[Experiences with streptokinase-streptodornase (Varidase) in the HNO clinic].
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During of potency for SK/SD solutions used as recall antigens in delayed hypersensitivity skin testing had not been determine. In a study of 50 normal subjects over a one-year period it was found that antigenicity diminished with time. At four months, however, there was no evidence of impaired potency at any of the dilutions tested. Authors suggest that reconstitution of SK/SD be made every three months when kept at room temperature and that increasing strengths be applied beginning at 4/1 units.
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STUDY OBJECTIVE: To investigate the effects of streptokinase and deoxyribonuclease (DNase) on the viscosity of pus to assess whether the DNase in the old preparation of streptokinase-streptodornase used intrapleurally to treat empyema was contributing to easier drainage of pus compared with purified streptokinase. DESIGN: In vitro measurement of pus viscosity. PATIENTS: Pus from three patients with surgically drained soft tissue abscesses and from six patients with empyema thoracis of varying etiology was studied. INTERVENTIONS: Pus samples were incubated with saline solution as control and with streptokinase, streptokinase-streptodornase, human recombinant DNase, and a mixture of streptokinase and DNase in concentrations approximating those achieved in clinical practice. RESULTS: Purified streptokinase had little effect on pus viscosity, with a mean reduction of 11.1% in the surgical specimens and 1.7% in the empyema samples. Streptokinase-streptodornase reduced viscosity by a mean of 52.8% in the surgical samples and 94.8% in the empyema samples. Human recombinant DNase reduced viscosity by a mean of 32. 79% in surgical samples and 93.4% in empyema samples. Adding streptokinase to human recombinant DNase produced no further reduction in viscosity. Final viscosities in samples treated with DNase were very similar whatever the starting viscosity. CONCLUSIONS: DNase significantly reduces pus viscosity, whereas streptokinase has little or no effect, and in empyema may work simply by breaking down loculations. Clinical studies should be undertaken to see if these in vitro changes produce clinical benefits. The simple viscometer devised for these experiments may also prove useful in other contexts.
Patients with loculated parapneumonic effusion or empyema are sometimes treated with streptokinase or urokinase in an attempt to facilitate pleural fluid drainage by liquefying the pleural exudate and destroying the fibrin membranes producing the loculation. This study evaluated the effectiveness of streptokinase, urokinase, and Varidase (the combination of streptokinase and streptodornase) in liquefying gummy, purulent, exudative material from loculated empyemas. An empyema was created by injecting 10(8) Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. Twenty specimens, each containing 0.5 g of purulent material obtained 5 days after empyema induction, were placed in test tubes. Streptokinase (15,000 IU), urokinase (10,000 IU), Varidase (4,000-15,000 IU streptodornase + 15,000 IU streptokinase) or saline was added to five sets of four test tubes each. The amount of nonliquefied material that remained after incubation with the fibrinolytic agents was quantitated. Over the 6-h incubation period, the amount of nonliquefied material decreased from 0.5 g to 0.02 g in the Varidase group but never decreased to less than 0.4 g in any of the other three treatment groups. Liquefaction of thick pleural exudates from rabbits with empyema can be achieved with Varidase but not with streptokinase or urokinase.
Human migration inhibitory factor (MIF) produced by peripheral blood mononuclear cells stimulated with purified protein derivative, tetanus toxoid, streptokinase-streptodornase, or Candida albicans antigen was analyzed by gel filtration and isoelectrofocusing. In all cases, supernatants harvested after a 24-hr exposure of the mononuclear cells to the antigen yielded only one MIF species with an isoelectric point of 5. In contrast, isoelectrofocusing of supernatants obtained from cells exposed to the antigen for an additional 24 hr demonstrated that different antigens induce the elaboration of different MIF species. Streptokinase-streptodornase and tetanus toxoid induced the production of one MIF species with an isoelectric point of 5 (pH 5-MIF). Stimulation of cells with Candida antigen elaborated a MIF species with an isoelectric point of 3 (pH 3-MIF). In contrast, stimulation of cells with purified protein derivative induced the production of both pH 3-MIF and pH 5-MIF.
In vitro lymphocyte proliferation in response to phytohemagglutinin and streptokinase-streptodornase and delayed dermal hypersensitivity to several antigens were assessed in patients with mild viral upper respiratory infections. The response to phytohemagglutinin in 18 patients was not diminished during the viral infection. Deoxyribonucleic acid synthesis induced by streptokinase-streptodornase remained unaffected by the viral illness in five patients, and skin test reactivity was not depressed during the viral infection. Thus, it appeared that localized viral upper respiratory infections were not associated with suppression of systemic cell-mediated immunity.
Serum specimens from 12 sick and 20 normal horses were examined for levels of different classes of immunoglobulin (Ig) by a single radial immunodiffusion. The level of IgA in the sera of sick horses was about 50% lower than in the sera of normal horses. By contrast, the level of serum IgG was higher in sick than in normal horses. Phytohemagglutinin (PHA) responsiveness of blood lymphocytes showed transient suppression during the stage of severe diarrhea. The regaining of PHA responsiveness of lymphocytes was observed simultaneously with the recovery process. However, the responsiveness of lymphocytes in recovered horses was still markedly lower than in normal horses. Allergic reactions in sick and normal horses were studied by observing dermal response to the injections of saline extracts from some of the horse feeds. A delayed hypersensitivity reaction to streptokinase-streptodornase and PHA was also studied. The allergic reactions to these extracts were not induced in either sick or normal horses; however, inflammatory response to the extracts was about 50% greater in normal than sick horses. Response to the intradermal injection, either streptokinase-streptodornase or PHA, was significantly greater in normal horses than sick horses. These findings are discussed with respect to the pathogenesis of chronic diarrhea and the complexity of immunodeficiency demonstrated in this disease. The possibility that transient defects of cell-mediated immunity may predispose to chronic diarrhea is proposed.
Cell-mediated immunity (CMI) was assessed during infection and after convalescence in 12 patients with influenza pneumonia and 10 patients with bacterial pneumonia. The patients with influenza pneumonia had a marked impairment of skin test reactivity, and their lymphocytes showed a diminished response to phytohemagglutinin and streptokinase-streptodornase stimulation in vitro. Suppression of CMI was related to the severity of the pneumonia. Patients with bacterial pneumonia showed as great a suppression of the response to phytohemagglutinin and streptokinase-streptodornase as the patients with viral pneumonia. All parameters of CMI returned to normal in both groups after convalescence. The depression of CMI could not be related to a decrease in the number of thymus-derived lymphocytes or to serum-suppressive factors in these patients.
During the course of preliminary clinical trials of an improved membrane filter blood culture system, filter plugging produced by a gelling of the lysing solution was observed when the patients had high leukocyte counts. A solution of streptokinase-streptodornase (Varidase, Lederle Laboratories) dissolved or prevented the gel and permitted rapid filtration without plugging. With streptokinase-streptodornase incorporated in the filtration procedure, a comparison of several culture systems was carried out on 176 blood cultures. Brucella broth with and without sodium polyanethol sulfonate, a prereduced osmotically stabilized broth, pour plates, and an improved aerobic membrane filter system were compared. The membrane filter system yielded 29 of the total of 37 positive cultures, far surpassing all other systems. Eight of these cultures were detected first by the filter technique, and 13 were positive only in this system. Nineteen of the 37 positive cultures were from patients on antimicrobial agents. Fourteen of these were detected by the filter, twice the number detected by any of the other systems.
Lymphocyte transformation responses to the antigen streptokinase-streptodornase were evaluated in a group of 14 healthy elderly subjects by enumeration of antigen-responsive cells, first-generation responding lymphocytes and progeny generated per responding cell. Peak lymphocyte transformation responses to the antigen were diminished in the elderly subjects when compared to a group of young adult subjects. Antigen-responsive cells were found by limiting-dilution analysis to be significantly decreased in the elderly subjects (geometric means of antigen-responsive cells per 10(5) mononuclear cells = 4.35 in the elderly versus 14.79 in the younger group, P less than 0.001). The number of cells recruited into the first-generation lymphocyte response per antigen-responsive cell were equivalent in the two groups. Also, the proliferation into progeny of each first-generation lymphocyte was of the same magnitude for the elderly and young subjects within the six to eight cell divisions required for this response. Therefore, in this system the diminished total lymphocyte transformation responses to the antigen streptokinase-streptodornase of cells from elderly humans can be accounted for by a reduction in the number of lymphocytes initially responsive to the antigen.
100 healthy persons were investigated to find out whether there is a correlation between a lymphocyte stimulation (3H-thymidine incorporation in the lymphocyte transformation test) with phytohaemagglutinin, pokeweed mitogen and concanavalin A and the in vivo reactivity to intracutaneous phytohaemagglutinin application (measured as medium diameter of infiltrates). Further we searched for an influence of positive or negative reactivity to the specific antigens trichophytin, candidin and streptokinase-streptodornase. 1. There is a good qualitative correlation in normal persons between in vitro lymphocyte stimulation by phytohaemagglutinin, pokeweed mitogen and concanavalin A and the medium diameter of infiltrates after intracutaneous application of 2 mug phytohaemagglutinin. Using lower doses of phytohaemagglutinin no such correlation could be found. A quantitative correlation between the medium diameter of infiltrates and lymphocyte transformation by phytohaemagglutinin and pokeweed mitogen cannot be demonstrated. For concanavalin A there is a negative correlation significant at the 99% level. 2. In vivo reactivity to phytohaemagglutinin does not differ in persons with negative and positive reactions to the specific antigens. 3. Lymphocyte stimulation by phytohaemagglutinin, pokeweed mitogen and concanavalin A of persons with positive reactions to trichophytin, candidin and streptokinase-streptodornase is significantly greater than in those with negative reactivity. 4. The results indicate in vivo phytohaemagglutinin testing as a good screening method to judge cell-mediated immunocompetence. The general applicability for differentiation of immunodeficient and immunocompetent patients is to be further investigated.
Cell-mediated and humoral immune responses were studied in 43 healthy volunteers aged between 15--77 years. Besides various skin tests with the antigens candida, trichophyton, mumps, streptokinase-streptodornase, tuberculin, DNCB and KLH also in vitro experiments measuring the immunoglobulin- and complement concentrations, the antibody production to KLH, the lymphocyte transformation rate to PHA, Pokeweed, Con A, PPD were done nearly in all patients. The responsiveness of lymphocytes to PHA and Con A and the sensitization of the skin with DNCB declines in the aged humans, beginning already at the 4th-5th decade. The skin tests with candida, trichophyton were not significantly different in the various age groups. The number of persons with positive skin reactions to the antigens mumps and streptokinase-streptodornase decreased also with advancing age. Lymphocyte transformation and skin test with PPD or tuberkulin were markedly increased beyond the age of 30. Serum levels of immunoglobulins, complement components, the antibody production to KLH, and the lymphocyte transformation rate to Pokeweed were not significantly different in the age groups. Correlation between the tests within each person could not be detected. We made the experience that only a few tests are not enough for the evaluation of an immunodeficient state, but that several tests, a so called TEST BATtery", are necessary.
We examined patients with rheumatoid arthritis for cellular sansitivity to native human Types I, II and III collagens. Mononuclear cells from 50 patients with rheumatoid arthritis, 21 with other inflammatory arthritides, 20 with osteoarthritis and 20 normal subjects were evaluated for the in vitro production of leukocyte inhibitory factor in response to collagen and a control antigen, streptokinase-streptodornase. By this assay, cells from 37 (74 per cent) and 39 (78 per cent) of the patients with rheumatoid arthritis responded to Types II and III collagens, respectively. In contrast, cells from the 41 patients with other kinds of arthritis and the normal group did not produce this lymphokine to collagens. There was no response to Type I collagen or to denatured alpha chains of these collagens. All four groups responded equivalently to streptokinase-streptodornase. These data demonstrate that most patients with rheumatoid arthritis exhibit cellular sensitivity to Types II and III collagens.