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PubMed1981

[Fibrinolytic treatment of acute myocardial infarction (author's transl)].

Fibrinolytic treatment of acute myocardial infarction with streptokinase and urokinase has now been under investigation for almost 20 years. Initially encouraging reports of beneficial effects of streptokinase were not substantiated by carefully controlled studies performed on coronary care and intensive care units. Studies carried out during the last tne years were characterized by non-uniform trial conditions and results. Similarly, to date no clearly beneficial effects of urokinase could be established. In order to provide more concise analysis, the "European Cooperative Study Group for Streptokinase Treatment in Myocardial Infarction" conducted a multi-center controlled trial. Patients were allocated to risk-groups. Three-hundred fifteen patients with medium and high risk were randomized to a 24-hour infusion of streptokinase or glucose. The overall mortality within six months was significantly lower in the streptokinase group (p less than 0.01) contributed primarily by eight of the eleven centers. Only 13.5% of patients with myocardial infarction, however, were eligible for the study. Interpretation of the results yielded no indication of the nature of the fibrinolytic effects nor how the benefit could be explained pathophysiologically. Furthermore, it remains questionable whether systemically-administered streptokinase can lyse coronary thrombosis or reduce the size of myocardial necrosis. An indirect effect of streptokinase through lowering of blood viscosity and subsequently, peripheral capillary resistance may represent a theoretical possibility. the indication of routine systemic administration of streptokinase has not yet been established. Recent reports of promising results obtained by direct, intracoronary infusion of thrombolytic agents indicate that this alternative may lead to realization of a specific effect in reduction of coronary thrombosis and, consequently, myocardial necrosis.

Acute Disease↗
PubMed1980

Restoring patency of occluded central venous catheters.

Thrombotic occlusion remains a major cause of central venous catheter removal prior to completion of therapy. Injection of a dilute solution of a potent fibrinolytic agent, urokinase or streptokinase, into the occluded Silastic central venous catheter consistently reestablishes its patency. This procedure was performed on 352 occluded silicone elastomer central venous catheters with only one failure and one minor complication. We recommend this technique for restoring patency of occluded silicone elastomer central venous catheters.

Catheters, Indwelling↗
PubMed1975

Lowering of the tumoricide activity of human serum with Varidase. II. Antibodies against Varidase in human serum measured by complement binding.

Active human serum manifests a tumoricide effect against cells of the Ehrlich ascites tumor. Sera of patients with Ca ventriculi show a higher effect than those of patients with a chronic streptococcal disorder, in comparison with intact subjects. This tumorcide effect is depressed by Varidase, the degree of depression being greatest in the group of patients with streptococcal infection, smaller in healthy subjects and least in carcinoma patients. The investigated sera contained antibodies against Varidase, but not against streptokinase. The anti-Varidase antibodies are found also in sera of the new-born children. The decline of the tumoricide activity of Varidase-treated sera is related to the quantity of anti-Varidase antibodies determined by complement fixing reaction in non-treated sera.

Adenocarcinoma↗
PubMed1969

Cellular immunity in vitro. Clonal proliferation of antigen-stimulated lymphocytes.

When sensitive lymphocytes are cultured with the appropriate antigen, lymphoblasts appear after 24-48 hr of incubation and the number of these increases steadily from the 2nd to the 6th or 7th day. Our problem was to discover, at a cellular level, how this increase takes place; whether it is a massive response of many cells, stepwise recruitment of cells into the lymphoblast class, or simply repeated division of a few cells to form clones. In these experiments lymphocytes were incubated with antigen in culture tubes for 2-4 days and then a few cells, usually less than 200, were transferred to special microchambers for further culture. In these microchambers the cells could be viewed continually with a microscope and their fate recorded over the next 3-5 days by time-lapse cinemicrography. Examination of the film produced in this way showed that lymphoblasts divided and redivided to produce clones of 64 cells or more. It was possible to measure generation times from the film for 301 cells; the majority were between 8 and 13 hr but the range was 7.5-38.0 hr. There was no clear difference between generation times of human lymphocytes stimulated with tuberculin, streptokinase-streptodrnase, extract of the American pokeweed, or in the mixed leukocyte reaction. Similar times were also found for rat cells in the mixed leukocyte reaction. While these observations show that clonal proliferation does occur and could reasonably account for all the increase of lymphoblasts in lymphocyte cultures, the experiments, because of their design, do not exclude the possibility that other mechanisms such as recruitment may play a role as well, particularly during the first 48 hr after contact between sensitive cells and antigens.

Animals↗
PubMed1975

Effect of prednisolone on the leukocyte counts of ponies and on the reactivity of lymphocytes in vitro and in vivo.

Treatment of ponies with a single dose of prednisolone markedly reduced the number of blood lymphocytes. A decrease of the number of eosinophils was also observed. In contrast, the number of neutrophils significantly increased. These profound changes were temporary and returned to the pretreatment level within 48 h. The number of monocytes did not show any of the significant changes post-prednisolone treatment. The reactivity of the blood lymphocytes of these ponies, in vitro, to stimulation with phytohemagglutinin (PHA) or streptokinase-strepto-dornase (SK-SD) was measured by incorporation of (3-H)thymidine by deoxyribonucleic acid of lymphocytes. The ponies' blood lymphocytes responded very well to PHA stimulation. The incorporation of (3-H)thymidine into deoxyribonucleic acid of the PHA-stimulated lymphocytes was 14 times greater than incorporation of the nonstimulated lymphocytes. SK-SD-stimulated lymphocytes incorporated only three times more (3-H)thymidine than nonstimulated lymphocytes. There was no significant difference in stimulation of lymphocytes with PHA or SK-SD before or after the prednisolone treatment. However, a significant decrease in the dermal response to the homologous antigen after this treatment in sensitive ponies was observed.

Animals↗
PubMed1984

A comparison between streptokinase/streptodornase and streptokinase on delayed hypersensitivity skin testing.

The use of streptokinase (SK) to replace streptokinase/streptodornase (SK/SD) in delayed hypersensitivity skin testing was evaluated in 325 patients. Sixty patients responded to SK/SD (100 U of SK per 25 U of SD) and 36 to SK (375 U). Thirty-two responded to SK/SD but not to SK, and eight responded to SK but not to SK/SD. SK, at the dosage used, is not a suitable substitute for SK/SD in delayed hypersensitivity testing. SD may be the more potent recall antigen. Perhaps more importantly is that of 250 positive responders to a recall-antigen battery consisting of SK/SD, SK, Candida, Trichophyton, tetanus toxoid, purified protein derivative, and coccidioidin, 99.2% (248) would have been detected had the testing for SK and SK/SD not been done.

Adult↗
PubMed1967

Studies on the proteolytic activity of gamma-globulin preparations.

1. The proteolytic activities of several gamma-globulin preparations were tested. These included sulphate-precipitated human and bovine preparations and human and bovine Cohn fraction II preparations as well as purified gamma-globulin preparations. Up to 14mg. of diffusible peptides and glycopeptides/g. of gamma-globulin was liberated after dialysis and up to 10mg. of peptides/g. after incubation and trichloroacetic acid precipitation, as products of the degradation process in incubated gamma-globulin. 2. in-Aminohexanoic acid and p-chloromercuribenzoic acid, as well as heating at 60 degrees for 40min., were shown to inhibit strongly these proteolytic activities. Streptokinase was shown to activate strongly the proteolytic activity of all the human preparations (sulphate-precipitated, Cohn fraction II, and purified gamma-globulin). 3. Two distinct pH optima were shown for human and bovine gamma-globulin preparations: one at pH8, the other at pH3.8 (the latter activity could be demonstrated only in the presence of cysteine). 4. Both (131)I-labelled human Cohn fraction II and bovine fibrinogen were attacked by a sulphate-precipitated preparation of gamma-globulin. Of the synthetic substrates tested toluene-p-sulphonyl-l-arginine methyl ester was hydrolysed by both the sulphate-precipitated and Cohn fraction II preparations, as was benzoyl-l-arginine amide at pH5, but only in the presence of cysteine. 5. These data are interpreted to indicate that at least two enzymes are present in gamma-globulin preparations, one being similar to the plasmin system, the other similar to cathepsin B.

Acids↗
PubMedDate not supplied

Effect of Varidase (streptokinase) on biofilm formed by Staphylococcus aureus.

Staphylococcus aureus forms a fibrin-rich biofilm in the presence of plasma which is highly resistant to attack by the human immune system and to chemotherapy. Varidase, composed mainly of streptokinase, is used for hydrolyzing clots. In this study, we attempted to destroy the biofilm of S. aureus with Varidase and to apply this drug in the treatment of staphylococcal infections. Four clinical isolates were used in the experiments. These organisms formed a several-millimeter-thick biofilm on type IV collagen coated coverslips in trypticase soy broth containing 50% human plasma. The biofilm was composed of bacterial cell which adhered to fibrillar fibers and of sediment derived from plasma. 10,000 U/ml of Varidase, the dose which is used clinically, removed the sediment and reduced the number of live bacteria in biofilms to less than 20% of control. 200 U/ml of Varidase was also effective against biofilms of the organisms. An equal combination of Varidase and ofloxacin had an additive effect on the bacteria. The results of this study demonstrate that Varidase is highly effective in destroying biofilms of S. aureus in vitro and suggest that this drug would be useful for treating staphylococcal infections.

Biofilms↗