The availability of genetically defined strains of mice, immunological reagents, cost and ease of handling are factors. A model was used to compare the efficacies of itraconazole and fluconazole. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. Phylogenetic and statistical analyses utilizing permutation tests were undertaken to assess correlations amongst the isolates. [2], "Hampshire Papers Series 2, Hampshire Field Club & Archaeological Society", "Dr Joseph Stevens (18181899?) David Stevens Professor Professor of Applied Mathematics, School of Mathematics Member, Centre for Ocean and Atmospheric Sciences Member, Fluid and Solid Mechanics https://orcid.org/0000-0002-7283-4405 Phone 2590 Email D.Stevens @uea.ac .uk 1.22 Sciences Overview Network Projects (14) Research output (109) To see if S. cerevisiae isolates form petite colonies in vivo, both mouse models were infected with parental grands of YJM128 and Y55. B Kemp, A Stevens, GR Dabbs, M Zabecki, JC Rose. Incremental increases in peak concentrations in serum were greatest at doses of less than or equal to 1,200 mg. To investigate whether long-term therapy altered concentrations in serum, serial data were studied by several methods. In candidosis, the number of sites of colonization correlates with invasion. Daniel's 5th outing as Bond gets bums back on seats in the cinema. Clearing of growth again by the highest drug concentrations produced a quadriphasic pattern in a tube dilution series. We noted paradoxical turbid growth of Candida albicans isolates in broth in some high (supra-MIC) concentrations. The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. The cellular DNA of each of 49 clinical and 11 nonclinical isolates of Saccharomyces was digested with the endonuclease EcoRI, and the resultant fragments were separated by electrophoresis. Macrophage inflammatory protein-1alpha (MIP-1alpha) production by BAM from BALB/c was significantly less than that from CD-1 in response to co-culture with Bd. Fluconazole is a broad-spectrum triazole. New possibilities in therapy produced plans for managing diverse clinical presentations. Randomized trials are lacking. : Twenty-one cases of vertebral aspergillosis treated with itraconazole or voriconazole were identified. Proceedings of the Society of California Archaeology 23:175-180. Comparison of the genotypes obtained by microsatellite analysis and those obtained by randomly amplified polymorphic DNA analysis, restriction fragment length polymorphism analysis, and internal transcribed sequence grouping was performed and showed that the microsatellite method could distinguish individual isolates; none of the other methods could do that. > present (Patron of the Association of Science and Discovery Centres) and [????] Who is Alice Roberts dating? Research has substantiated that animals improve human health, both psychologically and physiologically. Third Advances Against Aspergillosis Meeting 2008. The main strength of these expeditions was the recording of architecture: the plans of the DOG, in particular, are detailed, and in attempting to record how human activity impacted upon buildings, they often bridge the gap between architectural and archaeological plans (Borchardt and Ricke, 1980). Selected compounds are fungicidal towards a variety of pathogenic yeasts and molds, and a selected lead compound is efficacious in a mouse model of systemic candidosis. Intraparenchymal abscesses with inflammatory cells in their peripheries were found beginning on day 10. All AmBi-, FLC-, or AMB-treated animals survived and had prolonged lengths of survival compared with those for the controls (P < 0.0001). of Pulmonary & Critical Care Med. We also analysed gene expression with time in culture and found that while transposable elements and components of respiratory pathways tended to increase in expression with time, genes encoding ribosomal structural proteins and protein catabolism tended to sharply decrease in expression over time, particularly in yeast. Liked by David Stevens. Monotherapy studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences, Inc.) were efficacious. (Medical school lecturer of Anatomy) and [????] I am an archeologist (UCL) and award-winning lecturer and researcher and have worked in archeological projects in Arm. Date of birth. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro. Getty. My role at the University of Birmingham includes - alongside teaching and research - helping other academics to engage with wider audiences, beyond the university campus. Sixty isolates were grouped on the basis of the presence (group B) or absence (group A) of a 3-kb band. McCusker, R. W. Davis, and D.A. View details for DOI 10.3109/1040841X.2011.581223, View details for Web of Science ID 000295616800001. Concentrations of ITZ and its active metabolite, hydroxyitraconazole (OH-ITZ), in plasma and tissue samples were measured using high-performance liquid chromatography. A 56-year-old diabetic man presented with left upper lobe collapse and postobstructive pneumonitis. View the profiles of professionals named "David Stevens" on LinkedIn. The growth of A. benhamiae + and -, M. canis, and T. rubrum were all inhibited by progesterone in a dose-responsive manner, with 50% inhibition achieved at concentrations of 9.8 x 10(-6), 1.2 x 10(-5), 1.5 x 10(-5), and 2.7 x 10(-6) M. respectively,. In combination, Abelcet and caspofungin were equivalent to Abelcet alone.Abelcet proved to be efficacious, but not curative, in the treatment of CNS aspergillosis and was equivalent overall to conventional AmB. We would like to show you a description here but the site won't allow us. We think the most productive route to a fungal-specific vaccine may be a conjugate vaccine that combines the optimally configured glycan with a specific immunogenic protein. The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. With the urgent need for novel agents to combat emerging fungal resistance to existing drugs, activity in the exploration of small molecule DNA binders has increased. Cryptococcosis as a complication of the immunocompromised host has dramatically increased in frequency since the start of the AIDS epidemic. The possible adverse effects of chronic, high-dose fluconazole therapy are detailed from analysis of a multicenter, dose-escalating study of the therapy of invasive mycoses. WT and KO mice were dose-responsively susceptible. Groups of 10 received 0.8, 4, or 8 mg/kg of Abelcet, intravenously (iv), or caspofungin, intraperitoneally, 0.8 mg/kg of conventional amphotericin B (AmB) iv, or no treatment. Calderon, L., WILLIAMS, R., Martinez, M., Clemons, K. V., Stevens, D. A. Efficacy of micafungin alone or in combination against systemic murine aspergillosis. The immunological basis for a >10-fold resistance of outbred CD-1 mice compared to inbred BALB/c mice to pulmonary blastomycosis was investigated. Here we compare the virulence of a fos-1 deletion strain with that of the parental wild-type strain in a murine model of systemic aspergillosis. A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever. PMNs alone, added to hyphae, inhibited growth by 19% in the subsequent 20 h. Hyphae generated in the presence of micafungin (0.10 microg/ml) and subsequently cultured with micafungin for 24 h inhibited growth by 64%. It is demonstrated that allelic variation in any two isolates of a species can be scanned, mapped, and scored directly and efficiently without allele-specific polymerase chain reaction, without creating new strains or constructs, and without knowing the specific nature of the variation. In addition, we will address the potential of immunotherapy in combination with conventional therapy.The data derived from animal model studies of antifungal drug efficacy have proven to be predictive of clinical utility. The chemotherapy of fungal infection is also under study including the evaluation of agents in vitro; for their efficacy, pharmacology, and toxicology in animal models and in human disease. There was no significant advantage of one drug over the other for this indication. In separate previous studies, we have shown that lipid-complexed amphotericin B (Abelcet [ABLC]) and liposomal amphotericin B (AmBisome [AmBi]) are efficacious against coccidioidal meningitis in rabbits. View details for Web of Science ID 000177080400004. In a pilot reconstitution experiment in pulmonary blastomycosis, treatment of infected young mice with IFN-gamma (18.5 x 10(3) U, s.c.) on days 0, 1, and 2 significantly increased survival. In a set of serial isolates, an increase in azole resistance correlated with the loss of heterozygosity at the MTL locus, lending further strength to the correlation. She's a mother to two children and holds a post as Professor of Public Engagement in Science at the University of Birmingham. Stevens, D. A., Denning, D. W., Shatsky, S., Armstrong, R. W., Adler, J. D., Lewis, B. H. Activity of voriconazole combined with neutrophils or monocytes against Aspergillus fumigatus: Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Cytokine measurement showed HKY significantly promoted IFN, IL-6 and IL-17A production by spleen cells and lymph node cells (all P<0.05 and P<0.01, respectively). 3M-003 at 1 or 3 microM was optimal for the stimulation of PBMC to produce tumor necrosis factor-alpha and interleukin-12p40 in 24 h. For indirect tests, monolayers were treated with supernatants for 18 h, the supernatants were removed, and effector cells were tested; the supernatants enhanced (P<0.05-0.01) killing, in 2-4-h assays, by neutrophils from 42% to 73%, macrophages from 0% to 23%, and monocytes from 0% to 20%. In a second study, mice were challenged with 6.4 x 10(6) conidia and given no treatment, 8 mg/kg of Abelcet or caspofungin, alone or in combination. He believes that we must harness the human mind, especially working in focused groups, as the . Iodide in the Ocean:Distribution and Impact on Iodine Flux and Ozone Loss. Archaeologist David Sedat (MA, Anthropology, '72), an admired authority on Maya history and culture, reckons his professional life in archaeological terms. Fungal infections are increasing, with a changing landscape of pathogens and emergence of new groups at risk for invasive disease. This would allow macrophage production of proinflammatory cytokines, facilitating resistance to aspergillosis. Sugar, A. M., ALSIP, S. G., Galgiani, J. N., Graybill, J. R., Dismukes, W. E., Cloud, G. A., CRAVEN, P. C., Stevens, D. A. Available at: , School of Politics and International Relations. A more selective method was developed for use on samples suspected to be heavily contaminated with other organisms, using the strategy of increased salt concentration in a broth enrichment culture to further exploit Halomonas halotolerance, and thereby inhibit other organisms. An outbreak of Candida parapsilosis fungemia involving 17 neonatal intensive care unit (NICU) patients was studied. Fluconazole appears well tolerated and safe in these doses and durations. My husband [field archaeologist David Stevens] took on the role of primary carer when we were filming, and he came with me on all the shoots. de Pauw, B., Walsh, T. J., Donnelly, J. P., Stevens, D. A., Edwards, J. E., Calandra, T., Pappas, P. G., Maertens, J., Lortholary, O., Kauffman, C. A., Denning, D. W., Patterson, T. F., Maschmeyer, G., Bille, J., Dismukes, W. E., Herbrecht, R., Hope, W. W., Kibbler, C. C., Kullberg, B. J., Marr, K. A., Munoz, P., Odds, F. C., Perfect, J. R., Restrepo, A., Ruhnke, M., Segal, B. H., Sobel, J. D., Sorrell, T. C., Viscoli, C., Wingard, J. R., Zaoutis, T., Bennett, J. E. Comparison of lipid amphotericin B preparations in treating murine zygomycosis. White, T. C., Holleman, S., Dy, F., Mirels, L. F., Stevens, D. A. fos-1, a putative histidine kinase as a virulence factor for systemic aspergillosis. Should you have information that conflicts with anything shown please make us aware by email. The effect of trypanosomiasis on human cardiac stem cells is also being explored (in collaboration with Cardiovascular Medicine at Stanford).Current efforts concern study of a model of respiratory tree aspergillosis, to understand the predilection of lung transplant patients to invasive disease (in collaboration with the Div. Cortisone acetate gave results similar to dexamethasone, but cortisone acetate suppression of BAM responses lasted 7 days, > or = 4 days longer than dexamethasone suppression. (Medical school lecturer of Anatomy), [????] Winzeler, E. A., Richards, D. R., Conway, A. R., Goldstein, A. L., Kalman, S., McCullough, M. J., McCusker, J. H., Stevens, D. A., Wodicka, L., Lockhart, D. J., Davis, R. W. Stevens, D. A., Walsh, T. J., Bistoni, F., Cenci, E., Clemons, K. V., Del Sero, G., d'Ostiani, C. F., Kullberg, B. J., Mencacci, A., Roilides, E., Romani, L. Intergenic transcribed spacer PCR ribotyping for differentiation of Saccharomyces species and interspecific hybrids. It describes a range of group problem solving methodologies and illustrates vividly how they can aid modern business. Male. View details for Web of Science ID 000223373000006. BALB/c mice were vaccinated subcutaneously 3 times with HKY, a protective reagent, and bronchoalveolar lavage fluid, spleen, lymph nodes, and serum collected 2-5 weeks later. Posaconazole is a new azole antifungal with potent activity against Coccidioides species, the causative agent of coccidioidomycosis.Twenty patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were enrolled in a multicenter trial to study the safety and tolerability of posaconazole therapy, with efficacy as a secondary end point. View 5 David Ernest Stevens Age Guide: 45-49 Mortality from invasive pulmonary aspergillosis approaches 80% with few useful therapeutic options available. The addition of 5% human serum to caspofungin at 0.1 or 0.05 microg/ml increased the inhibition to 78.6% +/- 5.8% or 58.3% +/- 19.2%, respectively (n = 10; P < 0.01 versus controls and versus the drug without serum). Diagnosing invasive fungal disease in critically ill patients. In two experiments, neutropenic CD-1 male mice were infected intracranially with 510 conidia of Aspergillus fumigatus. View details for DOI 10.1196/annals.1406.039, View details for Web of Science ID 000250750700039, Cryptococcus neoformans (Cn) var. Since macrophage production of TNF-alpha is an important innate immune response, we examined a mouse peritoneal macrophage (PM) cell line (RAW) and resident PM from CD-1 mice to study TNF-alpha production by PM stimulated with heat-killed (HK) or live B. dermatitidis yeast cells. Brummer, E., Kethineni, N., Stevens, D. A. Efficacy of Abelcet and caspofungin, alone or in combination, against CNS aspergillosis in a murine model. This block has been demonstrated to occur in vivo in animal studies. With exception of CBA/J, which showed modest resistance, all inbred strains were similarly susceptible, including DBA/2, AKR/J, C3H/HeN, A/J and C57BL/6. In these studies, we examined protection against systemic murine coccidioidomycosis by vaccination with heat-killed Saccharomyces cerevisiae (HKY). BALB/c, the reference strain in repeated experiments, was susceptible, showing persistent infection with levels of cfu at day 6 falling within a range between a twofold decrease and a fourfold increase in relation to day 1 levels. But I dont really mind that; I feel quite comfortable in my forty-year-old skin. He has been involved in more than 1000 studies and projects with major government and multinational organisations in Australasia, the USA, the UK, Europe and the Asia-Pacific region. Furthermore, person-to-person contact and the proliferation of the use of S. cerevisiae as a health-food product, in home baking, and in home brewing may be a contributing factor in human colonization and infection with this organism. Based on a targeted minimum inhibitory concentration of 0.5 g/ml VRC, a dose of 20 mg per kg body weight for the multi-dose pharmacokinetic study was selected. Paracoccidioides is the causative agent of paracoccidioidomycosis, a systemic mycosis endemic to Latin America. Full name. Paradoxical growth of some Candida albicans isolates in the presence of caspofungin (CAS) in vitro has been demonstrated previously. The 3 newest drugs include posaconazole, micafungin, and anidulafungin, whose pharmacology, toxicology, and indications are presented. His methods were remarkably effective in drawing out the real issues, enabling considerable progress to be made., M.M.E. Adjunct Clinical Professor, Rural Clinical School, University of Notre Dame Australia. Coccidioidal meningitis is lethal in humans. The result of collectin binding to opportunistic fungal pathogens (Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans, Pneumocystis) or primary fungal pathogens (Blastomyces dermatitidis, Coccidioides, Histoplasma capsulatum, Paracoccidioides brasiliensis) on interaction with host defense cells relative to complement fixation, phagocytosis, and stimulation of cytokine/chemokine production is reviewed. RFLP subtype VII-1 and C. parapsilosis sensu stricto appear to be nearly identical; C. orthopsilosis, which can be subtyped by MLST, can also be subtyped by RFLP. A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Itraconazole appears useful as a steroid sparing agent. Mouse serum and heat-inactivated mouse serum inhibited TNF-alpha production 94% when macrophages were stimulated by B. dermatitidis, whereas mouse immunoglobulin G (IgG) did not have this effect. Significant enhancement of survival over the respective monotherapies was found only with the combination of Abelcet and voriconazole. Controls showed progressive disease, whereas animals treated with either dose of either drug showed few clinical signs of infection. Expert Opinion: What To Do When There Is Coccidioides Exposure in a Laboratory. To further characterize these isolates, a comparison of restriction fragment length polymorphism (RFLP) patterns and genetic analysis were done. Five patients received therapy for >or= 12 months. In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. The development of newer antifungal drugs is creating new potential combination therapies to combat the dismal mortality rate associated with invasive aspergillosis (IA). videos, We show that the resistant phenotype is first detectable after 24 h of drug exposure. Although other studies have suggested an association between some azole resistance mechanisms and caspofungin resistance, our studies with isolates susceptible and resistant to azoles (the latter including groups with defined resistance mechanisms and derived mutants) suggest a weak association at most with a paradoxical effect. Like a superhero of the coiffe, she spends her days as a regular hair dresser, giving people layers and funky bobs. We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses. Connect any celebrity with Alice Roberts to see how closely they are linked romantically! This would allow the production of proinflammatory cytokines by macrophages, facilitating resistance to A. fumigatus. Animal models of infection are invaluable tools in studies of pathogenesis, immunological response, and for the testing of experimental therapeutics, which cannot be done in humans. We tested the efficacy of micafungin (FK) alone or in combination with other antifungals against systemic murine aspergillosis. These models have been used to determine efficacy of experimental therapeutics, comparative virulence of different isolates of Aspergillus, genes involved in virulence, and susceptibility to infection with Aspergillus. It involves long hours, and often being away from home for days and weeks at a time. d*****@utah.gov. With a combination of these techniques, 14/15 cultures of dialysates and 10/38 from the outflow pathways of the machines were Halomonas positive, compared to 0/31 cultures from the inflow side of the machines (including water supplies and storing, mixing, and preparation tanks). We examined the global epidemiology of C. parapsilosis and assessed the discriminatory capabilities of restriction fragment length polymorphism (RFLP) and RAPD typing methods. Three of eight animals given 15 mg of AmBi per kg had no detectable infection in either tissue, whereas other doses of AmBi or FLC cleared either the brain or the spinal cord of infection in fewer rabbits. van Asbeck, E., Clemons, K. V., Martinez, M., Tong, A., Stevens, D. A. Joseph Stevens (born 14 April 1818, died 7 April 1899) was a British archaeologist, former medical doctor, and antiquarian. Fewer ABLC-treated rabbits (four of eight treated with 7.5 mg/kg and five of eight treated with 15 mg/kg) than controls (nine of nine) had meningitis at any level of severity (P, 0.015 or 0.043 for animals treated with ABLC at 7.5 or 15 mg/kg, respectively). This study indicates that treatment of mallard ducks with VRC might require a dosing interval of at least every 8-12 h at a dose of 20 mg/kg, but further studies are necessary. The infants had been hospitalized for at least six weeks, had received broad-spectrum antibiotics, and had received parenteral lipid nutrition via a central venous catheter. Stevens, D. A., Kan, V. L., Judson, M. A., Morrison, V. A., Dummer, S., Denning, D. W., BENNETT, J. E., Walsh, T. J., Patterson, T. F., Pankey, G. A. After a long period of relative inactivity in the introduction of new antifungals, more recently a few new drugs of already existing classes have been introduced. The efficacy of intravenously administered liposomal amphotericin B (AmBisome [AmBi]) for the treatment of experimental coccidioidal meningitis was compared with those of oral fluconazole (FLC) and intravenously administered conventional amphotericin B (AMB). PATHOGENICITY OF SACCHAROMYCES-CEREVISIAE IN COMPLEMENT FACTOR-5 DEFICIENT MICE. Of 35 speciated isolates, 22 were H. stevensii, 10 H. johnsoniae, and 3 H. hamiltonii. Male New Zealand White rabbits were infected with 5 x 10(4) Coccidioides posadasii arthroconidia by direct cisternal puncture. View details for DOI 10.1016/j.diagmicrobio.2010.06.010, View details for Web of Science ID 000283833100005. Differences among mouse strains in susceptibility to C. albicans, as seen in previous studies involving nonvaginal challenge routes, are not reflected in this vaginal candidiasis model; in general, such resistance patterns appear specific to the route of challenge administration. View details for Web of Science ID 000186262900004, View details for Web of Science ID 000184264100014. This review will detail the available in vitro, in vivo, and clinical experience with the newer antifungal and immunomodulatory therapies in development for treatment of invasive aspergillosis. Histopathologically, VCZ-treated birds did not have necrotic lesions and showed a trend toward fewer with acute inflammatory changes. Recovered colonies were counted and confirmed as grand or petite, and the frequency of petite colonies in the brain, the target organ, correlated with the in vitro results. In an assessment of innate responses, we found spleen cells from young mice produced three-fold less IFN-gamma and three-fold less IL-2 than adult spleen cells in response to 1 microg/ml concanavalin A (Con A). Other groups included conventional amphotericin B (1 mg/kg), Abelcet at 10 or 12 mg/kg or 5% dextrose water (diluent control).All controls died and all treatment regimens significantly prolonged survival. A. fumigatus DNA was detected in blood (88%), brain (96%), CSF (52%) and spinal cord (92%) samples. Self 1 episode, 2002 Ron Curley . Multiple Modes of Monumentality: Case Studies from the American South. Fluconazole at 10 mg/kg did not reduce the fungal burden in secondary sites, the lungs and kidneys, whereas this itraconazole dose was more effective in clearing the fungi from both organs (P < 0.05 and P < 0.001, respectively). It has been shown to be efficacious in various forms of superficial candidosis, including esophageal disease. Plasma samples were collected for ultra performance liquid chromatography (UPLC) or bioassay analysis. These data indicate that RCZ should be studied further. 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In frequency since the start of the AIDS epidemic considerable progress to be in... New possibilities in therapy produced plans for managing diverse clinical presentations plasma and tissue samples measured. Children and holds a post as Professor of Public Engagement in Science at the University of.. Causative agent of paracoccidioidomycosis, a systemic mycosis endemic to Latin America compared to inbred BALB/c mice to pulmonary was... Be studied further ; David Stevens & quot ; David Stevens & quot ; David &! Protein-1Alpha ( MIP-1alpha ) production by BAM from BALB/c was significantly less than that from CD-1 in response to with! High dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic.. Response to co-culture with Bd drugs include posaconazole, micafungin, and being. Methods were remarkably effective in drawing out the real issues, enabling considerable progress to be made. M.M.E., and 3 H. hamiltonii amongst the isolates I feel quite comfortable in my forty-year-old skin include,! Enhancement of survival over the respective monotherapies was found only with the combination Abelcet. A post as Professor of Public Engagement in Science at the University Notre... Cas ) in vitro has been shown to be efficacious in various of!
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