The Effect in Patients of Streptococcal Fibrinolysin (Streptokinase) and Streptococcal Desoxyribonuclease on Fibrinous, Purulent, and Sanguinous Pleural Exudations 1

Tillett, W.; Sherry, Sol

doi:10.1172/jci102046

Cited by 357 publications

(139 citation statements)

References 15 publications

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“…These changes were usually self-terminating within 24 hours following the infusion of SK. In earlier studies similar trends were observed in the chest fluid of patients with hemothorax and empyema treated locally with streptokinase (22).…”

Section: Sd~fmarysupporting

confidence: 79%

The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase)

Johnson

Tillett

1952

Journal of Experimental Medicine

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127

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1. Based upon quantitative estimations of the factors that promote or retard the development and activity of the streptococcal fibrinolytic phenomenon, an active lytic system was developed within the circulating blood stream of rabbits following the intravenous infusion of streptokinase. During the infusion of adequate doses of SK, an active lytic system was observed to be present within 30 minutes following the beginning of the experiment and remained present for periods of time ranging from 1 to 20 hours depending primarily upon the concentration of SK and the duration of the infusion. Some of the biochemical changes accompanying the lytic system in vivo were: (a) a striking fall in the plasminogen; (b) a moderate fall in the serum inhibitor and the fibrinogen; and, (c) a rise in the acid-soluble nitrogen. These changes were usually self-terminating within 24 hours following the infusion of SK. In earlier studies similar trends were observed in the chest fluid of patients with hemothorax and empyema treated locally with streptokinase (22). 2. Intravascular clots, induced artificially by local applications of sodium morrhuate within the ear vein of the rabbits, were observed to liquefy and disappear in 23 of 25 rabbits during the intravenous infusion of SK into the opposite ear. The average quantity of SK necessary to effect an active lytic system was found to be about 40,000 units per kilo per hour. The clot in the ear vein was observed to be lysed completely in periods of time ranging from 3 to 7 hours after the infusion of SK was begun. Maintenance of an active lytic system for 3 to 4 additional hours was required to prevent re-formation of the clots at the original site. In 3 of 4 rabbits in which clots did reform, ACTH had been given to combat the toxic effects of the streptococcal concentrates. 3. The toxicity of the unusually large dose of the streptococcal concentrates, containing measured amounts of SK, along with other identifiable and unknown substances, was considerable, inasmuch as 8 animals eventually died. No evidence of pulmonary infarction was observed at autopsy. The administration of ACTH appeared to prevent a fatal outcome in at least 3 of the rabbits. Further studies of toxicity are in progress.

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Section: Sd~fmarysupporting

confidence: 79%

The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase)

Johnson

Tillett

1952

Journal of Experimental Medicine

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127

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“…Up to the present time the most obvious clinical side effect has been a pyrogenic reaction with associated symptoms of malaise, headache, arthralgia and occasionally nausea (1,2). This reaction has been observed to begin about four to six hours after the local instillation of solutions of SK-SD; to reach its peak in 24 hours and to subside in the ensuing 24-48 hours.…”

mentioning

confidence: 94%

The Systemic Toxic Responses of Patients to Treatment With Streptokinase Streptodornase (Sk-Sd) 12

Hubbard¹

1951

J. Clin. Invest.

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This paper reports the results of investigations concerning possible toxicities associated with the therapeutic use of streptococcal concentrates containing streptokinase (SK) and streptodornase (SD).Up to the present time the most obvious clinical side effect has been a pyrogenic reaction with associated symptoms of malaise, headache, arthralgia and occasionally nausea (1, 2). This reaction has been observed to begin about four to six hours after the local instillation of solutions of SK-SD; to reach its peak in 24 hours and to subside in the ensuing 24-48 hours. The febrile response occurs in 60-75%o of the treated cases, with a suggestive higher frequency in patients with massive hemorrhage (hemothorax) than in those who have local suppurative disease of infectious origin. In patients receiving repeated injections the occurrence of the reaction has been unpredictable; sometimes appearing after the first injection and not subsequent ones and, on other occasions, after one or another of the later injections, but absent at the first treatment. Furthermore, the cause of the reaction has not yet been clearly determined but may be referable primarily either to the foreign materials of the solutions of SK-SD or to the breakdown products of their enzymatic action.The present study was undertaken to determine whether untoward effects, inapparent to general clinical examination but that might be brought out by detailed laboratory examination, followed the use of SK-SD.In addition to the routine need for such a study when a new agent is used therapeutically, there is a special need in the instance of SK-SD since 1This study was supported through a contract with disease is known to be associated with the presence of streptococci and their metabolic products within the body. It is useful, then, to look for laboratory changes that might indicate alterations suggestive of the specific toxicities of streptococcal products. MATERIALS AND METHODSTwenty-eight patients were studied, who received a total of 90 local instillations of SK-SD for a variety of suppurative and hemorrhagic diseases. Observations were made on the days before treatment; immediately prior to treatment; every one to three hours in the 12 hours after treatment; and then twice daily until control levels were obtained. In 10 patients, additional observations for possible delayed effects were made from 21 to 112 days after the last treatment.Urinalysis was performed on each voided specimen on the day of treatment and thereafter until control observations were duplicated. The first 15 patients studied had complete routine analyses on each voided specimen, but the last 13 patients had each specimen routinely analyzed only during the first 12 hours after treatment, unless some change was observed during this period. Since we wished to determine the time relationship between the appearance of formed elements in the urine and clinical and peripheral blood changes, the urine was not pooled for the usual Addis counts during the first 24 to 48 hours following treatment...

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“…Fe (20). The type of inhibition observed in undilute plasma is in contrast to the type of inhibition described with dilute plasma or purified systems where specific plasma inhibitors which combine with trypsin in stoichiometric fashion may be demonstrated (21,22 (24); plasminogen (16); and the presence of an active fibrin lysing system in the dogs plasma (25). On a number of instances the presence of circulating plasmin or trypsin was tested for by the hydrolysis of p-toluene sulfonyl I-arginine methyl ester (26,27), and the presence of circulating chymotrypsin tested for by the hydrolysis of acetyl 1-tyrosine ethyl ester (27).…”

Section: Methodsmentioning

confidence: 85%

The Enzymatic Dissolution Of Experimental Arterial Thrombi in the Dog by Trypsin, Chymotrypsin and Plasminogen Activators12

Sherry¹,

Titchener²,

Gottesman³

et al. 1954

J. Clin. Invest.

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The Effect in Patients of Streptococcal Fibrinolysin (Streptokinase) and Streptococcal Desoxyribonuclease on Fibrinous, Purulent, and Sanguinous Pleural Exudations 1

Cited by 357 publications

References 15 publications

The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase)

The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase)

The Systemic Toxic Responses of Patients to Treatment With Streptokinase Streptodornase (Sk-Sd) 12

The Enzymatic Dissolution Of Experimental Arterial Thrombi in the Dog by Trypsin, Chymotrypsin and Plasminogen Activators12

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