptomatic improvement. Prior to Rx, and 2 years after onset of unilateral hip pain, one of the four patients with high PAI-Fx and low stimulated tPA-Fx could walk only one block painfully. After 8 weeks on Stanozolol Rx, and continuing through 54 weeks on Rx, he walked 2 miles per day without pain, despite radiographic progression of ON. In three of the four patients with high PAI and with osteonecrosis present 0.3, 2, and 6 years prior to Stanozolol Rx, there was no clinical improvement after 14-156 weeks of Rx despite normalization of stimulated tPA-Fx and PAI-Fx. The fifth patient, 1 month after onset of disabling hip pain, had normal PAI-Fx but high Lp(a) (27 mg/dl), and MRI evidence of bone marrow edema ("transient osteoporosis").(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with Stanozolol. 771 67

CT- or MRI-guided stereotactic procedures should be a standard in a modern neurosurgical unit. Analysing 71 cases the indications and results of stereotactic neurosurgery are presented. In 53 patients stereotactic serial biopsies of different intraaxial lesions were performed, in 5 patients a spontaneous haemorrhage of the basal ganglia was removed by lysis with r-tPA. In 3 patients suffering from hydrocephalus due to diencephalic cysts a cystventricular shunt device was implanted. In 3 patients an intracerebral abscess was aspirated and drained. A stereotactic guided craniotomy and excision of small deep-seated lesions was performed in 6 cases. The accuracy of stereotactic tumour biopsies was 88.7% in our series, in accordance to other authors. The stereotactic aspiration and drainage of an intracerebral abscess provides accurate localization and minimal cortical damage and offers the possibility of intracavitary application of antibiotics. The stereotactic internal shunt implantation seems to be an alternative approach in the treatment of diencephalic cysts due to its minimal invasiveness and low operative risk. The aspiration of basal ganglia haematomas with insertion of an external drainage allows the lysis of the haematoma with r-tPA or urokinase. With stereotactic guidance small, deep-seated intraaxial lesions can be well localized and removed.
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PMID:[Value of stereotaxy in neurosurgery. Indications and analysis of results of 71 cases]. 880 10

Serial magnetic resonance (MR) imaging has not yet been validated in the therapy of experimental intracerebral hematomas in a rat model. It is possible to test the effect of local fibrinolysis and aspiration on the clot volume using serial magnetic resonance imaging and different MR-sequences. Experiments were carried out in 22 male Sprague-Dawley rats. Intracerebral hematoma was produced by injection of fresh autologous blood into the caudate nucleus using a double injection technique. Thirty minutes later 10 rats were treated by injecting 12 microliters of recombinant tissue plasminogen activator. MR-imaging was performed immediately after generation of the hematoma and after clot lysis. The clot volume measured in the magnetic resonance images was compared with that obtained in stained histological serial sections at the end of the experiment. Serial MR scanning demonstrated a significant reduction (p < 0.01) of hematoma volume after fibrinolysis followed by aspiration of the blood clot. The best correlation between MR- and histological volumetry was found on RF-spoiled FLASH 2D-images. This study documents the efficacy of MRI in detecting and delineating the size of acute intracerebral hematomas and its time course. Local fibrinolysis and aspiration can be simulated in an experimental rat model.
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PMID:Local fibrinolysis and aspiration of intracerebral hematomas in rats. An experimental study using MR monitoring. 961

Stroke in the human is most frequently caused by an intra-arterial clot. In order to investigate human stroke, appropriate and relevant animal models must be selected. Since the only approved treatment of stroke is that of recombinant tissue plasminogen activator (rtPA) the models selected should be amenable to thrombolytic treatment. We therefore describe a new model of embolic stroke in the rat in which a fibrin rich clot is placed via the internal carotid artery (ICA) at the origin of the middle cerebral artery (MCA). Data are summarized describing treatment of embolic stroke with rtPA administered at various times after stroke, the use of combination antiadhesion molecule and rtPA therapy, and the application of MRI to monitor the temporal evolution of physiological changes within ischemic tissue with and without rtPA intervention and to predict therapeutic efficacy.
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PMID:The clot thickens--thrombolysis and combination therapies. 1049 44

A cross-sectional observation was performed to assess the relationship between the coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population. Subjects were 445 workers (18.9-49.4, Av. 36.2 yrs) in viscose rayon manufacturing factories in Japan. Coagulation-fibrinolysis parameters determined were D-dimer(DD), thrombin antithrombin III complex (TAT), tissue plasminogen activator (TPA), and plasminogen activator inhibitor 1 (PAI1). The following indicators of arteriosclerosis were examined; systolic and diastolic blood pressure (SBP, DBP), stiffness parameter of the carotid artery using ultrasound (beta), pulse wave velocity of the aorta (PWV), and a number of lacunar infarctions from brain MRI. After age-stratification(-29, 30-39, 40+ yrs), the subjects were classified into quartiles by coagulation-fibrinolysis parameters. The mean values of SBP and DBP and beta and PWV, the prevalence of brain infarctions were compared across these quartiles by means of analysis of variance, chi-square test, respectively. Multivariate analysis was also employed to adjust other risk factors. In conclusion, SBP and DBP and beta, PWV were elevated by increase of PAI1, TAT, respectively, in the 40+ years group even after adjustment for other possible risk factors. DD had no relation to any of the indicators of arteriosclerosis. None of the coagulation-fibrinolysis parameters had any relation to brain infarctions.
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PMID:Relationship between the blood coagulation-fibrinolysis system and the subclinical indicators of arteriosclerosis in a healthy male population. 1069 59

Intravenous thrombolytic therapy using recombinant tissue plasminogen activator (rtpa) has been approved for the treatment of acute ischemic stroke in the USA, if treatment is initiated within 3-hours (NINDS tpa Stroke Study Group) but not 6 hours (ECASS II) after time of onset. Favorable outcome in the placebo arm was much higher than expected possibly because patients with TIA's are likely to be included as progressive ischemic stroke subjects when a brief 3-6 hours duration of stroke is defined as the therapeutic window. Yonas' group at the University of Pittsburg demonstrated that adding stable xenon inhalation to routine CT scanning performed during emergency screening of acute stroke, predicted which cases became irreversibly infarcted if thrombolytic therapy was not administered within a few hours of stroke onset, since non-contrasted CT scans are usually normal this early. Adding a few minutes for inhalation of 26% xenon is justified in order to measure LCBF values which predict size, severity and volumes of impending cerebral infarctions and rule out TIA's which have relatively normal CT-CBF values. CT-CBF measures provide positive indications for thrombolytic therapy. This is not possible by MRI and SPECT methods which are not sufficiently quantitative to discern LCBF values persistently below ischemic thresholds of 16 mls/100 gm/min, thereby predicting impending infarction.
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PMID:Why emergency XeCT-CBF should become routine in acute ischemic stroke before thrombolytic therapy. 1075 Mar 30

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

Treatment of patients with acute cerebral ischaemic events remains controversial. We investigated the reversibility of high signal intensity on diffusion-weighted (DW) MRI after acute local intra-arterial fibrinolysis (LIF) and the feasibility of DW MRI for selecting patients for acute LIF. Nine patients with acute middle cerebral artery embolic occlusion underwent single-photon emission computed tomography (SPECT) and DW MRI followed by acute LIF using tissue plasminogen activator. Recanalisation was observed in all patients, and eight improved clinically. The area of high signal intensity on pretreatment DW MRI was smaller than the low-uptake area on SPECT in all patients, and went on to infarction, as detected by MRI or CT 3 days after onset in all patients. It appears to correlate, at least clinically, with irreversible brain damage. Therefore, acute LIF should not be performed in patients with areas of high signal intensity in the cortex responsible for the symptoms. SPECT remains important, because areas normal on DW MRI with low uptake on SPECT often contribute to functional prognosis.
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PMID:Diffusion-weighted MRI and selection of patients for fibrinolytic therapy of acute cerebral ischaemia. 1087 62

A girl with Down's syndrome, moyamoya disease and sagittal sinus thrombosis is described. She was diagnosed after acute neurological deterioration by MRI and angiography. Recombinant tissue plasminogen activator (r-TPA) was injected locally to recanalise the thrombus. The patient's condition significantly improved and she was discharged. After 2 years of follow-up the child remains asymptomatic. Moyamoya syndrome and cerebral venous thrombosis should not be overlooked as a cause of acute neurological deterioration in a child with Down's syndrome. MRA appears to be a safe and accurate alternative to traditional angiography for the diagnosis of moyamoya disease. Local fibrinolysis with r-TPA is the treatment of choice for cerebral venous thrombosis due to its safety and efficacy.
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PMID:Moyamoya disease and sagittal sinus thrombosis in a child with Down's syndrome. 1121 82

A 56-year-old man without a previous history of stroke received intravenous recombinant tissue plasminogen activator (tPA) for an evolving myocardial infarction. During the infusion, the patient developed aphasia and right hemiparesis. The CT and MRI confirmed an ischemic stroke without evidence of hemorrhage. Although the cerebral hemorrhage after tPA infusion is relatively more common, in rare cases, tPA infusion may result in fragmentation of a cardiac thrombus resulting in an ischemic cerebral stroke.
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PMID:An ischemic stroke during intravenous recombinant tissue plasminogen activator infusion for evolving myocardial infarction. 1132 36


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