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)

To determine the ability of initial ST segment elevation and depression to predict infarct size limitation by thrombolytic therapy, data were analyzed in 721 patients with acute myocardial infarction who were admitted to a randomized, placebo-controlled study of intravenous recombinant tissue-type plasminogen activator. Patients with QRS duration of 120 msec or more or with previous history of myocardial infarction were excluded, leaving 322 in the treatment and 333 in the placebo group. Cumulative 72-hour release of alpha-hydroxybutyrate dehydrogenase and global ejection fraction as well as left ventricular wall motion derived from angiography were used as independent measures of infarct size. Electrocardiograms obtained at admission, 6 hours after start of therapy, and before discharge were analyzed. All ST measurements were made by hand at the J point and 60 msec after the J point. Patients with high ST segment elevation at admission (i.e., sum of ST elevation at 60 msec after the J point was 20 mm or more) had significantly larger infarction and higher hospital mortality when compared with those with lower (less than 20 mm) ST elevation. Reciprocal ST segment depression also showed a linear relation with infarct size and mortality, independent from ST elevation, both in anterior and inferior myocardial infarction. The sum of deviations measured at the J point and 60 msec after the J point differed significantly, especially in anterior myocardial infarction at admission (mean, 16 +/- 9 versus 23 +/- 11 mm). The prognostic value of one measurement was not, however, superior over the other. Treatment with recombinant tissue-type plasminogen activator was most effective in those with large ST deviations at admission, but patients with anterior infarction and smaller ST shifts also appeared to benefit from therapy. Results in individual patients were variable, and the overall correlation of initial ST shifts with enzymatic infarct size was rather low. In conclusion, the present study shows that the magnitude of initial ST elevation and also of reciprocal ST depression in the admission electrocardiogram is valuable for the management and assessment of thrombolytic therapy in patients with acute myocardial infarction.
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PMID:Significance of initial ST segment elevation and depression for the management of thrombolytic therapy in acute myocardial infarction. European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator. 211 63

In this study we report the effects of early thrombolytic therapy on the recovery of the right ventricle after an acute myocardial infarction. Sixty-five patients presenting with their first inferior myocardial infarction and predominant right ventricular involvement were consecutively treated as follows: group A (20 patients) conservatively (without thrombolytic therapy), group B (19 patients) with streptokinase and group C (26 patients) with recombinant tissue type plasminogen activator. Coronary angiography was performed within 72 h after admission in 52 patients (10 of group A, 18 of group B and in 24 patients of group C) followed by transluminal coronary angioplasty in 26. All groups had similar characteristics except for a higher mean age in group A. Within 3 months, a remarkable improvement in right ventricular function and a major increase in ejection fraction was observed for all three patient groups. Improvement of right ventricular function was more prominent in patients with residual flow through the infarct-related artery. The beneficial course was comparable in all the groups, unaffected by the type of medical treatment applied, or by the performance of coronary angioplasty. No further significant change occurred beyond this period. Thus, early thrombolytic therapy does not augment the generally favorable course of recovery of the right ventricle from acute infarction.
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PMID:Early thrombolytic therapy does not enhance the recovery of the right ventricle in patients with acute inferior myocardial infarction and predominant right ventricular involvement. 235 76

Forty-six patients with acute myocardial infarction (MI) were treated within three hours of the onset of chest pain with an intravenous bolus (IV) of 30 units of anisolated plasminogen activator streptokinase complex (APSAC). Reperfusion was detected in 31 patients (67%) by clinical, electrocardiographic, and enzymatic criteria. The mean time elapsed between the onset of the chest pain to thrombolytic therapy was 114 +/- 53 minutes. Left ventricular ejection fraction (LVEF) was significantly better in patients with anterior and inferior myocardial infarction who had successful reperfusion, as compared with those who did not (48.8 +/- 13.0 vs 35.3 +/- 10.9, p less than 0.05 and 59.7 +/- 12.6 vs 47.9 +/- 15.3, p less than 0.05, respectively). The rate of reocclusion within three weeks was 22%. The overall one-year mortality was 4%. There were no serious adverse reactions following the thrombolytic treatment. Thus bolus IV injection of 30 units of APSAC is both safe and effective in preserving left ventricular function when given early in the course of acute myocardial infarction.
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PMID:Improved left ventricular function in myocardial infarction following intravenous thrombolytic therapy with acylated plasminogen activator. 240 57

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. It usually occurs in relatively young patients and is frequently found at autopsy. Because of the low incidence, the treatment of choice for spontaneous coronary artery dissection is still not settled. Here the authors report a sixty-six-year-old woman with coronary lesions judged as spontaneous coronary artery dissection. She presented with chest pain. Under diagnosis of acute inferior myocardial infarction, she was treated with recombinant tissue-type plasminogen activator. Coronary arteriography performed two weeks later revealed a dissection involving a long segment of right coronary artery. The left coronary arteries and uninvolved portion of right coronary artery were smooth and patent. She suffered no hypertension and gave no definite history of trauma. This patient was treated medically with aspirin, isosorbide dinitrate, and metoprolol and remained in stable condition after a follow-up period of six months.
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PMID:Spontaneous coronary artery dissection in an elderly woman with acute inferior myocardial infarction. A case report. 766 90

We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.
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PMID:An autopsy case of intracranial hemorrhage during tissue plasminogen activator infusion. 840 27

Over a 2-year period 192 patients with acute myocardial infarction (AMI) were transported by helicopter and treated with recombinant tissue-plasminogen activator (tPA). All patients were entered into the Thrombolysis in Myocardial Infarction-Phase II (TIMI II) trial. Eighty-two of these patients were treated with tPA after aeromedical transport to a tertiary care center. One hundred ten patients had tPA treatment initiated by the flight crew prior to transport. The flight crews initiated therapy 28 +/- 11 minutes after arrival at the sending hospital. The post-flight treated patients received the tPA bolus 82 +/- 20 minutes after arrival at the sending hospital (P less than .0001), and 41 +/- 18 minutes after arrival at the receiving hospital (P less than .0001). Based on enzyme and electrocardiographic changes, all patients in the study had a confirmed diagnosis of AMI before discharge. Patients with inferior myocardial infarction (MI) treated with tPA in-flight were more likely to suffer from bradycardia and hypotension requiring atropine injection during transport than the post-flight treated patients or in-flight treated patients with anterior MI. There was no in-flight mortality in either group. Our experience indicates that patients with AMI can be transported safely during tPA therapy. Also, a trained team whose sole responsibility is the early evaluation and initiation of therapy in a patient with AMI can function as accurately and significantly more rapidly than tertiary care emergency department and ICU personnel following identical protocols.
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PMID:Early tPA treatment and aeromedical transport of patients with acute myocardial infarction. 1017 41

Spinal epidural hematoma is a rare complication of thrombolytic therapy (only 9 cases described in the literature). We report the case of a 59-year-old female with hypertension, admitted to the coronary care unit for acute inferior myocardial infarction and treated with tissue-type plasminogen activator 100 mg in 90 min, intravenous heparin 25,000 U, aspirin 100 mg, and metoprolol 50 mg orally once daily. On the third day she suffered from sudden and violent dorsal pain, followed 22 hours later by paraplegia. Magnetic resonance imaging showed a large posterior spinal epidural hematoma, with compression and anterior dislocation of the spinal cord. The patient underwent neurosurgery. After 1 year, she still cannot walk. In patients treated with thrombolytic therapy and presenting with sudden and violent spinal pain, the physician should take into consideration the diagnosis of epidural hemorrhage. Early neurosurgery can save the patient and facilitate neurological recovery.
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PMID:[ A rare complication of thrombolytic therapy: spinal epidural hematoma. A case report ]. 1465 65

A 51 year-old male was admitted to our institution with subacute inferior myocardial infarction. Coronary angiography showed thrombotic occlusion of the right coronary artery. Percutaneous coronary intervention including the delivery of 3 stents was unsuccessful (TIMI grade 0 flow). In addition to an ongoing systemic administration of tirofiban, a glycoprotein IIb/IIIa inhibitor, the patient received intracoronary thrombolysis (ICT) with alteplase (recombinant tissue type plasminogen activator, rt-PA). There was complete reperfusion on control angiography the following day (TIMI grade 3 flow); 7 months later, there was still TIMI grade 3 flow. To our knowledge, this is the first report on systemic administration of tirofiban combined with ICT.
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PMID:Successful recanalization of an occluded coronary artery by percutaneous coronary intervention, systemic administration of tirofiban, a glycoprotein IIb/IIIa inhibitor, and intracoronary thrombolysis with alteplase. 1516 Feb 77

In an effort to prevent metastasis of breast tumor cells- at the same time of inhibiting tumor growth with less toxic side effects, honokiol (HNK) was encapsulated into pH-sensitive polymeric micelles based on the conjugate of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (PEOz-PLA) with doxorubicin (DOX), denoted as PEOz-PLA-imi-DOX. PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of PEOz-PLA via acid-cleavable benzoic imine linker. HNK-loaded conjugate micelles (HNK/PP-DOX-PM) with a size of 21 nm and homogeneous spherical shape exhibited high drug-loading capacity. PEOz-PLA-imi-DOX and HNK/PP-DOX-PM displayed faster release of DOX at pH 5.0 than at pH 7.4. As anticipated, PEOz-PLA-imi-DOX maintained cytotoxicity of DOX against MDA-MB-231 cells. The synergistically enhanced in vitro antitumor effect of HNK/PP-DOX-PM was confirmed by their synergetic inhibition of MDA-MB-231 cell growth. Furthermore, the efficient prevention of tumor metastasis by HNK/PP-DOX-PM was testified by in vitro anti-invasion, wound healing and antimigration assessment in MDA-MB-231 cells, and in vivo bioluminescence imaging in nude mice. The suppression of growth and metastasis of tumor cells by HNK/PP-DOX-PM was attributed to the synergistic effect of pH-triggered drug release and HNK-aroused inhibition of matrix metalloproteinases and epithelial-mesenchymal transition, respectively. In addition, HNK/PP-DOX-PM exhibited superior biosafety than physically encapsulated dual-drug micelles. Consequently, the fabricated HNK/PP-DOX-PM may have great potential for safe and effective suppression of tumor growth and metastasis.
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PMID:Synergistically Enhanced Antimetastasis Effects by Honokiol-Loaded pH-Sensitive Polymer-Doxorubicin Conjugate Micelles. 2974 28

Combination therapy has been proved to be an effective strategy to inhibit metastasis, however, its efficacy is always compromised by the poor delivery efficiency of drugs. In this study, multi pH-sensitive polymer-drug conjugate mixed micelles were fabricated by the self-assembly of PEOz-PLA-ace-Cur, a conjugate of curcumin (Cur) with poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (PEOz-PLA) through the linkage of the pH-cleavable acetal bond, and PEOz-PLA-imi-DOX, a conjugate of doxorubicin (DOX) with PEOz-PLA through the linkage of the pH-cleavable benzoic imine bond. The mixed conjugate micelles (PP-Cur/PP-DOX-Mix-PMs) with accurately and conveniently controlled mass ratio of the two drugs were demonstrated to have a small particle size (40-128 nm), high drug loading capacity and pH-dependent drug release behavior. Notably, PP-Cur5/PP-DOX1-Mix-PMs exhibited slower DOX release under physiological conditions compared with PEOz-PLA-imi-DOX micelles, resulting in deeply reduced side effects in vivo. Furthermore, the mixed conjugate micelles showed synergistically enhanced inhibition of MDA-MB-231 cell growth and metastasis evidenced by the results of in vitro anti-invasion, wound healing and anti-migration assessment, and in vivo bioluminescence imaging in nude mice, and significant reduction of the side effects of DOX compared with dual drug physically loaded polymeric micelles. Mechanistic studies demonstrated that the possible inhibitory mechanism of PP-Cur5/PP-DOX1-Mix-PMs on tumor metastasis could be assigned to their inhibition of the invasion, migration, intravasation and extravasation of tumor cells. In conclusion, the multi pH-sensitive polymer-drug conjugate mixed micelles with synergistically enhanced anti-tumor and anti-metastasis activity are potential candidates for safe and effective cancer combination therapy.
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PMID:Multi pH-sensitive polymer-drug conjugate mixed micelles for efficient co-delivery of doxorubicin and curcumin to synergistically suppress tumor metastasis. 3281 57


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