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The Monte Carlo Transport Project at Lawrence Livermore National Laboratory develops two Monte Carlo transport codes used in production by a sizable internal user community. Mercury is a Monte Carlo particle transport code used to model the interaction of neutrons, gammas, and light ions with a material. Imp is an implicit Monte Carlo thermal x-ray photon transport code used to model the interaction of x-ray photons with a material. This paper describes the two codes and highlights recent developments.

BACKGROUND: Coccidioides infections often result in chronic relapsing disease that presents a challenge to the currently available therapy. Posaconazole, an oral extended-spectrum triazole agent, has been shown in vitro and in vivo to have potent activity against this fungus. METHODS: An open-label multinational study of posaconazole, 800 mg/d, administered in divided doses for the treatment of invasive fungal infection that has been refractory to previous therapy was conducted. The data were reviewed by an independent data review committee (DRC). Fifteen patients met the criteria for proven coccidioidal infection and disease refractory to previous therapy. Success was a complete or partial response; nonsuccess was stable disease, lack of response to therapy, or undetermined response. RESULTS: The sites of coccidioidal infection were pulmonary (seven patients) and disseminated (eight patients). Patients were refractory to previous therapy (including amphotericin B with or without an azole) for a median duration of 306 days. At the end of treatment (posaconazole treatment duration, 34 to 365 days), therapy for 11 of 15 patients (73%) was considered to be successful by the DRC. Four responses were complete and seven were partial; these included five patients with pulmonary sites and six patients with disseminated sites. In responders, improvement was seen within months of the initiation of therapy. Five patients received therapy for >or= 12 months. The side effects were minimal. CONCLUSIONS: Therapy for coccidioidomycosis remains a clinical challenge, especially when patients have not responded to therapy with drugs that were recommended in treatment guidelines. The success rate (73%) achieved in this case series suggests that oral posaconazole should be considered as an important agent for the treatment of refractory coccidioidomycosis. [ABSTRACT FROM AUTHOR]

Background. The dexamethasone (DEX) immunosuppressive effect on macrophage killing activity and cytokine production in response to Aspergillus fumigatus conidia is antagonized by granulocyte-macrophage colony-stimulating factor (GM-CSF). The molecular mechanism is unknown. We postulated that this antagonism is mediated by inhibitor kappa B (I kappa B) induction by DEX and is opposed by acceleration of I kappa B degradation by GM-CSF with or without conidia stimulation, with corresponding effects on translocation and activation of nuclear factor kappa B (NF- kappa B).Methods. We studied 2 types of cells, resident peritoneal macrophages from CD-1 mice and the murine macrophage RAW264.7 cell line. Cells were unstimulated or stimulated with conidia and simultaneously treated with DEX, GM-CSF, or DEX plus GM-CSF, for 2-4 hours. I kappa B degradation and NF- kappa B activation were assessed by Western blot.Results. Macrophages stimulated with conidia alone increased NF- kappa B translocation. DEX increased I kappa B levels in cytoplasm and blocked translocation of NF- kappa B to the nucleus in unstimulated and conidia-stimulated macrophages. Conversely, GM-CSF decreased I kappa B levels. GM-CSF reversed the effect of DEX on I kappa B levels. NF- kappa B levels were minimal in DEX-treated macrophage nuclear extracts, compared with those from GM-CSF-treated and GM-CSF plus DEX-treated macrophages.Conclusion. GM-CSF can reverse the DEX immunosuppressive effect by enhancing I kappa B degradation and promoting NF- kappa B translocation. This would allow macrophage production of proinflammatory cytokines, facilitating resistance to aspergillosis. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Emergency situations only recently have come to include terrorist threats, such as radiation, biological and chemical attacks, and bombings. The importance of emergency preparedness in health care facilities has increased as a result of recent terrorist threats. Perioperative leaders must meet the challenge of preparing their departments for a wide range of potential disasters. This article describes how a facility can prepare for both natural and man-made disasters and reviews modifications to the Joint Commission on Accreditation of Healthcare Organizations' disaster preparedness standards. [ABSTRACT FROM AUTHOR]

LY 303366, an inhibitor of 1, 3-β-D-glucan synthase, was tested alone, or in co-culture with neutrophils or monocytes, for antifungal activity against Aspergillus fumigatus using the XTT metabolism assay. LY 303366 at 0.1 mg/L for 48 h significantly inhibited growth by conidia in a microtest plate XTT assay system. Inhibition was similar if the drug was removed after only 24 h. Microscopically this correlated with less growth and stunted malformed hyphae. LY 303366 (0.1 mg/L) also inhibited the further growth of germlines (43%) in a 24 h assay. Antifungal activity of neutrophils against 24 h control hyphal growth was limited at an effector: target ratio of 400:1. In co-cultures of neutrophils plus drug with hyphal growth from 24 h LY 303366 cultures the antifungal activity was additive. Neutrophils had a similar additive effect event if the drug were not present (i.e. when germinating conidia were pretreated with drug). Under conditions where monocytes did not have significantly antifungal activity against hyphae, they collaborated with LY 303366 for significantly increased inhibition from 38% by LY 303366 alone to 67% by co-culture. Thus, LY 303366 has activity against germinating or germinated conidia of Aspergillus, human effector cells act co-operatively with LY 303366, and LY 303366 can sensitize germinating conidia for damage by host cells. [ABSTRACT FROM PUBLISHER]

Duplicate bioassays for itraconazole and hydroxy-itraconazole were run with 30 serum samples in five laboratories, each using a different method. Both itraconazole and hydroxy-itraconazole were used as standards. Despite quantitative variations, the results of the bioassays correlated sufficiently to indicate the relative level of antifungal activity in the test samples. [ABSTRACT FROM AUTHOR]

Abstract Background Aspergillus terreus causes invasive aspergillosis (IA) in immunocompromised individuals and can be the leading cause of IA in certain medical centers. We examined a large isolate collection (n = 117) for the presence of cryptic A. terreus species and employed a genome scanning method, Inter-Simple Sequence Repeat (ISSR) PCR to determine A. terreus population structure. Results Comparative sequence analyses of the calmodulin locus revealed the presence of the recently recognized species A. alabamensis (n = 4) in this collection. Maximum parsimony, Neighbor joining, and Bayesian clustering of the ISSR data from the 113 sequence-confirmed A. terreus isolates demonstrated that one clade was composed exclusively of isolates from Europe and another clade was enriched for isolates from the US. Conclusions This study provides evidence of a population structure linked to geographical origin in A. terreus.

Abstract Background The inflammation that accompanies the pain and swelling associated with osteo- and rheumatoid arthritis is mediated by complex interactions of inflammatory mediators. Cytokines play a pivotal role in orchestrating many of these processes, including inflammatory cell recruitment, adhesion and activation. In addition, prostaglandins are secreted into the synovial cavity and are involved in perpetuation of local inflammation, vasodilatation and vasoconstriction, and also with bone resorption. Pre-clinical models have been developed in order to correlate to the human disease and principle among these is the adjuvant-induced arthritis model in the rat. Methods We have developed a technique to quantitatively assess the contents of synovial fluid samples from rat joints. Two needles joined together are inserted into the knee joint of anaesthetised rats and connected to a Watson-Marlow perfusion pump. Sterile saline is infused and withdrawn at 100 μl min-1 until a 250 μl sample is collected. Results Our results demonstrate up to 125 fold increases in synovial IL1α and IL1β concentrations, approximately 30 fold increases in levels of IL6 and IL10 and a 200–300 fold elevation in synovial concentrations of TNFα during FCA-induced experimental arthritis. Finally, this novel technique has demonstrated a dose-response relationship between FCA and the total cell counts of synovial perfusates. Conclusion In summary, this new technique provides a robust method for quantifying inflammatory mediators and cells from the synovial cavity itself, thereby detailing the inflammatory processes from within the capsule and excluding those processes occurring in other tissues surrounding the entire articulation.