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Biomedical subjects

D T Durack

Publications and source records attributed to D T Durack.

At least 109 records · Page 6Linked to original sources
PubMed1981

Potential value of cefoperazone in bacterial meningitis: experimental studies.

To assess the potential value of cefoperazone in treating bacterial meningitis, its pharmacokinetics in the cerebrospinal fluid of rabbits were studied. Cefoperazone penetrated poorly into the cerebrospinal fluid of rabbits with uninflamed meninges, but in the presence of meningitis concentrations increased 2- to 3-fold. These concentrations were above the minimum inhibitory concentrations for the majority of Enterobacteriaceae, indicating the potential value of cefoperazone in treating bacterial meningitis. The half-lives of cefoperazone and moxalactam in cerebrospinal fluid, measured by a bioassay, were marked prolonged by meningeal inflammation. In contrast, the half-life of cefotaxime in cerebrospinal fluid was short. Consequently both cefoperazone and moxalactam provided significantly better antibacterial effect in cerebrospinal fluid than did cefotaxime.

Animals↗
PubMed1981

Influence of agglutinating antibody in experimental cryptococcal meningitis.

A model for chronic Cryptococcus neoformans meningitis in corticosteroid-treated rabbits was used to determine the influence of pre-formed agglutinating antibody to cryptococcal polysaccharide on the progress of this infection. Immunized rabbits developed serum agglutinating antibody with a geometric mean titre of 1:32, but none was detected in cerebrospinal fluid. Prior immunization did not enhance immunity to infection, had no effect on the number of viable cryptococci in cerebrospinal fluid, and did not prevent dissemination outside the central nervous system. Future investigations in this field should focus on cellular rather than humoral defence mechanisms.

Agglutinins↗
PubMed1980

Comparison of cotrimoxazole, ampicillin, and chloramphenicol in treatment of experimental Haemophilus influenzae type B meningitis.

To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of infected rabbits, reaching 40 and 26%, respectively, of their simultaneous serum levels. Levels measured 30 and 60 min after intravenous injection exceeded the minimum inhibitory concentration of this combination for H. influenzae by 10- to 100-fold. The mean ratio of trimethoprim to sulfamethoxazole in cerebrospinal fluid was 1:22. Cotrimoxazole was as effective as ampicillin in therapy of beta-lactamase-negative H. influenzae meningitis and as effective as chloramphenicol for a beta-lactamase positive strain. These findings corroborate favorable preliminary clinical experience reported by others and indicate that cotrimoxazole deserves further study in the therapy of bacterial meningitis.

Ampicillin↗
PubMed1980

Comparison of cefoperazone, cefotaxime, and moxalactam (LY127935) against aerobic gram-negative bacilli.

This study compares the minimum inhibitory concentrations of cefoperazone, cefotaxime, and moxalactam (LY127935) for 446 aerobic gram-negative bacillary isolates and further compares the minimum inhibitory concentrations of LY127935 and these third-generation cephalosporins with those of thienamycin for Pseudomonas aeruginosa. Each antibiotic at low concentrations inhibited nearly all Enterobacteriaceae tested. Minimum inhibitory concentrations for P. aeruginosa were higher, but for a majority of strains they fell below achievable serum levels. Thienamycin and cefoperazone showed significantly greater antipseudomonal activity than did cefotaxime or LY127935. Cefoxitin-inducible resistance to LY127935 and the two cephalosporins was demonstrated among Enterobacter species but did not occur with thienamycin.

Aerobiosis↗
PubMed1980

Chronic cryptococcal meningitis: a new experimental model in rabbits.

This paper describes the salient features of a new model for chronic cryptococcal meningitis in cortisone-treated rabbits. Normal rabbits soon recovered after intracisternal inoculation of Cryptococcus neoformans, but cortisone-treated animals developed chronic progressive meningitis that was fatal in 2-12 weeks. Incidence and severity of infection was related to cortisone dose, not to inoculum size. The number of mononuclear cells that migrated into the subarachnoid spaces and cerebrospinal fluid of infected rabbits was strikingly reduced by cortisone treatment. Rabbits with cryptococcal meningitis were febrile; their high body temperature did not confer resistance to this infection. Cortisone-treated rabbits provide a new and expedient laboratory model for cryptococcal disease. Potential applications include study of the pathogenesis of cryptococcosis, investigation of the immunobiology of the CNS in chronic meningitis, and in vivo evaluation of newer anticryptococcal treatment regimens.

Adult↗
PubMed1979

Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred.

The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0.5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The proband's twin as well as another sister also had extremely low levels of hemolytic C5(approximately 0.5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients' polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection.

Adult↗
PubMed1979

Neurotoxicity of human eosinophils.

Eosinophils contain a substance that is neurotoxic when injected intracerebrally or intrathecally into laboratory animals-an effect known as the "Gordon phenomenon." We found neurotoxic activity in eosinophils from three patients with eosinophilic syndromes by injecting cell preparations into rabbits and guinea pigs. These animals developed a syndrome of muscular rigidity and ataxia, progressing to severe paralysis. No neurotoxic activity was found in preparations of polymorphonuclear or mononuclear leukocytes from normal donors. Examination of the brains of affected animals confirmed widespread loss of Purkinje cells, as described by earlier investigators. A new finding was severe spongy change occurring in the white matter of the cerebellum, brainstem, and spinal cord. Electron microscopic examination showed that vacuoles formed within the myelin sheaths of axons by separation of lamellae. Associated axonal degeneration was common and was also seen occasionally in peripheral nerves. Gray matter in the cerebral hemispheres and spinal cord was normal. This eosinophil-derived neurotoxin was partially purified by ultracentrifugation of sonicated eosinophils and fractionation of the supernate by gel filtration. Fractions with neurotoxic activity eluted at a position consistent with a molecular weight of approximately 15,000. The neurotoxic activity of this material withstood lyophilization and dialysis but was destroyed by heating to 90 degrees C. Injection of eosinophil-derived neurotoxin into laboratory animals may provide a useful short-term experimental model for study of mechanisms of damage to myelinated nerve fibers. The clinical significance of the Gordon phenomenon has yet to be established.

Animals↗