Ellepola, Arjuna Nishanatha Bandara (2000) PhD Thesis: The post-antifungal effect (PAFE) and its impact on the pathogenic attributes of Candidaalbicans Abstract: The opportunistic fungal pathogen Candida albicans is the main aetiological agent of oral candidosis. The common antimycotics used in the treatment of candidoses comprise the polyenes (nystatin and amphotericin B), the azoles (ketoconazole and fluconazole), and the DNA analogue, 5-fluorocytosine. In the oral cavity the diluent and flushing action of saliva tend to reduce the availability of these agents with resultant limited exposure of pathogens to the drugs. However, the behaviour of fungi under the latter conditions is ill-understood. The post-antifungal effect (PAFE) is a novel concept which refers to the suppression of fungal growth following limited exposure to antimycotics and subsequent removal of the drug. This thesis relates to an enquiry into the P AFE of five different antimycotics on ten oral isolates of C. albicans and its impact on the pathogenic attributes of these isolates, including the adherence to denture acrylic surfaces and buccal epithelial \cells (BEC), the relative cell surface hydrophobicity (CSH) and germ tube formation. The mean PAFE of nystatin, amphotericin B, 5-fluorocytosine, ketoconazole and fluconazole on C. albicans isolates were 2.89, 2.83, 3.18, 0.65 and 0.16 hours, respectively. On evaluating the adherence to denture acrylic surfaces during the PAFE period, the foregoing antimycotics elicited a mean percentage reduction of 86.48%, 90.85% (p < 0.01 for all isolates), 66.72%, 65.88% and 47.42% (p < 0.01 for 70% to 85% of the isolates), respectively. A similar analysis of the adherence to BEC revealed a mean percentage reduction of 72.88% (p < 0.01), 16.52% (p < 0.01 for 30% of the isolates), 40.16% (p < 0.01) and 24.36% (p < 0.01 for 70% of the isolates), following exposure to nystatin, 5-fluorocytosine, ketoconazole and fluconazole, respectively. Ultrastructural analysis revealed a minority of internally collapsed cells with an intact cell wall leaving "cell ghosts" and deflated cells following exposure to nystatin though other drugs did not elicit perceptible changes. When the effect of drug exposure on the CSH of Candida was examined, a significant reduction was observed for nystatin (27.14%; p = 0.01) and ketoconazole (19.47%; p = 0.04) but not for the rest. Further, when the relationship between adhesion to BEC and CSH of the isolates was evaluated a positive correlation emerged in the yeasts pre- exposed to 5- fluorocytosine, ketoconazole and fluconazole (γ= 0.48 - 0.55; p<0.001 for all), but not nystatin. Evaluation of the ability to form germ tubes by these isolates following brief exposure to the two polyenes, the DNA analogue and the two azoles elicited a mean percentage reduction of 97.68%, 97.52% (p < 0.01 for all isolates), 12.63%,30.84%, and 15.93% (p< 0.01 for 10% to 50% of the isolates), respectively. On ultrastructural studies, abrogated attempts at germ tube formation was seen only with polyene-exposed cells. To conclude, the preceding investigations have comprehensively defmed the PAFE of common antimycotics and its possible impact on the pathogenic attributes of C. albicans. In clinical terms these novel fmdings imply that antimycotics help eliminate the pathogen at high concentrations while suppressing their virulence on minimal exposure to sub- therapeutic concentrations.
Agitation? Delirium? Both? and What to Do About It Kathryn T. Von Rueden RN, MS, ACNS-BC, FCCM Clinical Nurse Specialist, R Adams Cowley Shock Trauma Center, Assistant Professor University of Maryland, School of Nursing Delirium: “a part of the scenery ?” Ely, W: Semin Respir Crit Care Med. 2001;22(2) Delirium : DSM-IV Diagnostic Criteria reduced clarity of awareness of the
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