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)

The worldwide increase in the expenses of the National Health Services compels the legislation of some countries to take economizing regulatory measures. In Germany the existent and planned activities are an essential part of the German Structural Health Act of 1993. In the last years methods have been developed to estimate the cost-benefit relationship of special therapeutic interventions giving the physician an aid to avoid the application of those of low cost-efficiency. The cost-effectiveness and the cost-utility analyses are the recently most usual ones. The timely thrombolysis of the acute myocardial infarction is presented under the viewpoint of the economical drug use in cardiovascular disease. Investigations to evaluate the cost-effectiveness of streptokinase and the newer thrombolytics anistreplase and alteplase are carried out in some European countries and in the USA. Parameters of efficacy are the amelioration of cardiac functions, the shortening of the rehospitalization duration, and the extension of the survival time. The use of a thrombolytic within 4 to 6 hours after the onset of the first signs is recommended and economically justified especially in anterior myocardial infarction and also in patients aged 75 years and above. Streptokinase is designated by a low cost-effectiveness ratio. The successful thrombolysis does not result in a continous deterioration of the quality of life in the patients. In this review no attempt was made to extrapolate the findings to the recent situation because of possible national pecularities with regard to the morbidity of and the therapeutic procedures in the acute myocardial infarction and because of the changes in the cost structure and currency parity which occurred in the meantime.
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PMID:Cost-benefit analysis--a prerequisite of a rational pharmacotherapy in cardiovascular diseases. Timely thrombolysis in the acute myocardial infarction. 883 2

Streptokinase(SK), a plasminogen activator, is known to have multi-domain structure. The function of the C-terminal region of streptokinase was investigated with SK mutants constructed by truncating 26, 33, 37, 40, 41, 46, 47, 70 or 97 amino acid residues from the C-terminus. The truncated SKs were expressed in E. coli and purified. The 41 residue deletion (SKP373) from the C-terminus had not effect on the plasminogen activation activity. However, the deletion of 46 amino acid residues (SKP368) resulted in the dramatic reduction of the plasminogen activation efficiency. The result suggests that the C-terminal peptide from Met369 to Pro373 of SK may play an important role on the plasminogen activation.
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PMID:C-terminal peptide of streptokinase, Met369-Pro373, is important in plasminogen activation. 895 83

Our purpose was to evaluate the outcomes of patients with prior coronary angioplasty who underwent thrombolysis for new acute myocardial infarction (AMI) in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial. Baseline characteristics and clinical outcomes were compared between patients with (n = 1,647) and without (n = 39,150) previous angioplasty. The relations among prior angioplasty, clinical outcomes, and treatment effects were examined with logistic regression modeling. Patients with previous angioplasty tended to be younger and presented sooner after symptom onset, but had more multivessel disease and lower ejection fractions. Unadjusted mortality was significantly lower in the prior-angioplasty group at 24 hours (1.8% vs 2.7%, p = 0.03) and 30 days (5.6% vs 7.0%, p = 0.036). Although most of the survival advantage was due to low-risk characteristics in this group (lower age and heart rate and fewer anterior wall AMIs), prior angioplasty remained a weak but independent predictor of survival. Recurrent ischemia and reinfarction occurred more often in the prior-angioplasty group, as did bypass surgery (12.2% vs 8.5%) and repeat angioplasty (34.5% vs 21.4%). Patients with prior angioplasty and prior AMI had lower 30-day mortality than those with prior infarction alone (6.3% vs 12.6%, p < 0.01). Treatment effects on 30-day mortality were similar among patients with prior angioplasty (odds ratio 1.2 for accelerated tissue-plasminogen activator v. combined streptokinase arms, 95% confidence interval 0.73 to 1.9). Patients with prior angioplasty who present with AMI have fewer in-hospital adverse events and lower 30-day mortality than those without such a history.
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PMID:Thrombolytic therapy for patients with prior percutaneous transluminal coronary angioplasty and subsequent acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries. 897 Apr 3

Streptokinase (SK) is a bacterial plasminogen activator of multi-domain structure. In deletion analysis of the N-terminal region of SK, the deletion of 20 amino acids (SK delta N20) resulted in the dramatic reduction of plasminogen activator activity compared to deletion of 7 (SK delta N7) and 13 amino acids (SK delta N13). The incubation time to reach maximal active site generation in an equimolar mixture of SK delta N20 and plasminogen was the same as that for wild-type SK. To identify the functional residues important in plasminogen activation, several site-directed mutations were introduced at the region spanning Ser16-Val20 of SK. The results showed that Val19 residue is important for the activity of the SK-plasminogen complex.
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PMID:Identification of the functional importance of valine-19 residue in streptokinase by N-terminal deletion and site-directed mutagenesis. 904 49

Utilization of angiography after acute myocardial infarction (AMI) treated with thrombolytics has been shown in large clinical trials to be related primarily to the availability of the procedure and not individual clinical circumstances. This study evaluated the regional influence of overall population cardiovascular mortality on utilization of angiography in the United States participants of the Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO-1) trial. Published summary statistics from GUSTO-1 and U.S. Census Bureau 1991 data were evaluated using simple and multiple linear regression with analysis for outliers. Region predictor variables (age adjusted) included mean total cardiovascular deaths/100,000/year (ICD/9 codes 390 to 459), mean coronary artery disease deaths/ 100,000/year (ICD/9 codes 410 to 414), and mean stroke deaths/100,000/year (ICD/9 codes 430 to 438), with the major outcome being regional proportion of GUSTO-1 patients undergoing angiography during the hospital stay after treatment with thrombolysis. All 3 cardiovascular death rates varied significantly by region (p < 0.00002) with no significant difference in GUSTO-1 mortality by region (p = 0.25). Simple linear regression analysis revealed associations between regional death rates and angiography use (r = 0.60, p = 0.12; r = 0.39, p = 0.33; r = 0.81, and p = 0.015). Multiple stepwise linear regression analysis found regional death rate due to stroke as the strongest predictor of angiography use with 65.86% of the variation explained by the model. New England was found to be a consistent outlier with reduced angiography use because of its background regional disease burden. This study confirms regional bias in the use of angiography in GUSTO-1. This form of operator bias appears to be due to more aggressive practice patterns in regions, except New England, where the overall cardiovascular disease burden is greater in terms of lives lost per 100,000 per year.
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PMID:Influence of regional cardiovascular mortality on the use of angiography after acute myocardial infarction. 906 11

The role of heparin in conjunction with thrombolytic therapy for the management of patients with acute myocardial infarction continues to be controversial. Many issues, including the possible benefits and risks of this therapy, are unresolved. Administration of high-dose subcutaneous heparin in the presence of thrombolytic therapy results in a significant mortality reduction during the treatment period of 55 lives saved per 10,000 patients treated (p < 0.01). At 35 days mortality is not significantly decreased by 22 lives and 18 nonfatal infarctions, at a cost of 32 transfusions and 6 strokes (half of which result in full recovery) per 10,000 patients treated. There have been fewer than 1250 patients randomized in trials comparing intravenous heparin with no heparin in patients receiving thrombolytic therapy and aspirin. These trials are too small to draw reliable conclusions, although several trials have suggested that intravenous heparin is beneficial for maintaining patency after t-PA therapy. In the the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial, patients receiving streptokinase were randomized to receive either delayed subcutaneous heparin or intravenous heparin. There were no differences in clinical endpoints. However, despite 36% crossover to intravenous heparin among patients randomized to receive subcutaneous heparin with streptokinase, patency of the infarct-related artery was 17% higher (84% vs. 72%, p < 0.05) at 5-7 days in patients randomized to receive intravenous heparin and streptokinase. This significant difference could potentially translate into an important effect on long-term prognosis. Therapy for acute myocardial infarction should include aspirin and a thrombolytic agent for patients without contraindications. Based on the current evidence, it is reasonable to also administer intravenous heparin with either streptokinase or TPA.
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PMID:Is heparin of value in the management of acute myocardial infarction? 914 Jun 86

We evaluated allergic reactions in 20,201 patients randomized to the streptokinase arms of The Global Utilization of Streptokinase and t-PA (Tissue Plasminogen Activator) in Occluded Coronary Arteries (GUSTO-I) trial, and tested the hypothesis that patients with streptokinase allergy would exhibit higher mortality. After adjusting for baseline variables and time of death, we found comparable coronary patency, left ventricular function, mortality, and bleeding complications between patients with versus those without streptokinase allergy.
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PMID:Incidence and impact on outcome of streptokinase allergy in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA in Occluded Coronary Arteries. 916 91

Approximately 80 to 90% of cerebral ischaemic events that occur within 24 hours of symptom onset are due to atherothrombotic or thromboembolic occlusions. This forms the rationale for the use of thrombolytic agents in patients with acute ischaemic stroke. Early studies determined that recanalisation occurred in approximately 21 to 72% of patients with occluded cerebral arteries after intra-arterial or intravenous administration of streptokinase, urokinase, alteplase (recombinant tissue-type plasminogen activator; rt-PA) or duteplase (a 2-chain rt-PA). Initial reports suggested that frequencies of haemorrhagic transformation and parenchymatous haematoma in the carotid territory were similar whether patients with middle cerebral artery stroke received thrombolysis via intra-arterial or intravenous administration. The Multicentre Acute Stroke Trial-Europe (MAST-E), the Australia Streptokinase (ASK), and the Multicentre Acute Stroke Trial-Italy (MAST-I) trials, which evaluated intravenous streptokinase 1.5 x 10(6) IU in patients with acute ischaemic stroke, were terminated prematurely because of excessive early mortality and symptomatic intracranial haemorrhage in streptokinase recipients compared with those treated with placebo. However, those studies had not been preceded by dose-ranging trials. Intravenous administration of alteplase 0.9 mg/kg within 3 hours [National Institute of Neurological Disorders and Stroke (NINDS) trial], or 1.1 mg/kg within 6 hours [European Cooperative Acute Stroke Study (ECASS)], of symptom onset in patients with acute ischaemic stroke resulted in an absolute 11 to 13% treatment-associated improvement in clinical measurement scales; such as the modified Rankin scale and Barthel index, compared with placebo recipients. In the ECASS trial, those results were limited to a 'target population' restricted to those who satisfied all entry criteria. In both trials, the frequency of symptomatic haemorrhage was greater in patients treated with alteplase than with placebo and reinforced the importance of careful patient selection. Strict patient selection remains central to the success of this approach.
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PMID:Thrombolytic therapy in the treatment of stroke. 936 Aug 56

The use of outcome markers other than mortality reduction alone for evaluating thrombolytic agents in patients with acute myocardial infarction (AMI) is discussed. Mortality has been a primary endpoint in clinical trials evaluating thrombolytic agents for treatment of AMI. However, differences in mortality rates among thrombolytics are 1% or less and require tens of thousands of patients to detect. Broadening the endpoints studied will allow for more extensive data collection and more comprehensive cost-effectiveness analysis, enabling clinicians to make better decisions. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial measured not only mortality but issues related to the patency of the infarct-related artery and complications. Other potentially important outcome markers after AMI are left ventricular function; markers of reperfusion, such as early resolution of ST-segment elevation; and resolution of chest pain. Available long-term data show that the mortality benefit from alteplase is sustained over time and is correlated with enzymatically determined infarct size, left ventricular function, the number of diseased vessels, and Thrombolysis in Myocardial Infarction flow grade at the time of discharge from the hospital. Clinicians must also consider risk factors for stroke. Outcome measures other than mortality alone may help in determining which thrombolytic agent is most effective clinically and in financial decision-making without requiring large, expensive trials.
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PMID:Clinical trials in thrombolytic therapy, Part 1: Outcome markers that go beyond mortality reduction. 939 34

The open-artery hypothesis as supported by thrombolytic study results is discussed. The open-artery hypothesis states that survival after acute myocardial infarction (AMI) is maximized by achieving early and sustained patency of the infarct-related artery. However, two large multicenter trials did not detect any difference in mortality between patients given alteplase and patients given streptokinase, despite previous evidence that alteplase led to earlier recanalization of infarct-related arteries. The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial suggested that early and complete patency is essential for short-term survival after AMI. Subsequent observations indicated that an open infarct-related artery at the time of hospital discharge is associated with improved long-term survival. In the Reteplase Angiographic Phase II International Dose-Finding (RAPID-1) trial, complete patency was more frequent in patients who received a double-bolus regimen of reteplase than in patients who received standard-dose alteplase. Similar results were obtained in the Reteplase versus Alteplase Patency Investigation during Myocardial Infarction (RAPID-2) trial, which compared the same double-bolus reteplase regimen with an accelerated regimen of alteplase. In both RAPID studies, mortality was lower and other outcomes were more favorable in reteplase recipients. Reteplase seems more likely to produce normal blood flow soon after AMI than either standard-dose or accelerated alteplase and may be associated with a lower mortality rate. This lends further support to the open-artery hypothesis.
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PMID:Clinical trials in thrombolytic therapy, Part 2: The open-artery hypothesis and RAPID-1 and RAPID-2. 939 35


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