Brahm Segal

..This information suggests that strategies to target CD4+ T cell effector maturation may promote host immunity to Aspergillus and unexpectedly demonstrates the use for Af extract as a CD8+ T cell adjuvant...

..We review the epidemiology, diagnosis, and management of invasive mould infection in HSCT, with a focus on allogeneic recipients. We also discuss options for prevention and early treatment of invasive mould infections...

..Prophylactic antibiotics, BMT, and the use of exogenous cytokines, such as IFN-gamma and G-CSF, are appropriate for specific phagocytic disorders. Gene therapy is a promising strategy for several of the phagocytic disorders...

..We review data from in vitro and animal model studies as well as insights from clinical trials to discuss current thoughts and highlight the gaps in our knowledge surrounding combination antifungal therapy...

..This model is based on studies in mice and requires correlation in humans...

..Their roles in priming multiple host defense pathways are being exploited in vaccine development for cancer and infectious diseases...

..We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge...

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..g., vaccines). Immunotherapy must be tailored to specific immunocompromised states. Challenges exist in bringing promising immunotherapies from the laboratory to clinical trials...

..In addition, there has been an increased understanding of the immunology of Aspergillus infection, paving the way to novel immune augmentation strategies in animal models that merit evaluation in phase I clinic trials...

..Finally, we discuss the implications of newer antifungal agents and diagnostic adjuncts in the design of future clinical trials to evaluate prophylaxis and early prevention strategies...

..Macrophages are therefore a target for immune augmentation strategies that include administration of cytokines, colony-stimulating factors, and pathogen recognition receptor ligands...

..However, if such patients develop fever during neutropenia, they should be considered for outpatient empiric therapy with an oral quinolone-containing regimen if they meet criteria for low risk for complications...

..This article reviews the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of the major fungal pathogens in nontransplant patients with hematologic malignancies...

..g., inflammatory bowel disease). The mechanisms by which NADPH oxidase regulates inflammation are not well understood...

..The predominance of coagulative necrosis in our series may reflect the high doses of corticosteroids used to treat graft-versus-host disease (GVHD), which may have disabled leukocyte trafficking and hyphal killing...

..We will review insights gained in host defense against Aspergillus species and the immunopathogenesis of Aspergillus-related diseases as well as important advances made in fungal diagnostics and antifungal therapy...

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..Given that randomized studies are unrealistic, studies involving carefully selected, matched, contemporaneous control subjects are likely to be the most useful alternative...

..Finally there has been increasing interest on combination therapy for invasive aspergillosis due to the high rate of failure of the currently available antifungals, especially in the profoundly immunocompromised host...

..Collectively, these results show that ganciclovir suppresses T-lymphocyte proliferation in vitro by inhibiting DNA synthesis; with implications for T-lymphocyte function following allogeneic BMT...

..fumigatus challenge and also demonstrated unique features of CGD mice as a model for experimental aspergillosis...

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..Multiple courses may be necessary to achieve or maintain response in some patients, and prolonged BDP therapy is a feasible alternative to prolonged systemic corticosteroids...

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..In this preliminary study, salvage treatment with posaconazole was safe and effective...

..Despite advances in the diagnosis and management, invasive fungal diseases contribute substantially to the morbidity and mortality of patients with prolonged neutropenia...

..Together, our study demonstrated a role for ST6Gal-1, possibly from extramedullary sources (eg, produced in liver) in regulating inflammation, circulating neutrophil homeostasis, and replenishing granulocyte numbers...

..Applying this response surface method to a huge data set for a three-antifungal-agent combination is novel. This new paradigm has the potential to significantly advance the field of combination antifungal pharmacology...

..We speculate that this downmodulating effect may be mediated by promoting the transition from production of cytokines and chemokines involved in neutrophilic infiltration to a less injurious, chronic inflammatory response...

..Sequencing showed a G2576U mutation in the 23S rRNA gene. Because of the important niche of linezolid in cancer treatment, linezolid-resistant E. faecalis is noteworthy...

..This case demonstrates the potential risk for opportunistic fungal infections in patients treated with high-potency lipophilic inhaled corticosteroids...

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..This notion is only partially accurate. Immune-based therapies for fungal CNS disease are at an exploratory level and merit further evaluation in clinical trials...

..Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA...

..Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step...

..Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species...

..Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies...

..These data indicate that the NADPH oxidase-dependent respiratory burst stimulated by Pseudomonas infection contributes to host defense by modulating redox-dependent signaling through the NF-kappaB pathway...

..Our proposal will evaluate mechanisms by which NADPH oxidase regulates inflammation that will be important to our understanding of CGD, and will be broadly relevant to pathologic conditions, such as inflammatory disorders and cancer. ..