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At least 775 records · Page 43Linked to original sources
PubMed1993

Intraoperative streptokinase: a useful adjunct to balloon-catheter embolectomy.

Intraoperative thrombolysis was attempted in 31 acutely ischaemic legs after operative arteriography had demonstrated residual distal thrombus or occlusion following balloon-catheter thromboembolectomy. There were 30 patients, 16 men and 14 women, aged 43-82 (median 73) years. The indication for operation was severe ischaemia with sensorimotor loss in 25 limbs, failed percutaneous thrombolysis in three and acute graft occlusion in three. A total of 21 perfemoral, 11 perpopliteal and four graft embolectomies were initially performed. Following arteriography, 100,000 units streptokinase was infused down the isolated distal arterial tree over 30 min and arteriography repeated. Complete lysis was achieved in 11 legs (35 per cent) and partial lysis in 12 (39 per cent). Additional procedures required included six operative angioplasties and six bypass grafts. After operation pedal pulses were restored in 14 limbs (45 per cent), with a viable leg in 23 cases (74 per cent) at the time of patient discharge or death. There were five wound haematomas but no evidence of systemic fibrinolysis. Four amputations were required, none in the group undergoing successful lysis, and there were seven deaths, five from cardiac disease. Arteriography after balloon-catheter embolectomy is essential to detect residual thromboembolus and intraoperative streptokinase appears to be a safe and effective way of removing this.

Adult↗
PubMed1979

Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase.

In five patients with acute myocardial infarction, the effects of both intracoronary nitroglycerin (NTG) and subsequent intracoronary streptokinase application were evaluated. In addition, transluminal recanalization was performed in one of these patients. Injection of NTG into the infarct-related coronary artery resulted in improved distal filling of the subtotally occluded left circumflex artery in one patient, and in transient patency of the completely occluded right coronary artery in a second patient. In a third patient patency of the totally occluded left anterior descending artery (LAD) was achieved by transluminal recanalization with a guide wire. In a forth patient with occulsion of the LAD, there was no response to intracoronary NTG and mechanical recanalization was not attempted. Subsequent intracoronary infusion of streptokinase (1,000--2,000 U/min for 15--60 min) resulted in a further and long-term reduction of narrowing at the site of acute occlusion in patients I-III and in opening of the completely occluded LAD in patient IV. Improvement of lumen was paralleled by alleviation of symptoms. In a fifth patient, in whom the LAD was subtotally occluded, the degree of coronary obstruction could not be changed by intracoronary application of NTG or by lysis. In this patient, symptoms and ECG changes improved with reduction of pathologically elevated blood pressure values. The findings suggest that myocardial infarction had been caused by thrombotic occulsion in four patients, and that spasm of the infarct vessel could have been an additional factor in two of these patients. In the fifth patient, an increase of afterload in the presence of a subtotal lesion might have caused the critical imbalance between oxgen supply and demand, resulting in cell death.

Cardiac Catheterization↗
PubMed1983

Noninvasive markers of intravenous streptokinase coronary thrombolysis.

Early creatine kinase (CK) enzyme peaking, rapid electrocardiographic (EKG) changes toward normal, reperfusion arrhythmias, pain disappearance, and 201thallium myocardial scintigraphy appear useful to identify the success or failure of intravenous (i.v.) thrombolytic therapy in patients with acute myocardial infarction (AMI). Most patients with AMI are treated currently in community hospitals which do not possess coronary angiographic capabilities. Recent evidence indicates that early intravenous streptokinase results in coronary thrombolysis in the majority of patients treated. A composite of noninvasive markers of coronary reperfusion was assessed in two similar patients with transmural AMI. One received intravenous streptokinase (STK) 750,000 U 90 min after AMI onset; the other received intracoronary (i.c.) STK 4000 U/min 140 min after onset. Within one hour each showed a sudden change in elevated EKG ST segments toward normal, followed by frequent premature ventricular beats and pain disappearance. Posttreatment angiograms documented recanalization of each infarct-related artery. Early CK peaking occurred at 10 hours after the onset of chest pain in the first patient and at 12 hours in the second. This contrasts with delayed CK peaking at 26.4 hours among 384 patients reviewed with untreated AMI. Early CK peaking appears the most accurate indirect marker of successful coronary thrombolysis.

Arrhythmias, Cardiac↗
PubMed1984

Recent advances using streptokinase for acute coronary thrombosis.

Most important in comparison to earlier European trials, streptokinase (STK) is administered now at the earliest time possible after acute coronary thrombosis. In this series, STK was started 2.5 (+/- 1.5) h after onset of chest pain, with reperfusion achieved approximately 1 h later in 6 (55%) of 11 patients treated. Posttreatment angiograms will not be required to identify thrombolysis if noninvasive indicators will provide this information correctly. Early creatine kinase enzyme peaking 8 to 15 h after chest pain appears to be the most accurate marker available. Among untreated and unsuccessfully treated patients, creatine kinase peaking usually occurs 18-36 h after chest pain. A large intravenous STK loading dose of 1,500,000 IU produces a plasma concentration of approximately 500 IU/ml, equal to that concentration employed originally by intracoronary infusions. Such large doses have been employed in 60 patients thus far, without an unusual incidence or severity of hemorrhages. High dose, ultrashort-term treatment for only 1 h is being investigated now. Systemic STK penetrates most "blind coronary pouches" and gains access to acute thrombi, as identified by radiocontrast material washout during angiography in patients with severe coronary occlusions. Streptokinase exerts a significant anticoagulant effect, not previous considered, which may be beneficial in the prevention of new clot formation and the rapid dissolution of acute coronary thrombi.

Acute Disease↗
PubMed1987

Effectiveness of intravenous streptokinase on infarct size and left ventricular function in acute myocardial infarction. Prospective and randomized study.

Within 3 h after the onset of symptoms of myocardial infarction, 64 patients were randomly assigned to receive either a 1-h intravenous infusion of 1,500,000 IU of streptokinase (SK) or a conventional therapy. Infarct size was estimated in CK gram equivalent (CKg) by measurement of CK-MB every 3 hours during a 48-h period. Enzymatic study revealed that myocardial infarction of the SK group was significantly smaller (61.4 +/- 45 vs. 89.4 +/- 56 CKg, p less than .05). Angiograms were performed at early stage and five weeks after myocardial infarction. At first coronary angiogram, the infarct-related vessel was open in 82% in the SK group versus 12% in controls. The SK group had higher global ejection fraction at second angiogram (57 +/- 11% vs. 49 +/- 11%, p less than .02), but differences in regional wall motion were not significant. By analysis according to patency or occlusion of infarct-related vessel, global and regional ejection fractions were significantly better at first and at second angiograms in all patients and in anterior infarctions with a patent infarct-related coronary artery. There was no significant difference for inferior infarction. We conclude that intravenous streptokinase infusion early after the onset of myocardial infarction reduces infarct size and improves left ventricular function, chiefly in anterior infarction. This benefit appears to be closely correlated to patency of infarct-related vessels.

Acute Disease↗
PubMed2000

Prognostic role of plasminogen-activator-inhibitor-1 levels in treatment with streptokinase of patients with acute myocardial infarction.

BACKGROUND: The antifibrinolytic effect of plasminogen-activator-inhibitor type 1 (PAI-1) may be responsible for delays in reperfusion and/or reinfarctions after streptokinase (STK) therapy in patients with acute myocardial infarction (AMI). HYPOTHESIS: This study aimed to demonstrate the prognostic role of pretreatment PAI-1 levels for the outcome of STK therapy in patients with AMI, depending on reperfusion and/ or reinfarction. METHODS: The mean pretreatment PAI-1 level of 104 patients with AMI, treated with STK, determined by chromogenic method, was 5.8 +/- 8.6 U/ml, range 0.3-66.2 U/ml. Streptokinase therapy was successful when reperfusion was achieved, as assessed noninvasively, without subsequent reinfarction; it failed when reperfusion was delayed and/or reinfarction developed. RESULTS: Fibrinolysis with STK failed significantly in patients with elevated pretreatment PAI-1 levels (p < 0.05), especially with levels >4.0 U/ml (p< 0.01). The mean pretreatment PAI-1 level was significantly higher in unsuccessfully treated patients. Multivariate statistical testing demonstrated that among pretreatment variables, elevated PAI-1 activity was the most significant independent risk factor of failed fibrinolysis with STK. CONCLUSIONS: Among pretreatment variables, elevated pretreatment PAI-1 activity in patients with AMI was the most significant independent risk factor of failed fibrinolysis with STK, especially at levels > 4.0 U/ml.

Adult↗
PubMed1986

Expression of the streptokinase gene from Streptococcus equisimilis in Bacillus subtilis.

The previously cloned and sequenced streptokinase gene (skc) from Streptococcus equisimilis H46A was inserted into plasmid vectors capable of replication in Bacillus subtilis. The skc gene was expressed by use of its own transcription and translation signals which appeared to meet the stringent requirements of B. subtilis for efficient foreign gene expression. The secreted streptokinase activity began to decline toward the end of the exponential growth phase suggesting that B. subtilis exoproteases hydrolyzed and inactivated the foreign protein.

Bacillus subtilis↗
PubMed1996

Role of N-terminal domain of streptokinase in protein transport.

Streptokinase (SK), an extracellular protein of several haemolytic strains of Streptococcus, is utilized as a potent thrombolytic agent for the treatment of various myocardial disorders. Functional properties of SK remain unchanged when the first 13 N-terminal amino acid (aa) residues are removed. At present, role of this segment in protein structure function is unclear. skc gene encoding for the mature SK and its deletion variant, lacking its first 13 aa residues, were cloned and expressed in E. coli. Full length SK, deprived of any leader sequences, was able to translocate slowly, across the cyto-plasmic and outer membranes of E.coli. Whereas, SK derivative, devoid of its first 13 N-terminal aa residues, could not do so. Cell fractionation studies as well as genetic evidences utilizing alkaline phosphatase fusion, point towards the existence of additional information for protein transport, within the N-terminal domain of SK. To further investigate the role of this region in protein secretion, genetic fusions were created in between full length and 13 aa deleted SK with OmpA leader peptide. Studies on kinetics of SK export from E.coli, revealed that translocation of protein is 3-4 times faster when the first 13 N-terminal residues of SK are intact. On the basis of results obtained, it has been proposed that the N-terminus of mature SK maintains the export competent status of protein and, thus, confer speed and efficiency upon the translocation process of streptokinase.

Biological Transport↗
PubMed2000

Expression and regulation of the streptokinase gene.

Recent research in various areas has appreciably expanded our knowledge of streptokinase, a plasminogen activator produced by all human group A (GAS), group C (GCS), and group G (GGS) streptococci. Several molecular genetic approaches are described here to study the expression of the streptokinase gene, skn. Southern hybridization analysis demonstrated homology of synteny of ska, skc, and skg in the genomes of the above serogroups. S1 nuclease mapping, the use of transcriptional fusions to beta-galactosidase and luciferase reporter genes, in conjunction with site-directed mutagenesis, led to the localization of the core promoter region of skc and the identification of a cis-active upstream region required for full promoter activity. Circular permutation analysis of the promoter upstream region identified an intrinsic DNA bending locus as the pivotal DNA element stimulating the activity of the core promoter. The detection of skn allele-specific expression phenotypes, which proved not to be due to different skn mRNA half-lives, prompted allele swap experiments, showing that promoter activity is dictated by the host genetic background, rather than the sequence of the regulatory region. These findings suggest the involvement in skn expression of an as yet unidentified transcriptional activator that contacts the bent DNA region. Transcription termination of skc is directed by a bidirectional terminator whose structural requirements for termination efficiency were determined with base substitution mutants fused to a chloramphenicol acetyl transferase reporter. Finally, mutagenic plasmids are described for insertion-duplication and allele replacement mutagenesis of the skn locus.

Base Sequence↗
PubMed1992

Streptokinase is a flexible multi-domain protein.

The structure of streptokinase in solution has been studied by dynamic light scattering, small-angle X-ray scattering and circular dichroism spectroscopy. The Stokes' radius and radius of gyration of the protein monomer are 3.58 nm and 4.03 nm, respectively. The maximum intraparticle distance of the molecule is 14 nm. More than half of the amino acids of the molecule are organized in regular secondary structures. The X-ray scattering curve, the results from dynamic light scattering, and the finding that at least 50% of the amino acid residues are organized in regularly folded secondary structures are consistent with the following structural model. Streptokinase consists of four compact, separately folded, domains linked by mobile segments of the protein chain. The molecule exhibits the conformation of a flexible string-of-beads in solution.

Animals↗
PubMed1993

Genetic organization of the streptokinase region of the Streptococcus equisimilis H46A chromosome.

The complete nucleotide sequences of four genes and one open reading frame (ORF1) adjacent to the streptokinase gene, skc, from Streptococcus equisimilis H46A were determined. These genes are encoded on the opposite DNA strand to skc and are arranged as follows: dexB-abc-lrp-skc-ORF1-rel. The dexB gene, coding for an alpha-glucosidase (M(r) 61,733), and abc, encoding an ABC transporter (M(r) 42,080), are similar to the dexB and msmK genes, respectively, from the multiple sugar metabolism operon of S. mutans. The lrp gene specifies a leucine-rich protein (M(r) 32,302) that has a leucine-zipper motif at its C-terminus. The function of the Lrp protein is not known but appeared to be detrimental when overexpressed in Escherichia coli. Although lrp appears not to be an essential gene, as judged by plasmid insertion mutagenesis, it is conserved in all streptococcal strains carrying a streptokinase gene. The rel gene showed significant homology to the E. coli relA and spoT genes involved in the stringent response to amino acid deprivation. Multiple alignment of the amino acid sequences of Rel (M(r) 83,913), RelA and SpoT revealed 59.4% homology of the primary structures. Northern hybridization analyses of the genes in the skc region showed skc to be transcribed most abundantly. In addition to transcripts for skc, monocistronic mRNAs were detected for all three genes divergently transcribed from skc. Although there was also some read-through transcription from lrp into abc, and from abc into dexB, the transcription pattern suggests a high degree of transcriptional and functional independence not only of skc but also abc and dexB. Prominent structural features in intergenic regions included a static DNA bending locus located upstream and a putative bidirectional transcription terminator downstream of skc.

Amino Acid Sequence↗
PubMed1988

Comparison of saline and streptokinase-streptodornase in the treatment of leg ulcers.

In 31 patients with leg ulcers the wounds were randomly allocated to treatment either with a solution of streptokinase plus streptodornase in saline or physiological saline alone. The occurrence of pus and debris in the wounds was evaluated by a "blinded" investigator at the initiation of treatment and on Days 5, 10 and 15. In 12 out of 13 patients treated with the streptokinase-streptodornase solution and in 8 out of 16 saline-treated patients the wounds were clean by Day 10.

Aged↗
PubMed1995

Adverse reaction to streptokinase with multiple systemic manifestations.

We report the case of a 47-year-old woman with a history of mitral valve replacement with a mechanical prosthesis who was admitted to the hospital with a 3-month history of progressive exertional dyspnoea and was diagnosed as suffering from prosthetic valve thrombosis. Two consecutive courses of streptokinase were given as an intravenous infusion over 90 min at a dose of 1,500,000 IU each. Twenty minutes after the start of the second infusion (3 h and 20 min after the first one) she developed chills, fever, tachycardia and hypotension: symptomatic treatment was given and the infusion was completed. Two days later jaundice and choluria appeared with laboratory findings of hepatic cytolysis and cholestasis and renal insufficiency. The results of extensive microbiological and immunological investigations were not revealing. All the laboratory values spontaneously returned to baseline levels over the next 4 weeks. These abnormalities were attributed to an allergic reaction to streptokinase, although the exact pathogenic mechanisms involved are not known. We believe that further studies to elucidate the mechanism involved in the production of these effects are warranted in view of their potential clinical severity.

Female↗
PubMed1994

Neonatal portal vein thrombosis successfully treated by regional streptokinase infusion.

We report a case of portal vein thrombosis (PVT) in a term neonate following an exchange transfusion through an umbilical vein catheter which was left in situ for 16 h after the transfusion. The baby made a complete recovery after successful thrombolysis with regional streptokinase infusion. To our knowledge, this is the first reported case of a PVT following an indwelling portal venous catheter left in situ with complete resolution following thrombolysis with regional streptokinase infusion.

Humans↗
PubMed1993

Magnetic resonance angiography monitoring of streptokinase in occlusion of the middle cerebral artery.

A 77 year old woman was hospitalized one hour after the onset of right hemiplegia and aphasia. Magnetic resonance imaging (MRI) examination was negative and MRA indicated occlusion of the left middle cerebral artery. Treatment with streptokinase was instituted (a 60 minute intravenous infusion of 1.5 MU of streptokinase in 100 ml of saline solution). Two hours after infusion, the patient's motor function clearly improved. An MRA examination performed six hours later showed partial recanalization of the obstructed vessel. Our report demonstrates the potential usefulness of MRA monitoring during thrombolytic therapy.

Aged↗
PubMed1984

Treatment of acute embolus of the superior mesenteric artery by topical infusion of streptokinase.

Two patients with sudden onset of acute abdominal pain caused by embolic disease of the superior mesenteric artery (SMA) were evaluated angiographically. In one patient, the study was performed soon after the clinical onset of symptoms, and successful treatment with low-dose topical streptokinase infusion produced total lysis of the clot over a period of 30 h. In the second patient, the angiogram was obtained 6 days following the initial episode of pain. Radiographic and clinical findings indicated advanced gastrointestinal ischemia with bleeding which contraindicated the use of fibrinolytic therapy. Surgical resection of infarcted intestine was required. Early angiographic detection of acute mesenteric thrombus or embolus is crucial for the selection of patients for fibrinolytic therapy. Our cases suggest that with early diagnosis, streptokinase infusion is an alternative to surgical management of selected patients with acute mesenteric ischemia.

Acute Disease↗
PubMed1986

Selective low-dose streptokinase infusion in the treatment of acute transplant renal vein thrombosis.

A renal transplant recipient developed acute renal transplant vein thrombosis following surgery for a total hip replacement. As an alternative to standard surgical therapy, the patient was treated with selective intravenous low-dose infusion of streptokinase at doses of 5,000-20,000 units/h. The infusion was continued for 120 h with constant monitoring of PT, PTT, and fibrinogen levels. Therapy resulted in excellent preservation of renal function without complications. Low-dose selective infusion of streptokinase should be considered a potential alternative therapy for acute transplant renal vein thrombosis.

Acute Disease↗