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  • 1
    ISSN: 1432-2277
    Keywords: Kidney transplantation ; Legionella pneumonia ; Acute rejection ; Acute renal failure ; Thrombocytopenia ; Lung abscess
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A patient is described who developed cavitary Legionella pneumonia 2 weeks after kidney transplantation. The initial pulmonary symptoms were followed by severe thrombocytopenia and acute renal failure. Although acute irreversible graft rejection was suspected, this was not supported by the pathology findings in the resected kidney, which were compatible with tubular damage. We presume that the extrapulmonary symptoms were caused by Legionellosis.
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  • 2
    ISSN: 1432-0584
    Keywords: Key words Candidiasis ; Neutropenia ; Fluconazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections with Aspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.
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  • 3
    ISSN: 1432-0584
    Keywords: Candidiasis ; Neutropenia ; Fluconazole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections withAspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Disseminated fungal infections are increasing. However, the interactions between the body's largest population of tissue macrophages, the Kupffer cells and the fungal pathogens are scarcely understood. The aim of this study was to examine the involvement of Toll-like receptor 4 (TLR4) signalling in cytokine production, using primary cultures of rat and murine Kupffer cells exposed to Aspergillus fumigatus and Candida albicans hyphae and conidia. All fungal components induced the release of tumour necrosis factor-α (TNF-α), but with delayed kinetics compared with lipopolysaccharide (LPS). Candida albicans was the most potent inducer of TNF-α protein and mRNA and the only inducer of interleukin-10 (IL-10) in rat Kupffer cells. All fungal components induced enhanced mRNA levels of macrophage inhibitory protein-2 (MIP-2) in the cells, similar to LPS. Inhibitors of Src tyrosine kinases added to cells prior to stimulation led to attenuation in the release of both TNF-α (60%, P 〈 0.05) and IL-10 (70%, P 〈 0.05) induced by C. albicans conidia but did not influence the LPS-mediated cytokine release. Murine Kupffer cells (C57BL/10J) also released TNF-α as well as the chemokines keratinocyte-derived chemokine (KC) and MIP-2 in response to fungal component. Surprisingly, Kupffer cells from TLR4-deficient C57BL/ScCr mice exhibited significantly enhanced production of KC and MIP-2 upon stimulation by fungal components compared with control littermates (P 〈 0.05). Our study demonstrates that Aspergillus and Candida components induce cytokine production in rat Kupffer cells and that the response to C. albicans conidia involves Src tyrosine kinases. The experiments with TLR4-deficient Kupffer cells suggest that the cytokine response in these cells to fungal component is not mediated by TLR4.
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  • 5
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Achtundzwanzig neutropenische (〈500 Granulozyten/µl) Erwachsene mit einer mikrobiologisch oder klinisch nachgewiesenen, systemischen Mykose wurden randomisiert und behandelt mit Amphotericin B (0,5 mg/kg/Tag, n=14) oder mit einer Kombination von Amphotericin B (0,5 mg/kg/Tag) mit 5-Flucytosin (100 mg/kg/Tag, n=14) intravenös. Im Durchschnitt wurden beide Gruppen über 10 Tage behandelt, so daß sich eine totale Amphotericin B Dosis von 338 mg, bzw. 308 mg ergibt. Die Dauer der Granulozytopenie betrug durchschnittlich 18 Tage in der Amphotericin B Gruppe, und 20 Tage in der Gruppe mit Kombinationstherapie. Nur zwei Patienten in der Amphotericin B Gruppe und drei in der Kombinationsgruppe überlebten die Pilzinfektion. Die Nebenwirkungen waren vergleichbar in beiden Gruppen, mit einer Steigerung des Serum-Kreatinins bei sechs Patienten während der Verabreichung von Amphotericin B alleine, und bei sieben Patienten während der Kombinations-therapie. Andere ernsthafte Nebenwirkungen traten nicht auf. In beiden Gruppen war das Resultat der Behandlung enttäuschend, teilweise dadurch, daß die Mykose sich bereits am Anfang der Therapie zu weit entwickelt hatte und daß nur bei der Hälfte der Patienten ein Anstieg der neutrophilen Granulozyten stattfand.
    Notes: Summary Twenty-eight neutropenic (〈500 granulocytes/µl) adults with microbiologically or histologically proven systemic mycosis were randomly assigned to receive either amphotericin B alone (0.5 mg/kg/day; n=14) or amphotericin B (0.5 mg/kg/day) plus 5-flucytosine (150 mg/kg/day; n=14) intravenously. Therapy was given for an average duration of 10 days in both groups, amounting to a total dose of amphotericin B of 338 mg and 308 mg, respectively. The mean duration of granulocytopenia was 18 days in the amphotericin B group and 20 days in the combination group. Only two patients treated with amphotericin B alone and three given the combination survived. Adverse events were similiar in both groups with an elevation of the serum creatinine in six cases during the administration of amphotericin B alone and in seven cases treated with the combination. No other serious adverse events were encountered. Treatment with both regimens was disappointing partly because mycosis was too far advanced by the time therapy was begun and neutrophils were recovered in only half the patients.
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  • 6
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fungal infections are the primary cause of mortality in patients with severely impaired host defense mechanisms, such as neutropenic patients with acute leukemia or those who have undergone bone marrow transplantation. In view of the unacceptably high mortality due to disseminated candidiasis, it is rational to focus on augmentation of host defense mechanisms in addition to conventional antifungal therapy. In vitro, a variety of immunomodulators, including tumor necrosis factor, interferon-g, and the hematopoietic growth factors, enhance the killing ofCandida albicans, Aspergillus fumigatus, andCryptococcus neoformans. Various studies have demonstrated beneficial effects of immunomodulatory therapy in animal models of disseminated candidiasis. For further preclinical and clinical studies, recombinant interferon-g, interleukin-1, granulocyte colony-stimulating factor, and the other hematopoietic growth factors are currently the most promising immunomodulators.
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  • 7
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The interval from the time of admission to the emergency room until the administration of antibiotics in patients presenting with a serious infectious disease was analysed. Fifty patients presumptively diagnosed in the emergency room as having a serious infection (respiratory tract, urinary tract, erysipelas, fever with neutropenia or bacteremia) needing immediate empirical antibiotic treatment were enrolled in the study. A median interval from time of admission to administration of antibiotics of 5 hours was determined (range 0.6–13.3 h). The interval was significantly shorter in patients admitted at night than in patients admitted during office hours (3.7 vs. 6.0 h, P〈0.05). There was no difference with respect to the presenting features, body temperature, laboratory values at presentation or number of cultures performed. In 41 of the 50 patients blood samples were taken for culture. More than 80% of the patients received an antibiotic chosen in accordance with hospital guidelines. The analysis revealed that the median delay of 5 hours before patients received their initial dose of antibiotic depended on several factors. Attempts to provide optimal antimicrobial therapy should thus concentrate not only on the correct choice and dosage of a drug but also on prompt institution of therapy.
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