Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
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In this article we report on the development, introduction, and maintenance of a policy to promote rational use of thrombolytic drugs by hospital doctors. The work was undertaken within the framework of the voluntarily operated Riverside East drugs guide (formulary) management system (FMS). The policy was introduced in October 1988 and revised in November 1989 to coincide with the launch of the new, expensive thrombolytic drugs, alteplase (rt-PA, Actilyse) in 1988 and antistreplase (APSAC, Eminase) in 1989. Streptokinase was recommended as the first-line drug for patients who had not received it within the last 6 months. The policy was communicated to all staff in meetings and a drugs guide bulletin and reinforced by ward pharmacists. Results over a 15 month period show voluntary compliance by prescribers with the recommended policy. One hundred and seventy-four patients (22% cardiac admissions) presented with acute myocardial infarction. Of these 43 (25%) received streptokinase, the first-line recommended drug, 7 received alteplase and none received anistreplase. The savings in drug expenditure from using streptokinase rather than alteplase or anistreplase for the 15-month period of investigation were over pounds 27,000. This work represents an example of the effectiveness of the Riverside East FMS model in influencing prescribing behaviour.
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PMID:Medical audit and formulary management: a policy for rational use of thrombolytic drugs. 190 56

During a three-year period 77 patients (43 men and 34 women, aged 21-82 years, mean age 62.0 years) were treated with mechanical ventilation in a medical intensive care unit. Three patients were treated twice. The most common diagnoses (in decreasing order of frequency) were acute exacerbation of chronic obstructive pulmonary disease, acute myocardial infarction, cerebrovascular trauma and chronic ischemic cardiac disease. The mean duration of ventilation was 6.4 days. 41 patients (51.3%) survived--80% of whom could be discharged to their home. Patients with chronic pulmonary disease showed the highest survival rate, those with cerebrovascular disease the lowest, with the cardiac patients in-between. It is calculated that it cost NOK 207,000 to treat each patient who survived.
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PMID:[Results of respiratory treatment in a medical intensive care department]. 199 77

We study 40 patients, 55 +/- 7 years old with acute myocardial infarction treated early by thrombolytic therapy (20 STK and 20 rt-PA). All patients were angiographically studied in the following conditions: 1) baseline, before initiating therapy. 2) Three hours after treatment. 3) Twenty four hours later. 4) Before discharge. The infarct related artery was patent 24 hours after treatment in 31 patients (78%); five of them were patent before treatment, and we observed an early reperfusion in 20 patients (57%) and late reperfusion in 6 patients (17%). The number of patients with angiographic evidence of intraluminal thrombus decreased progressively through conditions while the grade TIMI of coronary perfusion increased in the absence of reocclusion. Final regional wall motion of infarct related myocardial zones and their degree of recovery were significantly higher in recanalized patients, as compared with non-reperfused patients. Similarly, left ventricular functional recovery was higher in patients with antegrade of collateral flow to the infarct area, as compared with totally occluded patients.
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PMID:[Coronary permeability and left ventricular function following thrombolytic therapy]. 206 55

Thrombolytic agents administered intravenously have been shown to have a salutary effect in the early management of acute myocardial infarction. However, a debate still is pending over the definite choice of an ideal thrombolytic agent. In our 83-bed community hospital, from January 1986 to September 1988, we treated 19 patients (n = 19) with acute myocardial infarction (average one patient every six weeks) with either intravenous streptokinase (IV STK) or intravenous tissue plasminogen (IV TPA) with a mean follow-up of 20.2 months. We compared both groups in terms of clinical reperfusion, morbidity and mortality, cost-effectiveness and long-term functional disability. Our results showed that most patients received their respective agents within four hours of the onset of chest pain (81% in the STK group, n = 11, versus 75% of the tPA group, n = 8). In the STK group, 90.9% showed clinical evidence of reperfusion compared to 87.5% in the TPA one, the difference not being statistically significant. Two patients in the STK group developed a treatable bradycardia, and one showed a junctional rhythm that was corrected. One patient in the TPA subset encountered a reversible ventricular tachycardia. However, we didn't note any bleeding complication in either group.
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PMID:Thrombolytic therapy in acute coronary thrombosis. 211 80

Of the 4.1 million population of Norway about 7500 patients between 20 and 75 years of age are admitted each year to hospital for acute myocardial infarction. Of these 1100 die in hospital, and 6400 are candidates for secondary prevention. On the basis of survival curves, we present a model for calculating potential benefits of secondary prevention. We use 'years of life gained' as a measure of outcome of secondary prevention. We consider three economic elements in secondary prevention: (a) Use of health services. The drug costs are moderate. The indirect costs are unknown, but probably moderate. (b) Resumed productivity is small. (c) Pensions and other transfers will increase the public expense. The net effect is an increase in public expense. Beta blockers reduce mortality by 25% and can be given prophylactically to about one third of the patients. So far, the effect is uncertain after two years. Secondary prevention for two years will cost Norway about 3.8 million NOK (526 000 US +) per year for drugs, give 597 extra survivors and provide 0.24 additional life years per patient treated. In case of life-long treatment and effect, the result will be 1.6 years of life per patient treated. About 50% of Norwegian patients smoke. If all the men stopped, there will be no costs, about 5120 extra survivors, and 3.3 additional years of life per patient who quits smoking. The effect is not limited in time.
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PMID:What is the economic impact of secondary prevention to society? 287 79

Using a mobile X-ray unit in the coronary care unit (CCU), intracoronary streptokinase (IC STK) administration was performed in 20 patients with acute myocardial infarction who arrived 2 to 5 hours after onset of symptoms. IC STK was infused at a rate of 4000 U/min. Of 20 patients, 17 had complete and 3 subtotal occlusion of the infarct-related artery. The IC STK infusion resulted within 15 to 80 min in reperfusion in 12 of 17 patients with occluded artery (70%). One patient died, 4 patients underwent early bypass grafting, in one PTCA was attempted and in one a femoral A-V fistula caused by the procedure required surgical revision. IC STK infusion is much more economical if performed in the CCU and the 24-hour coverage can be provided by an experienced invasive cardiologist on call service.
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PMID:Bedside intracoronary thrombolysis in the coronary care unit. 358 35

Fifty-five patients with acute myocardial infarction evaluated within 4 hours of the onset of symptoms were entered into an angiographically controlled trial of intracoronary streptokinase (IC STK). Forty-three patients with total occlusion of their infarct artery were randomized to either IC STK or intracoronary nitroglycerin (IC NTG), and 12 patients with less-than-complete occlusion received only IC NTG. Reperfusion of a totally occluded vessel was achieved in 69% of STK patients and 17% of IC NTG patients. Time from onset of symptoms to peak CK activity was significantly shorter in reperfused patients and patients with subtotal occlusion on initial angiography than in patients with total occlusion who were not reperfused (p less than 0.0001). Comparison of radionuclide ejection fractions (EF) determined acutely and 10 to 14 days after infarction failed to show improvement in either the STK or IC NTG group (mean decrease of 2.8% and 0.4%, respectively). In contrast, patients with subtotal occlusion on baseline angiography demonstrated a significant (p = 0.05) spontaneous improvement in EF over 2 weeks (7.3% increase).
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PMID:A randomized, angiographically controlled trial of intracoronary streptokinase in acute myocardial infarction. 642 Nov 38

A consecutive series of 184 patients with acute myocardial infarction (AMI) received thrombolytic therapy. The first 63 were treated in the catheterization laboratory with intracoronary streptokinase (IC-STK), and 44 (70%) had successful thrombolysis. One hundred twenty-one patients received intravenous (IV) STK immediately after diagnosis of AMI, and 99 (82%) were found to have an open infarct artery. Only 58% of patients (14 of 24) who required transfer from out-of-town hospitals for IC-STK treatment had successful thrombolysis; in contrast, IV-STK given in the local hospital resulted in an 85% (72 of 85) rate of thrombolysis (p = 0.005). IV-STK thus appears at least as effective as IC-STK for AMI and is more effective for patients treated in hospitals without catheterization facilities.
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PMID:Intravenous versus intracoronary streptokinase therapy for acute myocardial infarction in community hospitals. 646

To determine the effects of acute myocardial infarction on the extent and distribution of mural stress on surviving myocardial tissue, coronary artery occlusion was surgically produced in rats. Following haemodynamic measurements in vivo, the characteristics of cardiac anatomy were determined and found to consist of an increase in mid-chamber lumenal diameter and a decrease in wall thickness. The combination of these phenomena resulted in an eight-fold increase in diastolic wall stress on the remaining viable portion of the wall and severe impairment of left and right ventricular performance. Since insulin-like growth factor-1 (IGF1) and its receptor (IGF1R) are required for cell growth in vitro, the possibility was raised that an autocrine IGF1-IGF1R system may be present in vivo and may become activated in viable ventricular myocytes shortly after infarction. Therefore, the unaffected myocytes of the left ventricle were enzymatically dissociated and the expression of IGF1R and IGF1 mRNAs were measured at 12 h and at 1, 2-3, and 7 days after surgery. The level of IGF1R mRNA increased at 12 h and remained elevated at 1 and 2-3 days following coronary artery ligation. In addition, an increased level of IGF1R protein was found on these cells. This phenomenon was coupled with the enhanced expression of IGF1 mRNA in the muscle cells at all points. Thus, the marked elevation in ventricular loading after coronary occlusion may activate the IGF1-IGF1R autocrine system of the unaffected cells, modulating the cellular growth processes implicated in short-term ventricular remodelling of the infarcted heart.
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PMID:Myocardial infarction and the myocyte IGF1 autocrine system. 868 60

Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.
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PMID:[Natriuretic peptide system]. 928 3


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