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Combined use of stereotactic aspiration and intracerebral streptokinase infusion in the surgical treatment of hypertensive intracerebral hemorrhage.

Stereotactic aspiration is well known for its simplicity and safety in the surgical treatment of hypertensive intracerebral hemorrhage. Postoperative fibrinolytic infusion with urokinase or recombinant tissue plasminogen activator and drainage of liquified hematoma are often used to improve the removal of hematoma. We evaluated the safety and effectiveness of streptokinase in this treatment modality in patients with hypertensive intracerebral hemorrhage or cerebellar hemorrhage. Twelve patients with hypertensive intracerebral hemorrhage underwent stereotactic aspiration using streptokinase as a fibrinolytic agent. There were six cases of putaminal hemorrhage, three of thalamic hemorrhage, and three of cerebellar hemorrhage. All but one patient had a large hematoma and presented with intracranial hypertension. Stereotactic aspiration was undertaken to remove the hematoma. Postoperatively, streptokinase was infused into the residual hematoma every 6 to 12 hours via a catheter implanted during the operation. Liquified hematoma was aspirated by syringe manually just before each infusion of streptokinase. The average duration of the entire treatment was 6 days (range 1-7). The residual hematoma at the end of treatment was less than 10 mL in all patients. Intracranial hypertension also subsided significantly in all patients. Only one patient had aspiration-induced bleeding during the operation. We conclude that stereotactic aspiration of hypertensive intracerebral hemorrhage is relatively safe and simple. Streptokinase can be infused intracerebrally to drain residual hematoma without severe side-effects.

Adult↗

[Binding of an acylated plasminogen activator-streptokinase complex with fibrin and the fibrinolytic response in vitro].

Affinity and fibrinolytic properties of streptokinase and two new preparations of acylated plasminogen-streptokinase activator complexes, produced by dissimilar procedures, were studied. Even after 1-min exposure, blood clot lysis carried out by the acyl activating complex was continued in blood plasma more than for 4 hrs, while the streptokinase produced blood clot lysis was accomplished within 1.5 hrs. After 1-min contact with clot in blood plasma the rates of lysis by streptokinase and these acylated plasminogen-streptokinase activator complexes types 1 and 2 constituted 23%, 37% and 63%, respectively, as compared with the rates detected during permanent contact of thrombolytics with blood clot. The activator properties of the thrombolytic agents itself and its stability in blood plasma were of importance even in similar affinity ability of free and acylated activating complexes.

Acylation↗

Efficacy of low-dose streptokinase in acute arterial occlusion and graft thrombosis.

In a review of 35 patients undergoing local thrombolysis using selective infusion of low-dose streptokinase, the overall success rate was 43%. Streptokinase appears to be most effective in occlusion of native arteries, in high-flow segments, and in autogenous saphenous vein grafts. Local streptokinase was least effective in occluded prosthetic grafts in the femoropopliteal segment (19% success). Distal embolization and progression of thrombosis of the distal arterial tree may occur while the patient is undergoing local thrombolysis and may result in limb loss. Hence, local thrombolysis is not recommended when surgical treatment is an alternative. Despite the low dose, systemic fibrinolytic effects and hemorrhagic complications were common occurrences; hence, routine hematologic monitoring is mandatory in patients undergoing lytic therapy with local infusion of streptokinase.

Acute Disease↗

Early results of low dose intra-arterial streptokinase therapy in acute and subacute lower limb arterial ischaemia.

Thirty-two patients with acute and subacute limb-threatening peripheral arterial ischaemia were treated with low dose intra-arterial streptokinase infusions. The mean duration of infusion was 38 h. Six patients developed pericatheter thrombosis and two had distal embolization of fragments of thrombus but in all cases these responded to repositioning the catheter and continuing the infusion. Five patients developed groin haematomata and in three of these there was evidence of a systemic fibrinolytic effect from the streptokinase with plasma fibrinogen reduced below 1 g/l. The most serious complication was perforation of the popliteal and tibial arteries which occurred on two occasions and required cessation of the infusion. Twenty-two patients (69 per cent) achieved limb salvage, eight (25 per cent) suffered a major amputation and two (6 per cent) died. The outcome was not related to the site, nature or duration of the arterial occlusion but patients with loss of sensation or paralysis of the affected limb were significantly less likely to obtain limb salvage (P = 0.001). For occlusions greater than 30 cm in length a new technique was used where the thrombus was lysed from distal to proximal in short lengths by gradual catheter withdrawal. This was successful in five out of six cases. Low dose intra-arterial streptokinase has been confirmed as an effective, relatively safe method of treatment in recent arterial ischaemia and can be recommended in situations where the results of surgery may not be favourable. In particular, patients with arterial thromboses and no distal run-off, distal and late arterial emboli, thrombosed popliteal aneurysms and patients after a failed embolectomy, have all been shown to respond to thrombolytic therapy with intra-arterial streptokinase.

Adult↗

Recombinant tissue-type plasminogen activator is superior to streptokinase for local intra-arterial thrombolysis.

The results of local intra-arterial thrombolysis in 98 patients treated with streptokinase and 69 patients treated with recombinant tissue plasminogen activator (rtPA) have been compared. The two groups of patients were well matched and their treatment protocols were identical except with regard to the thrombolytic agent used. Strict criteria for defining successful thrombolysis were used. Successful lysis was achieved in 40 of 98 patients (41 per cent) receiving streptokinase and 40 of 69 patients (58 per cent) receiving rtPA (P less than 0.05). The time to lysis was significantly shorter with rtPA, median time 22 h, than with streptokinase, median time 40 h (P less than 0.002). There was no difference in the incidence of haemorrhagic complications. These results suggest that rtPA is superior to streptokinase for local intra-arterial thrombolysis.

Adult↗

Treatment of acute myocardial infarction with streptokinase does not appear to modulate circulating neutrophil function.

The administration of thrombolytic therapy is the most common method of achieving patency of the occluded coronary artery in patients with acute myocardial infarction (AMI). However, thrombolytic agents and the byproducts of fibrinolysis have the potential to affect neutrophil activation and thus function, thereby augmenting myocardial damage further. This study assessed the effect of streptokinase administration on the function of circulating neutrophils in patients with AMI. For this neutrophil adherence to human umbilical vein endothelial cells, homotypic neutrophil aggregation, and CD11b and L-selectin expression on the neutrophil membrane prior to and 1 h and 6 h after thrombolytic therapy was monitored. The study population included patients with AMI who received aspirin and streptokinase, and healthy laboratory workers who received aspirin only; all subjects acted as their own controls. Circulating fibrin degradation products and white cells were markedly raised following administration of streptokinase. No significant differences in neutrophil adherence to endothelium, homotypic neutrophil interactions, and CD11b or L-selectin expression were demonstrated between neutrophils, either pre- or post-thrombolytic therapy in the infarct group, or between neutrophils from the infarct group and from the control group. It was concluded that streptokinase produces an abrupt neutrophil leukocytosis together with a marked increase in circulating levels of fibrin degradation products. The assay systems used were unable to show significant sequential changes in circulating neutrophil adhesion and L-selectin or CD11b expression in patients with AMI following thrombolytic therapy or when these patients were compared with controls.

CD18 Antigens↗

Streptokinase gene polymorphism in group A streptococci isolated from Ethiopian children with various disease manifestations.

Certain variants of streptokinase from group A streptococci have been associated with acute post-streptococcal glomerulonephritis (APSGN). The streptokinase gene (ska) has previously been grouped into nine different polymorphic genotypes of which ska1, ska2, ska6, and ska9 were identified in group A streptococci associated with clinical and experimental APSGN. A total of 53 group A streptococci isolated from Ethiopian children: five from acute rheumatic fever, 18 from APSGN, ten each from tonsillitis, impetigo and healthy carriers, were analyzed for ska gene polymorphism using polymerase chain reaction (PCR) and restriction enzyme analysis. The frequency of the nephritis-associated streptokinase genotypes was 83% among the APSGN isolates and 74% in the non-ASPGN isolates. ska2 was the most commonly found genotype with a frequency of 64% among all isolates, 66% among the APSGN isolates, and 63% among the non-APSGN isolates. ska1 was identified in 13% among all isolates and 17% among the APSGN isolates. Seventeen non-APSGN isolates from Scandinavian countries were studied for comparison and all carried either ska1 or ska2. The other nephritis-associated ska6 and ska9 were not detected among the 53 Ethiopian isolates. ska1 was exclusively associated with serum opacity reaction (SOR) producers. ska2 was evenly distributed among SOR-positive and SOR-negative isolates. The other genotypes were detected only among SOR-negative strains. The findings of the present study showed an even distribution of the nephritis-associated streptokinase gene among group A streptococcal isolates with no correlation to disease pattern. Thus additional factors must also be operative in the pathogenesis of APSGN.

Acute Disease↗

Guillain-Barré syndrome following streptokinase therapy.

Clinical and laboratory data from a patient with Guillain-Barré syndrome indicated a probable etiological correlation of polyradiculitis to the intravenous administration of streptokinase. Oligoclonal IgG bands in the cerebrospinal fluid and serum were shown to be specific for streptokinase. Serum titers of streptokinase were elevated 64-fold for IgG, 16-fold for IgM, and 4-fold for IgA compared to controls. Clinical symptoms of Guillain-Barré syndrome are thought to result from streptokinase antibody complex mediated damage to the local blood-nerve barrier. The pathogenic relevance of autoantibodies to albumin and proteins of the central and peripheral nervous systems, occurring early after onset of symptoms, remains to be determined.

Autoantibodies↗

Conservation of the organization of the streptokinase gene region among pathogenic streptococci.

Using ten gene-specific probes from the cloned and sequenced streptokinase gene (skc) region (8,931 bp) of Streptococcus equisimilis H46A, a human serogroup C strain, the conservation of these genes and their linkage relationships were studied by Southern hybridization in pathogenic streptococci differing taxonomically, serologically, in regard to their host range, and in the class of plasminogen activator produced. The results indicate that in S. pyogenes (strains A374, NZ131 and SF130/13) and a human group G strain (G19,908) both gene content and gene order as determined for H46A (dexB-abc-lrp-skc-orfl-rel) are preserved. The same is true of an equine S. equisimilis isolate (87-542-W), the streptokinase gene of which has been shown to hybridize detectably with skc, a result at variance with that obtained previously by others. In contrast, the chromosomal DNA of three S. uberis strains (0140J, C198, C216) of bovine origin, two of which produced a plasminogen activator different from streptokinase, hybridized only with dexB-, abc- and rel-specific probes, and the homologues of these genes appeared to lie close to each other. The maintenance of the organization of the streptokinase gene region in strains differing in overall chromosomal character suggests that this gene arrangement is of selective advantage.

Bacterial Proteins↗

[Coagulation studies and rheological measurements during streptokinase therapy of myocardial infarction (author's transl)].

In a multicenter, randomized trial of streptokinase in acute myocardial infarction one group of patients was given streptokinase for 24 h; the remainder served as controls and received a placebo infusion instead. Coagulation assays and rheological measurements were serially performed on patients entered into the trial at one of the participating centers. Streptokinase was found to improve considerably the flow properties of blood for a period of time exceeding the duration of its administration. These results may well explain the positive clinical effect of streptokinase therapy observed in this trial.

Acute Disease↗

Streptokinase and concomitant oral anticoagulants in the treatment of deep venous thrombosis.

Fourty-four patients with deep venous thrombosis of the leg diagnosed by phlebography and not more than five days old were treated with streptokinase. Oral anticoagulant therapy was started at the same time. Complete lysis of thrombi was obtained in 6 cases and partial one in 25 cases. Lysis of proximal thrombi was better than that of distal ones. The age of the thrombi had no effect on the lysis. Urticaria and anaphylactic reactions occurred in 8 patients and treatment was discontinued. Haemorrhagic complications were present in 8 cases but remission was obtained by dicontinuing streptokinase infusion. Commencing oral anticoagulant therapy simultaneously with streptokinase reduces duration of treatment without increasing the risks and the results of lysis are equally good as with earlier studies. The use of streptokinase is recommended in the treatment of proximal deep venous thrombosis. This treatment offers a possibility of preventing a postthrombotic syndrome. The frequency of various complications should however be borne in mind.

Adult↗

Intrapericardial streptokinase for purulent pericarditis.

PURPOSE: Purulent pericarditis has become a rare disease since the introduction of antibiotics into clinical practice. Standard management consists of antibiotics and surgical drainage. In this study we also instilled streptokinase to obliterate the loculations and fibrin strands in patients with purulent pericarditis. METHODS: Between October 1997 and October 2002, we treated nine children with purulent pericarditis by pericardial drainage with streptokinase instillation and antibiotics. There were five boys and four girls aged between 3 and 13 years, with a mean age of 6.7 +/- 2.9 years. RESULTS: Pericardiocentesis revealed purulent effusion of 180-650 ml in the pericardial space in all patients. Blood pressure increased and central venous pressure decreased after the pericardial empyema was evacuated in all patients. None of the patients had systemic bleeding, arrhythmias, or hypotension suggesting an anaphylactic reaction. CONCLUSION: We found intrapericardial streptokinase to be safe and effective for dissolving fibrin layers and removing loculations, resulting in complete pericardial drainage. Therefore, intrapericardial streptokinase should be instilled to prevent constrictive pericarditis.

Adolescent↗

Thromboxane synthetase inhibition with CGS 13080 improves coronary blood flow after streptokinase-induced thrombolysis.

The focus of this investigation was to examine the potential beneficial effects of the selective thromboxane synthetase inhibitor CGS 13080 (imidazo [1,5-a] pyridine-5-hexanoic acid) on coronary blood flow after streptokinase-induced thrombolysis. Thrombotic occlusion of the circumflex coronary artery was produced by electrolytic (100 microA anodal current) injury to the intimal surface of the circumflex coronary artery at the site of a noncircumferential stenosis in dogs anesthetized with pentobarbital to have open-chest surgery. Intracoronary streptokinase, 6000 IU/kg in 3 ml saline solution, was infused at 0.05 ml/min for 1 hour, beginning 30 minutes after the formation of an occlusive thrombus. The animals were assigned randomly to two groups. In group I (n = 10) the intravenous infusion of vehicle was begun simultaneously with the intracoronary administration of streptokinase and continued for 2 hours after thrombolysis had been achieved. The animals in group II (n = 10) received intravenous CGS 13080 (1 mg/kg/hr) along with intracoronary streptokinase. Infarct size was assessed by a dual perfusion technique with Evans blue and triphenyltetrazolium stains to demarcate the normally perfused myocardium from the area at risk and the infarct zone within the risk region. The two groups did not differ with respect to baseline coronary blood flow, time to the development of coronary artery thrombotic occlusion, or time to achieve thrombolysis. Oscillations in coronary blood flow were more frequent in group I than in group II (group I, 9 +/- 2.2; group II, 4.4 +/- 0.8 oscillation/min X 100, p less than 0.05 [mean +/- SEM)].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intracoronary infusion of streptokinase in patients with acute myocardial infarction: effects of reperfusion on left ventricular performance.

Cardiac catheterization and coronary angiography were performed on hospital admission in 32 consecutive patients with acute myocardial infarction. Twenty-six patients had total occlusion of an infarct-related coronary artery and six had severe proximal stenosis with poor distal flow. In 18 of the 26 patients with total occlusion, intracoronary infusion of streptokinase resulted in reperfusion of the distal coronary artery. Seventeen of these 18 patients had severe coronary arterial stenosis at the site of the previous total occlusion. Hemodynamic indexes of left ventricular performance and ejection fraction determined by gated cardiac blood pool imaging did not change immediately after reperfusion (p [probability] = not significant [NS]). The mean (+/- standard deviation) left ventricular ejection fraction increased significantly (p = 0.007) from admission (44 +/- 15 percent) to hospital discharge (55 +/- 7 percent) in patients evidencing reperfusion of the occluded coronary artery. It did not change (p = NS) in this time span in the patients with severe stenosis alone, in those with total occlusion not demonstrating reperfusion after administration of streptokinase or in an additional 10 control patients with acute myocardial infarction not evaluated with coronary angiography. These data suggest that (1) coronary arterial thrombus is frequent in acute myocardial infarction and can be lysed by intracoronary streptokinase; (2) reperfusion with intracoronary streptokinase in acute myocardial infarction results in improved left ventricular performance between admission and hospital discharge.

Aged↗

Intracoronary prostaglandin E1 plus streptokinase in acute myocardial infarction.

Fourteen patients with acute myocardial infarction (duration of chest pain 5 +/- 2 hours) received intracoronary infusion of prostaglandin E1 (PGE1) and streptokinase. Intracoronary PGE1 was followed by intracoronary streptokinase in 10 patients (group A), with successful recanalization in all patients. Of 4 patients in whom recanalization failed with intracoronary streptokinase given first (group B), 2 had successful recanalization after addition of intracoronary PGE1. Immediately after successful recanalization, left ventricular ejection fraction increased from 50 +/- 9% to 62 +/- 10% (p less than 0.0008), left ventricular end-diastolic pressure decreased from 20 +/- 10 to 16 +/- 10 mm Hg (p less than 0.05) and stroke volume index increased from 34 +/- 10 to 44 +/- 12 ml/m2 (p less than 0.02). Infarct segment shortening improved from 9 +/- 5 to 18 +/- 4% (p less than 0.0002). Transient hypotension in 1 patient was the only complication. Follow-up catheterization in recanalized patients at 2 to 10 days showed maintained improvement in left ventricular global and infarct segment function. Reocclusion occurred in 1 patient. Thus, intracoronary infusion of PGE1 was effective in establishing reperfusion in all patients when followed by streptokinase and was associated with immediately improved left ventricular global and regional function. PGE1 deserves further evaluation in acute myocardial infarction.

Adult↗

Predictive factors of effectiveness of streptokinase in deep venous thrombosis.

In a prospective study, 174 patients (118 women and 56 men, average age 44 years, range 14 to 82) with proximal extensive thrombosis received streptokinase (100,000 U/hour) for an average of 2.8 days (range 0.5 to 7) through the catheter of a temporary caval filter. Twenty-seven of 45 (60%) patients with nonocclusive clots were completely free of clots at the second phlebography versus 17 of 116 (14%) with occlusive clots (p less than 0.001). Among nonocclusive clots, proximal ones (caval, iliac and femoral) were more easily lysed than popliteal clots (88 of 116 [76%] vs 26 of 58 [45%]; p less than 0.001). In 41 of 132 (31%) patients, a daily injection of contrast medium through the filter-carrying catheter enabled the observation of a clot in the filter, which was lysed by streptokinase. Seventy patients with follow-up greater than 2 years (median 34 months) were examined clinically. Nineteen of 22 (86%) patients with venograms free of clots at discharge were free of clinical sequelae versus 16 of 48 (33%) without normal venograms (p less than 0.001). It is concluded that: (1) in the case of occlusive clots, only a few patients were normalized after streptokinase; (2) proximal nonocclusive clots were most effectively lysed; (3) when venograms were free of clots at discharge, the majority of patients did not have venous sequelae at follow-up; and (4) embolic migration seems to occur frequently with streptokinase.

Adolescent↗

A difference between front-loaded streptokinase and standard-dose recombinant tissue-type plasminogen activator in preserving left ventricular function after acute myocardial infarction (the Central Illinois Thrombolytic Therapy Study).

A blinded, randomized trial compared the effects of front-loaded streptokinase with those of the conventional dose of intravenous recombinant tissue-type plasminogen activator (rt-PA) on left ventricular (LV) function after acute myocardial infarction (AMI). Thrombolytic therapy was administered in the emergency departments of 30 community hospitals in central Illinois, and subsequent studies were performed at 1 tertiary referral center. Patients aged < or = 75 years with a first AMI who could be treated within 4 hours of the onset of chest pain were randomly assigned to receive either streptokinase (375,000 IU bolus, followed by 1,125,000 IU over 1 hour) or rt-PA (10 mg bolus, followed by 50 mg in the first hour, and 20 mg/hour for the next 2 hours). All patients were treated with aspirin (325 mg) and intravenous heparin. Patients were transferred for angiography within 24 hours. During the 30-month study, 253 patients were treated with intravenous thrombolytic therapy 2.4 +/- 1.0 hour after the onset of AMI. In patients with anterior wall AMI (n = 90), global LV ejection fraction measured by angiography within 24 hours was 45 +/- 12% with rt-PA, and 39 +/- 13% with streptokinase (p < 0.03). Convalescent radionuclide angiography documented a persistent beneficial effect of rt-PA on LV regional wall contractility, but not global ejection fraction. There were no differences between rt-PA and streptokinase in preserving global or regional LV function in patients with inferior wall AMI.

Aged↗

Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis.

Although thrombolysis with streptokinase has been compared with heparin anticoagulation for treating acute proximal deep venous thrombosis in several randomized trials, no individual study has had a sample of sufficient size to determine with adequate power both efficacy and safety. Therefore, results were pooled from six randomized studies in which phlebography was used to confirm the diagnosis and to assess therapy. Thrombolysis was achieved 3.7 times more often among patients treated with streptokinase than among patients treated with heparin (95 percent confidence limits 2.5, 5.7; p less than 0.0001). Only three studies allowed comparison of these drugs for major bleeding complications, which were 2.9 times greater with streptokinase than with heparin (95 percent confidence limits 1.1, 8.1; p = 0.04). Thus, in aggregate, streptokinase-treated patients achieved thrombolysis but also seemed to experience major bleeding complications more frequently than those assigned at random to receive heparin. Future trials of sufficient sample size should be undertaken to evaluate efficacy and safety. Such trials, which should include newer fibrinolytic agents, are necessary to determine optimal therapy for acute proximal deep venous thrombosis.

Clinical Trials as Topic↗