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  • 1
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Tinea capitis is the most common dermatophytosis of childhood with increasing incidence. Whereas griseofulvin is considered by many as the mainstay of treatment, newer oral antifungal agents, including fluconazole, itraconazole and terbinafine have demonstrated higher efficacy, resulting in shorter treatment durations. Objectives We aimed to determine the optimum regimen for the treatment of childhood tinea capitis with itraconazole. Methods A mycological culture outcome-dependent combination of a 28-day continuous and facultative additional 14-day courses with itraconazole was used in 42 children (20 girls; 22 boys) aged 12–140 months (mean 66) with tinea capitis due to Microsporum canis (n = 26) and Trichophyton violaceum (n = 16). The drug was given orally according to the patients’ body weight (50 mg daily for 〈 20 kg; 100 mg daily for ≥ 20 kg) over 4 weeks. Direct microscopy and fungal culture as a parameter for efficacy were repeated 2 weeks after termination of treatment. Assessment of efficacy was based on the evaluation of results from light microscopy and culture at 8 weeks after initiation of treatment, and in the case of a further positive mycological culture at 14 and 20 weeks, respectively. A positive fungal culture at these times resulted in an additional course for 2 weeks with the initially chosen itraconazole dosage. Results In 34 of 42 patients a single 4-week course of itraconazole resulted in a complete mycological cure of lesions as demonstrated by light microscopy and mycological culture. Four of 42 patients had to be treated by a second itraconazole course for 2 weeks, and four children received a third course of itraconazole for 2 weeks until all lesions showed negative direct microscopy and mycological culture. No abnormal haematological or biochemical results occurred. Apart from transient, completely reversible indigestion in two children, no side-effects were observed. Conclusions A culture-based 28-day continuous therapeutic regimen plus facultative cultural outcome-dependent additional 14-day courses of a body weight-adapted dosage of itraconazole in tinea capitis due to M. canis and T. violaceum is discussed; this offers the advantage of an effective therapy with complete negative direct microscopy as well as negative cultural results, within a shorter active treatment period (cf. previous studies with continuous administration of itraconazole).
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Transfersome® is a drug delivery technology based on highly deformable, ultraflexible lipid vesicles which penetrate the skin when applied non-occlusively.Objectives  To assess the advantages of this carrier-based formulation in humans, the efficacy and the atrophogenic potential of triamcinolone acetonide (TAC) in Transfersome® was compared with commercially available TAC-containing cream and ointment.Methods  Healthy volunteers were enrolled in double-blind, placebo-controlled clinical trials with random study medication assignment to the test areas.Results  A 10-fold lower dose of TAC in Transfersome® (2·5 µg cm−2) was bioequivalent to 25 µg cm−2 TAC in conventional formulations as measured by erythema suppression (cream: P = 0·01, ointment: P 〈 0·001). A skin blanching assay revealed different kinetics of the formulations, with a delayed onset of action of the Transfersome® and ointment preparations. Ultrasonic measurements revealed a significantly reduced atrophogenic potential. There was a 12·1% reduction in skin thickness given by TAC in Transfersome® compared with a 21·1% reduction given by a bioequivalent dose in TAC cream after a 6-week treatment period (P = 0·007).Conclusions  Transfersome® may significantly improve the risk–benefit ratio of topically applied glucocorticosteroids.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Background Colonization of human skin by Staphylococcus aureus is a characteristic feature of several inflammatory skin diseases, which is often followed by tissue invasion and severe cell damage. A crucial role has been attributed to staphylococcal haemolysins in the cytotoxicity to epidermal structures. Objectives To investigate haemolysin-independent virulence to human keratinocytes. Methods The stable α-haemolysin, β-haemolysin double-negative S. aureus mutant DU 5720 was compared with the fully virulent parent strain 8325-4 and with its isogenic fibronectin-binding protein A/B-negative variant DU 5883 in an invasion model. Results This assay showed dose-dependent internalization of all the strains investigated by human HaCaT keratinocytes, with reduced internalization of DU 5883. Transmission electron microscopy revealed adhesion of staphylococci to cellular pilus-like extrusions, followed by the embedding of the bacteria in cellular grooves. Following attachment to the keratinocytes the staphylococci were engulfed into vesicles within the cytoplasm where some bacteria persisted for 24–48 h. Addition of cytochalasin D strongly reduced the bacterial uptake, suggesting an active keratinocyte process. Bacterial invasion was followed by severe keratinocyte cell damage showing the morphological changes of cytotoxic and, to a lesser extent, apoptotic cell death as determined by the trypan blue exclusion test and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay. The highest levels of lethal cytotoxicity were observed in haemolysin-producing strains, whereas the induction of apoptosis seemed to depend on internalization. Conclusions Staphylococcal invasion of human keratinocytes represents a potent staphylococcal virulence factor, which, independently of α- and β-haemolysins, leads to necrotic and apoptotic cell damage.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Fourteen patients suffering from acute, exacerbated atopic eczema were screened for changes in collagen I and collagen III metabolism in serum (n = 11), urine (n = 11) and skin biopsies (n = 9) before and after medium-dose ultraviolet (UV) A1 phototherapy (15 exposures of 50 J/cm2 over a 3-week period, total dose 750 J/cm2). Mature collagen I and, to a lesser extent, mature collagen III were found to be decreased after the therapy in skin samples from the irradiated patients. As markers of collagen I degradation, the cross-links pyridoline and deoxypyridoline were analysed in urine using high-performance liquid chromatography. Both cross-links were found to be mildly increased after UVA1 phototherapy, without reaching statistical significance. As markers of de novo collagen synthesis we screened for the procollagen I-carboxyterminal peptide (PICP) and procollagen III-aminoterminal peptide (PIIINP) levels in serum and skin. The ratio of PICP to PIIINP in serum dropped significantly after the UVA1 phototherapy, suggesting a different impact of UVA1 on the two collagens. These findings were paralleled by a diminished ratio of PICP to PIIINP in tissue samples. Staining for matrix metalloproteinase 1 (MMP-1) and its specific counterpart, tissue inhibitor of MMP-1 (TIMP-1), showed slight increases for both proteins by therapeutic UVA1; this was also seen in serum for TIMP-1 but not MMP-1. In our study, high-energy UVA1 doses induced changes of the skin collagens in patients with atopic eczema which are measurable by their metabolites in serum and urine.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 276 (1978), S. 379-381 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The diamonds analysed were classified into the different types using infrared and ultraviolet spectral characteristics, and conductivity measurements. Diamonds 1 to 6 (Table 1) were flawless light yellow octahedra. In all the other diamonds inclusions and flaws were visible at 50 magnification ...
    Type of Medium: Electronic Resource
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