Biomedical subjects
Publications and source records attributed to R Cheung.
The susceptibilities to erythromycin, rifampin, polymyxin B, ampicillin, tetracycline, gentamicin, fusidic acid, trimethoprim, and spectinomycin of 100 strains of Bordetella pertussis isolated between 1960 and 1981 were compared. No change in susceptibility to any of these drugs was noted.
Unadsorbed, regular production pertussis vaccine was treated with polymyxin B sulphate at concentrations of 25, 50 and 100 microgram/ml. The toxic activity of treated and untreated vaccines was compared using both the limulus amoebocyte lysate test and the mouse-weight-gain test. Protective efficacy was also assessed by the mouse protection test. No discernible effect on either toxicity or efficacy of the pertussis vaccine was observed. When the vaccine was treated with 5000 microgram/ml of polymyxin, endotoxic activity assessed by the limulus lysate test appeared to be abolished.
An accurate, plate diffusion bioassay for ticarcillin, utilizing the fast-replicating Beneckea natriegens and 4% salt agar, is described in this report. Zones of inhibition were well defined after 3 h, and the limit of sensitivity was around 5.0 mug/ml. The assay is simple to carry out, and duplicate assays can be performed on as little as 40 mul of serum.
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Cell surface receptors receive, transduce and relay a variety of environmental signals. These phenomena, which have been extensively characterized in non-lymphoid cells, also appear to play a crucial role in dictating the degree of lymphocyte responsiveness. The nature of these regulatory events is only beginning to be unraveled but the adenylate cyclase-cyclic AMP axis appears to be one of the important controlling systems. Lithium appears to be as important a modulator of lymphocyte responsiveness as previously shown for a variety of other cells and the mechanism of action, in general, is consistent with its role as a putative blocker of adenylate cyclase activation. Indeed, lithium may exert its role as a regulator of lymphocyte responsiveness by acting on specific lymphocyte subpopulations. Direct proof for this is still wanting and consideration of its capacity for action as an imperfect substitute for normal extra- or intracellular cations or on the physiochemical state of the plasma membrane is necessary. Nevertheless, these studies indicate the validity of using lithium for assessing the role of the lymphocyte adenylate cyclase-cyclic AMP system in the generation and expression of regulatory signals leading to modulation of the immune system.
The mouse model of intraperitoneal sepsis with Proteus rettgeri was used to evaluate the anti-endotoxic effect of polymyxin B sulfate. An unexpected reversal of the usual protective effect of polymyxin in experimental enterobacterial sepsis was observed in which the lethality of the infection was enhanced.
Antimicrobial susceptibility determinations for three commonly used and seven seldom used antibacterial drugs against 482 strains of shigellae isolated in Ontario during 1977 and 1978 were carried out. Resistance to the first-line treatment drugs, ampicillin and tetracycline, occurred in 20.5 and 39.2% of strains, respectively. The emergence of trimethoprim-sulfamethoxazole resistance was noted for the first time in 3.2% of the strains in 1978. All strains retained their susceptibility to gentamicin, nalidixic acid, and polymyxin but were variably susceptible to chloramphenicol, cephalexin, and rifampin.
An accurate plate diffusion bioassay for chloramphenicol is described, in which the fast-replicating Beneckea natriegens and 1.5% salt agar are used. Zones of inhibition were well defined after 3 h, and the limit of sensitivity of the method was around 2 mug/ml. The concurrent presence of gentamicin did not influence the assay. The assay is simple to carry out and duplicate assays can be performed with as little as 100 mug of capillary blood.
The mouse model of intraperitoneal enterobacterial sepsis was used to evaluate the anti-endotoxic effect of polymyxin B sulfate. Single or multiple therapeutic doses of polymyxin, administered either before or after lethal challenge with Serratia marcescens, produced statistically and clinically significant protective effects.
A total of 439 clinical isolates of Candida albicans were tested for susceptibility to miconazole by the agar dilution technique. When tests were read at 48 and 24 h, 56 and 84%, respectively, of the strains were completely inhibited by 4.0 mug of miconazole per ml, the estimated upper limit of probable clinical susceptibility.
A total of 100 and 97% of Haemophilus influenzae type b strains from major infections were susceptible, respectively, to levels of rifampin and sulfisoxazole attainable in saliva. It is theoretically feasible to eliminate Haemophilus influenzae from the nasopharynx with these drugs.
Candida endophthalmitis, caused by transient candidemia, developed in a 14-year-old white girl receiving intravenous hyperalimentation. Antifungal synergism was established in vitro for the combination of amphotericin B and rifampin against the C. albicans isolate. A combined ten-day course of intravenous amphotericin B and oral rifampin was followed by the elimination of the infection and the preservation of good visual acuity.
Depending on the hematocrit, duplicate or triplicate determinations of serum amphotericin B concentration may be made on as little as 100 mul of capillary blood obtained by finger prick. In an accurate plate diffusion bioassay, using Paecilomyces varioti as the indicator organism, levels of the drug in the therapeutic range can be determined fast enough for clinicians to modify their next dose.
The in vitro antifungal activities of amphotericin B (AMB) and amphotericin B methyl ester (AME) were compared against 465 clinical isolates of Candida albicans. AMB and AME possessed comparable activity against half of the strains, but against the remainder of the strains the activity of AME was slightly lower than that of AMB. Rarely did AME show superior antifungal activity to AMB.
Amphotericin B assays on frozen serum samples (-20 degrees C) generally underestimate the serum levels obtained on promptly processed samples. The degree of the discrepancy is variable and independent of the length of time stored.
The mouse model of intraperitoneal meningococcal sepsis was used to evaluate the antiendotoxic activity of polymyxin B sulfate independent of its antibiotic effects. Administered either before or after the infective challenge therapeutic doses of polymyxin B sulfate produced small but significant increases in survival over unprotected animals. These results also suggest that endotoxin contributes to the outcome in this variety of Gram-negative infection.
Several bacteriocins, bacterial proteinaceous antibiotics, are shown to markedly inhibit the division of various established (neoplastic) mammalian cell lines. The bacteriocins tested originated from Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae, and Vibrio eltor. Using exponentially growing L60T mouse fibroblasts, the inhibitory effect was concentration dependent, and a growth inhibitory unit, equivalent to cytotoxic index 50, was established. Expression of toxicity as a function of duration of exposure to pyocin required 3 to 4 hr. DNA synthesis was inhibited and reflected the effects on growth inhibition. Maximal sensitivity to the bacteriocin was observed prior to mitosis in the G2 phase of the cell cycle.
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