Chronic mucocutaneous candidiasis (CMC) constitutes a selective inability to clear infection with the yeast Candida, resulting in persistent debilitating inflammation of skin, nails, and mucous membranes. The underlying defect is unknown. Only recently, IL-17-producing T cells have been reported to be involved in clearing Candida infections. In order to characterize T cellular immune response to Candida, we analyzed T-cell cytokine secretion to Candida antigen and mitogenic stimuli in CMC patients, immunocompetent patients suffering from acute Candida infection, and healthy volunteers. Peripheral blood mononuclear cells (PBMCs) from CMC patients produced significantly lower amounts of IL-17 and IL-22 mRNA and protein when stimulated with Candida albicans or mitogen in vitro compared with that in matched healthy individuals. Additionally, PBMCs from immunocompetent Candida-infected patients secreted more IL-17 and IL-22 than those of both CMC patients and healthy, non-infected controls. Flow cytometry revealed a decreased number of CCR6+ IL-17-producing T cells in CMC patients, whereas the amount of CCR6+/CCR4+ cells was not altered. Levels of differentiating cytokines for human Th17 cells, IL-1beta and IL-6, tended to be higher in CMC patients. The inability to clear C. albicans in CMC patients could be due to a defect in the immune response of IL-17-producing T cells.
Introduction: In the literature, data on the effects of gender and age on the pressure data of anorectal manometry differ. Possible reasons are investigation of only small numbers of healthy people and comparison of only 2 groups with large age differences. In addition, data about the influence of gender or age on anorectal sensation are sparse. Therefore, the aim of the present study was to determine the influence of gender and age on anorectal manometry in a large healthy female and male cohort spanning a great age range. Methods: Anorectal manometry was performed in 72 women and 74 men with a median age of 64 years in both groups (ranges: women 22–90 years; men 23–88 years). We determined mean anal resting and squeeze pressure as well as minimal rectal balloon volume for perception and for urge/desire to defecate. The Mann-Whitney U test was used to analyze for gender differences, regression analysis to search for age influences. Results: Squeeze pressure (p = 0.007) and perception threshold (p < 0.001) are significantly lower in females, while the mean resting pressure and urge threshold are similar in females and males. Mean resting pressure (women p < 0.0001; men p = 0.03) and mean squeeze pressure decrease (women p < 0.0001; men p = 0.004) with age. An age-related increase in sensory thresholds (= decreased rectal sensitivity) is only seen in females (perception threshold p = 0.01; urge threshold p = 0.04). Conclusion: Most of the parameters measured by anorectal manometry (anal canal pressure, sensory thresholds) are influenced by gender and age. Therefore, the results of anorectal manometry must be interpreted in relation to sex- and age-adapted normal values.
The in vitro activity of voriconazole (UK-109, 496), a new antifungal triazole derivative, against 650 clinical isolates of yeasts, moulds and dermatophytes was compared with that of itraconazole, ketoconazole, amphotericin B and griseofulvin. The geometric means of the minimum inhibitory concentrations (MICs) of voriconazole were 0.05 microgram ml-1 against yeasts (n = 187), 0.58 microgram ml-1 against moulds (n = 260) and 0.08 microgram ml-1 against dermatophytes (n = 203). The overall activity of voriconazole against yeasts and moulds was good, being similar to that of itraconazole, ketoconazole and amphotericin B. Voriconazole was highly effective against Aspergillus fumigatus (mean MIC 0.23 microgram ml-1) and other Aspergillus species and showed noteworthy activity (mean MICs 0.08-0.78 microgram ml-1) against emerging and less common clinical isolates of opportunistic moulds, such as Alternaria spp., Cladosporium spp., Acremonium spp., Chrysosporium spp. and Fusarium spp. On the other hand, voriconazole was less active in vitro than the comparative agents studied against various species of zygomycetes, such as Mucor spp., Rhizopus spp. and Absidia spp. Voriconazole and the other two azoles, itraconazole and ketoconazole, were more active than griseofulvin in vitro against most dermatophytes tested.
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