THE RESISTANCE TO FIBRINOLYTIC ACTIVITY OF THE HEMO- LYTIC STREPTOCOCCUS WITH SPECIAL REFERENCE TO PATIENTS WITH RHEUMATIC FEVER AND RHEUMATOID (ATROPHIC) ARTHRITIS'
Recently Tillett and Garner (1) have demonstrated that broth cultures of hemolytic streptococci of human origin rapidly liquefy the fibrinclot of human plasma. Cultures of other species of bacteria obtained from human beings fail to exhibit this property. Tillett, Edwards and Garner (2) further found that the plasma clot from patients convalescent from acute hemolytic streptococcal infections was highly resistant to the action of broth cultures of a human hemolytic streptococcus. The observations of Tillett and his coworkers were confirmed by Hadfield, Magee and Perry (3). Previously, we (4, 5, 6) have studied groups of patients with rheumatic fever and rheumatoid arthritis to determine what, if any, relationship exists between streptococcal infection and these diseases. In continuing these studies, we have determined the resistance to fibrinolysis of the blood plasma of patients with rheumatic fever and rheumatoid arthritis and of control groups of patients. METHODS OF STUDY All patients were studied while in the hospital. The methods employed in the determination of the resistance to fibrinolysis of blood plasma followed closely the method described by Tillett and his coworkers (1, 2). At weekly intervals 5 cc. of blood were collected. Potassium oxalate, 0.01 gram per 5 cc. of blood, was employed as an anticoagulant. The plasma was separated by centrifugalization and was used within two hours after its withdrawal. A hour cultures of this organism were grown in veal muscle infusion broth, adjusted to a pH of 7.2 and containing one per cent of peptone and 0.2 per cent of Na2HPO4. To 0.2 cc. of fresh oxalated plasma was added 0.8 cc. of sterile physiological salt solution. To this 0.5 cc. of a fresh broth culture of the CO strain of the hemolytic streptococcus was added and well mixed. Then 0.25 cc. of a 0.25 per cent sterile solution of CaCl2 was added and well mixed. The tubes were placed immediately in a water bath at 37.5°C. With repeated observations the times of solid coagulation and, finally, complete dissolution of the clot were recorded. All tests in which the plasma clot was resistant to dissolution after 24 hours' incubation were arbitrarily terminated. The classification of the degree of resistance of the plasma clot as suggested by Tillett, Edwards and Garner (2) was followed. The highest degree of resistance shown by a patient's plasma during the period of observation was utilized in the classification shown in RESULTS Determinations of the resistance to fibrinolysis of 520 samples of plasma from 135 individuals were made. Their ages varied between thirteen and seventy years. No correlation could be established between the age of the individual and the ability to develop resistance to fibrinolysis. The plasmas from groups of individuals without evidence of hemolytic streptococcal infection were studied. Samples of plasma from fourteen apparently normal laboratory workers were followed at frequent intervals for several months. A group of twenty-two patients with pulmonary tuberculosis, lobar pneumonia, herpes zoster and lung abscess were studied on fifty-one occasions. 11
