Gentamicin nephrotoxicity--morphologic and pharmacologic features.
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Biomedical subjects
Publications and source records attributed to D N Gilbert.
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4-Hydroxycyclophosphamide, phosphoramide mustard, and nor-nitrogen mustard are compounds considered as candidates for the biologically active, alkylating metabolite of cyclophosphamide. These compounds were tested for inhibition of chemotaxis in neutrophils from normal human donors. Of those tested, only 4-hydroxycyclophosphamide caused a significant (p less than 0.01) decrease in the chemotactic index. The chemical precursor of 4-hydroxycyclophosphamide, 4-hydroperoxycyclophosphamide, caused a barely significant (p less than 0.05) decrease; 4-ketocyclophosphamide had no effect.
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The in vitro susceptibility of group D streptococci (enterococci) to ampicillin was studied comparing the results obtained in Mueller-Hinton broth (MHB) with those obtained in normal human serum (NHS). The rate of enterococcal killing was consistently faster in NHS than in MHB at equivalent ampicillin concentrations. Whereas an increasing media pH appeared to decrease the susceptibility of enterococci to ampicillin by determinations of the minimum bactericidal concentration (MBC) of ampicillin, an opposite increase in susceptibility was observed when the rate of bactericidal activity was studied. This difference may be explainable by the instability of ampicillin at higher pH values. In both MHB and NHS a paradoxical decrease in the rate and extent of enterococcal killing occurred as the ampicillin concentration was increased above the minimally effective concentration. These results demonstrate the inadequacies of the MBC test system and the need for standardizing test media used for determining the susceptibility of enterococci to ampicillin.
Five patients with a bacterial causation of postoperative osteitis pubis were treated during a three year period. In each patient, the bacterial cause was suggested by a known infectious process adjacent of the symphysis pubis. It is suggested that a bacterial causation be considered for the clinical and roentgenographic syndrome of osteitis pubis if a contigous infectious process is present.
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Squirrel monkeys were significantly depleted of complement by a nontoxic protein constituent of cobra venom, and the influence of cobra factor (CoF) treatment on the course of Escherichia coli bacteremia was studied. Striking neutropenia occurred rapidly in control animals while the rate of occurrence of neutropenia was 20 to 30 times slower in the CoF-treated animals, suggesting that the E. coli-induced neutropenia was at least partially a complement-mediated response. In the CoF-treated monkeys, the initial rate of clearance of the E. coli from the circulation tended to be slower and the resultant levels of bacteremia were higher than in control animals. These observations are consistent with a hypothesis that complement-mediated neutrophilic leucocyte function is an important host defense mechanism in gram-ngeative bacillary bacteremia.
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A 33-year-old woman with quiescent systemic lupus erythematosus developed meningitis due to a penicillin-resistant strain of Streptococcus pneumoniae. After an initial failure of penicillin therapy, the patient responded to cefotaxime. The meningitis was complicated by total neurosensory hearing loss. Howell-Jolly bodies noted on peripheral blood smear led to a radionuclide spleen scan, which documented functional asplenia. This woman is the second patient in the United States with meningitis caused by a strain of S. pneumoniae moderately resistant to penicillin G (minimal inhibitory concentration, 1.0 microgram/mL). The resistant isolate displayed resistance to penicillin that was not of enzymatic origin but rather was due to an alteration of penicillin-binding proteins. This experience illustrates the importance of testing the in vitro susceptibility of the pneumococcus to penicillin G.
This article describes the current collaborative effort of the U.S. Food and Drug Administration and the Infectious Diseases Society of America to generate new general and disease/organism-specific guidelines for the evaluation of anti-infective agents. The description includes examples of proposed changes from draft documents. If approved and implemented, the envisioned changes should enable investigators and sponsors to improve the quality of clinical trials of anti-infective drugs. The ultimate goal is to provide physicians with the best information about new drugs and thus to enhance the care of patients with infectious diseases.
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