Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnetic resonance imaging was employed to study the dependence of clot lysing patterns on two different modes of transport of urokinase into whole blood clots. In one group of clots (nonperfused clots, n1 = 10), access of urokinase to the fibrin network was possible by diffusion only, whereas in the other group (perfused clots, n2 = 10) bulk flow of plasma containing urokinase was instituted through occlusive clots by a pressure difference of 3.7 kPa (37 cm H2O) across 3 cm long clots with a diameter of 4 mm. It was determined separately that this pressure difference resulted in a volume flow rate of 5.05 +/- 2.4 x 10(-2) ml/min through occlusive clots. Perfused clots diminished in size significantly in comparison to nonperfused ones already after 20 min (p less than 0.005). Linear regression analysis of two-dimensional clot sizes measured by MRI showed that the rate of lysis was more than 50-times faster in the perfused group in comparison to the nonperfused group. It was concluded that penetration of the thrombolytic agent into clots by perfusion is much more effective than by diffusion. Our results might have some implications for understanding the differences in lysis of arterial and venous thrombi.
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PMID:Dependence of blood clot lysis on the mode of transport of urokinase into the clot--a magnetic resonance imaging study in vitro. 187 17

Dural sinus thrombosis, a relatively rare disease, is difficult to diagnose because of variable symptomatic manifestations. We successfully treated a case of dural sinus thrombosis by direct thrombolysis using an endovascular technique in combination with postoperative anticoagulant therapy. The patient, a 19-year-old female, developed a headache affecting her whole head on December 13, 1993. She was admitted to our hospital the next day. Neurological examination upon admission revealed no neurological abnormalities, nor was there any abnormality in CT scan, either plain or enhanced, taken on the day of admission. The patient's consciousness deteriorated in the early morning of December 22. MRI and cerebral angiography revealed thrombi from the confluence of the sinuses to the right transverse and sigmoid sinus, with disturbed circulation through deep cerebral veins. Systemic thrombolytics, steroid and mannitol were started, but, on the next day, the third ventricle was compressed by bilateral swelling of the basal ganglia, with hydrocephalus. Since her consciousness deteriorated further despite ventricular drainage and barbiturate therapy, direct thrombolytic therapy was performed on December 25. A catheter was placed in the superior sagittal sinus, and 600,000 units of urokinase was locally injected, followed by postoperative anticoagulant therapy. The patient's condition improved rapidly. On CT scan, the bilateral swelling of the basal ganglia disappeared along with the hydrocephalus. At about 1 month after endovascular surgery, MRI and cerebral angiography revealed recanalization of the deep cerebral veins, straight sinus and confluence of sinuses with improved opacification of the left transverse sinus, although the right transverse sinus was found to be re-occluded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case report of dural sinus thrombosis: direct thrombolytic therapy using endovascular surgery]. 773 71

A 67-year-old patient was admitted to our hospital owing to coma and tetraplegia. MRI showed T2 weighed high intensity areas in the pontine tegmentum, lower aspect of the right cerebellar hemisphere, left half of medulla oblongata, and bilateral paramedian thalamus. He showed marked recovery by urokinase injection becoming able to walk in a few months, but severe amnesia and hypersomnia persisted even 5 months after onset. EEG showed diffuse alpha activity with occasional delta waves in frontal leads. Intelligence was considered normal (WAIS score; verbal IQ 97, performance IQ 102, total IQ 99), through performance on Wechsler memory Scale-R (Revised Japanese edition, WMS-R) and Benton Visual Retention Test indicated impairment of both verbal and visual memory. Verbal memory was impaired to a greater degree than visual memory (Scores of WMS-R: verbal memory index 60, visual memory index 98, index of general memory 72, attention index 95, index of delayed memory 71). He was able to finish only 0 and 1 categories on two trials of the Wisconsin Card Sorting Test. FDG (18F-fluorodeoxyglucose)-PET showed diffuse areas of decreased metabolism in bilateral thalami, frontal lobes, cingulate gyri and medial temporal lobes. The bilateral thalamic lesion seemed to affect the following structures, as judged from MRI: 1) The anterior thalamic peduncle including most of the reciprocal connections between dorsomedial nucleus of thalamus (MD nucleus) and the frontal lobe, 2) The inferior thalamic peduncle which serves as the reciprocal pathway between MD nucleus and medial temporal lobe, especially the amygdala (component of Yakovlev circuit), and 3) The inferior part of mammillothalamic tract (component of Papez circuit).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[FDG-PET in an amnestic and hypersomnic patient with bilateral paramedian thalamic infarction]. 829 74

Contrast-enhanced MRI in patients with MS shows that increased permeability of the blood-brain barrier (BBB) commonly occurs. The changes in capillary permeability often precede T2-weighted MRI evidence of tissue damage. In animal studies, intracerebral injection of the matrix metalloproteinase (MMP) 72-kDa type IV collagenase (gelatinase A) opens the BBB by disrupting the basal lamina around capillaries. Steroids affect production of endogenous MMPs and tissue inhibitors to metalloproteinases (TIMPs). To determine the role of MMP activity in BBB damage during acute exacerbations of MS, we measured MMPs in the CSF of patients with MS. Patients (n = 7) given steroids to treat an acute episode of MS had CSF sampled before and after 3 days of methylprednisolone (1 g/day). Patients had a graded neurologic examination and gadolinium-enhanced MRI before treatment. CSF studies included total protein, cell count, and a demyelinating profile. We measured levels of MMPs, urokinase-type plasminogen activator (uPA), and TIMPs by zymography, reverse zymography, and Western blots. The MMP, 92-kDa type IV collagenase (gelatinase B), fell from 216 +/- 70 before steroids to 54 +/- 26 relative lysis zone units (p < 0.046) after treatment. Similarly, uPA dropped from 3880 +/- 800 to 2655 +/- 353 (p < 0.03). Four patients with gadolinium enhancement on MRI had the most pronounced drop in gelatinase B and uPA. Western immunoblots showed an increase in a complex of gelatinase B and TIMPs after treatment, suggesting an increase in a TIMP (p < 0.05). Reverse zymography of CSF samples showed that steroids increased a TIMP with a molecular weight similar to that of mouse TIMP-3 (p = 0.053). Our results suggest that increased gelatinase B is associated with an open BBB on MRI. Steroids may improve capillary function by reducing activity of gelatinase B and uPA and increasing levels of TIMPs.
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PMID:Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. 864 61

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

Cases of bilateral cartoid occlusion have often been reported in the literature, but most of them were not examples of simultaneous bilateral carotid occlusion. Simultaneous bilateral cartoid occlusion appears to be rare, so we report one such case in this paper. A 68-year-old woman suddenly became unconscious, and was delivered to our hospital by ambulance. On arrival, she was comatose and showed decerebrate rigidity upon pain stimulation. Results of CT scan were normal, but cerebral angiography showed bilateral internal carotid artery occlusion at the carotid bifurcation. The patient was treated with urokinase and osmotic diuretics, but these were not effective and she died on the eleventh day after admission. Autopsy revealed that the bilateral internal carotid artery was occluded by fresh thrombi at the carotid bifurcation. The mitral valve was thickened by fibrous adhesion, and this was thought to indicate mitral stenosis. MRI before onset had shown flow void sign in the bilateral internal carotid artery. From the clinical course, and radiological and autopsy findings, we consider this case to be one of simultaneous bilateral carotid occlusion due to cardiogenic thrombi. Previous cases of bilateral carotid occlusion are reviewed and discussed.
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PMID:[A case of simultaneous bilateral carotid occlusion]. 905 32

A 43-year-old woman was suffered from an increasing headache with nausea and vomiting for nine days. She had received danazol 400 mg daily for endometriosis last two months. CT scan and neurological examinations revealed no evidence of abnormality. MRI showed isosignal intensity on T1-weighted images and high signal intensity on T2-weighted images in the superior sagittal, right transverse, sigmoid and straight sinuses suggesting thrombosis. With angiography, we confirmed extensive dural sinus thrombosis in the superior sagittal, straight, right transverse and sigmoid sinuses. She, then, developed progressing neurological deterioration with dysarthria and drowsy. Microcatheter was placed directly into the thrombus at dural sinus via transfemoral route. Thrombolytic therapy with urokinase was performed in right transverse, confluens sinuum, superior sagittal and straight sinuses. Successful recanalization with remarkable improvement of symptoms was achieved except right transverse sinus. We believe danazol played a role in the occurrence of dural sinus thrombosis. MRI and MRV were noninvasive and useful for diagnosis and follow-up of dural sinus thrombosis. Direct thrombolysis should be considered for dural sinus thrombosis, especially when clinical symptoms are rapidly deterioration with conventional anticoagulant therapy.
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PMID:[Successful direct thrombolysis in a patient with extensive dural sinus thrombosis induced by danazol]. 924 40

We report a case of successful thromobolytic therapy in a patient with cerebral embolism during angiography. A 57 year-old male lost his consciousness during angiography. His neurologic symptoms were semi-comatose and right oculomotor palsy. According to these symptoms, we estimated the lesion in the right midbrain. Immediately after we denied a cerebral hemorrhage by computed tomography, we infused 60,000 u of urokinase intravenously within an hour from the onset followed by diffusion weighted magnetic resonance imaging (DW-MRI). DW-MRI showed hyper-intense lesion in the midbrain. We sequentially performed thrombolytic therapy with urokinase by selective cerebral angiography within three hours from the onset. His symptoms gradually resolved, but his consciousness was still confused state. His all neurologic symptom completely resolved in the next day after hyperbaric oxygenation therapy.
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PMID:[A case of successful thromobolytic therapy in a patient with cerebral embolism during angiography]. 1059 9

In Japan, all of the stroke center hospital equipped by high level diagnostic systems including MRI. Number of MRI is twice as that of U.S.A. Therefore, we can perform correct and effective treatment for ultra-acute cerebral infarction if rt-PA is permitted to clinical use for cerebral infarction. We are making Japan Standard Stroke Registry Study (JSSR Study) now, and already registered 2,740 acute stroke cases in 25 hospitals. Atherothrombotic embolism (artery to artery embolism) was found in 16.5% of the all atherothrombotic infarction. It suggests that diagnostic accuracy of our database is high level. Concerning with ultra acute thrombolysis, about 10,000 stroke patients per year are estimated to be treatable with rt-PA in Japan. Yamaguchi's study for acute cerebral infarction showed intra-arterial thrombolytic therapy using urokinase was significantly effective. Our JSSR Study also showed effectiveness of thrombolytic therapy using rt-PA or high dose urokinase in the patients with cerebral infarction treated within 6 hours. Therapeutic time windows for acute cerebral infarction using rt-PA is expected to be more longer by the newly developed free radical scavenger (edarabin). We must create evidence based medicine for Japanese stroke patients based on database system (JSSR).
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PMID:[Brain attack in Japan, now and future]. 1223 92

Two consecutive cases of children with vertebrobasilar thrombosis (VBT) were treated with high-dose intra-arterial urokinase within 4 h of presenting to the emergency room, after full evaluation by CT scan, MRI and MR angiography. Complete resolution of neurologic symptoms was achieved in both cases. Based on our limited pediatric experience, previous treatment of VBT at our institution and a review of the relevant literature, the authors suggest that VBT be specifically ruled out at initial diagnosis, and if present, full consideration be given to immediate treatment with intra-arterial thrombolytic therapy. This may lead to a significant reduction in the morbidity and mortality associated with VBT in children. A large prospective multi-institution study is needed to further evaluate the efficacy of this approach to childhood stroke.
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PMID:Vertebrobasilar thrombosis in children: report of two cases and recommendations for treatment. 1247 22


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