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

In occluded hemodialysis catheters, thrombolytic agents are used to dissolve fibrin clots, reestablish blood flow and allow the patient to continue with hemodialysis treatment. Prior to 2001, urokinase was the indicated fibrinolytic for hemodialysis catheter thrombolysis. However, when urokinase became unavailable in the United States, New Hanover Regional Medical Center developed and implemented a protocol for the use of another fibrinolytic, reteplase, to lyse catheter occlusions. The purpose of this retrospective analysis was to assess the safety and efficacy of reteplase in opening occluded catheters in a series of patients receiving hemodialysis. Between January 1 and June 30, 2002, 59 patients could not complete dialysis, because of either poor arterial blood flow or elevated venous resistance. Reteplase, 0.4 U, was administered to the lumen of occluded catheters. After 30 min dwell times, the lumens were aspirated. If flow could not be sufficiently reestablished, a second reteplase dose was administered. Efficacy endpoints were defined as the ability to complete hemodialysis and achieve flow rates of > or =250 ml/min. Safety endpoints were defined as the occurrence of allergic reactions or bleeding. Eighty-five percent (50/59) of the patients were able to complete their hemodialysis session following reteplase administration, with 70% (41/59) able to sustain blood flow rates of > or =250 ml/min. Of the 50 patients who successfully completed dialysis, 66% (33/50) required only one 0.4-unit dose of reteplase per lumen while 34% (17/50) required a second dose. No instances of bleeding or allergic reactions were noted.
 ...
PMID:The efficacy and safety of reteplase for thrombolysis of hemodialysis catheters at a community and academic regional medical center. 1498 96

A well-recognized complication of the anatomic correction (arterial switch operation) of transposition of the great arteries is obstruction of the translocated coronary arteries. Myocardial reperfusion has previously been achieved by surgical revascularization or percutaneous balloon angioplasty. We report the case of a 3-month-old infant who suffered myocardial infarction 11 weeks after the arterial switch operation, in whom myocardial reperfusion was established following infusion of recombinant tissue-type plasminogen activator (Alteplase).
 ...
PMID:Recombinant t-PA in myocardial ischemia after switch operation. 1505 63

(1) Alteplase is the first thrombolytic drug to be approved in France for the treatment of ischaemic stroke within three hours of symptom onset. (2) The clinical evaluation dossier contains nine placebo-controlled trials, of which six were relatively large. In the two NINDS trials (624 patients in total), treatment was started within the first three hours and it showed no survival benefit. Near-complete functional recovery was more frequent in the alteplase group than in the placebo group. In the two ECASS trials (620 and 800 patients) and the ATLANTIS trials (142 patients and 613 patients), treatment was started within the first six hours and it showed no significant benefit in terms of survival or functional recovery. (3) There are two meta-analyses of these trials. They confirm the lack of a survival benefit with alteplase. Using a combined endpoint, one meta-analysis showed that treating 1000 patients with alteplase prevented death or major disability (dependency) in 55 patients. The other meta-analysis underlined the importance of a short interval between the onset of symptoms and the beginning of treatment. (4) Intracranial haemorrhage is the most important adverse effect. One meta-analysis showed that alteplase caused 62 additional symptomatic intracranial haemorrhages (including 25 deaths) per 1000 treated patients. (5) Various retrospective subgroup analyses have tentatively identified subgroups of patients at a particularly high risk of adverse effects, but subgroup analyses provide only weak evidence. The patients most likely to benefit from alteplase, started within three hours of symptom onset, remain to be defined. (6) The current health infrastructure in France would allow only a small number of stroke patients to be treated with alteplase under the kind of conditions prevailing in clinical trials (imaging to confirm ischaemic stroke, and treatment very soon after the onset of symptoms). (7) In practice, there is a narrow margin between the wanted and unwanted effects of alteplase. This treatment should be used only by specialised teams and for strictly selected patients. Research must continue, particularly to identify those patients most likely to benefit from alteplase, and those most likely to be harmed in whom thrombolysis is contraindicated.
 ...
PMID:Alteplase: new indication. Inadequately assessed in ischaemic stroke. 1553 35

Even with the benefit of cardiopulmonary resuscitation, the prognosis of cardiac arrest remains poor. Multiple case series describe survival with the use of thrombolytic therapy for refractory cardiac arrest. Presumably thrombolysis treats that subset of cardiac arrest cases resulting from fulminant pulmonary embolism, or perhaps massive myocardial infarctions. Published reports to date have dealt exclusively with streptokinase, urokinase, reteplase, or recombinant tissue plasminogen activator. The authors report the first case of return of spontaneous circulation with the administration of tenecteplase. Tenecteplase is a recently developed reengineered isomer of tissue plasminogen activator that possesses many properties of the ideal cardiac arrest thrombolytic agent. It is bolus dosed, stable at room temperature before reconstitution, and is compatible with most other advanced cardiac life support medications. Because of clinical equivalency and its logistical advantages, tenecteplase should be evaluated as an alternative to other thrombolytics in future trials involving cardiac arrest.
 ...
PMID:Tenecteplase and return of spontaneous circulation after refractory cardiopulmonary arrest. 1555 35

Clinical studies have investigated the combination of glycoprotein (GP) IIb/IIIa inhibitors and thrombolytic agents for acute myocardial infarction. However, thrombolytic agents alone may possess direct antiplatelet properties that could affect reperfusion. Blood from 11 patients with coronary disease and five healthy subjects was incubated for 30 min with tenecteplase (4, 12, and 24 microg/ml), alteplase (1, 4, and 10 microg/ml), reteplase (1, 5, and 10 microg/ml) or control buffer. Platelet aggregation induced by 1, 20 and 50 micromol/l adenosine diphosphate (ADP), the stimulated expression of GP IIb/IIIa and P-selectin, and plasma fibrinogen levels were determined. Platelet aggregation in patients was inhibited by medium and high concentrations of alteplase when induced by 1 micromol/l ADP [1.6 +/- 0.5%, P = 0.001 and 0.9 +/- 0.2%, P = 0.002 versus 8.3 +/- 1.6% (control)] and 20 micromol/l ADP [46.9 +/- 3.9%, P = 0.001 and 46.2 +/- 4.8%, P = 0.001 versus 65.7 +/- 2.7% (control)]. High concentration tenecteplase was associated with lower aggregation by 20 micromol/l ADP (58 +/- 2.1% versus control, P = 0.033). There were no changes in GP IIb/IIIa activation or P-selectin expression in patients or healthy subjects. Platelet aggregation (1 micromol/l ADP) in healthy subjects was inhibited only by high doses of alteplase (P = 0.001). Plasma fibrinogen levels were significantly decreased after treatment with reteplase at 1 microg/ml(1.53 +/- 0.21 versus 2.65 +/- 0.31, P = .009) and 5 microg/ml(1.55 +/- 0.16 versus 2.65 +/- 0.31, P = .005). Alteplase inhibits platelet aggregation more than tenecteplase and reteplase. The attenuation of platelet aggregation by alteplase is dissociated from the expression of activated GP IIb/IIIa and P-selectin, and by fibrinogen degradation. These results suggest that alteplase exerts its antiplatelet effect independent of GP IIb/IIIa and P-selectin expressions and fibrinogen degradation. These findings may be directly relevant to the effect of alteplase on reperfusion and to future studies using combined platelet inhibitors and thrombolytic therapy.
 ...
PMID:The platelet-related effects of tenecteplase versus alteplase versus reteplase. 1565 May 39

Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after hematopoietic stem cell transplantation (HSCT), ranging from a mild reversible disease to a fulminant course with a mortality rate close to 100%. We retrospectively evaluated the clinical signs, diagnosis, prognosis, therapy, and outcome of 13 hepatic VOD cases which developed after HSCT. A total of 193 consecutive patients (age: 15-62 years; median 33 years) with various hematologic diseases underwent 197 HSCT (allogeneic HSCT, n = 128; autologous HSCT, n = 69). In general, the conditioning regimen consisted of cyclophosphamide combined either with total body irradiation or busulfan. Since 2000, to reduce hepatic complications, all patients received ursodexycolic acid and discontinuation of norethisterone which inhibits ovulation. VOD diagnosed clinically was mainly managed in supportive fashion. Five patients received thrombolytic therapy (t-plasminogen activator [t-PA], n = 3; defibrotide [DF], n = 2). VOD developed in 13 of 197 cases (6.6%). All except one were in the allogeneic group who had received a busulfan-containing conditioning regimen; Ten (77%) were severe. Thirty-three of 197 (17%) cases died before day 100 with VOD as the cause in eight (24%). All of the t-PA administered patients died with significant hemorrhagic complications. DF patients improved completely, even after renal and respiratory failure, despite high total bilirubin levels. Only one patient who received DF became a long-term survivor; the other died with sepsis during the following days. The dramatic improvement with regard to VOD during DF therapy was encouraging.
 ...
PMID:Time-related changes in the incidence, severity, and clinical outcome of hepatic veno-occlusive disease in hematopoietic stem cell transplantation patients during the past 10 years. 1596

Alteplase (recombinant human tissue type plasminogen activator, rt-PA) was identified as a naturally occurring plasminogen activator in 1975, cloned from a human melanoma cell line in 1981, introduced into clinical trials in 1982, and received a product licence for the treatment of acute myocardial infarction in 1986. The present review will concentrate on assessing its current status as a clinically effective thrombolytic agent, but will touch briefly on its biochemical, physiological and pharmacological properties. Since alteplase is an approved pharmaceutical name, the term tPA will be used to refer to the naturally occurring substance in its physiological context.
 ...
PMID:Alteplase. 1598 66

Reteplase (r-PA) is a genetically engineered deletion mutant of wild-type tissue-type plasminogen activator. The structural differences lead to different functional properties, such as a prolonged half-life. The compound demonstrated good thrombolytic efficacy in in vitro as well as in animal studies. In angiographically controlled patency studies (GRECO, GRECO-2 RAPID-1, RAPID-2), the double-bolus application scheme was established, and a superior patency profile for reteplase in comparison to alteplase was demonstrated. Mortality studies established reteplase as a safe drug with a 30-day mortality at least equivalent to streptokinase (INJECT) and very similar to alteplase (GUSTO-3). A possible advantage may be the double-bolus application without a need for weight adjustment, especially in a prehospital setting. Thus, reteplase can be regarded as an excellent alternative to streptokinase or alteplase for thrombolytic therapy in acute myocardial infarction.
 ...
PMID:Reteplase (r-PA): a new plasminogen activator. 1598 67

A pilot study was carried out to prospectively evaluate the efficacy and safety of Tenecteplase (TNKase) using a modified 'lyse and wait" technique with percutaneous transluminal angioplasty (PTA) to treat thrombosed hemodialysis arteriovenous grafts (AVG)s. Seven patients with eight hemodialysis AVGs were treated and followed up to 1 year. Dosing included 1 mg TNKase and 3,000-4,000 U of heparin. Technical and clinical success rates were 100% and 88%, respectively. No major complications occurred. Primary patency rates at 30, 90, and 180 days were 62%, 50%, and 33%, respectively. TNKase, used in this fashion, may be comparable to alteplase and reteplase for safe and effective thrombolysis of PTFE dialysis grafts.
 ...
PMID:Tenecteplase in the treatment of thrombosed hemodialysis grafts. 1600 Nov 42

Recent guidelines recommend bolus-dose alteplase for treating massive pulmonary embolism (PE). However, the safest and most effective treatment is as yet unknown. In the present study, a meta-analysis of published studies of alteplase infusion, bolus-dose alteplase and streptokinase was performed. The outcome measures were as follows: objective assessment of thrombolysis; all-cause mortality; deaths due to initial PE, major bleeding episodes and recurrent PE; and morbidity. In total, 26 studies were identified; however, only two comparative studies of alteplase infusion versus either bolus-dose alteplase or streptokinase were found. Meta-analysis revealed no significant difference between the three regimens, but was compromised by a paucity of data. Crude analysis of summated data on thrombolytic efficacy from all studies revealed that alteplase infusion was more effective than bolus-dose alteplase (relative risk (RR): 1.95; 95% confidence interval (CI): 1.19-3.2), whereas streptokinase was more effective than alteplase infusion (RR: 1.27; 95% CI: 1.09-1.47). Alteplase infusion had a lower mortality due to the initial PE than both bolus-dose alteplase and streptokinase (RR: 0.16; 95% CI: 0.05-0.59 and RR: 0.13; 95% CI: 0.04-0.46, respectively). In conclusion, this evidence suggests that the three thrombolytic agents may vary in efficacy. However, large-scale randomised controlled trials are needed to confirm these results.
 ...
PMID:Efficacy of thrombolytic agents in the treatment of pulmonary embolism. 1626 48


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>