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Biomedical subjects

A L Kisch

Publications and source records attributed to A L Kisch.

At least 19 recordsLinked to original sources

Withdrawal of immunosuppresive agents in the treatment of disseminated coccidioidomycosis.

Disseminated coccidioidomycosis is a systemic fungal infection that causes high mortality in the renal transplatn patient. Cell-mediated immunity, which appears to be the relevant host defense mechanism, is impaired by the immunosupressive agents used to prevent allograft rejection. In the case presented, immunosuppressive therapy was stopped as an adjunct to treatment of this infection. The patient has shown evidence of improvement, and his allograft has continued to function nine months after the withdrawal of immunosuppressive therapy and 18 months after the diagnosis. In vitro lymphocyte function studies indicate that the impairment in cell-mediated immunity detected prior to withdrawal of immunosuppressive therapy has persisted, probably accounting for allograft survival. Withdrawal of immunosuppressive therapy may prolong survival in renal transplant patients with disseminated coccidioidomycosis. Additionally, depression in cell-mediated immunity associated with the fungal infection itself may be sufficient to prevent allograft rejection in these patients.

Adult↗

Synergistic nephrotoxicity of amphotericin B and cortisone acetate in mice.

Striking mortality in mice receiving amphotericin B and cortisone acetate concomitantly prompted studies to characterize the toxic interaction of these two drugs further. Adult female CD-1 mice received daily injections of cortisone acetate (0--50 mg/kg subcutaneously) and/or amphotericin B (0--12.5 mg/kg intraperitoneally) in a checkerboard combination dosage pattern for 30 days. Dosages of amphotericin B and cortisone acetate that produced little or no mortality individually produced significant (P less than 0.005) mortality in combination. Light and electron microscopic studies of sections of brain, heart, lung, adrenal gland, liver, and kidney revealed only renal lesions. These appeared within six days, were dose-related in severity, and were not produced by either drug alone. The lesions consisted of focal swelling of proximal, distal, and collecting tubular cells which progressed to necrosis and intraluminal cast formation. These findings may be relevant to the development of nephrotoxicity in patients treated simultaneously with amphotericin B and corticosteroids.

Acetates↗

Comparison of the in vitro activity of several cephalosporin antibiotics against gram-negative and gram-positive bacteria resistant to cephaloridine.

The in vitro activity of each of two oral [cefatrizine (BL-S640), cephalexin] and three parenteral (cefamandole, cefazolin, cephapirin) cephalosporin antibiotics was compared with that of cephalothin against 168 clinical isolates of gram-negative and gram-positive bacteria selected as resistant to 20 mug of cephaloridine per ml on the basis of agar dilution susceptibility test data. Each of the five other cephalosporins inhibited a greater percentage of gram-negative bacillary isolates than did cephalothin or cephaloridine, with minimal inhibitory concentration values ranging 2- to 50-fold lower. Significant differences between minimal inhibitory concentrations of the compounds tested were also observed in tests against strains of Streptococcus faecalis and of methicillin-resistant Staphylococcus aureus. Potential advantages of including more than a single cephalosporin antibiotic in the panel of antibiotics used for routine susceptibility testing, suggested by these observations, are discussed.

Bacteria↗

Corticosteroids, serum, and phagocytosis: in vitro and in vivo studies.

The phagocytic-bactericidal capacity (PBC) of human polymorphonuclear leukocytes (PMNs) for strains of Klebsiella (K) and of Enterococcus (E) was unaffected in vitro by the presence of 100 mug of either hydrocortisone (HC) or of methylprednisolone (MP) per ml in the medium. At higher concentrations (500 to 2,000 mug/ml) both compounds impaired PBC-K and PBC-E, but the latter was less sensitive to steroid-induced inhibition. In addition to interfering with intracellular killing of both organisms by PMNs, 2,000 mug of HC per ml also inhibited ingestion of E, although not of K. Steroid-induced inhibition of PBC-K in vitro was completely abolished by increasing the concentration of serum used as opsonin. The PBC-K of human PMNs obtained 30 min after intravenous injection of 1 g of MP was unimpaired in vitro in the presence of 10 to 90% simultaneously obtained autologous serum containing 42 mug of MP per ml. These findings suggest that short-term, high-dosage administration of MP is unlikely to produce clinically significant impairment of intraleukocytic bacterial killing.

Blood↗

Dimethyl sulfoxide-induced reversion of several features of polyoma transformed baby hamster kidney cells (BHK-21). Alterations in growth and morphology.

Cells of a polyoma virus transformed clonal line (Cl-I) of baby hamster kidney fibroblasts (BHK-21) were grown in medium containing 2 percent dimethylsulfoxide (DMSO). Unlike the untransformed BHK-21 cells, Cl-I cells adapted to replication in the presence of DMSO, and they exhibited a rapidly reversible phenotypic reversion of a number of properties characteristic of the transformed state. Restoration of density dependent growth inhibition with accumulation of cells in the G(1) phase of the cell cycle occurred and was associated with restoration of contact dependent behavior and with reversion of histological and ultrastructural features towards those which characterize untransformed cells. Concomitantly, Cl-I cells grown in 2 percent DMSO lost the ability to form colonies in semisolid medium. The data presented suggest that DMSO alters the expression of cellular functions which were altered as a result of viral transformation and which may be involved in cell tumorigenicity.

Animals↗