Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urokinase (average 1670 IU/kg X h) and heparin (average 17 IU/kg X h) was infused over several days into the main pulmonary artery of 12 patients with acute massive pulmonary embolism, after diagnostic pulmonary angiography. Pulmonary artery pressures and blood clotting values were serially recorded. There was convincing improvement in the clinical condition of all patients: none died or had a recurrence of embolism. The heart rate and pulmonary vascular obstruction decreased, mean pulmonary artery pressure fell and arterial pO2 rose. There were other, also statistically significant, changes in a decrease of fibrinogen, rise in thrombin time and decrease in haemoglobin concentration. Pulmonary artery pressure after 24 hours had fallen slightly, after 5.8 days significantly. In two patients a haemoglobin fall of more than 3 g/dl required blood transfusion. The findings indicate that after massive pulmonary embolism local continuous infusion of urokinase can, after 5-6 days, normalize pulmonary haemodynamics; the pulmonary angiogram shows almost complete disappearance of the pulmonary vascular obstruction.
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PMID:[Local thrombolysis with urokinase in acute massive pulmonary embolism]. 669 63

Urokinase and streptokinase are the two fibrinolytics approved for clinical use. Streptokinase has the broader application, being used to treat deep vein thrombosis (DVT), pulmonary embolism (PE), arterial thromboembolism, and occluded arteriovenous shunts in renal dialysis. Bleeding, the most significant complication of fibrinolytic therapy, arises mostly from invaded sites and can be significantly reduced by minimizing venipuncture and other invasive procedures.
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PMID:Fibrinolytic guidelines in diabetes. 706 Sep 47

The history and physical examination were assessed in 215 patients with acute pulmonary embolism uncomplicated by preexisting cardiac or pulmonary disease. The patients had been included in the Urokinase Pulmonary Embolism Trial or the Urokinase-Streptokinase Embolism Trial. Presenting syndromes were (1) circulatory collapse with shock (10 percent) or syncope (9 percent); (2) pulmonary infarction with hemoptysis (25 percent) or pleuritic pain and no hemoptysis (41 percent); (3) uncomplicated embolism characterized by dyspnea (12 percent) or nonpleuritic pain usually with tachypnea (3 percent) or deep venous thrombosis with tachypnea (0.5 percent). The most frequent symptoms were dyspnea (84 percent), pleuritic pain (74 percent), apprehension (63 percent) and cough (50 percent). Hemoptysis occurred in only 28 percent. Dyspnea, hemoptysis or pleuritic pain occurred separately or in combination in 94 percent. All three occurred in only 22 percent. The most frequent signs were tachypnea (respiration ate 20/min or more) (85 percent), tachycardia (heart rate 100 beats/min or more) (58 percent), accentuated pulmonary component of the second heart sound (57 percent) and rales (56 percent). Signs of deep venous thrombosis were present in only 41 percent and a pleural friction rub was present in only 18 percent. Either dyspnea or tachypnea occurred in 96 percent. Dyspnea, tachypnea or deep venous thrombosis occurred in 99 percent. As a group, the identified clinical manifestations, although nonspecific, are strongly suggestive of acute pulmonary embolism. Conversely, acute pulmonary embolism was rarely identified in the absence of dyspnea, tachypnea or deep venous thrombosis.
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PMID:History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease. 746 69

The AA. utilized temporary vena cava filters (16 Filcard and 8 Lysofilters) in 24 patients affected by deep venous thrombosis (DVT) of the lower limbs for the prevention of primary and recurrent pulmonary embolism (PE). The diagnosis of thromboembolic disease was always achieved by means of Ultrasounds (echo-color doppler) and was punctually confirmed by a retrograde cavagram during the insertion of the device. 19 patients presented large free-floating thrombi at inferior caval, iliac or common femoral vein level whereas 5 patients presented thrombi mostly of occlusive aspect. There was clinical or scintigraphic evidence of PE in 6 of the patients enrolled. 20 patients, without contraindications, were treated by fibrinolysis (F) with Urokinase (2-10 days) whereas 4 patients underwent surgical thrombectomy (T) because of short time relation with surgical intervention or trauma. All of them were protected by temporary vena cava filters and heparinized. All the filters were removed within 10 days. The results were considered "very good" (complete regression of floating thrombi) in 16 cases (14 F + 2 T), "good" (nearly complete regression of floating thrombi) in 3 cases (2 F + 1 T) and "poor" (unchanged) in the remaining 5 cases (4 F + 1 T). We didn't observe any new case or relapse of PE in the whole group and, furtherly, in 2 cases (1 F and 1 T) we demonstrated the capture of big emboli by the filter's basket. These clots were subsequently dissolved by fibrinolysis. To achieve the diagnosis of thromboembolic disease the following methods were used: 1--Screening: echo-color doppler of lower limbs extended to iliac and inferiora cava veins for detection of DVT and echocardio-color doppler for the detection of cardiac signs of PE. 2--DIAGNOSIS: pulmonary scintigram, retrograde cavogram and, rarely, angioCT scan. 3--FOLLOW-UP: echo-color doppler of lower limbs and pulmonary scintigram. The percutaneous insertion sites were the basilic vein (Filcard) and the right jugular vein (Lysofilter). Left jugular vein was used in 1 case with a big thyroid goitre. In the present experience we had no accidents during filters introduction or removal and no thrombosis at the insertion site (1 case of phlebitis of basilic vein). Indications and effectiveness: our results seem to be favorable to the use of inferior vena cava temporary filters for primary and recurrent pulmonary embolism prevention in the cases with floating thrombi both on fibrinolysis and embolectomy. In the cases of occlusive thrombotic diseases they proved to be effective to prevent PE during surgical embolectomy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Temporary caval filters. Our experience. Preliminary analysis of 24 cases]. 824 12

The 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.
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PMID:Comparative tolerability profiles of thrombolytic agents. A review. 847 Nov 85

Information is lacking on the mechanisms involved in the organization, resolution, and repair of the vascular lumen after acute pulmonary thromboembolism. Because recent data suggest that the balance between plasminogen activators (PAs) and type 1 plasminogen activator inhibitor (PAI-1) plays a role in regulating cell migration within the extracellular matrix, we investigated the expression of these molecules by immunohistochemical and in situ hybridization analysis of pulmonary artery specimens from patients suffering fatal pulmonary embolism. The data were compared with the expression of these molecules in both patients' noninvolved pulmonary arteries and organ donor pulmonary arteries. Regions of initial organization and vascular remodeling were identified by a modified trichrome stain and by the presence of proliferating cell nuclear antigen (PCNA), a cell marker of proliferation. Staining for tissue-type PA antigen was low to undetectable in endothelial cells directly in contact with the fibrin-platelet thromboembolus and in areas in which the endothelial cell lining was replaced by cell growth into the thrombus. Urokinase-like PA (u-PA) expression was detected in mononuclear cells within the thrombus in the initial phase of thromboembolism and within cells migrating into the thrombus during the later stages of organization. PAI-1 expression was elevated in the monolayer of endothelial cells underlying the fresh platelet-fibrin thromboembolus and in a PCNA-positive cell population present between the pulmonary arterial intima and the thromboembolus that represents early organization. Increased expression of PAI-1 may play a role in inhibiting proteolysis and fostering the localization of the acute fibrin-platelet thrombus to the vascular wall, which is followed by the upregulation of u-PA in migrating cells during the reorganization process.
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PMID:Elevated expression of urokinase-like plasminogen activator and plasminogen activator inhibitor type 1 during the vascular remodeling associated with pulmonary thromboembolism. 959 41

The clinical usefulness of catheter fragmentation and aspiration therapy was studied in 8 patients with acute pulmonary embolism who received thrombolytic therapy using urokinase or tissue-type plasminogen activator (t-PA) (thrombolysis group) and 8 patients who underwent catheter fragmentation and aspiration therapy using a percutaneous transluminal coronary angioplasty (PTCA) guide catheter (catheter group). The patients were selected from 20 patients with a definite diagnosis of acute pulmonary embolism based on pulmonary arteriography and nuclear imaging. Urokinase (48 x 10(4) to 96 x 10(4) unit/day) or t-PA (12 x 10(6) unit/day) was administered intravenously for mean 4 days in the thrombolysis group. Pulmonary artery pressure was first measured using a Swan-Ganz catheter via the jugular vein or the femoral vein in the catheter group. Then, a PTCA guide catheter was advanced into the pulmonary artery, and the thrombus was disrupted repeatedly using a Radifocus wire, followed by manual aspiration. Subsequent treatment consisted of intravenous infusion of heparin (10,000 to 15,000 unit/day) and urokinase (24 x 10(4) to 48 x 10(4) unit/day) for mean 6 days. Partial revascularization was achieved in all patients in both groups. Five patients in the thrombolysis group died within 1 month due to respiratory failure, re-embolization, and/or hemorrhagic complications. One patient in the catheter group died of hemorrhagic shock. Pulmonary artery systolic pressure in the catheter group was significantly reduced from 47.4 to 26.5 mmHg (p < 0.01). Catheter treatment of acute pulmonary embolism associated with acute circulatory failure such as shock can lead to rapid hemodynamic improvement. In contrast, thrombolysis is an effective treatment, but bleeding problems are common and caution is required. Catheter fragmentation and aspiration therapy is effective for acute pulmonary embolism, is minimally invasive, and should be considered the treatment of first choice.
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PMID:[Clinical outcome of catheter fragmentation and aspiration therapy in patients with acute pulmonary embolism]. 1046 88

Authors present an interventional radiological technique used for a successful treatment of 12 patients with massive pulmonary embolism. The method for rapid statement of diagnosis and the range of indications are discussed. In massive pulmonary embolism, after a diagnostic angiography, in 12 patient's mechanical thrombus drilling, in 3 cases thrombus aspiration, in 8 cases thrombus explosion and in other 1 balloon recanalisation was performed combined with a low dose (20,000-60,000 IU/h Streptokinase or the double dose of Urokinase) local fibrinolytic infusion. No major complication was observed and all the patients were successfully treated.
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PMID:[Local fibrinolytic treatment in subtotal pulmonary embolism]. 1048 75

To increase thrombolytic specificity of urokinase (uPA), we engineered a recombinant chimeric plasminogen activator SZ51Hu-scuPA, which consists of a humanized monoclonal antibody (SZ-51Hu) specifically against P-selectin on activated human platelet and a single-chain urokinase (scuPA). The cDNA, encoding scuPA amino acids 1-411, was inserted in 5' end to 3' end orientation immediately after the CH3 of SZ-51Hu heavy-chain sequence in the expression vector alphaLys30. The resulting construct alphaLys30-SZ51VH/Hu-scuPA was used to transfect into SP2/0 murine myeloma cell line, which was pretransfected with SZ51Hu light chain. The fusion protein SZ51Hu-scuPA was expressed at 5 mg/L in the supernatant of cell culture. The fusion protein purified by affinity chromatography had a molecular weight of 160 kDa with fibrinolytic activity of 39,000 IU/mg and its affinity to activated human platelet was 67% of the parent murine mAb SZ-51. The thrombolytic property of the fusion protein was first characterized in an in vitro system, which consists of a 125I-fibrin-labeled human plasma clot containing different concentrations of human platelets suspended in citrated human plasma. Fifty percent lysis was reached with SZ51Hu-scuPA in 1 hour at a concentration of 20 IU/mL or in 2 hours at a concentration of 10 IU/ mL, which was much faster than uPA at the same concentration. The maximal lysis of the clots by SZ51Hu-scuPA was 4.1 to 8.4 times more potent than that by uPA. The fusion protein was further characterized in the hamster pulmonary embolism model with clots prepared from fresh platelet-rich human plasma containing 125I-labeled fibrinogen. The thrombolytic activity of SZ51-scuPA was 3.9 times more potent than that of uPA at 2,000 IU/kg in this model. Almost no significant fibrinogen breakdown was observed either in vitro and in vivo.
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PMID:A recombinant antibody-targeted plasminogen activator with high affinity for activated platelets increases thrombolytic potency in vitro and in vivo. 1068 Jun 44

During thrombosis, P-selectin is expressed on the surface of activated endothelial cells and platelets. We hypothesized that targeting a plasminogen activator (PA) to P-selectin would enhance local thrombolysis and reduce bleeding risk. Previously, a urokinase (uPA)/anti-P-selectin antibody (HuSZ51) fusion protein was shown to increase fibrinolysis in a hamster pulmonary embolism model. To explore the therapeutic potential of this targeting strategy, we fused the fibrin-selective Desmodus rotundus salivary PA alpha1 (dsPA alpha 1) to HuSZ51 and compared the fibrinolytic activity of P-selectin-targeted dsPA alpha 1 (HuSZ51-dsPA alpha 1) to unmodified dsPA alpha 1 in vitro and in vivo. HuSZ51-dsPA alpha 1 and dsPA alpha 1 were expressed in CHO cells and purified to homogeneity by affinity chromatography. HuSZ51-dsPA alpha 1 bound to thrombin-activated human and dog platelets with comparable affinities to that of parental antibody SZ51. The fusion protein retained the catalytic activities of dsPA alpha 1 in chromogenic and clot lysis assays, indicating that dsPA alpha 1 is fully functional when fused to HuSZ51. Compared to dsPA alpha 1, HuSZ51-dsPA alpha 1 had similar thrombolytic efficacy in a rat pulmonary embolism model and anti-thrombotic potency in a dog model of femoral artery thrombosis. However, HuSZ51-dsPA alpha 1 was less effective in lysis of preexisting arterial thrombi in the dog model. The reduced arterial thrombolysis was not due to the pharmacokinetic properties of HuSZ51-dsPA alpha 1 because antigen level and amidolytic activity were higher in plasma from HuSZ51-dsPA alpha 1-treated groups than corresponding dsPA alpha 1-treated groups. These data indicate that the thrombolytic efficacy of HuSZ51-dsPA alpha 1 varied dependent on the physical composition of thrombi. The lack of stimulation by fibrin in arterial thrombi may contribute to the attenuated thrombolytic efficacy of HuSZ51-dsPA alpha 1 in the dog model.
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PMID:P-selectin-targeting of the fibrin selective thrombolytic Desmodus rotundus salivary plasminogen activator alpha1. 1554 21


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